NKF Clinical Digest - COVID-19
NKF Clinical Digest — COVID-19
Current research regarding COVID-19 and its implications.
A message from our Chief Medical Officer
Welcome to the NKF Clinical Digest. This resource is an ongoing compilation of the latest clinical information regarding COVID-19, curated by NKF subject matter experts. Our goal is to make it easy for the interdisciplinary team to find current data on the implications of COVID-19 for people living with kidney diseases. The NKF Clinical Digest will also provide links to the most current patient resources and educational tools developed by NKF to support people living with kidney diseases through this crisis. This compendium of resources will also include information regarding NKF’s recent advocacy activities to improve the care and the safety of people living with kidney diseases. We hope that you find the NKF Clinical Digest – COVID-19 a valuable resource as you care for kidney patients during these extraordinary times.
– Joseph A. Vassalotti, MD
Chief Medical Officer, National Kidney Foundation
General information about COVID-19
COVID-19 Risk Factors among Health Workers
A rapid literature review of 11 studies indicates that COVID-19 presents an occupational health risk for health workers. The literature search included reports, reviews, and primary observational studies of health workers that reported COVID-19 risk factors regardless of their sample size. Risk factors included lack of personal protective equipment, exposure to infected patients, work over-load, poor infection control, and preexisting medical conditions.
Another COVID-19 risk factor was exposure to infected patients mainly through work in high-risk departments and contaminated fluid/aerosols. Work over-load was associated with lack of rest, longer exposure to infected patients, and working under pressure. Some improper infection control issues were related to direct contact with contaminated surfaces and suboptimal hand hygiene. A review of physician deaths from COVID-19 revealed the following risk factors: age >57 years (75% of deaths), male gender (90% of deaths), and preexisting conditions (HTN, DM, CVD, chronic lung disease, and immunocompromised individuals).
The authors conclude that “In the context of COVID-19, health workers face an unprecedented occupational risk of morbidity and mortality. There is need for rapid development of sustainable measures that protect health workers from the pandemic.”
Source: Mhango M, Dzobo M, Chitungo I, Dzinamarira T. COVID-19 risk factors among health workers: a rapid review. Saf Health Work. 2020;11:262-265.
COVID-19 Frequently Causes Neurological Injuries
A recent retrospective study has found that in approximately 1 in 7 hospitalized adult patients, COVID-19 may cause neurological dysfunction ranging from temporary confusion due to hypoxia to stroke and seizures in the most serious cases.
In this study, 606 hospitalized adult patients with COVID-19 and brain or other nerve-related medical conditions were monitored between March 10 and May 20, 2020. While there were no reported cases of brain or nerve inflammation, including conditions such as meningitis or encephalitis, the neurological complications of COVID-19 raised the risk of in-patient mortality by 38%. These complications also increased the likelihood of patients requiring long-term or rehabilitation therapy upon hospital discharge by 28%.
Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment scores (all P<0.05). Common neurological problems, such as chemical electrolyte imbalance confusion, severe infection, or kidney failure, usually arose within 48 hours of developing general COVID-19 symptoms, including fever, difficulty breathing, and cough.
The authors conclude that COVID-19 is known to attack multiple organs, including the lungs, which can result in diminished oxygen levels in the body and suggest various blood-oxygen-raising therapies may improve neurological problems in patients with COVID-19, including early intubation or extracorporeal membrane oxygenation.
Source: Frontera JA, Sabadia S, Lalchan R, et al. A prospective study of neurologic disorders in hospitalized COVID-19 patients in New York City. Neurology. 2020, Oct 5.
Reinfection with COVID-19: A Case Study
A case study using viral genomic sequencing indicates that a patient was infected by SARS-CoV-2 two separate times by a genetically distinct virus within a 48-day period. The patient was a 25-year-old male living in Washoe County, Nevada, with no history of clinically significant underlying conditions and no compromised immunity. The patient tested positive for SARS-CoV-2 in April 2020 (symptoms started on March 25, 2020), subsequently tested negative on two separate occasions, and tested positive again in June 2020 (symptoms started on May 28, 2020). Symptoms were more severe with the second infection. Of the four other reinfection cases reported in Belgium, the Netherlands, Hong Kong, and Ecuador, only the case in Ecuador and increased symptom severity.
The authors conclude that “previous exposure to SARS-CoV-2 might not guarantee total immunity in all cases. All individuals, whether previously diagnosed with COVID-19 or not, should take identical precautions to avoid infection with SARS-CoV-2. The implications of reinfections could be relevant for vaccine development and application.”
Source: Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet. Published online October 12, 2020.
Neonates Born to Mothers with COVID-19
To study the outcomes of neonates born to mothers with perinatal SARS-CoV-2 infection and the infection prevention and control (IPC) practices associated with these outcomes, a retrospective cohort analysis reviewed the medical records for maternal and newborn data for all 101 neonates born to 100 mothers positive for or with suspected SARS-CoV-2 infection from March 13 to April 24, 2020. Newborns were admitted to well-baby nurseries (WBNs) (82 infants) and neonatal intensive care units (19 infants) in 2 hospitals from a large medical center in New York, New York. Newborns from the WBNs roomed-in with their mothers, who were required to wear masks. Breastfeeding after proper hygiene was promoted.
The primary outcome was newborn SARS-CoV-2 test results. Maternal COVID-19 status was classified as either asymptomatic/mildly symptomatic or severe/critical. Newborn characteristics and clinical courses were compared along the maternal spectrum of COVID-19 severity. There were a total of 141 test results from 101 newborns (54 girls [53.5%]) on 0 to 25 days of life (DOL-0 to DOL-25) (median, DOL-1; interquartile range [IQR], DOL-1 to DOL-3). Two newborns had indeterminate test results, indicating low viral load (2.0%; 95% CI, 0.2%-7.0%); 1 newborn was never retested but was well at follow-up, and the other had negative results when retested.
Maternal severe/critical COVID-19 was associated with newborn delivery approximately 1 week earlier (median gestational age, 37.9 [IQR, 37.1-38.4] vs 39.1 [IQR, 38.3-40.2] weeks; P = .02) and increased risk for needing phototherapy (3 of 10 [30.0%] vs 6 of 91 [7.0%]; P = .04) compared with newborns of mothers with asymptomatic/mild COVID-19. Fifty-five newborns followed up in a COVID-19 Newborn Follow-up Clinic at DOL-3 to DOL-10 and were healthy. Twenty of these newborns plus 3 newborns followed up elsewhere had 32 nonroutine encounters at DOL-3 to DOL-25, and none showed evidence of SARS-CoV-2 infection, including 6 with negative retesting results.
No clinical evidence of vertical transmission was found in 101 newborns of mothers who were either positive for, or who were suspected of having, SARS-CoV-2 infection, despite most newborns underwent rooming-in and breastfeeding. The authors concluded that these results suggest that during the COVID-19 pandemic, separation of mothers affected by COVID-19 and their newborns may not be necessary, and that breastfeeding appears to be safe.
Source: Dumitriu D, Emeruwa UN, Hanft E, et al. Outcomes of neonates born to mothers with severe acute respiratory syndrome coronavirus 2 infection at a large medical center in New York City. JAMA Pediatr.2020. doi:10.1001/jamapediatrics.2020.4298
Patterns of COVID-19-reactive CD4+ T cells in Disease Severity
A small, international study investigating how CD4+ T cells respond to the SARS-CoV-2 virus has found that early in the illness course, patients hospitalized with severe cases of COVID-19 develop a novel T-cell subset that can potentially kill B cells and reduce antibody production.
The researchers studied samples from 40 COVID-19 patients who were separated into 2 groups (hospitalized and non-hospitalized). The hospitalized group included 22 patients (9 in ICU). The non-hospitalized group had 18 patients who had experienced milder COVID-19 symptoms.
Single-cell RNA-sequencing (RNA-seq) were used to analyze the types of CD4+ T cells that responded to SARS-COV-2 in these patients. The authors found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responded to SARS-CoV-2 and reduced a proportion of SARS-CoV-2-reactive regulatory T cells (TREGs). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness, which negatively correlated with antibody levels to SARS-CoV-2 spike protein.
The authors conclude that their analyses provide insights into patterns of SARS-CoV-2-reactive CD4+ T cells in disease severity.
Source: Meckiff, BJ, Ramírez-Suástegui, C, Fajardo, V, et al. Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19. Cell. 2020, Sep 30.
Covid-19 Transmission Among Bus Riders in Eastern China
A cohort study and case investigation of 128 participants (88.3% women, mean age 58.6 years) indicates that in a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus with air recirculation and a patient infected with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event.
On January 19, 2020, 128 individuals took 2 buses (bus 1 n=60 [46.9%] and bus 2 n=68 [53.1%]) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. In both buses, windows were closed, and central air conditioners were set on indoor recirculation mode. On bus 2, 24 of the 68 individuals (35.3% [including the source patient]) were diagnosed with COVID-19 after the event, while none of the 60 individuals in bus 1 were infected. Additionally, 7 (4.1%) out of the other 172 individuals at the worship event were subsequently diagnosed with having COVID-19. Individuals in bus 2 had a 34.3% higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 times more likely to have COVID-19 compared with all other individuals in attendance of the worship event. Individuals sitting closer to the source patient on bus 2 did not have a statistically higher risk of COVID-19 compared to those sitting further away. The authors conclude that “Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus.”
Source: Shen Y, Li C, Dong H, et al. Community Outbreak investigation of SARS-CoV-2 transmission among bus riders in eastern China. JAMA Intern Med. 2020, Sep 1.
Clinical Screening for COVID-19 in Asymptomatic Patients with Cancer
From April 30 through June 2, 2020, the Weill Cornell Medicine Division of Hematology and Medical Oncology in New York, New York, undertook a quality improvement study and performed 621 SARS-CoV-2 PCR tests on 537 asymptomatic patients (272 [50.7%] men) with hematologic or solid tumor malignant neoplasms. More than 90% of patients were receiving active cytotoxic or targeted therapy.
The rate of SARS-CoV-2 positivity was 0.64% (95% CI, 0.18%-1.64%), including 84 patients who had repeated SARS-CoV-2 tests, all of which were negative. Only 4 asymptomatic patients had test results positive for COVID-19, 2 each for hematologic and solid tumor neoplasms. They also performed serological tests from May 18 to June 2, 2020, on 238 asymptomatic patients. The rate of COVID-19 prior exposure in their asymptomatic cancer population was 4.23% (95% CI, 2.05%-7.65%).
The authors note that the rate of past infection in their clinically screened asymptomatic cancer population was extremely low, at approximately 4%, and the rate of SARS-CoV-2 PCR positivity was less than 1%. This starkly contrasts the COVID-19 prevalence in New York City at that time, which was near 20%. While the authors do not know the reason for this low prevalence rate, it is likely that these highly motivated patients adhered to social distancing recommendations, masking, and hygiene.
They observed that patients whose test results were negative for COVID-19 could receive chemotherapy without increasing the risk of contracting the disease, supporting the argument that clinicians may resume anticancer therapy in asymptomatic patients.
Despite study limitations, the authors contend that these data provide some reassurance to healthcare workers and patients that oncological treatment may safely continue. They conclude that cancer care should continue, since delays in treatment will lead to significantly worse patient outcomes.
Source: Shah MA, Mayer S, Emlen F, et al. Clinical screening for COVID-19 in asymptomatic patients with cancer. JAMA Netw Open. 2020;3:e2023121.
IDSA Guidelines on the Diagnosis of COVID-19: Serologic Testing
The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct best practice guidance related to SARS-CoV-2 serologic testing. Information on the clinical performance and utility of SARS-CoV-2 serologic tests are rapidly emerging. Based on available evidence, detection of anti-SARS-CoV-2 antibodies may be useful for confirming the presence of current or past infection in selected situations. The panel identified three potential indications for serologic testing including: 1) evaluation of patients with a high clinical suspicion for COVID-19 when molecular diagnostic testing is negative and at least two weeks have passed since symptom onset; 2) assessment of multisystem inflammatory syndrome in children; and 3) for conducting serosurveillance studies. The certainty of available evidence supporting the use of serology for either diagnosis or epidemiology was, however, graded as very low to moderate.
Source: Hanson KE, Caliendo AM, Arias CA, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing. Clin Infect Dis. 2020, Sep 12.
Gastrointestinal Complications in Critically Ill Patients With and Without COVID-19
A study that compared the incidence of gastrointestinal (GI) complications of critically ill patients with COVID-19-induced acute respiratory distress (ARDs) (n= 486, median age 60.5 years, 66.5% males) vs comparably ill patients with non-COVID-19 ARDS (n=244, median age 62 years, 54.9% males) indicates patients with COVID-19 were more likely to develop GI complications (74% vs 37%).
Ninety-two patients with COVID-19 and ARDS were propensity score matched to 92 patients with non–COVID-19 ARDS; adjusting for demographics (e.g., age, sex, body mass index, smoking status), comorbidities (e.g., chronic lung/kidney disease, congestive heart failure, coronary artery disease, hypertension, diabetes), and severity of illness on ICU admission. The patients with COVID-19 developed more transaminitis (55% vs 27%), severe ileus (48% vs 22%), and bowel ischemia (4% vs 0%). The authors report the explanation for this may be related to high expression of angiotensin-converting enzyme 2 receptors along the epithelial lining of the gut that act as host-cell receptors for SARS-CoV-2. They also attribute the disproportionately high rate of ileus and ischemic bowel disease to higher opioid requirements and COVID-19–induced coagulopathy. The authors conclude that “Further translational studies are warranted to examine the pathophysiology of these findings.”
Source: El Moheb M, Naar L, Christensen MA, et al. Gastrointestinal complications in critically ill patients with and without COVID-19. JAMA. 2020, Sep 24.
Association of SARS-CoV-2 Test Status and Pregnancy Outcomes
Researchers at the Karolinska University Hospital, Stockholm, Sweden compared pregnant women in labor who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those uninfected. They identified all women presenting in labor from March 25 to July 24, 2020 with reverse transcriptase–polymerase chain reaction (RT-PCR) testing of nasopharyngeal swabs on all women in labor, regardless of symptoms. If test results were positive, patient symptoms were documented. If a patient tested positive during pregnancy but negative when presenting in labor, she was considered exposed (n = 11). During the study period, 3 patients were positive for antibodies against SARS-CoV-2 during pregnancy and were not tested with RT-PCR, and they were considered exposed. Patients who tested positive were matched to those who were negative based upon information about multiple pregnancies and a propensity score (estimated with logistic regression) including age, parity, early-pregnancy body mass index, educational level, birth country, smoking, living with partner, and pre-pregnancy comorbidity.
Among 2682 patients presenting in labor, 156 (5.8%) were SARS-CoV-2 positive (142 [91%] at admission and 14 [9%] during pregnancy). Sixty-five percent who tested positive were asymptomatic. The authors matched 155 patients testing positive to 604 testing negative. After matching, the groups were well balanced on all covariates. Patients who tested positive were more likely to have preeclampsia (7.7% vs 4.3%; prevalence ratio, 1.84; 95% CI, 1.004-3.36) and less likely to have induced labor (18.7% vs 29.6%; prevalence ratio, 0.64; 95% CI, 0.45-0.90). Other maternal outcomes, including delivery mode, postpartum hemorrhage, and preterm birth, were not significantly different between groups. Infants did not differ in 5-minute Apgar score and birth weight for gestational age. All results were similar in the sensitivity analysis, but the association with preeclampsia was non-significant (prevalence ratio, 1.70; 95% CI, 0.89-3.25). SARS-CoV-2 test positivity in patients in labor was associated with a higher prevalence of preeclampsia and lower prevalence of induced labor.
The authors concluded from this data and other studies, that COVID-19 is less severe in pregnancy than the 2 previous coronavirus infections, severe acute respiratory syndrome–related coronavirus (SARS) and Middle East respiratory syndrome–related coronavirus (MERS). However, they do note reports of pregnant women requiring critical care, as well as reports of both mother and infant deaths associated with COVID-19.
Source: Ahlberg M, Neovius M, Saltvedt S, et al. Association of SARS-CoV-2 Test Status and Pregnancy Outcomes JAMA. 2020, Sep 23.
Frequency of Children vs Adults with Asymptomatic COVID-19
From March 1 to April 30, 2020, the frequency of COVID-19 among children admitted to a hospital in Milan for noninfectious disorders and no signs or symptoms of COVID-19 was compared with the frequency of COVID-19 among a similar population of adults.
Patients with any signs or symptoms associated with COVID-19, as well as those with a history of close and extensive contact with people who had tested positive for COVID-19, or, with a history of symptoms or signs consistent with COVID-19 in the previous 21 days, were excluded, as were individuals for whom only 1 nasopharyngeal swab was available. Data on age, sex, the reason for admission, and development of any COVID-19 signs of infection in the following 48 hours were collected retrospectively. A comparison of proportions between the pediatric and adult cohorts was made.
Of the 881 children who presented to the pediatric emergency department, 83 (34 girls and 49 boys; median [interquartile range] age, 5.3 [1.1-11.0] years) fulfilled the eligibility criteria. During the same period, of the 3610 adults presenting to the adult emergency department, 131 (51 women and 80 men; median [interquartile range] age, 77 [57-84] years) were included. Children were found to be less frequently positive than adults (1 in 83 children [1.2%] vs 12 in 131 adults [9.2%]; P = .02), with an odds ratio of 0.12 (95% CI, 0.02-0.95) compared with adults. Eleven of 12 adults were positive for COVID-19 at the first swab. None of the included participants developed signs or symptoms of SARS-CoV-2 infection in the 48 hours after the admission.
Despite study limitations, the authors conclude that these preliminary results can help to understand the epidemiology of COVID-19. Notably, these data do not support the hypothesis that children more frequently carry COVID-19 asymptomatically than adults.
Source: Milani GP, Bottino I, Rocchi A, et al. Frequency of children vs adults carrying severe Acute Respiratory Syndrome Coronavirus 2 asymptomatically. JAMA Pediatr. 2020, Set 14.
Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19
An observational study using cardiovascular magnetic resonance (CMR) imaging in 26 college athletes (mean age 19.5 years, 15 male) who tested positive for COVID-19 between June and August 2020 indicates that 4 (15%) had findings suggestive of myocarditis and 8 additional athletes (30.8%) had findings suggestive of prior myocardial injury.
None of the study subjects were hospitalized or received antiviral therapy specific for COVID-19. Twelve athletes (26.9%) had mild symptoms including sore throat, shortness of breath, myalgias, and fever, while others were asymptomatic. The 4 athletes with CMR findings suggestive of myocarditis had 2 main features of the Lake Loise Criteria: myocardial edema by elevate T2 signal and myocardial injury by presence of nonischemic late gadolinium enhancement (LGE). The authors conclude that “CMR may provide an excellent risk-stratification assessment for myocarditis in athletes who have recovered from COVID-19 to guide safe competitive sports participation.”
Source: Rajpal S, Tong MS, Borchers J, et al. Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol. 2020, Sep 11.
Asthma among Hospitalized Patient with COVID-19
A study of 1298 patents aged <65 years hospitalized with severe COVID-19 in the New York City area from February 11 to May 7, 2020 indicates that patients with asthma did not have worse outcomes, regardless of age, obesity, or other high-risk comorbidities (i.e., hypertension, hyperlipidemia, and diabetes). Patients with COPD were excluded from the study.
While the overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6% (n=163), the researchers found a higher prevalence (23.6%) in a subset of 55 patients less than 21 years of age. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission, or mortality between patients with and without asthma. The authors conclude that: “Associations between COVID-19 and asthma should be investigated further in a larger pediatric population. Also, population-based studies are needed to determine whether asthma is a risk factor for developing COVID-19 once universal testing becomes readily available.”
Source: Lovinsky-Desir S, Deshpande DR, De A, et al. Asthma among hospitalized patients with COVID-19 and related outcomes. J Allergy Clin Immunol. 2020, Aug 6.
Increased Risk of COVID-19 in Patients with Sleep Apnea
Obstructive sleep apnea (OSA), a condition characterized by complete or partial blockage of the airways during sleep, is often diagnosed in people who snore, appear to stop breathing, or make choking sounds during sleep.
In the United Kingdom, 1.5 million people have been diagnosed with OSA and the authors believe up to 85% of sleep apnea disorders are undetected. Many of the risk factors and comorbidities associated with OSA, such as diabetes, obesity, and hypertension, are similar to those associated with poor COVID-19 outcomes.
In this study, the researchers investigated whether patients with confirmed OSA diagnosis conferred an additional risk to these factors. With obesity rates and other related risk factors on the increase, the researchers also believe that rates of OSA are increasing.
The authors conducted a systematic review of 18 studies through June 2020 and evaluated patients with OSA and COVID-19. Eight of the studies focused on the risk of death from COVID-19 and 10 studies were related to diagnosis, treatment, and management of OSA. The researchers found that many patients who presented to intensive care had OSA and in diabetic patients the condition may confer an increased risk that is independent to other risk factors. In one large study, hospitalized COVID-19 patients with diabetes who were also receiving treatment for OSA, were at 2.8 times greater risk of dying on the 7th day after hospital admission.
Patients with diagnosed OSA should be cautioned about their potential additional risk for severe outcomes from COVID-19 and should take appropriate actions to reduce their exposure to the virus.
Source: Miller MA, Cappuccio FP. A systematic review of COVID-19 and obstructive sleep apnoea. Sleep Medicine Reviews. 2020, Sep 8.
Humoral Immune Response in COVID-19 in Iceland
A study that measured COVID-19-specific antibodies (using six assays) in up to 30,576 patients in Iceland beginning in early February 2020 and ending in early July 2020 indicates that antiviral antibodies against COVID-19 did not decline within 4 months after diagnosis. Antibodies peaked in 25 days after a positive diagnosis and remained stable thereafter in more than 90 percent of recovered patients.
Of the six antibody assays used, two targeted the entire span of IgG, IgA, and IgM antibodies rather than only one type. Antibody levels were higher with older age. After adjustment for multiple testing, the researchers found that body-mass index correlated positively with COVID-19 antibody levels; while smoking and use of anti-inflammatory medication were linked to lower antibody levels. COVID-19 antibody levels were most strongly associated with hospitalization and clinical severity of clinical symptoms such as fever, maximum temperature reading, and cough. The authors note that a relationship between a humoral immune response to COVID-19 and protection against reinfection by this virus has not been established in humans.
Source: Gudbjartsson DF, Norddahl GL, Melsted P, et al. Humoral Immune Response to SARS-CoV-2 in Iceland. N Engl J Med. 2020, Sep 1.
Pregnant Women with COVID-19: Premature Delivery & Intensive Care Admission
It’s been well documented that being older, overweight, and having other medical conditions increase the risk of having more serious disease with COVID-19. A newly published study found hospitalized pregnant women with COVID-19 are less likely to show symptoms, more likely to experience preterm birth, and their newborns are more likely to be admitted to a neonatal unit.
In addition, the authors found non-pregnant women of reproductive age as compared to pregnant and recently pregnant women with COVID-19 were less likely to report symptoms of fever and myalgia, but were more likely to need admission to an intensive care unit and require ventilation.
Maternal risk factors associated with severe COVID-19 include increased age, high body mass index, chronic high blood pressure, and pre-existing diabetes. A quarter of all babies born to mothers with COVID-19 were admitted to a neonatal unit and were at increased risk of admission than those born to mothers without the virus. However, stillbirth and newborn death rates were low.
In conclusion, the authors say healthcare professionals should be aware that pregnant women with COVID-19 might need access to intensive care and specialist baby care facilities and that new mothers with pre-existing comorbidities are at higher risk for severe COVID-19, along with those who are obese and of older age.
Source: Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020; 370:m3320.
Influenza in the COVID-19 Era
The threat of concurrent influenza and COVID-19 epidemics is cause for concern among public health officials and clinicians. In the US, annual influenza has resulted in approximately 12,000 to 61,000 deaths annually since 2010. The COVID-19 pandemic is associated with morbidity and mortality several fold higher than that of influenza. While COVID-19 and influenza are very different pathogens, they are both transmitted by respiratory droplets. Therefore, nonpharmacologic interventions (NPIs) such as face masks and other social distancing policies could be expected to affect the incidence of both infections to varying degrees. But of greater importance is seasonal influenza vaccination to minimize the viral reservoir in the population.
The clinical implications of influenza and COVID-19 are very different including approaches to management, presentation of symptoms, and virus identification. As the influenza season approaches, patients presenting with nonspecific respiratory viral infection should be tested for COVID-19. Another important issue for consideration is that since coinfection with influenza and COVID-19 has been reported, a positive result for one virus does not exclude infection with the other.
The authors conclude that “the 2 most effective infection prevention tools currently available are widespread implementation of seasonal influenza vaccination and preservation of NPIs until community immunity is achieved through an effective COVID-19 vaccine and/or natural infection.”
Source: Solomon DA, Sherman AC, Kanjilal S. Influenza in the COVID-19 Era. JAMA. 2020, Aug 14.
Evaluation of COVID-19 in Breast Milk from Infected Women
There have been concerns that COVID-19 may be transmitted to infants from breast milk. However, many organizations advise that women infected with COVID-19 breastfeed as long as protections are in place to prevent transmission of the virus through respiratory droplets.
To evaluate the risk of transmission of the virus via breast milk, a study was undertaken between March 27 and May 6, 2020 of 18 women with confirmed COVID-19 who were breastfeeding. Infants’ ages ranged from newborn to 19 months. Women gave between 1 and 12 samples, with a total of 64 samples collected at different times before and after the positive COVID-19 RT-PCR test result. All had symptomatic disease, except for 1 woman. One breast milk sample had detectable COVID-19 RNA. The positive sample was collected on the day when symptoms began; however, 1 sample taken 2 days prior to start of symptoms and 2 samples from days12 and 41 later tested negative for viral RNA. The breastfed infant was not tested. No replication-competent virus was detected in any sample, including the sample that was positive for viral RNA.
The authors conclude that these data suggest that COVID-19 does not represent replication-competent virus and that breast milk may not cause infection in the infant. In addition, when control samples spiked with replication-competent COVID-19 virus were treated with Holder pasteurization, no replication-competent virus or viral RNA was detected. These results are reassuring given the benefits of breastfeeding and the use of human milk from milk banks.
Source: Chambers C, Krogstad P, Bertrand K, et al. JAMA. 2020, Aug 19.
Effect of Quarantine on Sleep Quality and BMI
Objectives of the study were to investigate the effect of quarantine on sleep quality (SQ) and body mass index (BMI), and if change in SQ was related to working modalities. The study enrolled 121 adults (age 44.9 ± 13.3 years and 35.5% males). Anthropometric parameters, working modalities and physical activity were studied. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. At baseline, the enrolled subjects were assessed in outpatient clinic and after 40 days of quarantine/lockdown by phone interview.
Overall, 49.6% of the subjects were good sleepers (PSQI < 5) at the baseline and significantly decreased after quarantine (p < 0.001). In detail, sleep onset latency (p < 0.001), sleep efficiency (p = 0.03), sleep disturbances (p < 0.001), and daytime dysfunction (p < 0.001) significantly worsened.
There was also a significant increase in BMI values in normal weight (p = 0.023), in subjects grade I (p = 0.027) and II obesity (p = 0.020). In all cohort, physical activity was significantly decreased (p = 0.004). However, analyzing the data according gender difference, males significantly decreased physical activity as well as females in which there was only a trend without reaching statistical significance (53.5% vs 25.6%; p = 0.015 and 50.0% vs 35.9%, p = 0.106; in males and females, respectively).
The study found that quarantine was associated to a worsening of SQ and to an increase in BMI values.
Source: Barrea L, Pugliese G, Framondi L, et al. Does Sars-Cov-2 threaten our dreams? Effect of quarantine on sleep quality and body mass index. J Transl Med. 2020;18:318.
African Americans May Be Predisposed to COVID-19-related Cardiac Complications
One in every 13 African Americans has a genetic variant placing them at increased risk for ventricular arrhythmias and sudden cardiac death. The proarrhythmic potential of the African-specific p.Ser1103Tyr-SCN5A common ion channel variant is activated by risk factors observed in hospitalized COVID-19 patients such as hypoxemia, electrolyte abnormalities, and QT-prolonging drug use, as well as some antibiotics and antifungal medications.
Direct and/or indirect myocardial injury or stress has emerged as a prominent, prognostic feature in COVID-19. Acute myocardial injury in patients with COVID-19 may be caused by a direct COVID-19 myocardial infection; the exaggerated immune response known as the cytokine storm; or hypoxia. The profound hypoxia observed in many COVID-19 patients, raises reasonable concern that p.Ser1103Tyr-SCN5A could produce a similar, African American susceptibility to ventricular arrhythmia and sudden cardiac death from the SARS-CoV-2 infection.
The authors suggest there may be a link between p.Ser1103Tyr-SCN5A and rates of sudden death and COVID-19-related mortality in African Americans and note that this genetic risk factor, coupled with socioeconomic and cultural factors, may contribute to the racial health disparities that have been documented in victims of the COVID-19 pandemic.
Source: Giudicessi JR, Roden DM, Wilde AAM, Ackerman MJ. Genetic susceptibility for COVID-19–associated sudden cardiac death in African Americans. Heart Rhythm. 2020. In Press.
Newly Identified Cancer Before and During the COVID-19 Pandemic
A cross-sectional study of patients in the United States who received testing for any cause, and whose ordering physicians assigned them International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes associated with any of 6 cancers (breast, colorectal, lung, pancreatic, gastric, and esophageal), was performed from January 1, 2018, to April 18, 2020. Mean (SD) weekly numbers of newly diagnosed patients were compared between baseline period (January 6, 2019, to February 29, 2020) and the COVID-19 period (March 1 to April 18, 2020). The study included 278,778 patients, 258,598 (92.8%) from the baseline period and 20,180 (7.8%) from the COVID-19 period. During baseline, the mean (SD) weekly number of newly identified patients was 2,208 (335) with breast cancer, 946 (134) with colorectal cancer, 695 (88) with lung cancer, 271 (39) with pancreatic cancer, 96 (14) with gastric cancer, and 94 (14) with esophageal cancer.
During onset of the pandemic, the weekly number decreased 46.4% (from 4,310 to 2,310) for the 6 cancers combined, with significant decreases in all cancer types, ranging from 24.7% for pancreatic cancer (from 271 to 204; P = .01) to 51.8% for breast cancer (from 2,208 to 1,064; P < .001). The authors conclude that delays in cancer diagnosis observed in this study will likely lead to presentation at more advanced stages and worse clinical outcomes.
Source: Kaufman HW, Chen Z, Niles J, et al. Changes in the number of us patients with newly identified cancer before and during the Coronavirus Disease 2019 (COVID-19) pandemic. JAMA Netw Open. 2020;3(8):e2017267.
Modeling the Onset of Symptoms of COVID-19
A study of over 55,000 patients infected with COVID-19 indicates that symptoms may occur in a predictable order. The researchers applied a Markov Process to a graded partially ordered set based on clinical observations of COVID-19 cases to determine the most likely order of detectible symptoms (i.e., fever, cough, nausea/vomiting, and diarrhea) in COVID-19 patients. They also compared the progression of these symptoms in COVID-19 to other respiratory diseases, such as influenza, SARS, and MERS, to see if the diseases present differently.
The model predicts that influenza initiates with cough, whereas COVID-19 like other coronavirus-related diseases initiates with fever. However, COVID-19 differs from SARS and MERS in the order of gastrointestinal symptoms in that the upper GI tract (i.e., nausea/vomiting) seems to be affected before the lower GI tract (i.e., diarrhea) in COVID-19, which is the opposite from MERS and SARS.
The authors suggest that fever should be used to screen for entry into facilities as regions begin to reopen after the outbreak of Spring 2020.
Source: Larsen JR, Martin MR, Martin JD, Kuhn P, Hicks JB. Modeling the Onset of Symptoms of COVID-19. Frontiers in Public Health. 2020, Aug 13.
Continued ACEi/ARB use in Hypertensive COVID-19 Patients
A retrospective single-center study observed the difference between continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in 614 hypertensive COVID-19 patients during hospitalization. To adjust for confounders, patient sub-groups included those who developed hypotension and acute kidney injury (AKI) during the index hospitalization, and therefore ACEi/ARBs were withheld on clinical grounds, Mortality (22% vs 17%, p>0.05) and intensive-care-unit (ICU) admission (26% vs 12%, p>0.05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs during hospitalization had a significantly lower ICU admission rate (12% vs 26%, p=0.001, OR=0.347 [95% CI:0.187-0.643]) and mortality rate (6% vs 28%, p=0.001, OR=0.215 [95% CI:0.101-0.455]) as compared with patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after adjusting for hypotension or AKI. The authors concluded that continued ACEi/ARB use confers improved outcomes in hypertensive COVID-19 patients.
Source: Lam KW, Chow KW, Vo J, et al. Continued in-hospital ACE inhibitor and ARB Use in hypertensive COVID-19 patients is associated with positive clinical outcomes. J Infectious Dis. 2020, Jul 23.
High neutralizing antibody titer in ICU patients with COVID-19
This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU.
The study found that NAb against COVID-19 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs (671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. The data suggested that ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.
Source:Liu Li, To KW, Chan KH, et al. High neutralizing antibody titer in intensive care unit patients with COVID-19. Emerg Microbes Infect. 2020, Jul 3.
COVID-19 and Loss of Smell: The Role of Non-Neuronal Cell Damage
Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether COVID-19 affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells.
Researchers identified cell types in the olfactory epithelium and olfactory bulb that express COVID-19 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in COVID-19 entry, ACE2 and TMPRSS2.
However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse.
These findings suggest that COVID-19 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.
Source:BrannD, Tsukahara T, Weinreb C, Lipovsek M, et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science Advances. 2020, Jul 28.
Racial and Ethnic Disparities, Kidney Disease, and COVID-19: A Call to Action
According to a recent editorial, social determinants of health including access to healthcare, socioeconomic status, employment, food security, education, housing, environment, and social support are factors that contribute to the devastating and disproportionate consequences of COVID-19 for communities of color. The authors state: “People of African American, American Indian or Alaska Native American descent are five times more likely to be hospitalized due to COVID-19 than Whites, while Hispanics are approximately four times more likely to be hospitalized. One in four Americans dying of COVID-19 are Black or African American, even though members of this community represent only 13 percent of the US population.” Additionally, many of the healthcare and socioeconomic disparities that increase risk of COVID-19 in communities of color also increase their risk of kidney disease. Communities of color often have high rates of diabetes and high blood pressure, which are the major causes of kidney failure.
To address these challenges, the National Kidney Foundation (NKF) is advocating for access to affordable healthcare; to increase our federal investment in research, prevention, and innovations in care for people with kidney disease; and to ensure that racial and ethnic communities are not left behind. This call to action is coupled with NKF’s efforts to address areas of concern for people with kidney disease during the COVID-19 pandemic which include prioritizing kidney patients’ and clinicians’ access to personal protective equipment, preserving access to essential kidney-related surgical procedures, and fighting policies that discriminate against kidney patients.
Source: Longino K, Kramer H. Racial and ethnic disparities, kidney disease, and COVID-19: a call to action.Kidney Medicine.2020, Jul 20.
Why COVID-19 Silent Hypoxemia is Baffling to Physicians
A research study provides possible explanations for COVID-19 patients who present with extremely low, potentially life-threatening levels of oxygen, but no signs of dyspnea. New understanding of the condition, known as silent hypoxemia or "happy hypoxia," may prevent unnecessary intubation and ventilation in patients during the current and any subsequent wave of coronavirus outbreak.
The study was conducted in 16 COVID-19 positive patients with extremely low levels of oxygen (as low as 50%) but without shortness of breath or dyspnea and included the initial assessment of a patient’s oxygen level with a pulse oximeter.
The authors note that pulse oximeters are accurate when oxygen readings are high but appear to exaggerate the severity of low levels of oxygen when readings are low. In fact, some COVID-19 patients do not exhibit any shortness of breath until oxygen falls to dangerously low levels. In addition, more than half of the patients in this small study had low levels of carbon dioxide, which may diminish the impact of an extremely low oxygen level.
In conclusion, the authors acknowledge the need for further study and suggest this new information may help to avoid unnecessary endotracheal intubation and mechanical ventilation.
Source: Tobin MJ, Laghi F, Jubran A. Why COVID-19 Silent Hypoxemia is Baffling to Physicians. Am J Respir Crit Care Med. 2020, Jun 15.
Risk of Ischemic Stroke in Patients with COVID-19 vs Patients with Influenza
A retrospective cohort study of adult patients from 2 New York City Hospitals indicates that an acute ischemic stroke was seen in 31 of 1916 patients (1.6%, median age 69 years, 58% male) with COVID-19 from March 4, 2020 through May 2, 2020 compared to 3 of 1486 patients (0.2%, median age 62 years, 45% men) with influenza from January 1, 2016 through May 31, 2018. Compared with the 1916 patients with COVID-19, the 1486 patients with influenza were on average younger; more often women; less often had hypertension, diabetes, coronary artery disease, chronic kidney disease, or atrial fibrillation; and more often had hyperlipidemia. In addition, patients with COVID-19 infection who had an ischemic stroke were much more likely to die than patients with COVID-19 infection who did not have an ischemic stroke.
Possible explanations for the higher rate of ischemic stroke seen in patients with COVID-19 vs influenza include: 1) Acute viral infections increase the short-term risk of ischemic stroke and other arterial thrombotic events due to inflammation, prothrombotic coagulopathy, and endothelial injury. COVID-19 infection is associated with a robust inflammatory response accompanied by coagulopathy. 2) Patients with COVID-19 infection are at greater risk for medical complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke. 3) Baseline stroke risk factors were more common in the cohort of patients with COVID-19, however, when adjusted for the number of vascular risk factors, the researcher found a higher risk of ischemic stroke with COVID-19 than with influenza.
The authors conclude that based on these findings "clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability."
Source: Merkler AE, Parikh NS, Mir S, et al. Risk of Ischemic Stroke in Patients with Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol. 2020 Jul 2.
High Incidence of Barotrauma in Patients with COVID-19 Infection on Invasive Mechanical Ventilation
A large New York City hospital conducted a retrospective study of COVID-19 positive inpatients from 03/01/2020 to 04/06/2020 that experienced barotrauma associated with invasive mechanical ventilation. Using clinical and imaging data, these patients were compared to patients without COVID-19 infection during the same period. Historical comparison was made for barotrauma rates in patients with acute respiratory distress syndrome (ARDS) from 02/01/2016 to 02/01/2020.
Of 601 patients with COVID-19 infection who had invasive mechanical ventilation (63 ± 15 years, 71% men), there were 89 patients (15%) with one or more barotrauma events, for a total of 145 barotrauma events (24% overall events) (95% CI 21-28%). At the same time, 196 patients without COVID-19 infection (64 ± 19 years, 52% male) with invasive mechanical ventilation had 1 barotrauma event (rate of 0.5%, 95% CI, 0-3%, p<.001 vs. the group with COVID-19 infection).
Of 285 patients with ARDS over the prior 4 years on invasive mechanical ventilation (68 ± 17 years, 60% men), 28 patients (10%) had 31 barotrauma events, with overall barotrauma rate of 11% (95% CI 8-15%, p<.001 vs. the group with COVID-19 infection). Barotrauma was found to be an independent risk factor for death in COVID-19 (OR=2.2, p=.03), and was associated with longer hospital length of stay (OR=.92, p<.001).
The authors concluded that patients with COVID-19 infection and invasive mechanical ventilation had a higher rate of barotrauma than patients with ARDS and patients without COVID-19 infection. In patients with COVID-19 infection who needed invasive mechanical ventilation, barotrauma occurred high rates, and was related to longer hospital stay and death.
Source: McGuinness G, Zhan C, Rosenberg N, et al. High Incidence of Barotrauma in Patients with COVID-19 Infection on Invasive Mechanical Ventilation. Radiology. 2020,Jul 2.
Viral and host factors related to COVID-19 Outcomes
A study analyzed the clinical, molecular and immunological data from 326 patients with confirmed COVID-19 infection in Shanghai. The genomic sequences of COVID-19, assembled from 112 samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes.
Lymphocytopenia, especially reduced CD4+ and CD8+ T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes.
Source: Zhang X, Tan Y, Ling Y, et al. Viral and host factors related to the clinical outcome of COVID-19. Nature. 2020 May 20.
Presymptomatic COVID-19 Infections and Transmission in a Skilled Nursing Facility
Investigators conducted two serial point-prevalence surveys, 1 week apart, in which residents in a skilled nursing facility were tested for COVID-19, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms from the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with COVID-19 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.
Twenty-three days after the first positive test result in one resident, 57 of 89 residents (64%) tested positive for COVID-19. Of 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 eventually became symptomatic (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. Since April 3, of the 57 infected residents, 11 were hospitalized (3 in intensive care) and 15 died (mortality, 26%). Of the 34 residents, 27 (79%) had specimen sequences that fit into two clusters with a difference of one nucleotide.
The authors concluded that rapid and widespread transmission of COVID-19 had occurred in this facility. More than half of residents who tested positive were asymptomatic when tested, and therefore very likely contributed to transmission. Infection-control measures applied only to symptomatic residents were not adequate for preventing transmission after COVID-19 exposure within this facility.
Source: Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-Cov-2 infections and transmission in a skilled nursing facility. NEJM 2020;382:2081-2090.
Simple Blood Test May Predict Disease Severity in Patients with COVID-19
An early prognosis factor that could be a key to determining who will suffer greater effects from COVID-19, and help clinicians better prepare for these patients, may have been uncovered by researchers at The University of Texas Health Science Center at Houston. In this study, the authors were seeking identify a prognostic factor that could aid hospital workers in managing COVID-19. They discovered evidence of a relationship between lymphocytopenia and disease severity in critically ill patients.
Performing a retrospective cohort review study on 57 patients from a local Houston hospital, the researchers analyzed basic, clinical, and laboratory data from a simple blood draw and found that patients who were admitted into an ICU showed signs of lymphocytopenia compared to patients who were not in the ICU. At the time of hospital admission, patients who ended up in the ICU had more frequent lymphocytopenia by an odds ratio of 3.40 (95% CI: 1.06‐10.96; P = .04) in comparison to those not needing ICU admission, revealing that blood lymphocyte count might be a predictive marker in identifying patients who may be admitted into the ICU.
Additionally, researchers found that patients with lymphocytopenia were more likely to develop an acute kidney injury (AKI) during admission by an odds ratio of 4.29 (95% CI: 1.35‐13.57; P = .01). While acknowledging the study’s limitations (small sample size at a single community hospital), the authors concluded their findings may demonstrate lymphocytopenia serves as prognostic marker of AKI and is potentially predictive of disease severity in COVID-19 patients.
Source: Wagner, J, DuPont, A, Larson, S, Cash, B, Farooq, A. Absolute lymphocyte count is a prognostic marker in Covid‐19: A retrospective cohort review. Int J Lab Hematol. 2020;00:1-5.
Type 1 IFN Deficiency and Severe COVID-19
COVID-19 is characterized by distinct patterns of disease progression suggesting diverse host immune responses. Researchers performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severities.Researchers identified an impaired type I interferon (IFN) response in severe and critical COVID-19 patients, accompanied by high blood viral load and an excessive inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling.
These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.The authors propose that severe COVID-19 patients might be potentially relieved from the IFN deficiency by IFN administration and from exacerbated inflammation by adapted anti-inflammatory therapies targeting IL-6 or TNF-α, a hypothesis worth cautious testing.
Source: Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020, Jul 13.
Higher Rates of New Coronavirus Infection Seen in Latinx Populations
In a new analysis of COVID-19 test results for nearly 38,000 people has found a positivity rate among Latinx populations about 3 times higher than for any other racial and ethnic group.
Investigators analyzed results of diagnostic tests performed between March 11 and May 25 across 5 Johns Hopkins Health System hospitals, including emergency departments and 30 outpatient clinics in the Baltimore-Washington area.
Out of 37,727 adults and children tested, 6,162 tests came back positive. Of those tests, the positivity rate for Latinx was 42.6%, significantly higher than those who identified as Black (17.6%); Other (17.2%); or White (8.8%). Among those who tested positive, 2,212 were admitted to a Johns Hopkins Health System hospital.
The study data show that Latinx patients were less likely to be admitted to the hospital (29.1%) compared with Black (41.7%) and White (40.1%) patients. Of the patients who were hospitalized, Latinx patients were younger (18 to 44 years); more likely to be male (64.9%); and had much lower rates of comorbidities, such as hypertension (44.8%), congestive heart failure (41.1%), pulmonary disease (20.7%) and chronic obstructive pulmonary disease (COPD) (19.2%) than Black or White patients.
According to the authors, these findings highlight coronavirus health disparities and add more evidence that COVID-19 infection rates are much higher among US minorities, particularly in Latinx communities.
Source: Martinez DA, Hinson JS, Klein EY, et al. SARS-CoV-2 Positivity rate for Latinos in the Baltimore-Washington, DC region. JAMA. Published 2020, Jun 18.
New-Onset Diabetes in COVID-19
An international group of researchers are investigating the bidirectional relationship between diabetes and COVID-19 by establishing a global registry of patients with COVID-19-related diabetes (http://covidiab.e-dendrite.com/). Not only is diabetes associated with a higher risk of severe COVID-19, but new-onset diabetes and severe metabolic complications have been seen in patients with COVID-19. Since COVID-19 binds to ACE2 receptors, it is possible that the virus may cause pleiotropic changes of glucose metabolism that could have an impact on the pathophysiology of preexisting diabetes or lead to new mechanisms of disease.
To help guide immediate clinical care, as well as follow-up and monitoring of this patient population, the researchers are looking for answers to the following questions: How frequent is the phenomenon of new-onset diabetes, and is it classic type 1 or type 2 diabetes or a new type of diabetes? Do these patients remain at higher risk for diabetes or diabetic ketoacidosis? In patients with preexisting diabetes, does Covid-19 change the underlying pathophysiology and the natural history of the disease? The authors conclude that an understanding of how COVID-19–related diabetes develops, the natural history of this disease, and appropriate management will be helpful. The study of Covid-19–related diabetes may also uncover novel mechanisms of disease.
Source: Rubino F, Amiel SA, Zimmet P, et al. New-onset diabetes in COVID-19. N Engl J Med. 2020 Jun 12;. doi: 10.1056/NEJMc2018688.
Genomewide Association Study of Severe Covid-19 with Respiratory Failure
There is considerable variation in disease behavior among patients infected with severe COVID-19. A genomewide association study was conducted for the identification of potential genetic factors involved in the development of COVID-19. The study involved 1980 patients with COVID -19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the COVID-19 pandemic in Europe.In total, 8,582,968 single-nucleotide polymorphisms were analyzed.
The study identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with COVID-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1.
Source: Ellinghaus D, Degenhardt F, Bujanda L, et al. Genomewide Association Study of Severe Covid-19 With Respiratory Failure. N Engl J Med. 2020 Jun 17.
Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure
Among 88 COVID-19 patients with severe hypoxemic respiratory failure admitted to the intermediate care unit at a large New York City hospital, 29 were found eligible for prone positioning. Selected patients were asked to lie on their stomach for as long as tolerated, up to 24 hours/day. While 25 had at least 1 awake session of the prone position for more than 1 hour, 4 refused prone positioning and were intubated. One hour after prone positioning, SpO2 increased compared with baseline. Improvement in SpO2 ranged from 1% to 34% (median [SE], 7% [1.2%]; 95% CI, 4.6%-9.4%). Therefore, the authors concluded that the prone position for awake, spontaneously breathing patients with COVID-19 severe hypoxemic respiratory failure was associated with improved oxygenation.
In addition, a 95% or greater SpO2 after 1 hour of prone positioning was associated with a lower rate of intubation. The mean difference in the intubation rate between patients with SpO2 of 95% or greater and those with SpO2 less than 95% 1 hour after initiating prone positioning was 46% (95% CI, 10%-88%). The authors recommend randomized clinical trials to determine if improved oxygenation due to prone positioning in awake, non-intubated patients improves survival.
Source: Thompson AE, Ranard BL, Wei Y, et al. Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure. JAMA Intern Med. 2020, Jun 17.
Thromboelastographic Results and Hypercoagulability in Critically Ill Patients with COVID-19
A retrospective cohort study of 21 patients (mean age 68 years; 12 men) admitted to the ICU of Baylor St Luke’s Medical Center with confirmed COVID-19 indicates that higher thromboses rates were associated with thromboelastographic (TEG) results outside reference ranges. Among these patients, 20 had comorbidities, with a mean of 3 comorbidities each. Four patients (19%) were at risk for thromboembolism due to atrial fibrillation, a history of malignant tumors, or chronic kidney disease.
A total of 19 patients (90%) demonstrated hypercoagulable TEG, including 14 patients (74%) with hypercoagulable TEG as defined by fibrinogen activity and maximum amplitude (MA) criteria and 5 patients (26%) with hypercoagulable TEG as defined by MA criteria alone. There were no statistically significant differences in prothrombin time, INR, partial thromboplastin time, or platelet levels between 10 patients with at least 2 thrombotic events vs 11 patients with fewer than 2 events. In comparison, elevated MA was observed in 10 patients (100%) in the high event rate group vs 5 patients (45%) in the low event rate group. Innate TEG MA provided 100% sensitivity and 100% negative predictive value. According to the authors these finding suggest that alterations of diagnostic and prophylactic treatment guidelines may be critical for the successful treatment of coagulopathies associated with COVID-19.
Source: Mortus JR, Manek SE, Brubaker LS, et al. Thromboelastographic results and hypercoagulability syndrome in patients with coronavirus disease 2019 who are critically ill. JAMA Netw Open. 2020;3:e2011192.
Noninvasive Ventilation in the Prone Position for COVID-19 Patients
On April 2, 2020, in San Raffaele Scientific Institute, Milan, Italy, COVID-19 patients with acute respiratory distress syndrome (ARDS) were treated either in the intensive care unit (ICUs) (n = 48) or medical wards (n = 202). Noninvasive ventilation was used for 62 patients with mild to moderate ARDS who had saturation less than 94% on face mask with high-oxygen concentration, applying 10 cm H2O continuous positive airway pressure and 0.6 fraction of inspired oxygen (FIO2). A cross-sectional survey was performed to identify all patients undergoing the prone position NIV outside the ICU, irrespective of the day they started using this technique. Respiratory parameters were measured at 3 time points: before NIV, during NIV in pronation (60 minutes after start), and 60 minutes after NIV end.
Fifteen patients receiving NIV in the prone position outside the ICU on April 2 were identified. The median number of NIV cycles in the prone position on April 2 was 2 (IQR, 1-3 cycles) for a total duration of 3 hours (IQR, 1-6 hours). Compared with baseline, all patients had a reduction in respiratory rate during and after pronation (P < .001 for both); all patients had an improvement in oxygen saturation as measured by pulse oximetry (SpO2)and PaO2:FIO2 during pronation (P < .001 for both); 12 patients (80%) had an improvement in SpO2 and PaO2:FIO2 respiratory rate after pronation; 2 (13.3%) had the same value; and 1 (6.7%) had worsened. Providing NIV in the prone position to patients with COVID-19 and ARDS on the general wards in 1 hospital in Italy was feasible. The respiratory rate was lower and the oxygenation was higher during and after pronation than they were at baseline. Whether intubation was avoided or delayed remains to be determined.
Source: Sartini C, Tresoldi M, Scarpellini P, et al. Respiratory parameters in patients With COVID-19 after using noninvasive ventilation in the prone position outside the intensive care unit. JAMA. 2020 May 15
Venous Thrombosis and Critically Ill Patients with COVID-19
A prospective study of 34 consecutive patient cases included a systematic assessment of deep vein thrombosis among patients with severe COVID-19 in an intensive care unit (ICU) in France. The authors prospectively performed a venous ultrasonogram of the inferior limbs for all patients at admission to the ICU. Due to the high prevalence of venous thrombosis at admission, the authors systematically repeated venous ultrasonography after 48 hours if the first examination was normal. As recommended, all patients received anticoagulant prophylaxis on admission. Deep vein thrombosis was found in 22 patients (65%) at admission and in 27 patients (79%) when the venous ultrasonograms were performed 48 hours after ICU admission. Eighteen patients (53%) had bilateral thrombosis, and 9 patients (26%) had proximal thrombosis. This population had high levels of D-dimer (mean, 5.1 μg/mL), fibrinogen (mean, 760 mg/dL) and C-reactive protein (mean, 22.8 mg/dL). Prothrombin activity (mean, 85%) and platelet count (mean, 256 × 103/μL) were normal. In view of the high rate of deep vein thrombosis reported in this study, the authors concluded that prognosis could be improved with early detection and prompt initiation of anticoagulation. Despite anticoagulant prophylaxis, 15% of patients developed deep vein thrombosis only 2 days after ICU admission. The authors suggest that systematic assessment for deep vein thrombosis for all ICU patients with COVID-19 should be considered.
Source: Nahum J, Morichau-Beauchant T, Daviaud F, et al. Venous Thrombosis Among Critically Ill Patients with Coronavirus Disease 2019 (COVID-19). JAMA Network Open. 2020;3:e2010478.
Pulmonary Complications and Mortality in Post-Operative COVID-19 Patients
COVID-19 patients who undergo surgery experience substantially worse postoperative outcomes than would be expected for similar patients who do not have COVID-19 infection based on data for 1,128 patients from 235 hospitals in Europe, Africa, Asia, and North America.
The study authors found overall 30-day mortality was 23.8%. Mortality was disproportionately high across all subgroups, including elective surgery (18.9%), emergency surgery (25.6%), minor surgery such as appendectomy or hernia repair (16.3%), and major surgery such as hip surgery or colon cancer surgery (26.9%).
The study identified mortality rates were higher in men (28.4%) versus women (18.2%), and in patients aged 70 years or over (33.7%) versus those aged under 70 years (13.9%). In addition to age and sex, risk factors for postoperative death included severe pre-existing medical problems, undergoing cancer surgery or major procedures, and emergency surgery. In the 30 days following surgery 51% of patients developed pneumonia, acute respiratory distress syndrome, or required unexpected ventilation. Most of the patients who died (81.7%) experienced pulmonary complications.
The authors conclude that postoperative pulmonary complications occur in half of patients with perioperative COVID-19 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing nonurgent procedures and promoting nonoperative treatment to delay or avoid the need for surgery.
Source: Bhangu A, Nepogodiev D, Glasbey JC, et al for the COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet. 2020 May 29.
Hypertension and COVID-19 Severity
An observational study of 310 patients diagnosed with COVID-19 at two hospitals in Wuhan, China explored the effect of hypertension on disease progression and prognosis in patients with COVID-19. Multivariate analysis (adjusted for age and sex) did not show that hypertension was an independent risk factor for COVID-19 mortality or severity. However, COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease.
Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05).
Source: Huang S, Wang J, Liu F, et al. COVID-19 Patients With Hypertension Have More Severe Disease: A Multicenter Retrospective Observational Study. Hypertens Res. 2020 Jun 1.
Children and Adolescents with Severe COVID-19
While most children infected with the novel coronavirus have mild symptoms, a subset requires hospitalization and a small number require intensive care. A new report from physicians at Children’s Hospital at Montefiore (CHAM) and Albert Einstein College of Medicine, describes the clinical characteristics and outcomes of children hospitalized with COVID-19, during the early days of the pandemic.
This report compares 46 children between the ages of 1 month and 21 years, who received care either on a general unit or in the Pediatric Critical Care Unit (PCCU) at CHAM. This is the largest single-center study from the United States to date to describe in detail the full spectrum of COVID-19 disease in hospitalized children.
The authors found that children requiring intensive care had higher levels of inflammation and needed additional breathing support, compared to those who were treated on a general unit. Of the children being cared for in the PCCU, almost 80% had Acute Respiratory Distress Syndrome (ARDS), which is more commonly associated with critically ill adult COVID-19 patients, and almost 50% of children with ARDS were placed on ventilators.
In addition, over half of the children had no known contact with a COVID-positive person. The authors concluded this may signify that the virus can be spread by asymptomatic people and COVID-19 may be more prevalent in communities with a high population density.
Source: Chao JY, Derespina KR, Herold BC, et al. Clinical characteristics and outcomes of hospitalized and critically ill children and adolescents with coronavirus disease 2019 (COVID-19) at a tertiary care medical center in New York City. J Peds. May 6, 2020.
Interpreting COVID-19 Test Results
The COVID-19 pandemic continues to affect much of the world. Knowledge of diagnostic tests for COVID-19 is still evolving, and a clear understanding of the nature of the tests and interpretation of their findings is important. The following resources describe how to interpret certain diagnostic tests commonly in use for COVID-19 infections.
Characteristics and Outcomes of ICU Patients with COVID-19
A retrospective observational study of 1591 laboratory confirmed cases (82% male, mean age 63 years) of COVID-19 admitted to the ICU in the Lombardy region of Italy between February 20, 2020 and March 18, 2020 indicates 88% needed mechanical ventilation and high levels of positive end-expiratory pressure (PEEP, mean 14 cm H20), and ICU mortality was 26%. Baseline characteristics show that 68% of patients had at least one comorbidity with hypertension (49%) being the most common. The second most common comorbidities were cardiovascular disease (21%) and hypercholesterolemia (18%). A history of chronic obstructive pulmonary disease was present in only 4% of patients. All patients older than 80 years and 76% of patients older than 60 years had at least 1 comorbidity. This data may be used for comparison in other countries and regions.
Source: Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6.
Neurological impact of COVID-19
Increasing research reports neurological manifestations of COVID-19 patients. A systematic analysis found an increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that COVID-19 is a new neuropathogen. Common reported neurological symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.
Source: Montalvan V, Lee J, Bueso T, De Toledo J, Rivas K. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clin Neurol Neurosurg. 2020 May 15.
Genomic Analysis of COVID-19
Next-generation sequencing found that COVID-19 shares 73% of its genome with severe acute respiratory syndrome (SARS) and 50% of its genome with Middle East respiratory syndrome (MERS). COVID-19 also shares 88% of its genome with two bat-derived SARS-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China. Structural analysis suggests that COVID-19 binds to the angiotensin-converting enzyme 2 receptor in humans.
Source: Lu R, Zhao X, Li J,et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.
COVID-19 and Ketosis or Ketoacidosis
This study of 658 hospitalized patients infected with COVID-19 found that the disease may cause ketosis or ketoacidosis, and induce diabetic ketoacidosis for patients with diabetes. The study found that 6.4% of the patients presented with ketosis on admission with no obvious fever or diarrhea. Ketosis increased the length of hospital stay and mortality in the study.
Source: Li J, Wang X, Chen J, Zuo X, Zhang H, Deng A. COVID-19 infection may cause ketosis and ketoacidosis. Diabetes Obes Metab. 2020 Apr 20.
Sinonasal Pathophysiology of COVID-19
The ongoing COVID-19 pandemic is highly contagious with high morbidity and mortality. The role of the nasal and paranasal sinus cavities is increasingly being recognized for COVID-19 symptomatology and transmission. Researchers conducted a systematic review, synthesizing existing scientific evidence about sinonasal pathophysiology in COVID-19.
In all, 19 studies were identified suggesting that the sinonasal cavity may be a major site of infection by COVID-19. The authors noted that sinonasal symptomatology, such as rhinorrhea or congestion, appears to be a rarer symptom of COVID-19, anosmia without nasal obstruction is reported as a highly specific predictor of COVID-19+ patients.
The authors concluded the sinonasal tract may be an important site of infection while sinonasal viral shedding may be an important transmission mechanism – including healthcare-associated infection – and anosmia without nasal obstruction may be a highly specific indicator of COVID-19.
Source: Gengler, I, Wang, JC, Speth, MM, Sedaghat, AR. Sinonasal pathophysiology of SARS‐CoV‐2 and COVID‐19: a systematic review of the current evidence. Laryngoscope Investigative Otolaryngology. 2020. Accepted Author Manuscript. doi:10.1002/lio2.384.
Risk of Severe Illness from COVID-19 Increases with each Decade of Age
A study has shown a strong age gradient in risk of death for people with COVID-19. The study examined data of individuals from 38 countries who tested positive for COVID-19. In the study, the mean duration from onset of symptoms to hospital discharge was 24.7 days and to death was an estimated 17.8 days. The study found that found that risk of death from the disease rose with each decade of age. The death rate (infection fatality ratio) among laboratory-confirmed cases was ~0.03% for people 20-29; 0.08% for people 30-39; 1.16% for people 40-49; 0.59% for people 50-59; 1.93% for people 60-69; 4.28% for people 70-79; and 7.80% for people ≥80.Older individuals with underlying conditions were at highest risk for severe disease and death.
Source: Verity R, Okell L, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet. 2020 Mar 30 [Epub ahead of print].
Ocular Findings of Patients with COVID-19
A study found that COVID-19 can lead to conjunctivitis (“pink eye”) and other eye problems. The novel coronavirus is thought to be transmitted through the eyes in addition to the nose and mouth routes. In this case series including 38 patients with COVID-19, 12 patients or about 1 in 3 had ocular manifestations, such as epiphora, conjunctival congestion, or chemosis. These commonly occurred in patients with more severe systemic COVID-19 manifestations. The study also showed SARS-CoV-2 was detected in the conjunctival swabs of 2 of 12 patients, supporting the possibility of transmission of the virus through the eyes.
Source: Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. 2020 Mar 31. [Epub ahead of print].
COVID-19 Infection in Patients Taking Angiotensin Drugs
The use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) is the standard of care in reducing proteinuria and in slowing the progression of proteinuric CKD. Recently these angiotensin drugs have come under scrutiny due to the hypothesis that these drugs may put patients at increased risk for infection with COVID-19 virus. But experts agree that this assumption is based on limited animal data and there is no evidence to support stopping angiotensin drugs. ACEI and ARB increase angiotensin converting enzyme 2 (ACE2) expression. ACE2 is an enzyme attached to the outer surface of cells in the lungs, arteries, heart, kidney, and intestines. In addition to lowering blood pressure ACE2 also serves as a receptor for some coronaviruses. However, there are no clinical data indicating that patients taking ACEIs/ARBs have increased severity of illness or risk of mortality during COVID-19 infection.
Recent studies in Wuhan China further support continued use of these drugs. A retrospective, single-center case series of 1178 hospitalized patients (median age 55 years, 46.3% male) with COVID-19 infections from January 15 to March 15, 2020 indicates there was no difference in severity of the disease, complications, and risk of death in those who were taking ACEI/ARB compared with those not treated with these medications.1 An earlier retrospective, multi-center study of 1128 patients with hypertension hospitalized with COVID-19 including 188 taking ACEI/ARB (median age 64 years, 53.2% male) and 940 not using ACEI/ARB or using a different class of anti-hypertensive agent (median age 64 years, 53.5% male) from December 31, 2019 to February 20,2020, indicates inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users.2 These studies support current guidelines and recommendations for the use if ACEI/ARB in treating hypertension.
Sources:
1. Li J, Wang X, Chen J, et al. Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA Cardiol. 2020 Apr 23.
2. Zhang P, Zhu L, Cai J, et al. association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res. 2020 Apr 17.
Alterations in Smell or Taste in Mildly Symptomatic COVID-19 Patients
A study found that alterations in smell or taste were frequently reported by mildly symptomatic patients with COVID-19 and often were the first apparent symptom. The telephone survey found that any altered sense of smell or taste was reported by 64.4% of patients. OF these patients, 34.6% reported an altered sense of smell or taste, while 34.6% also reported blocked nose. Other frequent symptoms were fatigue (68.3%), dry or productive cough (60.4%), and fever (55.5%).
Source: Spinato G, Fabbris C, Polesel J, et al. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 Apr 22.
Endothelial cell infection and COVID-19
COVID-19 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells. Post-mortem histology of this patient case series (n=3) revealed the presence of viral bodies and lymphocytic endotheliitis in the lung, heart, kidney, and liver cell necrosis. The findings indicate a direct consequence of viral involvement and of the host inflammatory response in several organs.
Source: Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 Apr 20.
Characteristics and Outcomes of COVID-19 Hospitalized Patients in the NYC Area
A case series of hospitalized patients (n=5700) with COVID-19 in the New York City area found that the most common comorbidities were hypertension (56.6%), obesity (41.7%), and diabetes (33.8%). During hospitalization, 14.2% of patients were treated in the intensive care unit care, 12.2% received invasive mechanical ventilation, and 3.2% were treated with kidney replacement therapy, while 21% died.
Source: Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr 22.
Diabetes and COVID-19
A retrospective study of study of 28 patients with diabetes and COVID-19 at a hospital in Wuhan, China found poor outcomes among ICU patients. Half of these patients were in ICU and the other half were in isolation. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the non-ICU group.
Source: Wang F, Yang Y, Dong K, et al. Clinical characteristics of 28 patients with diabetes and covid-19 in Wuhan, China. Endocr Pract. 2020 May 1.
Characteristics and Outcomes of Adults Hospitalized with COVID-19
A cohort study of 305 hospitalized adult patients with COVID-19 in Georgia (primarily metropolitan Atlanta) indicates that 61.6% were aged <65 years (median age 60 years), 50.5% were female, and 83.2% with known race/ethnicity were black.
Overall, 225 (73.8%) patients had comorbid conditions considered high-risk for severe COVID-19. These conditions, which had similar prevalence in black and non-black patients, included diabetes 39.7%, cardiovascular disease 25.6%, chronic lung disease 20.3%, asthma 10.5%, chronic obstructive pulmonary disease 5.2%, and severe obesity (BMI ≥40) 2.7% with median BMI higher in black (31.4%) than in nonblack patients (29.6%). Hypertension (not considered a high-risk condition) was documented in 67.5% of patients and was more common among black versus nonblack patients (69.6% versus 54.0%).
The authors conclude that given the overrepresentation of black patients within this cohort, it is important that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Increased awareness of the risk for serious illness from COVID-19 among all adults, regardless of underlying conditions or age, is also needed.
Source: Gold JAW, Wong KK, Szablewski CM, et al. Characteristics and clinical outcomes of adult patients hospitalized with COVID-19 - Georgia, March 2020. Morb Mortal Wkly Rep. 2020 May 8;69(18):545-550.
Gastrointestinal and Hepatic Manifestations of COVID-19
A retrospective study in two New York City hospitals explored the gastrointestinal (GI) and hepatic manifestations of COVID-19 in 1059 adult patients. Nearly one third of patients reported GI symptoms, most often diarrhea. The authors note that the high rate of diarrhea may be due to the COVID-19 virus's high affinity for the angiotensin-converting enzyme 2 receptor. Sixty-two percent of patients presented with at least one elevated liver enzyme, but elevated total bilirubin or alkaline phosphatase was not common, and no cases of clinically significant acute liver injury or acute liver failure due to COVID-19 were noted. Having liver injury on presentation of COVID-19, however, was associated with a significantly higher risk of ICU admission and death. The authors suggest that the high rate of hepatic injury may be due to direct viral infection of liver cells. The authors conclude that COVID-19 patients frequently have GI manifestations and that liver injury is common on initial presentation and is independently associated with poor clinical outcomes. These results may contribute to clarifying the diagnostic criteria for COVID-19 and may be helpful in stratifying risk.
Source: Hajifathalian K, Krisko T, Mehta A, Kumar S, Schwartz R, Fortune B, Sharaiha R, on behalf of the WCM-GI research group. Gastrointestinal and hepatic manifestations of 2019 novel coronavirus disease in a large cohort of infected patients from New York: clinical implications. Gastroenterology.2020 May 1.
Olfactory Dysfunction in COVID-19: Diagnosis and Management
Several studies report that COVID-19 frequently impairs the sense of smell in mild or even asymptomatic cases. COVID-19 disrupts cells in the olfactory neuroepithelium which may result in inflammatory changes that impair olfactory receptor neuron function, cause subsequent olfactory receptor neuron damage, and/or impair subsequent neurogenesis. These changes may cause temporary or longer-lasting OD. Since olfactory dysfunction (OD) may act as a marker for disease in patients who are otherwise minimally symptomatic or asymptomatic, organizations including the American Academy of Otolaryngology-Head and Neck Surgery, ENT UK, and CDC recommend inclusion of sudden-onset loss of smell and/or taste as part of the diagnostic criteria for COVID-19 disease. A model of clinical assessment includes subjective self-assessment (view with caution) or psychophysical assessment (more reliable), followed by a period of self-isolation and SAR-CoV-2 testing when possible. Olfactory assessment in patients requiring acute hospitalization should only be performed when clinically appropriate. The efficacy of treatment of persistent COVID-19 OD is unknown but may include olfactory training and adjuvant medication (intranasal vitamin A and systemic omega-3). The authors conclude that research is needed to delineate the natural history and appropriate management of chemosensory impairment caused by COVID-19.
Source: Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020 May 20.
Protective Immunity against COVID-19 Re-exposure in Rhesus Macaques
Individuals who recover from certain viral infections typically develop virus-specific antibody responses that provide robust protective immunity against re-exposure, but some viruses do not generate protective natural immunity, such as HIV-1.
A study showed that COVID-19 infection in rhesus macaques induced humoral and cellular immune responses and provided protective efficacy against COVID-19 rechallenge. The study raises the possibility that immunologic approaches to the prevention and treatment of COVID-19 may possible. However, are differences between COVID-19 infection in macaques and humans, with many parameters still yet to be defined in both species. Rigorous clinical studies will be required to determine whether COVID-19 infection effectively protects against COVID-19 re-exposure in humans.
Source: Chandrashekar A, Liu J, Martinot A, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 2020 May 20.
Telemedicine and COVID-19: Evidence from the Field
One of the largest healthcare systems in New York City, NYU Langone Health (NYULH), has 8077 healthcare providers from 4 hospitals and over 500 outpatient locations that all use one electronic health record (EHR) system. NYULH also leverages deep integration with the Vidyo platform to enable its virtual health services. Using data from these technology platforms, this study assessed the feasibility and impact of video-enabled telemedicine use among patients and providers for both urgent and non-urgent healthcare delivery from New York City during the COVID-19 outbreak.
Between 03/02/20 and 04/14/20, telemedicine visits increased from 102.4 daily to 801.6 daily (683% increase) in urgent care after the system-wide expansion of virtual urgent care staff, in response to COVID-19. Of all virtual visits post expansion, 56.2% and 17.6% urgent and non-urgent visits, respectively, were related to COVID-19. COVID-19 has led to a rapid increase in telemedicine use for urgent care and non-urgent care visits, indicating a significant change in telemedicine usage that other healthcare systems will likely experience and for which they should prepare for now and well into the future.
Source: Mann D, Chen J, Chunara R, Testa P, Nov N. COVID-19 transforms health care through telemedicine: Evidence from the field. J Am Med Inform Assoc. 2020 Apr 23.
Estimating Potential Spread and Seasonality of COVID-19 Based on Temperature, Humidity, and Latitude Analysis
A cohort study that examined climate data from 8 cities with substantial community spread of COVID-19 (Wuhan, China; Tokyo, Japan; Daegu, South Korea; Qom, Iran; Milan, Italy; Paris, France; Seattle, US; and Madrid, Spain) between January to March 10, 2020 indicates they were located roughly on the 30° N to 50° N corridor and had consistently similar weather patterns consisting of mean temperatures of between 5 and 11°C (41 and 52°F), combined with low specific humidity (3-6 g/kg) and low absolute humidity (4-7 g/m3). Cities without COVID-19 cases were studied for comparison, representing all regions of the globe. Substantial community transmission was defined as at least 10 reported deaths in a country as of March 10, 2020.
The distribution of the substantial community outbreaks of COVID-19 along restricted latitude, temperature, and humidity measurements were consistent with the behavior of a seasonal respiratory virus. The authors conclude that using weather modeling; it may be possible to estimate the geographic regions most likely to be at higher risk of substantial community spread of COVID-19 in the upcoming weeks and months, allowing for a concentration of public health efforts on surveillance and containment.
Source: Sajadi M, Habibzadeh P, Vintzileos A, Shokouhi S, Miralles-Wilhelm F, Amoroso A. Temperature, humidity, and latitude analysis to estimate potential spread and seasonality of Coronavirus Disease 2019 (COVID-19). JAMA Netw Open. 2020;3:e2011834.
Public health & COVID-19
Alcohol Consumption Sharply Rises During COVID-19 Pandemic
Adults in the United States have increased their consumption of alcohol during the shutdown triggered by the coronavirus pandemic.
A research letter detailed the results of a national survey of 1,540 adults and found the overall frequency of alcohol consumption increased by 14% among adults over age 30, compared to the same time last year. The increase was 19% among all adults aged 30 to 59, 17% among women (with 41% reporting heavy drinking episodes of 4 or more drinks within a couple of hours), and 10% among non-Hispanic white adults.
According to the authors, the alcohol spike seen among women, younger adults, and non-Hispanic white adults highlights the need for primary care providers, behavioral health providers, and family members to be aware of the risks of increased alcohol use and heavy drinking during the pandemic.
The findings also suggest that future research should examine whether increases in alcohol use persist as the pandemic continues, and whether psychological and physical well-being are subsequently affected.
Source: Pollard MS, Tucker JS, Green HD. Changes in adult alcohol use and consequences during the COVID-19 pandemic in the US. 2020;3:e2022942.
Community-Level Disparities of COVID-19 in Large US Metropolitan Areas
In this cross-sectional study, researchers examined the association of neighborhood race/ethnicity and poverty with COVID-19 infections and related deaths in urban US counties, hypothesizing disproportionate burdens in counties with a larger percentage of the population belonging to minority racial/ethnic groups and a higher rate of poverty. This study is among the first to investigate such associations in US metropolitan areas.
Counties were grouped by US Office of Management and Budget–defined combined statistical areas (CSAs). Information regarding county-level poverty rates and median household income was obtained from the 2018 US Census Small Area Income and Poverty Estimates Program.Of 158 counties, 81 (51.3%) were considered less-poverty counties and 77 (48.7%), more-poverty counties.
In more-poverty counties, those with substantially non-White populations had an infection rate nearly 8 times that of counties with substantially White populations (RR, 7.8; 95% CI, 5.1-12.0) and a death rate more than 9 times greater (RR, 9.3; 95% CI, 4.7-18.4).
Among both more-poverty and less-poverty counties, those with substantially non-White or more diverse populations had higher expected cumulative COVID-19 incident infections compared with counties with substantially White or less-diverse populations (e.g., more diverse counties with less poverty: RR, 3.2; 95% CI, 2.3-4.6).
While the excess burden of both infections and deaths was experienced by poorer and more diverse areas, racial and ethnic disparities in COVID-19 infections and deaths existed beyond those explained by differences in income.
Source:Adhikari S, Pantaleo N, Feldman J, et al. Assessment of Community-Level Disparities in Coronavirus Disease 2019 (COVID-19) Infections and Deaths in Large US Metropolitan Areas. JAMA. 2020, Jul 28.
Genomic Surveillance of COVID-19 in a Healthcare Setting
A study examined the use of rapid COVID-19 sequencing combined with detailed epidemiological analysis to investigate health-care associated COVID-19 infections and inform infection control measures.In this prospective surveillance study, rapid COVID-19 nanopore sequencing from PCR-positive diagnostic samples were set up and collected from a hospital in Cambridge, UK, and random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. Researchers established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. Between March 13 and April 24, 2020, researchers collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. 1000 samples were sequenced producing 747 high-quality genomes.
Researchers combined epidemiological and genomic analysis of the 299 patients and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. Results were fed back to clinical, infection control and hospital management teams, leading to infection-control interventions and informing patient safety reporting.
The authors report the establishment of real-time genomic surveillance of COVID-19 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled them to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections.
Source: Meredith L, Hamilton W, Warne B, et al. Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study. Lancet. 2020, 14 Jul 14.
Asymptomatic Transmission: The Achilles’ Heel of Current Strategies to Control Covid-19
At first, public health authorities focused on the symptom similarities between COVID-19 and the SARS outbreak in 2003, such as high genetic relatedness, transmission primarily through respiratory droplets, and the frequency of lower respiratory symptoms (fever, cough, and shortness of breath), with both infections developing a median of five days post exposure.
Based on these similarities, public health officials used interventions that had proved effective in 2003 such as “symptom-based case detection and subsequent testing to guide isolation and quarantine.” While this initial approach was justified, in hindsight, Monica Gandhi et al, recognize that the results “strongly demonstrate that our current approaches are inadequate.”
The authors noted that, “despite the deployment of similar control interventions, the trajectories of the two epidemics have veered in dramatically different directions.” After eight months, SARS-CoV-1 virus was well contained and had infected around 8,100 people worldwide with outbreaks limited to specific geographic areas.
With the number of COVID-19 cases surging, the authors conclude there is “clear evidence that COVID-19 transmissions from asymptomatic people and the eventual need to relax current social distancing practices argue for broadened COVID-19 testing to include asymptomatic persons in prioritized settings” such as skilled nursing facilities, prisons, mental health facilities, and homeless shelters.
Source: Gandhi M, Yokoe DS, Havlir, DV. Asymptomatic transmission, the Achilles' heel of current strategies to control Covid-19.N Engl J Med. 2020;382:2158-2160.
Prevalence of Asymptomatic COVID-19 Infection
It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing COVID-19 pandemic.A review and analysis of available studies on asymptomatic COVID-19 infection found that asymptomatic persons seem to account for approximately 40% to 45% of COVID-19 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography, indicating that the absence of COVID-19 symptoms in persons infected with SARS-CoV-2 might not necessarily imply an absence of harm, although more research is needed in this area.The authors also concluded that the focus of testing programs for COVID-19 should be substantially broadened to include infected persons who do not have symptoms.
Source: Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review.Ann Intern Med. 2020, 3 Jun.
Reduction of COVID-19 secondary transmission in households by face mask use, disinfection, and social distancing
A retrospective cohort study of 335 people in 124 families with at least one laboratory confirmed COVID-19 case indicates the effectiveness of mask use, disinfection, and social distancing in preventing COVID-19. The overall secondary transmission rate in households was 23%. Facemasks were 79% effective and disinfection was 77% effective in preventing transmission. In contrast, close frequent contact in the household increased the risk of transmission 18 times.
In the univariate analysis, wearing a mask after illness onset was significant, but in multivariate analysis, only wearing it before symptom onset was effective. Viral load is highest in the two days before symptom onset and on the first day of symptoms and up to 44% of transmission is during the pre-symptomatic period in settings with substantial household clustering. This study showed that social distancing within the home is effective and having close contact (within 1 meter or 3 feet, such as eating around a table or sitting together watching TV) is a risk factor for transmission. The study also provides evidence of effectiveness of chlorine or ethanol-based household disinfection in areas with high community transmission.
The results of this study may be informative for families of high-risk groups such as health workers, quarantined individuals, or situations where cases of COVID-19 can be managed at home.
Source: Wang Y, Tian H, Zhang L, et al. Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China. BMJ Glob Health. 2020 May 5.
Early Spread of COVID-19 in New York City
COVID-19 is the cause of one of the largest non-influenza pandemics of this century. Phylogenetic analysis of 84 distinct COVID-19 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. The study also found evidence for community transmission of COVID-19 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
Early introductions by cases that were identified based on their known travel histories did not seed the larger community clusters, suggesting that their early quarantine and hospitalization were effective in curtailing further spread. However, the study shows that the COVID-19 epidemic in NYC was mainly sourced from untracked transmission between the US and Europe, with limited evidence of direct introductions from China where the virus originated.
Source: Gonzalez-Reiche A, Hernandez M, Sullivan M, et al. Introductions and Early Spread of SARS-CoV-2 in the New York City Area. Science. 2020 May 29.
Reducing Spread of COVID-19 Transmission through Aerosol and Droplets
Aerosol transmission of viruses must be acknowledged as a key factor leading to the spread of infectious respiratory diseases. Evidence suggests that COVID-19 is silently spreading in aerosols exhaled by highly contagious infected individuals with no symptoms. Owing to their smaller size, aerosols may lead to higher severity of COVID-19 because virus-containing aerosols penetrate more deeply into the lungs. It is essential that control measures be introduced to reduce aerosol transmission. A multidisciplinary approach is needed to address a wide range of factors that lead to the production and airborne transmission of respiratory viruses, including the minimum virus titer required to cause COVID-19; viral load emitted as a function of droplet size before, during, and after infection; viability of the virus indoors and outdoors; mechanisms of transmission; airborne concentrations; and spatial patterns. Masks and testing are necessary to combat asymptomatic spread in aerosols and droplets.
Source: Prather P, Wang C, Schooley R. Reducing Transmission of SARS-CoV-2. Science. 2020 May 27.
Airborne lifetime of small speech droplets and COVID transmission
Speech droplets generated by asymptomatic carriers of COVID-19 are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.
Source: Stadnytskyi V, Bax C, Bax A, Anfinrud P. The Airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission. Proc Natl Acad Sci USA. 2020 May 13;202006874.
Misinformation and COVID-19
A study found that among the most viewed English videos regarding COVID-19 on YouTube, 27.5% contained non-factual information originating from entertainment news, internet news and consumer sources, reaching 62 million views worldwide. Videos from professional and government organizations were the most informative and had the highest quality content but were greatly under-represented in terms of viewership. Strategies that can be employed by government and public health agencies to increase the viewership of their quality content on COVID-19 were identified. The authors recommend that public health agencies collaborate with a wider range of YouTube producers (e.g., entertainment news, internet news and influential consumers) to disseminate high-quality video content.
Source: Li HO, Bailey A, Huynh D, Chan J. YouTube as a source of information on COVID-19: a pandemic of misinformation? BMJ Glob Health. 2020 May 5.
Social Distancing Measures and COVID-19 Spread
A study evaluated the impact of social distancing measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020 and April 27, 2020. Measures included event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). The study found that adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4% after 1-5 days, 6.8% after 6-10 days, 8.2% after 11-15 days, and 9.1% after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million).
Source: Courtemanche C, Garuccio J, Le A, Pinkston J, Yelowitz A. Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate. Health Aff (Millwood). 2020 May 14.
Exposure to Air Pollution and COVID-19 Mortality in the United States
United States government scientists recently estimated that COVID-19 may kill between 100,000 and 240,000 Americans. The majority of the pre-existing medical conditions that increase the risk of death for COVID-19 are the same diseases that are affected by long-term exposure to air pollution.
Results from a study conducted by Harvard University researchers, Xiao Wu, MS; Rachel C Nethery, PhD; Benjamin M Sabath, MA; Danielle Braun, Phd; and Francesca Dominici, PhD demonstrate “the importance of continuing to enforce existing air pollution regulations during the COVID-19 crisis and failure to do may potentially increase COVID-19 deaths and hospitalization admissions.” The study found that an increase of only 1 µg/m3 in fine particulate matter (PM2.5) is associated with a 15% increase in the COVID-19 death rate, 95% confidence interval (CI) (5%, 25%).
Source: Wu X, Nethery RC, Sabath MB, Braun D, Dominici F. Exposure to air pollution and COVID-19 mortality in the United States. medRxiv. 2020.04.05.20054502.
Public Health Interventions and Epidemiology of COVID-19 in Wuhan, China
A cohort study of 32,583 patients (median age 56.7 years, 48.4% men, 51.6% women) with laboratory confirmed COVID-19 in Wuhan, China between December 8, 2019 and March 8, 2929 indicates that a series of public health interventions was temporally associated with reduced effective reproduction number of SARS-CoV-2 (secondary transmission) and the number of confirmed cases per day across age groups, sex, and geographic regions. The public health interventions included condons sanitaire, traffic restriction, social distancing, home confinement, centralized quarantine, and universal symptom survey. This data may be used to inform public health policy in other countries and regions.
Source: Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-1062.
Aerodynamic analysis of COVID-19
A study by Liu et al investigated the aerodynamic nature of COVID-19 measuring viral RNA in aerosols in different areas of two Wuhan hospitals. The study found that concentration of COVID-19 RNA in aerosols detected in isolation wards and ventilated patient rooms was very low, but it was elevated in the patients' toilet areas. Levels of airborne COVID-19 RNA in the majority of public areas was undetectable except in two areas prone to crowding, possibly due to infected carriers in the crowd. The results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of COVID-19 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.
Source: Liu Y, Ning Z, Chen Y, et al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020 Apr 27.
Population Scale Testing of COVID-19
Epidemiological modelling shows that identification and isolation of the majority of infectious individuals, including those who may be asymptomatic, can suppress the spread of COVID-19. The intervention is based on: (1) testing every individual (2) repeatedly, and (3) self-quarantine of infected individuals. Modelling also indicates that unlike sampling-based tests, population-scale testing does not need to be very accurate: false negative rates up to 15% could be tolerated if 80% comply with testing every ten days, and false positives can be almost arbitrarily high when a high fraction of the population is already effectively quarantined.
Source: Taipale J, Romer P, Linnarsson S. Population-scale testing can suppress the spread of COVID-19. MedRxiv. 2020 May 1.
Racial Disparities and COVID-19
Racial and ethnic disparities in the U.S. COVID-19 pandemic have been reported. Contributors for this this disparity can include increased likelihood of exposure to the virus, increased susceptibility to severe consequences of the infection, and lack of health care access.
African Americans and Latinos are overrepresented among cases of and deaths from COVID-19, both nationally and in many of the areas hardest hit by the pandemic. Minority communities are more likely to be exposed to the virus because they are overrepresented in the low-wage, essential workforce at the front lines, including low-wage health care workers who often move between clinics, hospitals, and nursing homes to make a living, thereby magnifying their risk. Poor communities may face challenges implementing social distancing because of housing density and overcrowding, and minority populations are overrepresented in congregate settings, such as homeless shelters and prisons, that increase exposure risk. Minority communities may be more susceptible to severe forms of COVID-19 because of existing disparities in underlying conditions known to be associated with COVID-19 mortality, including hypertension, cardiovascular disease, kidney disease, and diabetes.
Bibbins-Domingo K1. This Time Must Be Different: Disparities During the COVID-19 Pandemic. Ann Intern Med. 2020 Apr 28.
Projecting COVID-19 Transmission through the Postpandemic Period
A model of COVID-19 transmission projects that recurrent wintertime outbreaks of COVID-19 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity.
Source: Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020 Apr 14.
Mental health & COVID-19
Depression Levels in the US during the COVID-19 Pandemic
COVID-19 and the associated social distancing and lockdown restrictions are expected to have substantial and enduring mental health effects. In this study, researchers aimed to assess depression levels before and during the COVID-19 pandemic in the United States. The findings indicate that there is likely to have been a rise in depression since during the COVID-19 pandemic. A particularly large increase in depression among young adults is a cause for concern, according to the authors.
The Patient Health Questionnaire-2 (PHQ-2) brief screening instrument was used to detect probable depression in two nationally representative surveys of US adults. Pre-pandemic levels of depression were assessed (5,075 adults) from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Depression was assessed in March (N = 6,819) and April 2020 (N = 5,428) in the Understanding America Study, a representative sample of the US population.
The percentage of US adults with depression increased significantly from 8.7% in 2017–2018 to 10.6% in March 2020 and 14.4% in April 2020. Statistically significant increases in depression levels were observed for all population subgroups examined with the exception of those aged 65+ years and Black participants. Young adults (aged 18–34) experienced a marked increase in depression of 13.4 percentage points that was larger than any other age group. Additional analyses of depression trends in NHANES from 2007/2008–2017/2018 showed that the substantial increase in depression in April 2020 was unlikely to be due to typical year-to-year variation.
The findings suggest that depression levels have risen substantially during the COVID-19 pandemic and reinforce recent findings indicating that young adults may be particularly vulnerable to the mental health effects of the pandemic, according to the authors.
Source: Daly M, Sutin AR, Robinson E. Depression reported by US adults in 2017-2018 and March and April 2020. J Affect Disord. 2020;278;131-135.
The Implications of COVID-19 for Mental Health and Substance Use
The COVID-19 pandemic and the resulting economic recession have negatively affected many people’s mental health and created new barriers for people already suffering from mental illness and substance use disorders.
A report by the Kaiser Family Foundation found that mid-July, 53% of adults in the United States reported that their mental health has been negatively impacted due to worry and stress over the coronavirus. This is significantly higher than the 32% reported in March.
Many adults are also reporting specific negative impacts on their mental health and wellbeing, such as difficulty sleeping (36%) or eating (32%), increases in alcohol consumption or substance use (12%), and worsening chronic conditions (12%), due to worry and stress over the coronavirus. As the pandemic wears on, ongoing and necessary public health measures expose many people to experiencing situations linked to poor mental health outcomes, such as isolation and job loss, according to the report.
Researchers also found that that a significantly higher share of households experiencing income or job loss reported that worry or stress over the coronavirus outbreak caused them to experience at least one adverse effect, such as difficulty sleeping or eating, increases in alcohol consumption or substance use, and worsening chronic conditions, on their mental health and wellbeing compared to households with no lost income or employment (59% vs. 46%, respectively).
Source: Panchal N, Kamal R, Orgera K, et al. The Implications of COVID-19 for Mental Health and Substance Use. Kaiser Family Foundation. 2020, Aug 21.
Impact of COVID-19 on Mental Health in the General Population
The COVID-19 pandemic has led to unprecedented hazards to mental health globally. A systematic search found that relatively high rates of symptoms of anxiety (6.33% to 50.9%), depression (14.6% to 48.3%), post-traumatic stress disorder (7% to 53.8%), psychological distress (34.43% to 38%), and stress (8.1% to 81.9%) are reported in the general population during the COVID-19 pandemic in China, Spain, Italy, Iran, the US, Turkey, Nepal, and Denmark. Risk factors associated with distress measures include female gender, younger age group (≤40 years), presence of chronic/psychiatric illnesses, unemployment, student status, and frequent exposure to social media/news concerning COVID-19.
The authors concluded that the COVID-19 pandemic is associated with highly significant levels of psychological distress that, in many cases, would meet the threshold for clinical relevance. Mitigating the hazardous effects of COVID-19 on mental health is an international public health priority.
Source: Xiong J, Lipsitz O, Nasri F, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020, Aug 8.
Short and Long-term Mental Health Effects of COVID-19
Most people with severe coronavirus infections (ie, SARS, MERS, and COVID-19) appear to recover without experiencing mental illness. However, recent studies indicate delirium is not uncommon in hospitalized patients in the acute stages of severe SARS, MERS, and COVID-19 illness.
Analysis of data from two studies that systematically assessed common symptoms of patients hospitalized with SARS and MERS found that confusion occurred in 28% (36/129) of patients, suggesting delirium was common during acute illness. There were also frequent reports of low mood (42/129; 33%), anxiety (46/129; 36%), impaired memory (44/129; 34%), and insomnia (34/208; 12%) during the acute stage.
Twelve studies focusing on COVID-19 note a similarity, with evidence of delirium (confusion in 26/40 intensive care unit patients, 65%; agitation in 40/58 ICU patients, 69%; and altered consciousness in 17/82 patients who subsequently died, 21%) while acutely ill.
In the longer-term, the analysis suggests that SARS and MERS survivors may be at increased risk for mental illnesses such as depression, anxiety, fatigue, and post-traumatic stress disorder in the months and years following discharge from hospital.
While previous coronavirus outbreak data and analyses may provide insights, they cannot be deemed exact predictors of psychiatric complication prevalence in severely ill COVID-19 patients. On the other hand, there is value in recognizing that delirium in acute-stage COVID-19 patients may be a precursor to a several long-term mental illnesses.
Source: Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psych. 2020 May 18.
The Impact of COVID-19 on Mental Wellbeing
A national poll indicates that Americans have stress and anxiety caused by the COVID-19 pandemic, which is having an effect of people’s physical and mental health. Among the findings, nearly half of Americans (48%) are anxious about the possibility of getting COVID-19 coronavirus, and 62% are anxious about the possibility of family and loved ones getting COVID-19 coronavirus. Most (59%) feel COVID-19 coronavirus is having a serious impact on their day-to-day lives. Considering these findings, APA CEO and Medical Director Saul Levin, M.D., M.P.A. emphasizes the need to maintain self-care and manage stress. Clear consistent communications on how to prevent the spread of COVID-19 is also important.
Source: American Psychiatric Association. New Poll: COVID-19 Impacting Mental Well-Being: Americans Feeling Anxious, Especially for Loved Ones; Older Adults are Less Anxious.
Mental Health and the COVID-19 Pandemic
Public health emergencies may affect the health, safety, and well-being of both individuals and communities. Extensive research in disaster mental health has established that emotional distress is ubiquitous in affected populations — a finding certain to be echoed in populations affected by the COVID-19 pandemic. Health care workers have an important role in addressing these emotional outcomes as part of the pandemic response. Health care systems will also need to address the stress on individual workers.
Source: Pfefferbaum B, North CS. Mental Health and the Covid-19 Pandemic. N Engl J Med. 2020 Apr 13.
Natural Mood Regulation and Depression
Periods of lockdown during the COVID-19 pandemic are likely to exacerbate problems with mood regulation. Situations in which personal choices of activities are constrained, such as during times of social isolation and lockdown, natural mood regulation is impaired potentially leading to depression.
A study from Taquet et al suggests a new target for treating and reducing depression is supporting natural mood regulation. This study looked at 58,328 participants from low-, middle-, and high-income countries, and compared people with low mood or a history of depression with those of high mood. In a series of analyses, the study investigated how people regulate their mood through their choice of everyday activities and how they are more vulnerable to depression when their ability to choose activities is restricted.
According to the authors, these research findings open the door to new opportunities for developing and optimizing treatments for depression, which could potentially be well adapted to treatments in the form of smartphone apps and made available to a large population that lacks access to existing treatments.
Source: Taquet M, Quoidbach J, Gross JJ, Saunders KEA, Goodwin GM. Mood homeostasis, low mood, and history of depression in 2 large population samples. JAMA Psychiatry. April 22, 2020.
Mental Health of Health Care Workers
A cross-sectional survey-based study of 1257 health care workers in 34 hospitals in China found that participants reported experiencing significant psychological burden. The study found that a considerable proportion of participants reported symptoms of depression (50.4%), anxiety (44.6%), insomnia (34.0%), and distress (71.5%). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers.
Source: Lai J, Ma S, Wang Y, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020;3:e203976.
Research on COVID-19 treatments
Association Between Early Treatment with Tocilizumab and Mortality Among Critically Ill Patients With COVID-19
A multicenter cohort study of 4485 adults with COVID-19 admitted to intensive care units (ICU) in 68 hospitals within the US from March 4 to May 10, 2020 was undertaken to determine if tocilizumab decreases mortality in critically ill adults with COVID-19. Critically ill adults with COVID-19 were classified according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU.
A total of 1544 patients (39.3%) died, including 125 (28.9%) who received tocilizumab and 1419 (40.6%) who did not receive tocilizumab. The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab–treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%).
The authors concluded that among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients who were not treated with tocilizumab. They also determined, however, that the results could be susceptible to confounding, and that further research from randomized clinical trials is needed.
Source: Gupta S, Wang W, Hayek SS, et al. Association Between Early Treatment with Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Internal Medicine. 2020, Oct 20.
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate COVID-19
A multicenter, randomized, open-label, controlled study was conducted on hospitalized patients with suspected or confirmed COVID-19 who were either on no supplemental oxygen or on oxygen at a maximum of 4 liters per minute. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine, 400 mg twice daily, or standard care plus hydroxychloroquine, 400 mg twice daily plus azithromycin, 500 mg once daily, for 7 days. The primary outcome was clinical status at 15 days determined by a seven-level ordinal scale, with higher levels indicating a worse condition in the modified intention-to-treat population (patients with a confirmed diagnosis of COVID-19). Safety was also evaluated. A total of 667 patients were randomized and 504 patients with confirmed COVID-19 and were included in the modified intention-to-treat analysis.
Compared with standard care, the odds of a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% CI, 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolonged QT interval and increased liver enzymes occurred more in patients who received hydroxychloroquine, alone or with azithromycin, than in those who did not receive either drug. Among hospitalized patients with mild-to-moderate COVID-19, hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days compared to standard care.
Source: Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Eng J Med. 2020, Jul 23.
Neutralizing Activity of mRNS-1273 Vaccine against COVID19 in Nonhuman Primates
A study of nonhuman primates given mRNA-1273 vaccine to prevent COVID-19 indicates the vaccine induced robust COVID-19 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung.
The study was conducted in 24 Indian-origin rhesus macaques (12 of each sex; age range 3-6 years) who were arbitrarily assigned to receive either 10 or 100 µg of vaccine at week 0 and at week 4, or no vaccine. The study showed that mRNA-1273 induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses.
The authors conclude that this data on mRNA-1273 immunogenicity and protection of the upper and lower airways in nonhuman primates complements the immunogenicity and safety data established by a phase 1 clinical study involving humans.
Source: Corbett K, Flynn B, Foulds K, et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. . N Eng J Med.2020, Jul 28.
Phase 1/2 Study Results of COVID-19 Adenovirus-Vectored Vaccine Candidate ChAdOx1 nCoV-19
Researchers assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of COVID-19. Researchers conducted a phase 1/2, single-blind, randomized controlled trial in five trial sites in the UK using ChAdOx1 nCoV-19 compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed COVID-19 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine.
In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralizing antibody responses against COVID-19were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralizing activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralizing antibody responses correlated strongly with antibody levels measured by ELISA (R2=0•67 by Marburg VN; p<0•001).
Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0•05). There were no serious adverse events related to ChAdOx1 nCoV-19.
The authors noted that ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 program.
Source: Folegatti, PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020, Jul 20.
Dexamethasone in Hospitalized Patients with COVID-19 — Preliminary Report (The RECOVERY Collaborative Group)
A controlled, open-label study randomly assigned patients with COVID-19 to receive oral or intravenous dexamethasone (6 mg once daily) for up to 10 days, or to receive usual care alone. The primary outcome was mortality at 28 days. Of 2104 patients who received dexamethasone and 4321 who received usual care, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The incidence of death was lower in the dexamethasone group than in the usual care group among patients on invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those on oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those without any respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).
The authors concluded in this preliminary report that for inpatients with COVID-19, dexamethasone resulted in lower 28-day mortality among those who were either on invasive mechanical ventilation or oxygen alone at randomization but not among those without any respiratory support.
Source: Lim WS, EmbersonJR, MafhamW, et al. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report (The RECOVERY Collaborative Group). N Engl J Med. 2020, Jul 17.
Coronavirus Antibodies Fall Dramatically in First 3 Months After Mild Cases of COVID-19
A study by UCLA researchers in a recently published New England Journal of Medicine Letter to the Editor has shown that in people with mild cases of COVID-19, antibodies against COVID-19 drop sharply over the first 3 months post infection, decreasing by roughly half every 73 days. If sustained at that rate, the expectation is that antibodies would fully disappear within about a year.
Previous reports have suggested that antibodies against the novel coronavirus are short-lived, but the rate at which they decrease has not been carefully defined. This is the first study to carefully estimate the rate at which the antibodies disappear.
The researchers studied 20 women and 14 men who recovered from mild cases of COVID-19. Antibody tests were conducted at an average of 36 days and again at 82 days after the initial symptoms of infection.
The authors report their findings raise concerns about antibody-based “immunity passports,” the potential for herd immunity, and the reliability of antibody tests for estimating past infections. In addition, the findings may have implications for the durability of antibody-based vaccines.
Source: Ibarrondo FJ, Fulcher JA, Good-Meza D, et al.Rapid decay of anti–SARS-CoV-2 antibodies in persons with mild Covid-19 [Correspondence]. N Eng J Med. 2020:00;1-25.
Phase 1 Study Results of COVID-19 RNA Vaccine Candidate mRNA-1273
Researchers conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified.
After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site.Of the three doses evaluated, the 100-μg dose elicits high neutralization responses and Th1-skewed CD4 T cell responses, coupled with a reactogenicity profile that is more favorable than that of the higher dose.
The authors conclude that these findings support further development of this vaccine.
Source: Jackson L, Anderson E, Rouphael N, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020, Jul 14.
Phase 1/2 Study Results of COVID-19 RNA Vaccine Candidate BNT162b1
Phase 1 results of a trial using the RNA-based SARS-CoV-2 vaccine to prevent COVID-19 indicate a good tolerability and safety profile, as well as robust immunogenicity.
The study was conducted in 45 healthy subjects (mean age 35.4 years) who were randomized to receive either 10 µg (n=12), 30µg (n=12), or 100µg (n=12) of vaccine vs placebo (n=9). RBD-binding IgG concentrations were detected at 21 days after the first dose and showed a marked increase 7 days after the second dose given at Day 21. The most common side effects were mild to moderate fatigue and headache. Fever and other moderate side effects were seen at higher doses. Although the investigators used convalescent sera as a comparator, the kind of immunity (T cells vs B cells or both) and the level of immunity needed to prevent COVID-19 are unknown.
The authors conclude that these clinical findings are encouraging and support further study.
Source: Mulligan M, Lyke K, Kitchin N, et al. Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. MedRxiv. 2020, Jul 1.
BTK Inhibition in Patients with Severe COVID-19
A prospective study of 19 hospitalized patients with severe COVID-19 (11 on supplemental oxygen and 8 on a ventilator) were given the selective bruton tyrosine kinase (BTK) inhibitor, acalabrutinib, off-label. Patients received 100 mg acalabrutinib either orally or via feeding tube twice daily for 10 days (patients on supplemental oxygen) or 14 days (ventilated patients). Acalabrutinib improved oxygenation in most of the patients, usually within 1-3 days, without signs of toxicity. C-reactive protein and IL-6 rapidly returned to normal in most patients, as did lymphopenia, in association with improved oxygenation.
After treatment, 8/11 (72.7%) patients in the supplemental oxygen group were discharged on room air, and 4/8 (50%) patients in the ventilator group were successfully extubated, with 2/8 (25%) discharged on room air. Due to the activation of BTK and production of IL-6 that the authors observed in COVID-19 monocytes, they proposed that BTK inhibitors target monocyte/macrophage activation and decrease the intensity of cytokine storm, which appears to have been the case in this small cohort. This study underscores the potential benefit of BTK inhibition in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.
Source: Roschewski M, Lionakis MS, Sharman JP, et al. Inhibition of bruton tyrosine kinase in patients with severe COVID-19. Science Immunology. 2020;5:1-18.
https://immunology.sciencemag.org/content/immunology/5/48/eabd0110.full.pdf
Overinterpretation of Results Regarding the Use of Hydroxychloroquine for COVID-19
A study reported a higher frequency of SARS–CoV-2 clearance after 6 days of treatment with hydroxychloroquine (HCQ) versus an untreated control group (14 of 20 patients [70%] vs. 2 of 16 patients [13%]). While some limitations of this study may be acceptable; other methodological flaws may affect the validity of the findings, even in the current pandemic setting. A major consequence has been an inadequate supply of HCQ for patients in whom efficacy is established, including indications for rheumatoid arthritis and of systemic lupus erythematosus. At this time most experts discourage the off-label use of HCQ until justified and supply is bolstered.
Source: Kim AHJ, Sparks JA, Liew JW, et al. A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19. Ann Intern Med. 2020 Mar 30. [Epub ahead of print].
Effectiveness of Convalescent Plasma Therapy in Severe COVID-19 patients
Currently, there are no known antiviral agents to prevent or treat COVID-19. Clinical treatment options are limited consisting of supportive care, including supplemental oxygen and mechanical ventilatory support when indicated.
The FDA recently announced new guidelines permitting the use of convalescent plasma (CP) as an investigational treatment for patients with moderate or severe COVID-19 infections. CP must be collected from someone who has recovered from COVID-19 infection.
Kai Duan of the China National Biotec Group Company Limited and other researchers explored the feasibility of CP transfusion to rescue 10 patients with severe disease. The results of this small study demonstrated that CP was well tolerated, significantly increased or maintained neutralizing antibodies at a high levels, and cleared viremia within 7 days indicating that a larger randomized trial is warranted.
Source: Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 6. [Epub ahead of print].
Pharmacologic Treatments for COVID-19
No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding COVID-19 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against COVID-19, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.
Source: Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A Review. JAMA. 2020 Apr 13. doi: 10.1001/jama.2020.6019.
The COVID-19 Vaccine Pipeline
A collective urgency has fueled research vaccines against COVID-19 in an effort to confront this global public health challenge. Several efforts to develop COVID-19 vaccines are underway. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. The first vaccine to undergo preliminary study in humans in the United States uses a messenger RNA platform to result in expression of the viral spike protein in order to induce an immune response (www.clinicaltrials.gov: NCT04283461). Multiple clinical trials COVID-19 vaccine candidates are underway in the US: www.clinicaltrials.gov: NCT04327206, NCT04341389, NCT04299724, NCT04336410).
Source: Chen WH, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 Vaccine Pipeline: an Overview. Curr Trop Med Rep. 2020 Mar 3:1-4.
NIH Study: Remdesivir Accelerates Recovery from Advanced COVID-19
Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1063 patients. Preliminary results indicate that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059).
The trial (known as the Adaptive COVID-19 Treatment Trial, or ACTT), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19.
Source: NIAID. NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19.
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report.N Engl J Med. 2020 May 22.
Dexamethasone and COVID-19
Initial results from the RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial show that dexamethasone reduces death in hospitalized patients with severe respiratory complications of COVID-19. A total of 2104 patients were randomized to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomised to usual care alone.
The study found that dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75; p=0.14).
Source: University of Oxford. Dexamethasone reduces death in hospitalied patients with severe respiratory complications of COVID-19.
Kidney disease & COVID-19
Kidney Disease or Injury Increases Mortality Risk for COVID-19 Patients in ICU
COVID-19 patients in intensive care units (ICUs) who have chronic kidney disease (CKD) or those who develop acute kidney injury (AKI) as a result of developing COVID-19 are at increased risk of mortality.
In this study, researchers examined the association between AKI and CKD with clinical outcomes in 372 patients with COVID-19 admitted to 4 regional ICUs in the United Kingdom between March 10 and July 23, 2020. The average patient age was 60 years, 72% were male, and 76% of patients were of Black, Asian, and minority ethnic (BAME) background.
A total of 216 (58%) patients had some form of kidney impairment (45% developed AKI during their ICU stay, while 13% had pre-existing CKD), while 42% had no CKD or AKI. The patients who developed AKI had no history of serious kidney disease before their ICU admission (confirmed by blood tests at hospital admission or from medical records).
Overall, patients with no AKI or CKD had a mortality of 21% (32/156 patients). COVID-19 patients with new onset AKI had a mortality of 48% (81/168) and mortality for patients with pre-existing CKD (Stages 1-4) was 50% (11/22). In patients with end-stage kidney failure (ie, CKD stage 5), where they already required regular out-patient dialysis, mortality was 47% (9/19). Mortality was highest in COVID-19 patients with kidney transplants, with 6 out of 7 patients (86%) dying, highlighting that these patients are an extremely vulnerable group.
Renal replacement therapy (RRT) rates were also evaluated and out of 216 patients with any form of kidney impairment, 121 (56%) patients required RRT. Of the 48 survivors who needed dialysis for the first time during their ICU stay, 9 patients (19%) had to continue with dialysis after discharge from ICU, suggesting COVID-19 may lead to chronic kidney problems.
The reasons for the increased mortality in patients with kidney problems are not clearly understood. There are several theories, including that the COVID-19 virus causes endotheliitis, an inflammation of the blood vessels in the kidneys, which is similar to the damage COVID-19 is known to cause in the lungs. Other reports have suggested that there could be direct kidney injury from the cytokine-induced immune system inflammatory response and also death of kidney tissue related to multi-organ failure caused by COVID-19.
Source: Gasparini M, Khan S, Patel JM, et al. Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID‐19: a multicentre observational study. Anaesthesia. 2020, Oct 15.
Outcomes among Patients Hospitalized With COVID-19 and AKI
A retrospective cohort study investigates the survival and kidney outcomes of patients hospitalized with COVID-19 and acute kidney injury (AKI). The study included patients (age ≥18) hospitalized with COVID-19 at 13 hospitals in metropolitan New York, between March 1, 2020 – April 27, 2020, and followed until hospital discharge. The study found that AKI in hospitalized patients with COVID-19 was associated with significant risk for death.
Among 9657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1000 patient-days. The incidence rates of in-hospital death among patients without AKI, with AKI not requiring kidney replacement therapy (AKI non-KRT) and with AKI receiving KRT (AKI-KRT) were 10.8, 31.1 and 37.5/1000 patient-days, respectively. The risks of in-hospital death for patients with AKI-non KRT and AKI-KRT were greater than among those without AKI (HR 5.6 [95% CI 5.0-6.3] and HR 11.3 [95% CI 9.6 - 13.1], respectively).
After adjusting for demographics, comorbidities, and illness severity, the risk of death remained higher among those with AKI non-KRT and AKI-KRT compared to those without AKI. Among patients with AKI non-KRT who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI-KRT who survived, 30.6% remained on dialysis at discharge, and pre-hospitalization CKD was the only independent risk factor associated with needing dialysis at discharge.
Source: Ng J, Hirsch J, Hazzan A, et al. Outcomes among patients hospitalized with COVID-19 and acute kidney injury. Am J Kidney Dis. 2020, Sep 19.
Pre-existing Kidney Disease and COVID-19 Admitted to ICUs
Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. A study examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. The study found that that having pre-existing kidney disease was associated with higher in-hospital mortality rates, with the strength of this association varying by degree of baseline kidney dysfunction.
4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease).
More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44).
The authors conclude that the findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population.
Source: Flythe JE, Assimon MM, Tugman MJ, et al. Characteristics and outcomes of individuals With pre-existing kidney disease and COVID-19 admitted to intensive care units in the United States. Am J Kidney Dis. 2020, Sep 19.
suPAR and AKI in Patients with COVID-19
Researchers in an observational study found patients with COVID-19 experience elevated levels of soluble urokinase receptor (suPAR), an immune-derived pathogenic protein that is strongly predictive of kidney injury.
According to the study authors, suPAR levels of 352 patients were tested upon admission to the hospital for COVID-19 infection. A quarter of the patients developed acute kidney injury (AKI) while hospitalized, and their median suPAR levels were more than 60% higher than those other patients.
In addition, the risk of needing dialysis was increased 20-fold in patients with the highest suPAR levels. Overall, median suPAR levels for these hospitalized patients with severe COVID-19 were almost 3 times higher than levels found in healthy people.
The authors concluded that measuring suPAR levels of COVID-19 patients upon hospital admission will provide an important risk stratification tool with respect to patient outcomes such as intubation or kidney failure and identify patients with higher risk of running a more severe COVID-19 course.
These findings require further study to determine whether suPAR is a cause of COVID-19 associated AKI. If so, can AKI in COVID-19 infected patients be prevented by keeping plasma suPAR levels low? This hypothesis is supported by the study findings, which showed COVID-19 infected patients with a suPAR level below 4.6 ng/ml did not require dialysis. A newly developed and specific suPAR apheresis device is about to enter a clinical pilot trial where this scenario will be tested.
Source: Azam TU, Shadid HR, Blakely P, et al and International Study of Inflammation in COVID-19. Soluble urokinase receptor (SuPAR) in COVID-19–related AKI. J Am Soc Nephrol. 2020, Sep 21.
In Press.
In Press.
AKI in Hospitalized Patients with COVID-19
In a retrospective observational study, the authors compared the incidence, risk factors, and outcomes of AKI in hospitalized adults with and without COVID-19 in a large New York City health system. Because acute kidney injury (AKI) is common in patients with COVID-19 and is associated with worse outcomes, a retrospective, observational study using data from the electronic health records of patients ≥18 years with COVID-19 admitted to the Mount Sinai Health System, was performed for the period of February 27 to May 30, 2020. Of 3993 hospitalized patients with COVID-19, 1835 (46%) patients developed AKI, and 347 (19%) of those patients required dialysis. The patient groups with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, with 745 (76%) experiencing AKI.
Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors for severe AKI were chronic kidney disease (CKD), male gender, and higher serum potassium upon admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI, 35% had not returned to baseline kidney function at discharge. However, an additional 28 of 77 (36%) patients whose kidney function had not returned to baseline at discharge did so by the time of post-discharge follow-up. AKI is common in hospitalized COVID-19 patients and is associated with high mortality. Of all patients with AKI, only 30% survived with return to baseline kidney function at the time of discharge.
Source: Chan L, Chaudhary K, Saha A, et al. AKI in Hospitalized Patients with COVID-19. J Am Soc Nephrol. 2020, Sep 3.
AKI in Hospitalized Patients with and without COVID-19
Centers have reported a wide range of AKI incidence rates among patients hospitalized with coronavirus disease 2019 (COVID-19). In a retrospective observational study, the authors compared the incidence, risk factors, and outcomes of AKI in hospitalized adults with and without COVID-19 in a large New York City health system. Compared with patients without COVID-19 and with historical controls, patients with COVID-19 had a significantly higher incidence of AKI; were more likely to require RRT, intensive care unit admission, and mechanical ventilation; and were more likely to experience in-hospital death. The study found a higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Male sex, Black race, and older age were associated with AKI, but these associations were not unique to COVID-19. Select initial vital signs at hospital admission and inflammatory markers were predictors of severe AKI. Initial laboratory data demonstrated those with AKI had higher markers of inflammation including white blood cell (WBC), neutrophil/lymphocyte ratio, fibrinogen, C-reactive protein, lactate dehydrogenase, and D-dimer compared with those without AKI. The authors concluded that vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI.
Source: Fisher M, Neugarten J, Bellin E, et al. AKI in Hospitalized Patients with and without COVID-19: A Comparison Study. J Am Soc Nephrol. 2020;31:2145-2157.
The Exclusion of Patients with CKD in COVID-19 Clinical Trials
The exclusion of patients with CKD from clinical trials has been a barrier to therapeutic advancement in CKD for the last two decades. This study aimed to assess the CKD-related inclusion and exclusion criteria for COVID-19 trials, using data from data available on the World Health Organization International Clinical Trials Registry Platform4 (WHO-ICTRP; data extracted April 22nd, 2020). The data suggest that patients with CKD are being excluded from almost half of all registered clinical trials for COVID-19.
In total, 484 trials were identified from WHO-ICTRP and included in the analysis; 364 pharmaceutical trials testing 120 different medications were identified. Forty (33.3%) medications either were contraindicated or had insufficient data available to assess their suitability in CKD. Twenty-five medications (20.8%) were categorized as appropriate for use in CKD with caution. In total, 218 (45.0%) trials had exclusion criteria on the basis of CKD. Sixty-three (13.0%) trials excluded CKD but gave an unclear or vague description of CKD, such as “kidney dysfunction.” Additionally, 189 (51.9%) of the clinical trials were classified by the investigators as “late-phase” (2b, 3, or 4) clinical trials.
Pharmaceutical trials involving participants from China, particularly those testing chloroquine/hydroxychloroquine, antivirals, and antibacterials, were more likely to exclude individuals with CKD, whereas those from Europe were less likely.
The authors concluded that the scientific community has a responsibility to build an evidence base for the treatment of all patients with COVID-19, including those with CKD who may be the most clinically vulnerable.
Source: Major R, Selvaskandan H, Makkeyah YM, Hull K, Kuverji A, Graham-Brown M. The Exclusion of Patients with CKD in Prospectively Registered Interventional Trials for COVID-19-a Rapid Review of International Registry Data. J Am Soc Nephrol. 2020 Sep 8.
CKD: A Key Risk factor for COVID-19 Mortality
A new study uses the OpenSAFELY health analytics platform to identify risk factors for COVID-19 mortality. This analysis, which includes data for more than 17 million people in the UK, suggests that patients with chronic kidney disease (CKD) are at higher risk than those with other known risk factors.
Previous reports either did not include information on CKD or failed to state the definition of CKD used in the study. By contrast, the study by Williamson et al. includes data for three subgroups with CKD (those with an estimated glomerular filtration rate (eGFR) of 30–60 ml/min/1.73 m2, those with an eGFR of <30 ml/min/1.73 m2 and those who were receiving maintenance dialysis) as well as a subgroup of solid organ transplant recipients. Although transplant type is not reported, the majority of this latter group will have received a kidney transplant. When the data for the CKD subgroups are compared, it becomes clear that a graded association exists between the level of kidney dysfunction and the risk of COVID-19 mortality.
These data also demonstrate that patients with severe forms of CKD have a very high risk of COVID-19 mortality, which is even higher than that of other known high-risk groups, including patients with hypertension, obesity, chronic heart disease or lung disease.
Sources:
Gansevoort RT, Hilbrands LB. CKD is a key risk factor for COVID-19 mortality. Nat Rev Nephrol. 2020, Aug 26. Access the study
Williamson, E J, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020:584;430-436. Access the study
AKI in Critically Ill Children with COVID-19
A retrospective observational study examined incidence and treatment of AKI in pediatric patients with COVID-19 in a hospital in Wuhan, China during the early stages of the COVID-19 pandemic.
Among 238 confirmed COVID-19 cases, three were critically ill and needed intensive care unit (ICU) admission. All three developed AKI, but AKI was not detected in any non-critically ill patients outside the ICU.
Two of the three patients with AKI had prodromal gastrointestinal symptoms. Significantly elevated interleukin-6 (IL-6) levels and complement activation were observed in these patients with AKI. The three patients with AKI were treated with plasma exchange (PE) and continuous kidney replacement therapy (CKRT), resulting in one complete recovery, one partial recovery, and one mortality due to critical illness.
The authors concluded that critically ill children with COVID-19 may develop AKI, especially following prodromal gastrointestinal symptoms. An inflammatory storm and complement-mediated injury may underlie AKI development in children with COVID-19.
Source: Wang X, Chen X, Tang F, et al. Be aware of acute kidney injury in critically ill children with COVID-19. Pediatr Nephrol. 2020, Aug 26.
Immune Response to COVID-19 Following Organ Transplantation
Chronically ill patients with impaired immune systems are at increased risk for severe disease following COVID-19 infection. Transplant recipients are at especially high risk since they have (1) had a chronic illness, which led to organ failure and subsequent transplantation and (2) lifelong immunosuppression treatment.
In-depth immune monitoring provides clinicians with information on the immune response COVID-19 in patients taking immunosuppressive drugs. In this case study, a pancreas-kidney transplant recipient was capable of achieving an adequate immune response while undergoing immunosuppressive treatment.
While analysis of circulating T-cell subsets with activated memory phenotype provided information on general immune activation levels, analysis of COVID-19 reactive cellular and humoral immunity provided specific information on antiviral response. Combined immune response monitoring facilitated informed clinical decisions based on risk-adjusted guidance and resulted in both an effective immunosuppressive regimen in a transplant recipient and recovery from COVID-19 infection.
Source: Babel N, Anft M, Blazquez-Navarro A, et al. Immune monitoring facilitates the clinical decision in multifocal COVID-19 of a pancreas-kidney transplant patient. Am J Transplant. 2020, Aug 10.
AKI and Severe Infection and Fatality in Patients with COVID-19
This study aimed to investigate whether the presence of acute kidney injury (AKI) might increase the risk of severe infection and fatality in COVID-19 patients. A total of 40 studies involving 25,278 patients with COVID-19 were included in a meta-analysis. The incidence of AKI was 10% (95% CI 8%-13%) in COVID-19 patients. The patients had higher severe infection and fatality rates (55.6% vs. 17.7% and 63.1% vs. 12.9%, respectively, all P < 0.01) with COVID-19.
AKI was a predictor of fatality (OR = 14.63, 95% CI: 9.94 - 21.51, P < 0.00001) and severe infection (OR = 8.11, 95% CI: 5.01-13.13, P < 0.00001) in patients with COVID-19. Higher levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were associated with a significant increase in fatality [Scr: mean difference (MD): 20.19 μmol/L, 95% CI: 14.96-25.42, P < 0.001; BUN: MD: 4.07 mmol/L, 95% CI: 3.33-4.81, P < 0.001] and severe infection (Scr: MD: 7.78 μmol/L, 95% CI: 4.43-11.14, P < 0.00001, BUN: MD: 2.12 mmol/L, 95% CI: 1.74-2.50, P < 0.00001) in COVID-19 patients.
The study found that AKI is associated with severe infection and higher fatality rates in patients with COVID-19. The authors noted that special care and monitoring are needed in COVID-19 patients with AKI to reduce the risk of severe infection and improve prognosis.
Source: Shao M, Li XM, Liu F, Tian T, Luo J, Yang Y. Acute kidney injury is associated with severe infection and fatality in patients with COVID-19: a systematic review and meta-analysis of 40 studies and 25,278 patients. Pharmacol Res. 2020, Jul 30.
Renal Replacement in Critically Ill Patients with COVID-19
A single-center study at an ICU in the Netherlands aimed to investigate mortality and renal recovery in patients with acute kidney injury (AKI) and renal replacement therapy (RRT) due to COVID-19. All patients with COVID-19 infection admitted to the ICU between March 16th 2020 to May 10th 2020 were retrospectively studied. Patients were categorized in a AKI-group and a non-AKI-group.
Thirty-seven patients were included. The study found that 22 (60%) patients developed AKI. Mortality in the AKI-group was 41% compared to 20% in the non-AKI group. Comparable mortality was seen in the RRT (39%) and the non-RRT group (44%). Renal function recovered to a KDIGO-stage 1 in 64% of the patients with AKI when discharged from the ICU. Life time for the CVVH filters (n = 53) was 27 h (14–63)[2–78]. No difference was found with various methods of anticoagulation.
The authors concluded that the need for RRT in critically ill patients with COVID-19 was reversible in this cohort and RRT was not associated with an increased mortality compared to AKI without the need for RRT. Higher levels of anticoagulation were not associated with prolonged filter life.
Source: Wilbers TJ, Koning MV. Renal replacement therapy in critically ill patients with COVID-19: A retrospective study investigating mortality, renal recovery and filter lifetime. J Crit Care. 2020, Jul 30.
Impact of COVID-19 and Nephrology follow-up care
Patients with CKD require specialized management. However, the current situation of CKD management is unclear during the coronavirus disease 2019 (COVID-19) pandemic. In April 2020, researchers included patients who underwent kidney biopsy from January 2017 to December 2019 in a referral center of China, and then initiated a survey via telephone on different aspects of follow-up during the COVID-19 pandemic. Researchers collected and analyzed demographic data, diagnoses, follow-up conditions, and telemedicine experience.
Researchers reached 1190 CKD patients with confirmed kidney biopsies, and included 1164 patients for analysis after excluding those on dialysis. None of the patients have had COVID-19, although more than 50% of them were complicated with other comorbidities, and over 40% were currently using immunosuppressive treatments.
Face-to-face clinic visits were interrupted in 836 (71.82%) participants. Medicine adjustments and routine laboratory examinations were delayed or made irregular in about 60% of patients. To continue their follow-ups, 255 (21.90%) patients utilized telemedicine, and about 80% of them were satisfied with the experience. The proportion of telemedicine users was significantly higher in patients with immunosuppressive treatments than those without (31.88% vs. 17.12%, p < 0.001).
The risk of COVID-19 was mitigated in patients with CKD and other co-existing risk factors when proper protection was utilized. The routine medical care was disrupted during the pandemic, and telemedicine could be a reasonable alternative method.
Source: Chen C, Zhou Y, Xia J, et al. When the COVID-19 pandemic changed the follow-up landscape of chronic kidney disease: a survey of real-world nephrology practice. Ren Fail. 2020, Jul 13..
AKI in Critically Ill COVID-19 Patients
A single-center cohort was conducted from March 3, 2020 to April 14, 2020 in 4 intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. Acute kidney injury (AKI) was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
On admission, patients’ basal serum creatinine (SCr) was 69±21 μmol/l on average (normal is up to 100 μmol/l, approximately, depending on test procedure); AKI was present in 8/71 patients (11%) at that time with median follow-up was 17 (12-23) days. AKI developed in a total of 57/71 patients (80%), with 35% Stage 1, 35% Stage 2 and 30% Stage 3 with 18% (10/57) requiring renal replacement therapy (RRT).
Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%) with a median urinary protein/creatinine ratio of 82 (54-140) mg/mmol and albuminuria/proteinuria ratio of 0.23±20, indicating predominantly tubulo-interstitial injury. Only 2 patients (4%) had glycosuria. Seven days after AKI onset, 6 patients (11%) were still on RRT, 9 (16%) had SCr >200 μmol/l, and 4 (7%) had died. Renal recovery occurred in 28% after 7 days and in 52% after 14 days.
The authors conclude that kidney involvement in critically ill COVID-19 patients is frequent, persistent, and severe with AKI duration >3 days and RRT needed in almost 20% of patients. The study underscores the importance of follow-up nephrological care of patients after hospital discharge since AKI patients are at higher risk of developing chronic kidney disease and end-stage renal disease.
Source: Rubin S, Orieux A, Prevel R, et al, Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019. Clinical Kidney Journal. 2020.
Available at: https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfaa099/5854260
Acute Kidney Injury in Hospitalized COVID-19 Patients
A retrospective observational cohort study of 5,449 adult patients (median age 64 years) hospitalized with COVID-19 from March 1, 2020 to April 5, 2020 in a large New York Health System (13 hospitals) indicates 1,993 (36.6%) developed AKI during their hospitalization. During this time, 780 (39%) were still hospitalized, 519 (26%) were discharged, and 694 (35%) died. Independent risk factors for AKI included older age, black race, hypertension, diabetes mellitus, cardiovascular disease, vasopressor use, and need for ventilation.
Urine studies were available at the time of AKI development in 646 of the 1993 patients. The median urine specific gravity was high (1.020) and most patients (65.6%) had urinary sodium less than 35 mEq/L. The authors suggest that since a cytokine storm often occurs in close temporal proximity to respiratory failure, it is possible that circulating substance or other related factors could contribute to AKI. However, it was beyond the scope of the current study to evaluate for these possibilities. While there were fairly high rates of proteinuria (2-3+ positive in 42.1%) and hematuria (2+ to 3+ positive in 46.1%), inferences are limited since indwelling urethral catheter status at the time of urine collection could not be ascertained.
The authors conclude that: AKI occurs frequently among patients with COVID-19. It was strongly linked to the occurrence of respiratory failure and was rarely a severe disease among patients who did not require ventilation. The development of AKI in hospitalized patients with COVID-19 is associated with a poor prognosis. Further study is needed to better understand the causes of AKI and patient outcomes.
Source: Hirsch JS, Ng JH, Ross DW, et al., on behalf of the Northwell COVID-19 Research Consortium and the Northwell Nephrology COVID-19 Research Consortium, Acute kidney injury in patients hospitalized with COVID-19. Kidney International. 2020 May 5.
Fishbane S. Acute kidney injury in COVID-19 — How one New York system dealt with it. NEJM Journal Watch Podcast. 2020 May 19.
CKD is Associated with Severe COVID-19 infection
A meta-analysis explored the potential association between CKD and severity of COVID-19 infection. Based on a search of electronic databases and contrite meta-analysis of early and preliminarily available data, CKD seems to be associated with enhanced risk of severe COVID-19 infection. When data of individual studies were pooled, a significant association of CKD with severe COVID-19 was observed, with no relevant heterogeneity [OR 3.03 (95% CI 1.09–8.47), I2=0.0%, Cochran’s Q, p=0.84]. Clinicians are encouraged to engage in close monitoring of CKD patients with suspected COVID-19, for timely detecting signs of disease progression. The presence of CKD should also be regarded as an important factor in future risk stratification models for COVID-19, according to the authors.
Source: Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID‑19) infection. Int Urol Nephrol. 2020 Mar 28. [Epub ahead of print].
Kidney Disease and In-Hospital Death of Patients with COVID-19
A study by Cheng et al found that the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. The prospective cohort study included 701 hospital-admitted patients with COVID-19. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 mL/min/1.73m2 were 14.4%, 13.1% and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. The authors believe that clinicians should increase their awareness of kidney disease in patients with severe COVID-19.
Source: Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 Mar 20.
The Aftermath of COVID-19: Devastation or a New Dawn for Nephrology?
In this perspective, Dr. Ragiv Agarwal of Indiana University School of Medicine provides examples of how the COVID-19 pandemic is already inducing change in the practice of medicine at large and for nephrology in particular. Areas of impact include collaboration, innovation, telemedicine, dialysis delivery, virtual learning, disaster preparedness, infection control, research, and social determinants of health.
Source: Agarwal R. The aftermath of coronavirus disease of 2019: devastation or a new dawn for nephrology? Nephrol Dial Transplant. 2020 Apr 17.
Watch the accompanying video
Dialysis & COVID-19
Dialysis Care during the COVID-19 Pandemic
This review discusses dialysis patients' care during COVID-19, addressing measures for patient and health care personnel protection and care of dialysis patients with suspected or confirmed COVID-19. There is a scarcity of real-world data regarding hemodialysis patients and COVID-19. The atypical presentation and higher risks of transmission and mortality warrant specific protocols for caring dialysis patients with COVID-19. In this time of a public health emergency, it is essential to prevent transmission and use evidence-based medicine in caring for dialysis patients to avoid any interruption in their usual care.
Source: Verma A, Patel AB, Tio MC, Waikar SS. Caring for Dialysis Patients in a Time of COVID-19. Kidney Med. 2020, Oct 14.
Impact of the COVID-19 Pandemic on Commercial Airlines: Implications for the Kidney Transplant Community
Many deceased-donor and living-donor kidney transplants (KTs) rely on commercial airlines for transport. However, the COVID-19 pandemic has drastically impacted the commercial airline industry. To understand potential pandemic-related disruptions in the transportation network of kidneys across the United States, national flight data was used to compare scheduled flights during the pandemic versus 1-year earlier, focusing on organ procurement organization (OPO) pairs between which kidneys historically most likely traveled by direct flight (High-Volume by direct Air transport OPO Pairs, HVA-OPs).
Across the US, there were 39% fewer flights in April 2020 versus April 2019. Specific to the kidney transportation network, there were 65.1% fewer flights between HVA-OPs, with considerable OPO-level variation (IQR 54.7%-75.3%, range 0%-100%). This translated to a drop in median number of flights between HVA-OPs from 112 flights/week in April 2019 to 34 in April 2020 (p<0.001), and a rise in wait time between scheduled flights from 1.5 hours in April 2019 (IQR 0.76-3.3) to 4.9 hours in April 2020 (IQR 2.6-11.2) (p<0.001).
Fewer flights and longer wait times can impact logistics as well as cold ischemia time. The findings motivate an exploration of creative approaches to KT transport as the impact of this pandemic on the airline industry evolves.
Source: Strauss AT, Cartier D, Gunning BA, et al. Impact of the COVID-19 pandemic on commercial airlines in the United States and implications for the kidney transplant community. Am J Transplant. 2020, Aug 29.
COVID-19 Incidence and Course of Illness: French National Cohort of Dialysis Patients
A study of the dialysis population in France (n=48,669) indicates a relatively low frequency of COVID-19 among dialysis patients in contrast to what was expected. The prevalence of COVID-19 varied from less than 1% to 10% between regions. Of the 1,621 (3.3%) infected patients reported on the French national ESRD REIN registry from March 16, 2020 to May 4, 2020, 344 died (21%). The mortality of patients admitted to the ICU was higher (34%) in comparison to patients who were not admitted to the ICU (15.5%).
The risk of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Mortality in diagnosed cases was associated with the same causes as in the general population including higher age, hypoalbuminemia, and the presence of an ischemic heart disease. Home dialysis was associated with a lower probability of being infected. The authors note that “despite relatively low incidence, maintenance dialysis patients with COVID-19 have high mortality due to similar risk factors observed in the general population.”
Source: Cécile C, Florian B, Carole A, et al., in the name of the French REIN registry, Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients. Kidney Int. 2020, Aug 25.
Estimating Shortages in Capacity to Deliver CKRT during the COVID-19 Pandemic
During the COVID-19 pandemic, New York encountered shortages in continuous kidney replacement (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis (AKI 3D). To inform planning for current and future crises, mathematical models were used to study estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. The models projected nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation (IHME) model, the Harvard Global Health Institute model, and published literature. The study included data on US patients hospitalized during the initial wave of the COVID-19 pandemic (02/06/2020 to 08/04/2020).
Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval: 910-1,568) machines, and shortages in 6 states at peak resource utilization. In sensitivity analyses, varying assumptions around (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of AKI 3D requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3-8 states (933-1,282 machines) and 4-8 states (945-1,723 machines), respectively. In the best-case and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines).
The authors concluded that several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. The– while based on limited data on CKRT demand and capacity – suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.
Source: Reddy YNV, Walensky RP, Mendu ML, Green N, Reddy KP. Estimating shortages in capacity to deliver continuous kidney replacement therapy during the COVID-19 pandemic in the United States. AJKD. 2020, Jul, 27.
Home Dialysis in the COVID-19 Era
This review addresses the challenges posed by the COVID-19 pandemic for patients on home dialysis, the impact of COVID-19 on various aspects of their care, and the resultant rapid adaptations in policy/health-care delivery mechanisms with implications for the future care of patients on home dialysis. Among the findings, the COVID-19 pandemic has had a significant impact on patients with end stage kidney disease (ESKD) and their care. Patients on home dialysis have an advantage over in-center patients because of a lower risk of exposure to infection but may face some unique challenges, including but not limited to, dialysis supply chain constraints, dialysis safety, perceived lack of help with problem solving, social isolation, and vascular access issues. However, many such issues can be effectively managed by telehealth. The use of telehealth and remote monitoring technologies along with strategizing for potential challenges can help effectively take care of patients on home dialysis during the COVID-19 pandemic.
Source: Yerram Y, Misra M. Home Dialysis in the Coronavirus Disease 2019 Era. ACKD. 2020 Aug 10.
Dialysis, COVID-19, Poverty, and Race
The objective of this study was to examine the correlation of SARS-CoV-2 positivity rate per capita and COVID-19 associated deaths with number of dialysis stations and demographics of residents within ZIP codes in Cook County, Illinois. Number of dialysis stations and stations per capita within a ZIP code was calculated. The SARS-CoV-2 positive tests per capita was calculated as number of positive tests divided by the ZIP code population. COVID-19 deaths per capita were calculated as the COVID-19 deaths among residents for a given ZIP code divided by the ZIP code population.
Among the 163 Cook County ZIP codes, there were 2501 dialysis stations. Positive tests per capita were significantly associated with number of dialysis stations (r = 0.25; 95% CI 0.19, 0.29; P < 0.005) but not with dialysis stations per capita (r=0.02; 95% CI -0.03, 0.08; P = 0.7). Positive tests per capita also correlated significantly with number of households living in poverty (r= 0.57; 95% CI 0.53, 0.6; P < 0.005), and percentage of residents reporting Black race (r = 0.28 p < 0.005, CI = 0.23, 0.33) and Hispanic ethnicity (r = 0.68 p < 0.001, CI: 0.65 — 0.7). COVID-19 deaths per capita correlated significantly with the percentage of residents reporting Black race (r=0.24; 95% CI 0.19, 0.29; P < 0.005) and with percentage of households living in poverty (r=0.34; 95% CI 0.29, 0.38; P < 0.005).
The authors concluded that the number of dialysis stations within a ZIP code correlates with COVID-19 positivity rate per capita in Cook County, Illinois and this correlation may be driven by population density and the demographics of the residents. These findings highlight the high risk of COVID-19 exposure for patients with ESRD living in poor urban areas.
Source: Bhayani S, Sengupta R, Markossian T, et al. Dialysis, COVID-19, Poverty, and Race in Greater Chicago: An Ecological Analysis. Kidney Medicine.2020, Jul 29.
COVID-19 Risk and Nursing Home Residents Receiving Dialysis
In a Maryland nursing home, long-term care residents on kidney dialysis were 3 times more likely to test positive for COVID-19, resulting in increased morbidity and mortality, compared patients not receiving dialysis treatment.
Investigation into this COVID-19 outbreak identified a significantly higher prevalence among dialysis-receiving residents (47%) than among those not receiving dialysis (16%). Nursing home residents undergoing dialysis are likely to be at a higher risk for COVID-19 infection due to their exposure to staff members and other dialysis patients, especially in a centralized dialysis setting.
Given their higher risk for infection, it may be appropriate for nursing homes to house residents requiring dialysis in single rooms closer to the dialysis center to help minimize exposure to other patients. In addition, early identification of cases, coupled with aggressive infection prevention and control actions, are recommended to help protect medically vulnerable populations.
Source: Bigelow BF, Tang O, Toci GR, et al. Transmission of SARS-CoV-2 involving residents receiving dialysis in a nursing home — Maryland, April 2020. MMWR Morb Mortal Wkly Rep. ePub: 11 August 2020.
COVID-19 in Hospitalized Patients on Chronic Peritoneal Dialysis
A study described the clinical characteristics, presentations, clinical course, and outcomes of ESKD patients on PD hospitalized with COVID-19. Data from 13 major hospitals in a NY health system were included. The study found that of 419 hospitalized patients with ESKD, 11 were on chronic PD therapy (2.6%). Among those 11, 3 patients required mechanical ventilation, 2 of whom died. Of the entire cohort, 9 of the 11 patients (82%) were discharged alive. While fever was a common presentation, more than half of the patients also presented with diarrhea. Three patients were diagnosed with culture-negative peritonitis during their hospitalization. Seven patients reported positive COVID-19 exposure from a member of their household. The authors concluded that hospitalized patients on PD with COVID-19 had a relatively mild course, and majority of them were discharged home.
Source: Sachdeva M, Uppal N, Hirsch J, et al. COVID-19 in Hospitalized Patients on Chronic Peritoneal Dialysis: A Case Series. Am J Nephrol. 2020, Jul 30.
Serologic Detection of Latent COVID-19 in Hemodialysis Centers
A study evaluated the prevalence of COVID-19 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese MHD patients. From Dec 1, 2019 to Mar 31, 2020, 1027 maintenance hemodialysis patients (MHD) patients in five large hemodialysis centers in Wuhan, China were enrolled. Patients were screened by blood tests, chest computed tomography, NAT and antibody tests for COVID-19.
Of the 1027 MHD patients, 99 cases have been identified as COVID-19 infection, equivalent to a prevalence of 9.6%. In the 99 cases, 52 (53%) patients were diagnosed with COVID-19 infection by positive NAT; 47 (48%) patients were identified by positive IgG or IgM antibodies against COVID-19 with negative NAT. The spectrum of antibody profiles in these 47 patients showed IgM antibodies in 5 (11%), IgG antibodies in 35 (75%), and both positive IgM and IgG antibodies in 7 (15%). 51% of the infected patients were asymptomatic during the epidemic. Patients with hypertensive kidney disease were more often identified with infection by COVID-19 infection and they tended to be more symptomatic than other patient groups.
Source: Tang H, Tian JB, Dong JW, et al. Serologic Detection of Latent SARS-CoV-2 Infections in Hemodialysis Centers: A Multi-center, Retrospective Study in Wuhan, China. Am J Kidney Dis. 2020, Jul 3.
First Reported COVID-19 Outbreak in a Pediatric Dialysis Unit
An epidemiological study indicates that a hospital outbreak of COVID-19 was due to person-to-person transmission between healthcare workers and patients in a pediatric dialysis unit at the University Hospital of Munster, Germany. This nosocomial outbreak of COVID-19 involved 48 cases (15 male, 33 female), including 28 healthcare workers (HCWs), 13 patients and 7 accompanying persons (APs); with average ages 46 year, 10 years, and 32 years respectively.
Contacts were identified based on potential exposure to the index case (HCW) on the day of the index case’s symptom onset. For the purposes of this outbreak investigation, day 0 was considered as two days prior to the day of first symptoms for the index case. Persons with contact to COVID-19 infected individuals were assessed for their type of exposure (type I, Ia, Ib, II or III) including duration, personal protective equipment (PPE) used, distance to the infective source and potential infectivity of body fluids. All laboratory-confirmed COVID-19 cases were categorized as type I, Ib, or II-exposure, all without use of PPE. No cases were categorized as type III, with use of PPE. After establishing adequate hygienic measures for all HCWs, patients and ACP from day 4 on, no further laboratory confirmed COVID-19 infection was uncovered.
After examining the use of contact tracing, assessment of exposure, and symptom-based testing strategies the investigators concluded that the application of appropriate infection control measures is essential to prevent outbreaks of COVID-19 within hospital settings.
Source: Schwierzeck V, König JC, Kühn J, et al.First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit.Clin Infect Dis.2020, Apr 2.
Asymptomatic COVID-19 Spread in a Hemodialysis Unit: A first-month experience
This study describes the experience of the first month of the COVID-19 pandemic in a hospital hemodialysis (HD) unit serving the district of Madrid with the second highest incidence of COVID-19 (almost 1,000 patients in 100,000h). A high prevalence of COVID-19 was detected, with a high percentage detected by screening, underscoring the need for proactive diagnosis to stop the pandemic.
The unit started with 90 patients on HD: 37 (41.1%) had COVID-19, of whom 17 (45.9%) were diagnosed through symptoms detected in triage or during the session, and 15 (40.5%) through subsequent screening of those who, until that time, had not undergone COVID-19 PCR testing. Fever was the most frequent symptom, 50% had lymphopenia and 18.4% <95% O2 saturation. Sixteen (43.2%) patients required hospital admission and 6 (16.2%) died.
In terms of staff, of the 44 people involved, 15 (34%) had compatible symptoms, 4 (9%) were confirmed as COVID-19 PCR cases by occupational health, 9 (20%) required some period of sick leave, temporary disability to work (ILT), and 5 were considered likely cases.
Source: Albalate M, Arribas P, Torres E, et al. High Prevalence of Asymptomatic COVID-19 in Haemodialysis: Learning Day by Day in the First Month of the COVID-19 Pandemic. Nefrologia. 2020;40:279-286.
Hospitalizations among Medicare Beneficiaries
The Centers for Medicare & Medicaid Services (CMS) is calling for a renewed national commitment to value-based care based on Medicare claims data that provides an early snapshot of the impact the COVID-19 pandemic on the Medicare population. The data shows that older Americans and those with chronic health conditions are at the highest risk for COVID-19 and confirms long-understood disparities in health outcomes for racial and ethnic minority groups and among low-income populations.
In addition, individuals with receiving dialysis had the highest rate of hospitalization among all Medicare beneficiaries, with 1,341 hospitalizations per 100,000 beneficiaries. Patients receiving dialysis are also more likely to have chronic comorbidities associated with increased COVID-19 complications and hospitalization, such as diabetes and heart failure.
Sources:
CMS Report. Preliminary Medicare COVID-19 Data Snapshot.
CMS Announcement. Trump Administration Issues Call to Action Based on New Data Detailing COVID-19 Impacts on Medicare Beneficiaries.
Mitigating Risk of COVID-19 in Dialysis Facilities
Kliger AS, Silberzweig J. Mitigating Risk of COVID-19 in Dialysis Facilities. Clin J Am Soc Nephrol. 2020 Mar 20. [Epub ahead of print]. This resource outlines critical points in mitigating the risk of COVID-19 at dialysis facilities.
COVID-19 and Dialysis Units
Ikizler TA. COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do? Am J Kidney Dis. 2020 Mar 23. [Epub ahead of print]. This resource addresses what clinicians should do to prevent and control COVID-19 infections in outpatient hemodialysis facilities.
COVID-19 and Patients Receiving Dialysis
Patients receiving maintenance hemodialysis are at increased risk for COVID-19 and its complications. The following resources contain recommendations on the prevention and control of COVID-19 among patients receiving dialysis.
Centers for Disease Control and Prevention. Interim Additional Guidance for Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed COVID-19 in Outpatient Hemodialysis Facilities.
This resource addresses what clinicians should do to prevent and control COVID-19 infections in outpatient hemodialysis facilities.
Ikizler TA. COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do? Am J Kidney Dis. 2020 Mar 23. [Epub ahead of print].
Ikizler TA. COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do? Am J Kidney Dis. 2020 Mar 23. [Epub ahead of print].
This resource outlines critical points in mitigating the risk of COVID-19 at dialysis facilities.
Kliger AS, Silberzweig J. Mitigating Risk of COVID-19 in Dialysis Facilities. Clin J Am Soc Nephrol. 2020 Mar 20. [Epub ahead of print].
Kliger AS, Silberzweig J. Mitigating Risk of COVID-19 in Dialysis Facilities. Clin J Am Soc Nephrol. 2020 Mar 20. [Epub ahead of print].
Peritoneal Dialysis during the (COVID-19) Pandemic
El Shamy et al report on their experience at Mount Sinai Hospital, East Harlem, NY with caring for dialysis patients during this crisis in the outpatient setting, as well as their procedures to use acute peritoneal dialysis to combat the inexorable rise in the number of admitted patients requiring kidney replacement therapy (KRT) in the inpatient setting.
Source: El Shamy O, Sharma S, Winston J, Uribarri J. Peritoneal Dialysis During the Coronavirus 2019 (COVID-19) Pandemic: Acute Inpatient and Maintenance Outpatient Experiences. Kidney Medicine. April 23, 2020.
Asymptomatic Seroconversion of Immunoglobulins to COVID-19 in a Pediatric Dialysis Unit
Serial COVID-19 antibody levels were measured in patients, nurses, physicians, and staff in a freestanding outpatient 5-bed/3–isolation room pediatric hemodialysis unit at Riley Hospital for Children, Indianapolis, Indiana. Thirteen patients, 9 dialysis nurses, 2 nurse practitioners, 4 staff, and 10 physicians participated in the study. This study found a high prevalence of subclinical seroconversion in individuals interacting in a pediatric dialysis unit. The prevalence of subclinical seroconversion in the health care workers suggests that more health care workers may be antibody-positive than would otherwise be expected.
By day 21, 11 of 25 health care workers (44%) and 3 of 13 patients (23%) had positive COVID-19 antibodies. No participants developed symptoms between days 7 and 21. No health care workers who directly cared for the PCR-positive patient seroconverted. Replication in additional sites is needed to define the broad applicability of these findings, as is longer-term follow up to determine the persistence of the antibody response to COVID-19.
Source: Hains d, Schwaderer a, Carroll a, et al. asymptomatic seroconversion of Immunoglobulins to SARS-CoV-2 in a pediatric dialysis unit. JAMA. 2020 May 14.
Kidney transplant & COVID-19
Back-to-School Safety Guidelines for Pediatric Solid Organ Transplant Recipients
Throughout the COVID-19 pandemic, pediatric solid organ transplant (SOT) recipients have been categorized as high-risk due to their use of immunosuppressive medications, frequent presence of additional medical issues, and elevated risk for more severe outcomes from other viral respiratory infections. While there is no specific evidence that pediatric SOT recipients fare worse from COVID-19, parents of children with SOT may be concerned about school starting in just a few weeks.
A group of pediatric infectious disease experts from across the United States was convened to develop back-to-school safety guidelines for SOT recipients.
The consensus statements are grouped into 3 areas: 1) SOT patient-specific risk factors, 2) community transmission and public health responses, and 3) school-related interventions. A number of questions were addressed on topics of interest to parents, caregivers, and healthcare providers, such as masking, virtual learning, and infection prevention measures.
The panel fully supports efforts to allow all children to safely return to in-person education this academic year and have provided recommendations for transplant patients, families, and providers to help meet this goal.
Source: Downs KJ, Danziger-Isakov LA, Cousino MK, et al. Return to school for pediatric solid organ transplant recipients in the United States during the COVID-19 pandemic: expert opinion on key considerations and best practices. J Pediatric Infect Dis Soc. 2020, Aug 4.
COVID-19 in Kidney Transplant Recipients: A Single-Center Report from Belgium
A prospective single-center cases series included 22 kidney transplant recipients diagnosed with COVID-19 infection out of a cohort of 1,200 kidney transplant recipients at a center in Belgium.
Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients.
Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n=3), moderate (n=8), extensive (n=1), severe (n=2), and critical (n=1) involvement. Immunosuppression reduction was initiated in all patients.
Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died.
The authors noted that the clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.
Source: Devresse A, Belkhir L, Vo B, et al. COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium.Kidney Medicine. 2020. 15, Jun.
Kidney Transplantation Safety during the COVID-19 Pandemic: A Simulation Study
A simulation study was conducted to quantify the benefit/harm of kidney transplantation in the context of various COVID-19 scenarios. The study compared immediate-kidney transplantation scenarios versus delay-until-after-pandemic scenarios for different patient phenotypes. A calculator was implemented, and machine learning approaches were used to evaluate the important aspects of the modeling.
The simulation suggests that even after weighing the potential risks of COVID-19 infection, kidney transplantation still provides survival benefit to transplant candidates in most scenarios. If local resources allow, it might be reasonable to continue kidney transplantation unless evidence emerges of extremely high case fatality rates of COVID-19 among recipients.
Source: Massie A, Boyarsky B, Werbel W, et al. Identifying scenarios of benefit or harm from kidney transplantation during the COVID-19 pandemic: a stochastic simulation and machine learning study. Am J Transplant. 2020 Jun 9.
https://onlinelibrary.wiley.com/doi/epdf/10.1111/ajt.16117
Early Outcomes of outpatient management of kidney transplant recipients with COVID-19
A single-center study of 41 kidney transplant recipients with known or suspected COVID-19 found that 54% had confirmed COVID-19 and 46% were suspected cases. Patients most commonly reported fever (80%), cough (56%), and dyspnea (39%).
At the end of follow-up, 32% required hospitalization a median of 8 days (range, 1–16) after symptom onset, and 56% had outpatient symptom resolution a median of 12 days (4–23) after onset. Patients who required hospitalization were more likely to have reported dyspnea (77% versus 21%, P50.003) and had higher baseline creatinine (median, 2.0 versus 1.3 mg/dl, P50.02), but there were no other differences between groups. This wide interval underscores the need for increased vigilance approximately 1 week following the onset of symptoms and also, the need for continued close outpatient follow-up for the early detection of clinical deterioration during the second week.
Source: Husain SA, Dube G, Morris H, et al. Early outcomes of outpatient management of kidney transplant recipients with coronavirus disease 2019. Clin J Am Soc Nephrol. 2020 May 18.
Kidney Transplantation and COVID-19 Induced Pneumonia
COVID-19 induced pneumonia is characterized by high risk of progression and significant mortality, according to limited cohort of long-term kidney transplant patients. The preliminary findings studying 20 kidney transplant patients describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with COVID-19 induced pneumonia.
Alberici F, Delbarba E, Manenti C, et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int. 2020 Apr 9.
COVID-19 and Kidney Transplantation at a NYC Hospital
At Montefiore Medical Center, clinicians identified 36 adult kidney-transplant recipients who tested positive for COVID-19 between March 16 and April 1, 2020. At this institution, kidney-transplant recipients with Covid-19 had less fever as an initial symptom, lower CD3, CD4, and CD8 cell counts, and more rapid clinical progression than persons with COVID-19 in the general population. The number of patients with very low CD3, CD4, and CD8 cell counts indirectly supports the need to decrease doses of immunosuppressive agents in patients with COVID-19, especially in those who have recently received antithymocyte globulin, which decreases all T-cell subsets for many weeks.
Source: Akalin E, Azzi Y, Bartash R, et al. Covid-19 and Kidney Transplantation. Engl J Med. 2020 Apr 24.
Kidney Allograft Recipients and COVID-2019: A Single Center Report
A retrospective chart review of 54 adult kidney transplant patients diagnosed with COVID-19 in a New York City hospital system suggest that a strategy of systematic screening and triage to outpatient or inpatient care, close monitoring, early management of concurrent bacterial infections and judicious use of immunosuppressive drugs rather than cessation is beneficial.
Thirty-nine patients with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid-free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs 40%). In addition, 50% of hospitalized patients were treated for concurrent bacterial infections including pneumonia, urinary tract infections and sepsis. Acute kidney injury occurred in 51% of hospitalized patients.
At a median of 21 days follow up, 67% of patients had their symptoms resolved or improved and 33% had persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired.
Source: Lubetsky M, Aull M, Craig-Shapiro R, et al. Kidney allograft recipients diagnosed with coronavirus disease-2019: a single center report. MedRxiv. 2020 May 5.
Kidney Transplant Procedures: Prevention and control measures
The experiences conducting kidney transplants at a hospital in Wuhan, China are outlined in this study. Strict prevention and control measures were implemented and working methods and procedures were adjusted to ensure the safe and orderly work of the department. Prevention and control measures, included kidney transplant outpatient management, kidney transplantation ward management, management of kidney transplant surgery, dialysis management of patients waiting for kidney transplantation, personal protection of medical staff and follow‐up management of discharged patients after kidney transplantation.
Source: Li Y, Yang N, Li X, Wang J, Yan T. Strategies for prevention and control of the 2019 novel coronavirus disease in the Department Of Kidney Transplantation. Transpl
Transplant Outpatient Management and COVID-19
This article offers guidance for clinicians caring for ambulatory kidney transplant recipients who have COVID-19. The recommendations include insights on prevention, diagnostics, management of immunosuppression, and therapies for COVID-19 and their potential drug interactions with immunosuppressive medications. The guidance is based on the experience of a hospital in managing other infections in kidney transplant recipients and the experience managing their first 21 patients testing positive for COVID-19 and 41 patients with symptoms who tested negative.
Source: Gleeson S, Formica R, Marin E. Outpatient Management of the Kidney Transplant Recipient during the SARS-CoV-2 Virus Pandemic. Clin J Am Soc Nephrol. 2020 Apr 28.
Organ Procurement and Transplantation during the COVID-19 Pandemic
Since the onset of the COVID-19 pandemic, France and the United States have experienced a significant reduction in the number of organ donations and solid organ (kidney, liver, heart, and lung) transplant procedures. In early April, transplant centers in both countries reported conducting far fewer deceased donor transplants compared to March, with the number of procedures dropping by 91% in France and 50% in the United States.
To quantify the impact of the COVID-19 outbreak on organ donation and transplantation, the authors analyzed validated national data from 3 federal agencies, including the United Network for Organ Sharing (UNOS), to study trends in France and the United States.
A strong link was observed between the surge of COVID-19 infections and significant decline in donated organs and overall solid organ transplants. In the United States, the number of recovered organs dropped from over 110 a day on March 6 to fewer than 60 per day on April 5. During the same timeframe, the number of transplanted kidneys dropped from nearly 65 a day to about 35 per day. Researchers also observed that regions with fewer COVID-19 cases, or limited exposure to the disease, also experienced a significant reduction in transplant rates – suggesting a global and nationwide effect beyond the local infection prevalence.
The team suggests these findings could be useful for public health agencies, professional societies and patient advocacy organizations in their planning and risk mitigation. Researchers also say that specific mapping of local trends in organ donation and transplant activity will enable public health leaders to identify areas where the number of donations and transplants continues to remain lower than normal.
Source: Loupy A, Aubert O, Reese PP, Bastien O, Bayer F, Jacquelinet C. Organ procurement and transplantation during the COVID-19 pandemic. Lancet. 2020 May 11.
Nutrition
Vitamin D Deficiency May Increase Risk for COVID-19
Vitamin D is a known immune system booster and vitamin D supplementation has previously been shown to lower the risk of viral respiratory tract infections. A retrospective study of patients tested for COVID-19 found an association between vitamin D deficiency and an increased risk of coronavirus infection.
Researchers evaluated 489 University of Chicago Medicine patients whose vitamin D level was measured within a year before being tested for COVID-19. Patients who had untreated vitamin D deficiency (<20ng/ml) were almost twice as likely to test positive for the COVID-19 coronavirus compared to patients who had sufficient levels vitamin D.
Vitamin D deficiency is common in the United States with 50% of adults having insufficient levels of the nutrient. Vitamin D deficiency rates are higher in African Americans, Hispanics, and people living in areas like Chicago where there is limited winter sun exposure.
The authors emphasize the importance of experimental studies to determine whether vitamin D supplementation can reduce the risk, and potential severity, of COVID-19. They also highlight the need for additional studies and determining appropriate strategies for the most effective vitamin D supplementation in specific populations.
Source: Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open. 2020;3:e2019722.
Obesity Linked to Higher Risk for COVID-19 Complications & Limited Vaccine Efficacy
Obesity is associated with several underlying risk factors for COVID-19, including hypertension, heart disease type 2 diabetes, and chronic kidney and liver disease, as well as an increased likelihood of developing more severe complications from the virus.
Roughly 40% of people living in the United States are obese, and the pandemic’s resulting lockdown has made it more difficult for people to achieve or sustain a healthy weight. Economic hardships and food insecurity have increased unhealthy food consumption resulting in greater population obesity and complications in patients with COVID-19.
Researchers from the University of North Carolina at Chapel Hill reviewed immunological and biomedical data on COVID-19 patients and found that those with obesity (BMI >30) were at a greatly increased risk for hospitalization (113%), more likely to be admitted to an intensive care unit (74%), and had a higher risk of death (48%) from the virus.
Previous studies have shown the influenza vaccine is less effective in adults with obesity. The authors are concerned that the efficacy of a future COVID-19 vaccine may also be limited in obese adults and should be viewed as a modifying factor in vaccine testing.
Source: Popkin BM, Du S, Green WD, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obesity Reviews. 2020;1-17.
Guidance & Strategies for Clinicians to Optimize Care in the ICU
The society of Critical Care Medicine (SCCM) and the American Society for Parenteral and Enteral Nutrition (ASPEN) have published guidelines on Nutrition Support for Critically Ill Patients with COVID-19 Disease. Relevant key recommendations include estimating protein/calorie needs; timing of nutrition delivery; route, tube placement and method of nutrition delivery; nutrition dose, advancing to goal, and adjustments; formula selection; monitoring nutrition tolerance; nutrition for the patient undergoing prone positioning; and nutrition therapy during extracorporeal membrane oxygenation.
In addition to general key recommendations for enteral and parenteral nutrition for this patient population, there are recommendations for AKI as follows:
- Recommendation # 9A With AKI requiring CRRT dose protein at 2.0-2.5 gm/kg/d
- Recommendation # 9B Monitor and replace micronutrients in AKD on CRRT (especially zinc, iron, selenium, Vit D, Vit C)
Faculty: Stephen McClave, MD, and Mary Rath, RDN, CSNC, LD
Provider: Abbott Nutrition Institute (ANHI) https://anhi.org/resources/podcasts-and-videos/nutrition-care-of-the-covid-19-patient-series
Nutrition Therapy in the patient with COVID-19 Disease Requiring ICU Care, SCCM and ASPEN – updated April 1, 2020
Selenium Status and Outcome Of COVID-19
A population-based retrospective analysis in 17 cities outside of Hubei, China indicates that the COVID-19 cure rate was significantly associated with selenium status, as measured by the amount of selenium in hair. These data are consistent with evidence of the antiviral effects of selenium from previous studies in other viral infections including HIV. While it is important not to overstate this finding, this data indicates the need for further research regarding the role selenium may play in COVID-19 that may help to guide ongoing public-health decisions.
Note: There are currently no recommendations for selenium supplementation in patients with CKD. The current Recommended Dietary Allowance (RDA) for selenium is 55mcg/d for men and women. Whether similar amount of intake is recommended in various stages of CKD and maintenance dialysis is unknown.
Source: Jinsong Z, Taylor EW, Bennett K, et al. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr. 2020 Apr 28.
Vitamin D Deficiency and Severe COVID-19
An observational study on 186 consecutive patients hospitalized with COVID-19 found that patients with severe COVID-19 show lower median serum 25(OH)D and a higher percentage of vitamin D deficiency at intake than a season/age-matched reference population. The correlation between vitamin D deficiency and the need for hospitalization due to COVID-19 was only seen in male patients. In males but not females, the percentage of vitamin D deficient patients also increased with more advanced COVID-19 disease stage as measured by CT. The data indicates a strong statistical correlation between the degree of vitamin D deficiency and severity of COVID-19 lung disease.
Source: De Smet D, De Smet K, Herroelen P, Gryspeerdt S. Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics. MedRxiv. 2020 May 5.
NKF Advocacy during the COVID-19 pandemic
NKF has identified and been actively advocating on several key areas of concern for our community in the context of the COVID-19 pandemic:
- Prioritize kidney patients and clinicians access to personal protective equipment
- Preserve access to essential kidney-related surgical procedures, including organ transplantation and vascular access
- Fight policies that discriminate against kidney patients
NKF is also working with several partners to implement policies that:
- Accelerate patients' access to home dialysis
- Ensure timely implementation of kidney care payment models
- Ensure kidney patients and transplant patients can access greater-than-30-day supplies of critical prescriptions including immunosuppressive drugs
- Ensure that vulnerable home dialysis, transplant patients, and living donors can receive needed blood draws in their homes
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