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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

 

 

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.

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.

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.

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.

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.

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].

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].

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.

 

 

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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].

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].

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.

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.

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.

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.

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.

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.

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..

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.

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.

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].

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.

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.

 

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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.

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.

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.

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.

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.

 

 

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.

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.

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.

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].

 

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].

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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:

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

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.

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.