NKF Clinical Digest - COVID-19

NKF Clinical Digest — COVID-19

Current research regarding COVID-19 and its implications.

A message from our Chief Medical Officer

Welcome to the NKF Clinical Digest. This resource is an ongoing compilation of the latest clinical information regarding COVID-19, curated by NKF subject matter experts. Our goal is to make it easy for the interdisciplinary team to find current data on the implications of COVID-19 for people living with kidney diseases. The NKF Clinical Digest will also provide links to the most current patient resources and educational tools developed by NKF to support people living with kidney diseases through this crisis. This compendium of resources will also include information regarding NKF’s recent advocacy activities to improve the care and the safety of people living with kidney diseases. We hope that you find the NKF Clinical Digest – COVID-19 a valuable resource as you care for kidney patients during these extraordinary times.

 

– Joseph A. Vassalotti, MD
Chief Medical Officer, National Kidney Foundation

General information about COVID-19

Venous Thrombosis and Critically Ill Patients with COVID-19
A prospective study of 34 consecutive patient cases included a systematic assessment of deep vein thrombosis among patients with severe COVID-19 in an intensive care unit (ICU) in France. The authors prospectively performed a venous ultrasonogram of the inferior limbs for all patients at admission to the ICU. Due to the high prevalence of venous thrombosis at admission, the authors systematically repeated venous ultrasonography after 48 hours if the first examination was normal. As recommended, all patients received anticoagulant prophylaxis on admission. Deep vein thrombosis was found in 22 patients (65%) at admission and in 27 patients (79%) when the venous ultrasonograms were performed 48 hours after ICU admission. Eighteen patients (53%) had bilateral thrombosis, and 9 patients (26%) had proximal thrombosis. This population had high levels of D-dimer (mean, 5.1 μg/mL), fibrinogen (mean, 760 mg/dL) and C-reactive protein (mean, 22.8 mg/dL). Prothrombin activity (mean, 85%) and platelet count (mean, 256 × 103/μL) were normal. In view of the high rate of deep vein thrombosis reported in this study, the authors concluded that prognosis could be improved with early detection and prompt initiation of anticoagulation. Despite anticoagulant prophylaxis, 15% of patients developed deep vein thrombosis only 2 days after ICU admission. The authors suggest that systematic assessment for deep vein thrombosis for all ICU patients with COVID-19 should be considered.
 
Source: Nahum J, Morichau-Beauchant T, Daviaud F, et al. Venous Thrombosis Among Critically Ill Patients with Coronavirus Disease 2019 (COVID-19). JAMA Network Open. 2020;3:e2010478.
Pulmonary Complications and Mortality in Post-Operative COVID-19 Patients
COVID-19 patients who undergo surgery experience substantially worse postoperative outcomes than would be expected for similar patients who do not have COVID-19 infection based on data for 1,128 patients from 235 hospitals in Europe, Africa, Asia, and North America.
 
The study authors found overall 30-day mortality was 23.8%. Mortality was disproportionately high across all subgroups, including elective surgery (18.9%), emergency surgery (25.6%), minor surgery such as appendectomy or hernia repair (16.3%), and major surgery such as hip surgery or colon cancer surgery (26.9%).
 
The study identified mortality rates were higher in men (28.4%) versus women (18.2%), and in patients aged 70 years or over (33.7%) versus those aged under 70 years (13.9%). In addition to age and sex, risk factors for postoperative death included severe pre-existing medical problems, undergoing cancer surgery or major procedures, and emergency surgery. In the 30 days following surgery 51% of patients developed pneumonia, acute respiratory distress syndrome, or required unexpected ventilation. Most of the patients who died (81.7%) experienced pulmonary complications.
 
The authors conclude that postoperative pulmonary complications occur in half of patients with perioperative COVID-19 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing nonurgent procedures and promoting nonoperative treatment to delay or avoid the need for surgery.
 
Source: Bhangu A, Nepogodiev D, Glasbey JC, et al for the COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet. 2020 May 29.
Hypertension and COVID-19 Severity
An observational study of 310 patients diagnosed with COVID-19 at two hospitals in Wuhan, China explored the effect of hypertension on disease progression and prognosis in patients with COVID-19. Multivariate analysis (adjusted for age and sex) did not show that hypertension was an independent risk factor for COVID-19 mortality or severity. However, COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease.
 
Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05).
 
Source: Huang S, Wang J, Liu F, et al. COVID-19 Patients With Hypertension Have More Severe Disease: A Multicenter Retrospective Observational Study. Hypertens Res. 2020 Jun 1.
Children and Adolescents with Severe COVID-19
While most children infected with the novel coronavirus have mild symptoms, a subset requires hospitalization and a small number require intensive care. A new report from physicians at Children’s Hospital at Montefiore (CHAM) and Albert Einstein College of Medicine, describes the clinical characteristics and outcomes of children hospitalized with COVID-19, during the early days of the pandemic.
 
This report compares 46 children between the ages of 1 month and 21 years, who received care either on a general unit or in the Pediatric Critical Care Unit (PCCU) at CHAM. This is the largest single-center study from the United States to date to describe in detail the full spectrum of COVID-19 disease in hospitalized children.
 
The authors found that children requiring intensive care had higher levels of inflammation and needed additional breathing support, compared to those who were treated on a general unit. Of the children being cared for in the PCCU, almost 80% had Acute Respiratory Distress Syndrome (ARDS), which is more commonly associated with critically ill adult COVID-19 patients, and almost 50% of children with ARDS were placed on ventilators.
 
In addition, over half of the children had no known contact with a COVID-positive person. The authors concluded this may signify that the virus can be spread by asymptomatic people and COVID-19 may be more prevalent in communities with a high population density.
 
Source: Chao JY, Derespina KR, Herold BC, et al. Clinical characteristics and outcomes of hospitalized and critically ill children and adolescents with coronavirus disease 2019 (COVID-19) at a tertiary care medical center in New York City. J Peds. May 6, 2020.
Interpreting COVID-19 Test Results
The COVID-19 pandemic continues to affect much of the world. Knowledge of diagnostic tests for COVID-19 is still evolving, and a clear understanding of the nature of the tests and interpretation of their findings is important. The following resources describe how to interpret certain diagnostic tests commonly in use for COVID-19 infections.
 
 
Characteristics and Outcomes of ICU Patients with COVID-19
A retrospective observational study of 1591 laboratory confirmed cases (82% male, mean age 63 years) of COVID-19 admitted to the ICU in the Lombardy region of Italy between February 20, 2020 and March 18, 2020 indicates 88% needed mechanical ventilation and high levels of positive end-expiratory pressure (PEEP, mean 14 cm H20), and ICU mortality was 26%. Baseline characteristics show that 68% of patients had at least one comorbidity with hypertension (49%) being the most common. The second most common comorbidities were cardiovascular disease (21%) and hypercholesterolemia (18%). A history of chronic obstructive pulmonary disease was present in only 4% of patients. All patients older than 80 years and 76% of patients older than 60 years had at least 1 comorbidity. This data may be used for comparison in other countries and regions.
 
Source: Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6.
Neurological impact of COVID-19
Increasing research reports neurological manifestations of COVID-19 patients. A systematic analysis found an increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that COVID-19 is a new neuropathogen. Common reported neurological symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.
 
Source: Montalvan V, Lee J, Bueso T, De Toledo J, Rivas K. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clin Neurol Neurosurg. 2020 May 15.
Genomic Analysis of COVID-19
Next-generation sequencing found that COVID-19 shares 73% of its genome with severe acute respiratory syndrome (SARS) and 50% of its genome with Middle East respiratory syndrome (MERS). COVID-19 also shares 88% of its genome with two bat-derived SARS-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China. Structural analysis suggests that COVID-19 binds to the angiotensin-converting enzyme 2 receptor in humans.
 
Source: Lu R, Zhao X, Li J,et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.
COVID-19 and Ketosis or Ketoacidosis
This study of 658 hospitalized patients infected with COVID-19 found that the disease may cause ketosis or ketoacidosis, and induce diabetic ketoacidosis for patients with diabetes. The study found that 6.4% of the patients presented with ketosis on admission with no obvious fever or diarrhea. Ketosis increased the length of hospital stay and mortality in the study.
 
Source: Li J, Wang X, Chen J, Zuo X, Zhang H, Deng A. COVID-19 infection may cause ketosis and ketoacidosis. Diabetes Obes Metab. 2020 Apr 20.
Sinonasal Pathophysiology of COVID-19
The ongoing COVID-19 pandemic is highly contagious with high morbidity and mortality. The role of the nasal and paranasal sinus cavities is increasingly being recognized for COVID-19 symptomatology and transmission. Researchers conducted a systematic review, synthesizing existing scientific evidence about sinonasal pathophysiology in COVID-19.
 
In all, 19 studies were identified suggesting that the sinonasal cavity may be a major site of infection by COVID-19. The authors noted that sinonasal symptomatology, such as rhinorrhea or congestion, appears to be a rarer symptom of COVID-19, anosmia without nasal obstruction is reported as a highly specific predictor of COVID-19+ patients.
 
The authors concluded the sinonasal tract may be an important site of infection while sinonasal viral shedding may be an important transmission mechanism – including healthcare-associated infection – and anosmia without nasal obstruction may be a highly specific indicator of COVID-19.
 
Source: Gengler, I, Wang, JC, Speth, MM, Sedaghat, AR. Sinonasal pathophysiology of SARS‐CoV‐2 and COVID‐19: a systematic review of the current evidence. Laryngoscope Investigative Otolaryngology. 2020. Accepted Author Manuscript. doi:10.1002/lio2.384.
Risk of Severe Illness from COVID-19 Increases with each Decade of Age
A study has shown a strong age gradient in risk of death for people with COVID-19. The study examined data of individuals from 38 countries who tested positive for COVID-19. In the study, the mean duration from onset of symptoms to hospital discharge was 24.7 days and to death was an estimated 17.8 days. The study found that found that risk of death from the disease rose with each decade of age. The death rate (infection fatality ratio) among laboratory-confirmed cases was ~0.03% for people 20-29; 0.08% for people 30-39; 1.16% for people 40-49; 0.59% for people 50-59; 1.93% for people 60-69; 4.28% for people 70-79; and 7.80% for people ≥80.Older individuals with underlying conditions were at highest risk for severe disease and death.
 
Source: Verity R, Okell L, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet. 2020 Mar 30 [Epub ahead of print].
Ocular Findings of Patients with COVID-19
A study found that COVID-19 can lead to conjunctivitis (“pink eye”) and other eye problems. The novel coronavirus is thought to be transmitted through the eyes in addition to the nose and mouth routes. In this case series including 38 patients with COVID-19, 12 patients or about 1 in 3 had ocular manifestations, such as epiphora, conjunctival congestion, or chemosis. These commonly occurred in patients with more severe systemic COVID-19 manifestations. The study also showed SARS-CoV-2 was detected in the conjunctival swabs of 2 of 12 patients, supporting the possibility of transmission of the virus through the eyes.
 
Source: Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. 2020 Mar 31. [Epub ahead of print].
COVID-19 Infection in Patients Taking Angiotensin Drugs
The use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) is the standard of care in reducing proteinuria and in slowing the progression of proteinuric CKD. Recently these angiotensin drugs have come under scrutiny due to the hypothesis that these drugs may put patients at increased risk for infection with COVID-19 virus. But experts agree that this assumption is based on limited animal data and there is no evidence to support stopping angiotensin drugs. ACEI and ARB increase angiotensin converting enzyme 2 (ACE2) expression. ACE2 is an enzyme attached to the outer surface of cells in the lungs, arteries, heart, kidney, and intestines. In addition to lowering blood pressure ACE2 also serves as a receptor for some coronaviruses. However, there are no clinical data indicating that patients taking ACEIs/ARBs have increased severity of illness or risk of mortality during COVID-19 infection.
 
Recent studies in Wuhan China further support continued use of these drugs. A retrospective, single-center case series of 1178 hospitalized patients (median age 55 years, 46.3% male) with COVID-19 infections from January 15 to March 15, 2020 indicates there was no difference in severity of the disease, complications, and risk of death in those who were taking ACEI/ARB compared with those not treated with these medications.1 An earlier retrospective, multi-center study of 1128 patients with hypertension hospitalized with COVID-19 including 188 taking ACEI/ARB (median age 64 years, 53.2% male) and 940 not using ACEI/ARB or using a different class of anti-hypertensive agent (median age 64 years, 53.5% male) from December 31, 2019 to February 20,2020, indicates inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users.2 These studies support current guidelines and recommendations for the use if ACEI/ARB in treating hypertension.
 
Sources:
 
1. Li J, Wang X, Chen J, et al. Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA Cardiol. 2020 Apr 23.
 
2. Zhang P, Zhu L, Cai J, et al. association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res. 2020 Apr 17.
Alterations in Smell or Taste in Mildly Symptomatic COVID-19 Patients
A study found that alterations in smell or taste were frequently reported by mildly symptomatic patients with COVID-19 and often were the first apparent symptom. The telephone survey found that any altered sense of smell or taste was reported by 64.4% of patients. OF these patients, 34.6% reported an altered sense of smell or taste, while 34.6% also reported blocked nose. Other frequent symptoms were fatigue (68.3%), dry or productive cough (60.4%), and fever (55.5%).
 
Source: Spinato G, Fabbris C, Polesel J, et al. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 Apr 22.
Endothelial cell infection and COVID-19
COVID-19 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells. Post-mortem histology of this patient case series (n=3) revealed the presence of viral bodies and lymphocytic endotheliitis in the lung, heart, kidney, and liver cell necrosis. The findings indicate a direct consequence of viral involvement and of the host inflammatory response in several organs.
 
Source: Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 Apr 20.
Characteristics and Outcomes of COVID-19 Hospitalized Patients in the NYC Area
A case series of hospitalized patients (n=5700) with COVID-19 in the New York City area found that the most common comorbidities were hypertension (56.6%), obesity (41.7%), and diabetes (33.8%). During hospitalization, 14.2% of patients were treated in the intensive care unit care, 12.2% received invasive mechanical ventilation, and 3.2% were treated with kidney replacement therapy, while 21% died.
 
Source: Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr 22.
COVID-19, CVD and Angiotensin Medications
An observational study of 8,910 hospitalized patients with COVID-19 from 169 hospitals in Asia, Europe, and North America found that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with COVID-19. Factors that were found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years, coronary artery disease, heart failure, cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking.
 
The study did not find an increased risk of in-hospital death associated with the use of ACE inhibitors or ARBs. The results did not confirm previous concerns regarding a potential harmful association of these medications and COVID-19.
 
Source: Mehra M, Desai S, Kuy S, Henry T, Patel A. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. 2020 May 1.
Diabetes and COVID-19
A retrospective study of study of 28 patients with diabetes and COVID-19 at a hospital in Wuhan, China found poor outcomes among ICU patients. Half of these patients were in ICU and the other half were in isolation. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the non-ICU group.
 
Source: Wang F, Yang Y, Dong K, et al. Clinical characteristics of 28 patients with diabetes and covid-19 in Wuhan, China. Endocr Pract. 2020 May 1.
Characteristics and Outcomes of Adults Hospitalized with COVID-19
A cohort study of 305 hospitalized adult patients with COVID-19 in Georgia (primarily metropolitan Atlanta) indicates that 61.6% were aged <65 years (median age 60 years), 50.5% were female, and 83.2% with known race/ethnicity were black.
 
Overall, 225 (73.8%) patients had comorbid conditions considered high-risk for severe COVID-19. These conditions, which had similar prevalence in black and non-black patients, included diabetes 39.7%, cardiovascular disease 25.6%, chronic lung disease 20.3%, asthma 10.5%, chronic obstructive pulmonary disease 5.2%, and severe obesity (BMI ≥40) 2.7% with median BMI higher in black (31.4%) than in nonblack patients (29.6%). Hypertension (not considered a high-risk condition) was documented in 67.5% of patients and was more common among black versus nonblack patients (69.6% versus 54.0%).
 
The authors conclude that given the overrepresentation of black patients within this cohort, it is important that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Increased awareness of the risk for serious illness from COVID-19 among all adults, regardless of underlying conditions or age, is also needed.
 
Source: Gold JAW, Wong KK, Szablewski CM, et al. Characteristics and clinical outcomes of adult patients hospitalized with COVID-19 - Georgia, March 2020. Morb Mortal Wkly Rep. 2020 May 8;69(18):545-550.
Gastrointestinal and Hepatic Manifestations of COVID-19
A retrospective study in two New York City hospitals explored the gastrointestinal (GI) and hepatic manifestations of COVID-19 in 1059 adult patients. Nearly one third of patients reported GI symptoms, most often diarrhea. The authors note that the high rate of diarrhea may be due to the COVID-19 virus's high affinity for the angiotensin-converting enzyme 2 receptor. Sixty-two percent of patients presented with at least one elevated liver enzyme, but elevated total bilirubin or alkaline phosphatase was not common, and no cases of clinically significant acute liver injury or acute liver failure due to COVID-19 were noted. Having liver injury on presentation of COVID-19, however, was associated with a significantly higher risk of ICU admission and death. The authors suggest that the high rate of hepatic injury may be due to direct viral infection of liver cells. The authors conclude that COVID-19 patients frequently have GI manifestations and that liver injury is common on initial presentation and is independently associated with poor clinical outcomes. These results may contribute to clarifying the diagnostic criteria for COVID-19 and may be helpful in stratifying risk.
 
Source: Hajifathalian K, Krisko T, Mehta A, Kumar S, Schwartz R, Fortune B, Sharaiha R, on behalf of the WCM-GI research group. Gastrointestinal and hepatic manifestations of 2019 novel coronavirus disease in a large cohort of infected patients from New York: clinical implications. Gastroenterology.2020 May 1.
Olfactory Dysfunction in COVID-19: Diagnosis and Management
Several studies report that COVID-19 frequently impairs the sense of smell in mild or even asymptomatic cases.  COVID-19 disrupts cells in the olfactory neuroepithelium which may result in inflammatory changes that impair olfactory receptor neuron function, cause subsequent olfactory receptor neuron damage, and/or impair subsequent neurogenesis. These changes may cause temporary or longer-lasting OD. Since olfactory dysfunction (OD) may act as a marker for disease in patients who are otherwise minimally symptomatic or asymptomatic, organizations including the American Academy of Otolaryngology-Head and Neck Surgery, ENT UK, and CDC recommend inclusion of sudden-onset loss of smell and/or taste as part of the diagnostic criteria for COVID-19 disease. A model of clinical assessment includes subjective self-assessment (view with caution) or psychophysical assessment (more reliable), followed by a period of self-isolation and SAR-CoV-2 testing when possible. Olfactory assessment in patients requiring acute hospitalization should only be performed when clinically appropriate. The efficacy of treatment of persistent COVID-19 OD is unknown but may include olfactory training and adjuvant medication (intranasal vitamin A and systemic omega-3). The authors conclude that research is needed to delineate the natural history and appropriate management of chemosensory impairment caused by COVID-19.
 
Source: Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020 May 20.
Protective Immunity against COVID-19 Re-exposure in Rhesus Macaques
Individuals who recover from certain viral infections typically develop virus-specific antibody responses that provide robust protective immunity against re-exposure, but some viruses do not generate protective natural immunity, such as HIV-1.
 
A study showed that COVID-19 infection in rhesus macaques induced humoral and cellular immune responses and provided protective efficacy against COVID-19 rechallenge. The study raises the possibility that immunologic approaches to the prevention and treatment of COVID-19 may possible. However, are differences between COVID-19 infection in macaques and humans, with many parameters still yet to be defined in both species. Rigorous clinical studies will be required to determine whether COVID-19 infection effectively protects against COVID-19 re-exposure in humans.
 
Source: Chandrashekar A, Liu J, Martinot A, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 2020 May 20.

Public health & COVID-19

Reduction of COVID-19 secondary transmission in households by face mask use, disinfection, and social distancing
A retrospective cohort study of 335 people in 124 families with at least one laboratory confirmed COVID-19 case indicates the effectiveness of mask use, disinfection, and social distancing in preventing COVID-19. The overall secondary transmission rate in households was 23%. Facemasks were 79% effective and disinfection was 77% effective in preventing transmission. In contrast, close frequent contact in the household increased the risk of transmission 18 times.
 
In the univariate analysis, wearing a mask after illness onset was significant, but in multivariate analysis, only wearing it before symptom onset was effective. Viral load is highest in the two days before symptom onset and on the first day of symptoms and up to 44% of transmission is during the pre-symptomatic period in settings with substantial household clustering. This study showed that social distancing within the home is effective and having close contact (within 1 meter or 3 feet, such as eating around a table or sitting together watching TV) is a risk factor for transmission. The study also provides evidence of effectiveness of chlorine or ethanol-based household disinfection in areas with high community transmission.
 
The results of this study may be informative for families of high-risk groups such as health workers, quarantined individuals, or situations where cases of COVID-19 can be managed at home.
 
Source: Wang Y, Tian H, Zhang L, et al. Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China. BMJ Glob Health. 2020 May 5.
Early Spread of COVID-19 in New York City
COVID-19 is the cause of one of the largest non-influenza pandemics of this century. Phylogenetic analysis of 84 distinct COVID-19 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. The study also found evidence for community transmission of COVID-19 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
 
Early introductions by cases that were identified based on their known travel histories did not seed the larger community clusters, suggesting that their early quarantine and hospitalization were effective in curtailing further spread. However, the study shows that the COVID-19 epidemic in NYC was mainly sourced from untracked transmission between the US and Europe, with limited evidence of direct introductions from China where the virus originated.
 
Source: Gonzalez-Reiche A, Hernandez M, Sullivan M, et al. Introductions and Early Spread of SARS-CoV-2 in the New York City Area. Science. 2020 May 29.
Reducing Spread of COVID-19 Transmission through Aerosol and Droplets
Aerosol transmission of viruses must be acknowledged as a key factor leading to the spread of infectious respiratory diseases. Evidence suggests that COVID-19 is silently spreading in aerosols exhaled by highly contagious infected individuals with no symptoms. Owing to their smaller size, aerosols may lead to higher severity of COVID-19 because virus-containing aerosols penetrate more deeply into the lungs. It is essential that control measures be introduced to reduce aerosol transmission. A multidisciplinary approach is needed to address a wide range of factors that lead to the production and airborne transmission of respiratory viruses, including the minimum virus titer required to cause COVID-19; viral load emitted as a function of droplet size before, during, and after infection; viability of the virus indoors and outdoors; mechanisms of transmission; airborne concentrations; and spatial patterns. Masks and testing are necessary to combat asymptomatic spread in aerosols and droplets.
 
Source: Prather P, Wang C, Schooley R. Reducing Transmission of SARS-CoV-2. Science. 2020 May 27.
Airborne lifetime of small speech droplets and COVID transmission
Speech droplets generated by asymptomatic carriers of COVID-19 are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.
 
Source: Stadnytskyi V, Bax C, Bax A, Anfinrud P. The Airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission. Proc Natl Acad Sci USA. 2020 May 13;202006874.
Misinformation and COVID-19
A study found that among the most viewed English videos regarding COVID-19 on YouTube, 27.5% contained non-factual information originating from entertainment news, internet news and consumer sources, reaching 62 million views worldwide. Videos from professional and government organizations were the most informative and had the highest quality content but were greatly under-represented in terms of viewership. Strategies that can be employed by government and public health agencies to increase the viewership of their quality content on COVID-19 were identified. The authors recommend that public health agencies collaborate with a wider range of YouTube producers (e.g., entertainment news, internet news and influential consumers) to disseminate high-quality video content.
 
Source: Li HO, Bailey A, Huynh D, Chan J. YouTube as a source of information on COVID-19: a pandemic of misinformation? BMJ Glob Health. 2020 May 5.
Social Distancing Measures and COVID-19 Spread
A study evaluated the impact of social distancing measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020 and April 27, 2020. Measures included event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). The study found that adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4% after 1-5 days, 6.8% after 6-10 days, 8.2% after 11-15 days, and 9.1% after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million).
 
Source: Courtemanche C, Garuccio J, Le A, Pinkston J, Yelowitz A. Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate. Health Aff (Millwood). 2020 May 14.
Exposure to Air Pollution and COVID-19 Mortality in the United States
United States government scientists recently estimated that COVID-19 may kill between 100,000 and 240,000 Americans. The majority of the pre-existing medical conditions that increase the risk of death for COVID-19 are the same diseases that are affected by long-term exposure to air pollution.
 
Results from a study conducted by Harvard University researchers, Xiao Wu, MS; Rachel C Nethery, PhD; Benjamin M Sabath, MA; Danielle Braun, Phd; and Francesca Dominici, PhD demonstrate “the importance of continuing to enforce existing air pollution regulations during the COVID-19 crisis and failure to do may potentially increase COVID-19 deaths and hospitalization admissions.” The study found that an increase of only 1 µg/m3 in fine particulate matter (PM2.5) is associated with a 15% increase in the COVID-19 death rate, 95% confidence interval (CI) (5%, 25%).
 
Source: Wu X, Nethery RC, Sabath MB, Braun D, Dominici F. Exposure to air pollution and COVID-19 mortality in the United States. medRxiv. 2020.04.05.20054502.
Public Health Interventions and Epidemiology of COVID-19 in Wuhan, China
A cohort study of 32,583 patients (median age 56.7 years, 48.4% men, 51.6% women) with laboratory confirmed COVID-19 in Wuhan, China between December 8, 2019 and March 8, 2929 indicates that a series of public health interventions was temporally associated with reduced effective reproduction number of SARS-CoV-2 (secondary transmission) and the number of confirmed cases per day across age groups, sex, and geographic regions. The public health interventions included condons sanitaire, traffic restriction, social distancing, home confinement, centralized quarantine, and universal symptom survey. This data may be used to inform public health policy in other countries and regions.
 
Source: Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-1062.
Aerodynamic analysis of COVID-19
A study by Liu et al investigated the aerodynamic nature of COVID-19 measuring viral RNA in aerosols in different areas of two Wuhan hospitals. The study found that concentration of COVID-19 RNA in aerosols detected in isolation wards and ventilated patient rooms was very low, but it was elevated in the patients' toilet areas. Levels of airborne COVID-19 RNA in the majority of public areas was undetectable except in two areas prone to crowding, possibly due to infected carriers in the crowd. The results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of COVID-19 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.
 
Source: Liu Y, Ning Z, Chen Y, et al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020 Apr 27.
Population Scale Testing of COVID-19
Epidemiological modelling shows that identification and isolation of the majority of infectious individuals, including those who may be asymptomatic, can suppress the spread of COVID-19. The intervention is based on: (1) testing every individual (2) repeatedly, and (3) self-quarantine of infected individuals. Modelling also indicates that unlike sampling-based tests, population-scale testing does not need to be very accurate: false negative rates up to 15% could be tolerated if 80% comply with testing every ten days, and false positives can be almost arbitrarily high when a high fraction of the population is already effectively quarantined.
 
Source: Taipale J, Romer P, Linnarsson S. Population-scale testing can suppress the spread of COVID-19. MedRxiv. 2020 May 1.
Racial Disparities and COVID-19
Racial and ethnic disparities in the U.S. COVID-19 pandemic have been reported. Contributors for this this disparity can include increased likelihood of exposure to the virus, increased susceptibility to severe consequences of the infection, and lack of health care access.
 
African Americans and Latinos are overrepresented among cases of and deaths from COVID-19, both nationally and in many of the areas hardest hit by the pandemic. Minority communities are more likely to be exposed to the virus because they are overrepresented in the low-wage, essential workforce at the front lines, including low-wage health care workers who often move between clinics, hospitals, and nursing homes to make a living, thereby magnifying their risk. Poor communities may face challenges implementing social distancing because of housing density and overcrowding, and minority populations are overrepresented in congregate settings, such as homeless shelters and prisons, that increase exposure risk. Minority communities may be more susceptible to severe forms of COVID-19 because of existing disparities in underlying conditions known to be associated with COVID-19 mortality, including hypertension, cardiovascular disease, kidney disease, and diabetes.
 
Bibbins-Domingo K1. This Time Must Be Different: Disparities During the COVID-19 Pandemic. Ann Intern Med. 2020 Apr 28.
Projecting COVID-19 Transmission through the Postpandemic Period
A model of COVID-19 transmission projects that recurrent wintertime outbreaks of COVID-19 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity.
 
Source: Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020 Apr 14.

Mental health & COVID-19

Short and Long-term Mental Health Effects of COVID-19
Most people with severe coronavirus infections (ie, SARS, MERS, and COVID-19) appear to recover without experiencing mental illness. However, recent studies indicate delirium is not uncommon in hospitalized patients in the acute stages of severe SARS, MERS, and COVID-19 illness.
 
Analysis of data from two studies that systematically assessed common symptoms of patients hospitalized with SARS and MERS found that confusion occurred in 28% (36/129) of patients, suggesting delirium was common during acute illness. There were also frequent reports of low mood (42/129; 33%), anxiety (46/129; 36%), impaired memory (44/129; 34%), and insomnia (34/208; 12%) during the acute stage.
 
Twelve studies focusing on COVID-19 note a similarity, with evidence of delirium (confusion in 26/40 intensive care unit patients, 65%; agitation in 40/58 ICU patients, 69%; and altered consciousness in 17/82 patients who subsequently died, 21%) while acutely ill.
 
In the longer-term, the analysis suggests that SARS and MERS survivors may be at increased risk for mental illnesses such as depression, anxiety, fatigue, and post-traumatic stress disorder in the months and years following discharge from hospital.
 
While previous coronavirus outbreak data and analyses may provide insights, they cannot be deemed exact predictors of psychiatric complication prevalence in severely ill COVID-19 patients. On the other hand, there is value in recognizing that delirium in acute-stage COVID-19 patients may be a precursor to a several long-term mental illnesses.
 
Source: Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psych. 2020 May 18.
The Impact of COVID-19 on Mental Wellbeing
A national poll indicates that Americans have stress and anxiety caused by the COVID-19 pandemic, which is having an effect of people’s physical and mental health. Among the findings, nearly half of Americans (48%) are anxious about the possibility of getting COVID-19 coronavirus, and 62% are anxious about the possibility of family and loved ones getting COVID-19 coronavirus. Most (59%) feel COVID-19 coronavirus is having a serious impact on their day-to-day lives. Considering these findings, APA CEO and Medical Director Saul Levin, M.D., M.P.A. emphasizes the need to maintain self-care and manage stress. Clear consistent communications on how to prevent the spread of COVID-19 is also important.
 
Source: American Psychiatric Association. New Poll: COVID-19 Impacting Mental Well-Being: Americans Feeling Anxious, Especially for Loved Ones; Older Adults are Less Anxious.
Mental Health and the COVID-19 Pandemic
Public health emergencies may affect the health, safety, and well-being of both individuals and communities. Extensive research in disaster mental health has established that emotional distress is ubiquitous in affected populations — a finding certain to be echoed in populations affected by the COVID-19 pandemic. Health care workers have an important role in addressing these emotional outcomes as part of the pandemic response. Health care systems will also need to address the stress on individual workers.
 
Source: Pfefferbaum B, North CS. Mental Health and the Covid-19 Pandemic. N Engl J Med. 2020 Apr 13.
Natural Mood Regulation and Depression
Periods of lockdown during the COVID-19 pandemic are likely to exacerbate problems with mood regulation. Situations in which personal choices of activities are constrained, such as during times of social isolation and lockdown, natural mood regulation is impaired potentially leading to depression.
 
A study from Taquet et al suggests a new target for treating and reducing depression is supporting natural mood regulation. This study looked at 58,328 participants from low-, middle-, and high-income countries, and compared people with low mood or a history of depression with those of high mood. In a series of analyses, the study investigated how people regulate their mood through their choice of everyday activities and how they are more vulnerable to depression when their ability to choose activities is restricted.
 
According to the authors, these research findings open the door to new opportunities for developing and optimizing treatments for depression, which could potentially be well adapted to treatments in the form of smartphone apps and made available to a large population that lacks access to existing treatments.
 
Source: Taquet M, Quoidbach J, Gross JJ, Saunders KEA, Goodwin GM. Mood homeostasis, low mood, and history of depression in 2 large population samples. JAMA Psychiatry. April 22, 2020.
Mental Health of Health Care Workers
A cross-sectional survey-based study of 1257 health care workers in 34 hospitals in China found that participants reported experiencing significant psychological burden. The study found that a considerable proportion of participants reported symptoms of depression (50.4%), anxiety (44.6%), insomnia (34.0%), and distress (71.5%). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers.
 
Source: Lai J, Ma S, Wang Y, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020;3:e203976.

Research on COVID-19 treatments

Overinterpretation of Results Regarding the Use of Hydroxychloroquine for COVID-19
A study reported a higher frequency of SARS–CoV-2 clearance after 6 days of treatment with hydroxychloroquine (HCQ) versus an untreated control group (14 of 20 patients [70%] vs. 2 of 16 patients [13%]). While some limitations of this study may be acceptable; other methodological flaws may affect the validity of the findings, even in the current pandemic setting. A major consequence has been an inadequate supply of HCQ for patients in whom efficacy is established, including indications for rheumatoid arthritis and of systemic lupus erythematosus. At this time most experts discourage the off-label use of HCQ until justified and supply is bolstered.
 
Source: Kim AHJ, Sparks JA, Liew JW, et al. A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19. Ann Intern Med. 2020 Mar 30. [Epub ahead of print].
Effectiveness of Convalescent Plasma Therapy in Severe COVID-19 patients
Currently, there are no known antiviral agents to prevent or treat COVID-19. Clinical treatment options are limited consisting of supportive care, including supplemental oxygen and mechanical ventilatory support when indicated.
 
The FDA recently announced new guidelines permitting the use of convalescent plasma (CP) as an investigational treatment for patients with moderate or severe COVID-19 infections. CP must be collected from someone who has recovered from COVID-19 infection.
 
Kai Duan of the China National Biotec Group Company Limited and other researchers explored the feasibility of CP transfusion to rescue 10 patients with severe disease. The results of this small study demonstrated that CP was well tolerated, significantly increased or maintained neutralizing antibodies at a high levels, and cleared viremia within 7 days indicating that a larger randomized trial is warranted.
 
Source: Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 6. [Epub ahead of print].
Pharmacologic Treatments for COVID-19
No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding COVID-19 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against COVID-19, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.
 
Source: Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A Review. JAMA. 2020 Apr 13. doi: 10.1001/jama.2020.6019.
The COVID-19 Vaccine Pipeline
A collective urgency has fueled research vaccines against COVID-19 in an effort to confront this global public health challenge. Several efforts to develop COVID-19 vaccines are underway. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. The first vaccine to undergo preliminary study in humans in the United States uses a messenger RNA platform to result in expression of the viral spike protein in order to induce an immune response (www.clinicaltrials.gov: NCT04283461). Multiple clinical trials COVID-19 vaccine candidates are underway in the US: www.clinicaltrials.gov: NCT04327206, NCT04341389, NCT04299724, NCT04336410).
 
Source: Chen WH, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 Vaccine Pipeline: an Overview. Curr Trop Med Rep. 2020 Mar 3:1-4.
NIH Study: Remdesivir Accelerates Recovery from Advanced COVID-19
Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1063 patients. Preliminary results indicate that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059).
 
The trial (known as the Adaptive COVID-19 Treatment Trial, or ACTT), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19.
 
Source: NIAID. NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19.
 
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report.N Engl J Med. 2020 May 22.

Kidney disease & COVID-19

Acute Kidney Injury in Hospitalized COVID-19 Patients
A retrospective observational cohort study of 5,449 adult patients (median age 64 years) hospitalized with COVID-19 from March 1, 2020 to April 5, 2020 in a large New York Health System (13 hospitals) indicates 1,993 (36.6%) developed AKI during their hospitalization. During this time, 780 (39%) were still hospitalized, 519 (26%) were discharged, and 694 (35%) died. Independent risk factors for AKI included older age, black race, hypertension, diabetes mellitus, cardiovascular disease, vasopressor use, and need for ventilation.
 
Urine studies were available at the time of AKI development in 646 of the 1993 patients. The median urine specific gravity was high (1.020) and most patients (65.6%) had urinary sodium less than 35 mEq/L. The authors suggest that since a cytokine storm often occurs in close temporal proximity to respiratory failure, it is possible that circulating substance or other related factors could contribute to AKI. However, it was beyond the scope of the current study to evaluate for these possibilities. While there were fairly high rates of proteinuria (2-3+ positive in 42.1%) and hematuria (2+ to 3+ positive in 46.1%), inferences are limited since indwelling urethral catheter status at the time of urine collection could not be ascertained.
 
The authors conclude that: AKI occurs frequently among patients with COVID-19. It was strongly linked to the occurrence of respiratory failure and was rarely a severe disease among patients who did not require ventilation. The development of AKI in hospitalized patients with COVID-19 is associated with a poor prognosis. Further study is needed to better understand the causes of AKI and patient outcomes.
 
Source: Hirsch JS, Ng JH, Ross DW, et al., on behalf of the Northwell COVID-19 Research Consortium and the Northwell Nephrology COVID-19 Research Consortium, Acute kidney injury in patients hospitalized with COVID-19. Kidney International. 2020 May 5.
 
Fishbane S. Acute kidney injury in COVID-19 — How one New York system dealt with it. NEJM Journal Watch Podcast. 2020 May 19.
CKD is Associated with Severe COVID-19 infection
A meta-analysis explored the potential association between CKD and severity of COVID-19 infection. Based on a search of electronic databases and contrite meta-analysis of early and preliminarily available data, CKD seems to be associated with enhanced risk of severe COVID-19 infection. When data of individual studies were pooled, a significant association of CKD with severe COVID-19 was observed, with no relevant heterogeneity [OR 3.03 (95% CI 1.09–8.47), I2=0.0%, Cochran’s Q, p=0.84]. Clinicians are encouraged to engage in close monitoring of CKD patients with suspected COVID-19, for timely detecting signs of disease progression. The presence of CKD should also be regarded as an important factor in future risk stratification models for COVID-19, according to the authors.
 
Source: Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID‑19) infection. Int Urol Nephrol. 2020 Mar 28. [Epub ahead of print].
Kidney Disease and In-Hospital Death of Patients with COVID-19
A study by Cheng et al found that the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. The prospective cohort study included 701 hospital-admitted patients with COVID-19. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 mL/min/1.73m2 were 14.4%, 13.1% and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. The authors believe that clinicians should increase their awareness of kidney disease in patients with severe COVID-19.
 
Source: Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 Mar 20.
The Aftermath of COVID-19: Devastation or a New Dawn for Nephrology?
In this perspective, Dr. Ragiv Agarwal of Indiana University School of Medicine provides examples of how the COVID-19 pandemic is already inducing change in the practice of medicine at large and for nephrology in particular. Areas of impact include collaboration, innovation, telemedicine, dialysis delivery, virtual learning, disaster preparedness, infection control, research, and social determinants of health.
 
Source: Agarwal R. The aftermath of coronavirus disease of 2019: devastation or a new dawn for nephrology? Nephrol Dial Transplant. 2020 Apr 17.
 

Dialysis & COVID-19

Mitigating Risk of COVID-19 in Dialysis Facilities
Kliger AS, Silberzweig J. Mitigating Risk of COVID-19 in Dialysis Facilities. Clin J Am Soc Nephrol. 2020 Mar 20. [Epub ahead of print]. This resource outlines critical points in mitigating the risk of COVID-19 at dialysis facilities.
COVID-19 and Dialysis Units
Ikizler TA. COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do? Am J Kidney Dis. 2020 Mar 23. [Epub ahead of print]. This resource addresses what clinicians should do to prevent and control COVID-19 infections in outpatient hemodialysis facilities.
COVID-19 and Patients Receiving Dialysis
Patients receiving maintenance hemodialysis are at increased risk for COVID-19 and its complications. The following resources contain recommendations on the prevention and control of COVID-19 among patients receiving dialysis.
 
Centers for Disease Control and Prevention. Interim Additional Guidance for Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed COVID-19 in Outpatient Hemodialysis Facilities.
 
This resource addresses what clinicians should do to prevent and control COVID-19 infections in outpatient hemodialysis facilities.
Ikizler TA. COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do? Am J Kidney Dis. 2020 Mar 23. [Epub ahead of print].
 
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].
Peritoneal Dialysis during the (COVID-19) Pandemic
El Shamy et al report on their experience at Mount Sinai Hospital, East Harlem, NY with caring for dialysis patients during this crisis in the outpatient setting, as well as their procedures to use acute peritoneal dialysis to combat the inexorable rise in the number of admitted patients requiring kidney replacement therapy (KRT) in the inpatient setting.
 
Source: El Shamy O, Sharma S, Winston J, Uribarri J. Peritoneal Dialysis During the Coronavirus 2019 (COVID-19) Pandemic: Acute Inpatient and Maintenance Outpatient Experiences. Kidney Medicine. April 23, 2020.

Kidney transplant & COVID-19

Early Outcomes of outpatient management of kidney transplant recipients with COVID-19
A single-center study of 41 kidney transplant recipients with known or suspected COVID-19 found that 54% had confirmed COVID-19 and 46% were suspected cases. Patients most commonly reported fever (80%), cough (56%), and dyspnea (39%).
 
At the end of follow-up, 32% required hospitalization a median of 8 days (range, 1–16) after symptom onset, and 56% had outpatient symptom resolution a median of 12 days (4–23) after onset. Patients who required hospitalization were more likely to have reported dyspnea (77% versus 21%, P50.003) and had higher baseline creatinine (median, 2.0 versus 1.3 mg/dl, P50.02), but there were no other differences between groups. This wide interval underscores the need for increased vigilance approximately 1 week following the onset of symptoms and also, the need for continued close outpatient follow-up for the early detection of clinical deterioration during the second week.
 
Source: Husain SA, Dube G, Morris H, et al. Early outcomes of outpatient management of kidney transplant recipients with coronavirus disease 2019. Clin J Am Soc Nephrol. 2020 May 18.
Kidney Transplantation and COVID-19 Induced Pneumonia
COVID-19 induced pneumonia is characterized by high risk of progression and significant mortality, according to limited cohort of long-term kidney transplant patients. The preliminary findings studying 20 kidney transplant patients describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with COVID-19 induced pneumonia.
 
Alberici F, Delbarba E, Manenti C, et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int. 2020 Apr 9.
COVID-19 and Kidney Transplantation at a NYC Hospital
At Montefiore Medical Center, clinicians identified 36 adult kidney-transplant recipients who tested positive for COVID-19 between March 16 and April 1, 2020. At this institution, kidney-transplant recipients with Covid-19 had less fever as an initial symptom, lower CD3, CD4, and CD8 cell counts, and more rapid clinical progression than persons with COVID-19 in the general population. The number of patients with very low CD3, CD4, and CD8 cell counts indirectly supports the need to decrease doses of immunosuppressive agents in patients with COVID-19, especially in those who have recently received antithymocyte globulin, which decreases all T-cell subsets for many weeks.
 
Source: Akalin E, Azzi Y, Bartash R, et al. Covid-19 and Kidney Transplantation. Engl J Med. 2020 Apr 24.
Kidney Allograft Recipients and COVID-2019: A Single Center Report
A retrospective chart review of 54 adult kidney transplant patients diagnosed with COVID-19 in a New York City hospital system suggest that a strategy of systematic screening and triage to outpatient or inpatient care, close monitoring, early management of concurrent bacterial infections and judicious use of immunosuppressive drugs rather than cessation is beneficial.
 
Thirty-nine patients with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid-free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs 40%). In addition, 50% of hospitalized patients were treated for concurrent bacterial infections including pneumonia, urinary tract infections and sepsis. Acute kidney injury occurred in 51% of hospitalized patients.
 
At a median of 21 days follow up, 67% of patients had their symptoms resolved or improved and 33% had persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired.
 
Source: Lubetsky M, Aull M, Craig-Shapiro R, et al. Kidney allograft recipients diagnosed with coronavirus disease-2019: a single center report. MedRxiv. 2020 May 5.
Kidney Transplant Procedures: Prevention and control measures
The experiences conducting kidney transplants at a hospital in Wuhan, China are outlined in this study. Strict prevention and control measures were implemented and working methods and procedures were adjusted to ensure the safe and orderly work of the department. Prevention and control measures, included kidney transplant outpatient management, kidney transplantation ward management, management of kidney transplant surgery, dialysis management of patients waiting for kidney transplantation, personal protection of medical staff and follow‐up management of discharged patients after kidney transplantation.
 
Source: Li Y, Yang N, Li X, Wang J, Yan T. Strategies for prevention and control of the 2019 novel coronavirus disease in the Department Of Kidney Transplantation. Transpl
Transplant Outpatient Management and COVID-19
This article offers guidance for clinicians caring for ambulatory kidney transplant recipients who have COVID-19. The recommendations include insights on prevention, diagnostics, management of immunosuppression, and therapies for COVID-19 and their potential drug interactions with immunosuppressive medications. The guidance is based on the experience of a hospital in managing other infections in kidney transplant recipients and the experience managing their first 21 patients testing positive for COVID-19 and 41 patients with symptoms who tested negative.
 
Source: Gleeson S, Formica R, Marin E. Outpatient Management of the Kidney Transplant Recipient during the SARS-CoV-2 Virus Pandemic. Clin J Am Soc Nephrol. 2020 Apr 28.
Organ Procurement and Transplantation during the COVID-19 Pandemic
Since the onset of the COVID-19 pandemic, France and the United States have experienced a significant reduction in the number of organ donations and solid organ (kidney, liver, heart, and lung) transplant procedures. In early April, transplant centers in both countries reported conducting far fewer deceased donor transplants compared to March, with the number of procedures dropping by 91% in France and 50% in the United States.
 
To quantify the impact of the COVID-19 outbreak on organ donation and transplantation, the authors analyzed validated national data from 3 federal agencies, including the United Network for Organ Sharing (UNOS), to study trends in France and the United States.
 
A strong link was observed between the surge of COVID-19 infections and significant decline in donated organs and overall solid organ transplants. In the United States, the number of recovered organs dropped from over 110 a day on March 6 to fewer than 60 per day on April 5. During the same timeframe, the number of transplanted kidneys dropped from nearly 65 a day to about 35 per day. Researchers also observed that regions with fewer COVID-19 cases, or limited exposure to the disease, also experienced a significant reduction in transplant rates – suggesting a global and nationwide effect beyond the local infection prevalence.
 
The team suggests these findings could be useful for public health agencies, professional societies and patient advocacy organizations in their planning and risk mitigation. Researchers also say that specific mapping of local trends in organ donation and transplant activity will enable public health leaders to identify areas where the number of donations and transplants continues to remain lower than normal.
 
Source: Loupy A, Aubert O, Reese PP, Bastien O, Bayer F, Jacquelinet C. Organ procurement and transplantation during the COVID-19 pandemic. Lancet. 2020 May 11.

Nutrition

Guidance & Strategies for Clinicians to Optimize Care in the ICU
The society of Critical Care Medicine (SCCM) and the American Society for Parenteral and Enteral Nutrition (ASPEN) have published guidelines on Nutrition Support for Critically Ill Patients with COVID-19 Disease. Relevant key recommendations include estimating protein/calorie needs; timing of nutrition delivery; route, tube placement and method of nutrition delivery; nutrition dose, advancing to goal, and adjustments; formula selection; monitoring nutrition tolerance; nutrition for the patient undergoing prone positioning; and nutrition therapy during extracorporeal membrane oxygenation.
 
In addition to general key recommendations for enteral and parenteral nutrition for this patient population, there are recommendations for AKI as follows:
  • Recommendation # 9A With AKI requiring CRRT dose protein at 2.0-2.5 gm/kg/d
  • Recommendation # 9B Monitor and replace micronutrients in AKD on CRRT (especially zinc, iron, selenium, Vit D, Vit C)
Faculty: Stephen McClave, MD, and Mary Rath, RDN, CSNC, LD
Provider: Abbott Nutrition Institute (ANHI) https://anhi.org/resources/podcasts-and-videos/nutrition-care-of-the-covid-19-patient-series
Nutrition Therapy in the patient with COVID-19 Disease Requiring ICU Care, SCCM and ASPEN – updated April 1, 2020
Selenium Status and Outcome Of COVID-19
A population-based retrospective analysis in 17 cities outside of Hubei, China indicates that the COVID-19 cure rate was significantly associated with selenium status, as measured by the amount of selenium in hair. These data are consistent with evidence of the antiviral effects of selenium from previous studies in other viral infections including HIV. While it is important not to overstate this finding, this data indicates the need for further research regarding the role selenium may play in COVID-19 that may help to guide ongoing public-health decisions.
 
Note: There are currently no recommendations for selenium supplementation in patients with CKD. The current Recommended Dietary Allowance (RDA) for selenium is 55mcg/d for men and women. Whether similar amount of intake is recommended in various stages of CKD and maintenance dialysis is unknown.
 
Source: Jinsong Z, Taylor EW, Bennett K, et al. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr. 2020 Apr 28.
Vitamin D Deficiency and Severe COVID-19
An observational study on 186 consecutive patients hospitalized with COVID-19 found that patients with severe COVID-19 show lower median serum 25(OH)D and a higher percentage of vitamin D deficiency at intake than a season/age-matched reference population. The correlation between vitamin D deficiency and the need for hospitalization due to COVID-19 was only seen in male patients. In males but not females, the percentage of vitamin D deficient patients also increased with more advanced COVID-19 disease stage as measured by CT. The data indicates a strong statistical correlation between the degree of vitamin D deficiency and severity of COVID-19 lung disease.
 
Source: De Smet D, De Smet K, Herroelen P, Gryspeerdt S. Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics. MedRxiv. 2020 May 5.

NKF Advocacy during the COVID-19 pandemic

NKF has identified and been actively advocating on several key areas of concern for our community in the context of the COVID-19 pandemic:

NKF is also working with several partners to implement policies that:

  • Accelerate patients' access to home dialysis
  • Ensure timely implementation of kidney care payment models
  • Ensure ​kidney patients and transplant patients ​can access greater-than-30-day supplies ​of critical prescriptions including immunosuppressive drugs
  • Ensure that vulnerable home dialysis, transplant patients, and living donors can receive needed blood draws in their homes

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Advocacy inquiries

Sharon Pearce
Senior Vice President, Government Relations
sharon.pearce@kidney.org