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

Blood Group Type and Risk of COVID-19

An observational cohort study of 107,796 (mean age 42 years, 77% female) patients testing positive for COVID-19 indicated there was no association with blood type and susceptibility to COVID-19 infection or disease severity.
The U.S. study utilized an electronic health records database covering 24 hospitals and 215 clinics in 3 states. Inclusion criteria included individuals who were tested for SARS-CoV-2 between March 3 and November 2, 2020 and had a recorded blood type. The researchers compared the following: positive vs negative COVID test results, hospitalized vs non-hospitalized patients, and ICU vs non-ICU patients. For patients with COVID-19 hospitalization and ICU admission was associated with male gender and older age. Non-white race was associated with viral positivity and hospitalization. However, blood type was not associated with disease susceptibility or severity, including viral positivity, hospitalization, or ICU admission.
The authors conclude that “Given the large and prospective nature of our study and its strongly null results, we believe that important associations of SARS-CoV-2 and COVID-19 with ABO groups are unlikely and will not be useful factors associated with disease susceptibility or severity on either an individual or population level for similar environments and ancestries. Additional studies, closely controlled for genetics, geography, and viral strain, are required before accepting blood group as a determinant of predisposition to or severity of COVID-19.”
Source: Anderson JL, May HT, Knight S, et al. Association of sociodemographic factors and blood group type with risk of COVID-19 in a US population. JAMA Netw Open. 2021 Apr 1.

COVID-19 Outcomes Among Hospitalized Health Care Workers

A propensity-matched multicenter cohort study matching 122 healthcare workers (HCWs) hospitalized with COVID-19 to 366 hospitalized non-HCWs with COVID-19 was conducted to evaluate the association between HCW status and outcomes among hospitalized COVID-19 patients. Although HCWs are at higher risk for contracting COVID-19, it is uncertain whether they are at risk for worse outcomes.


This retrospective, observational cohort study included consecutive adult patients hospitalized with a diagnosis of laboratory-confirmed COVID-19 across 36 North American centers from April 15 to June 5, 2020. Data were collected from 1992 patients. The primary outcome was reaching the need for mechanical ventilation or death.


Of the 1790 patients included, there were 127 HCWs and 1663 non-HCWs. After 3:1 propensity score matching, 122 HCWs were matched to 366 non-HCWs. In the matched cohort, the odds of the primary outcome, mechanical ventilation or death, were not significantly between HCWs and non-HCWs (AOR, 0.60; 95% CI, 0.34-1.04). The HCWs were less likely to need admission to an intensive care unit (AOR, 0.56; 95% CI, 0.34-0.92) and were also less likely to need admission for longer than 7 days (AOR, 0.53; 95% CI, 0.34-0.83). There were no differences between matched HCWs and non-HCWs in the need for mechanical ventilation (AOR, 0.66; 95% CI, 0.37-1.17), death (AOR, 0.47; 95% CI, 0.18-1.27), or vasopressors (AOR, 0.68; 95% CI, 0.37-1.24).


In conclusion, this study found that HCW status is not associated with worse outcomes as compared with non-HCWs hospitalized with COVID-19. HCW status was also associated with a shorter hospital admission and less likelihood for intensive care unit admission.


Source: Yang JU, Parkins MD, Canakis A, et al. Outcomes of COVID-19 among hospitalized health care workers in North America. JAMA Netw Open. 2021;4(1):e2035699.

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Respiratory Function in Infants and Young Children Wearing Masks During the COVID-19 Pandemic

To study whether the use of surgical face masks in the pediatric population is associated with oxygen desaturation or respiratory distress, a cohort study of 47 infants and young children were observed wearing surgical face masks for 30 minutes. The study was conducted from May through June 2020 in a secondary-level hospital pediatric unit in Italy. Subjects included 47 healthy children divided by age (group A, aged ≤24 months, and group B, aged >24 months to ≤144 months). All subjects were monitored every 15 minutes for changes in respiratory parameters for the first 30 minutes while not wearing a surgical face mask and for the next 30 minutes while wearing a face mask. Children aged 24 months and older then participated in a walking test for 12 minutes.
Among 47 children, 22 (46.8%) were 24 months or younger (group A), with 11 boys (50.0%) and median (interquartile range [IQR]) age 12.5 (10.0-17.5) months, and 25 (53.2%) were between 24 months to 144 months, with 13 boys (52.0%) and median (IQR) age 100.0 (72.0-120.0) months. In the 2 groups, there was no significant change between 30 minute intervals with and without a mask in group A in median (IQR) partial pressure of end-tidal carbon dioxide (PETCO2, 33.0 [32.0-34.0] mm Hg, P for Kruskal Wallis = .59); oxygen saturation (SaO2, 98.0% [97.0%-99.0%], P for Kruskal Wallis = .61); pulse rate (PR, 130.0 [115.0-140.0] pulsations/min, P for Kruskal Wallis = .99); or respiratory rate (RR, 30.0 [28.0-33.0] breaths/min, P for Kruskal Wallis = .69), or, for group B in median (IQR) PETCO2 (36.0 [34.0-38.0] mm Hg, P for Kruskal Wallis = .97), oxygen saturation (SaO2, 98.0% [97.0%-98.0%], P for Kruskal Wallis = .52); pulse rate (PR, 96.0 [84.0-104.5] pulsations/min, P for Kruskal Wallis test = .48); or respiratory rate (RR, 22.0 [20.0-25.0] breaths/min, P for Kruskal Wallis = .55). After the group B walking test, as compared with before the walking test, there was a significant increase in median (IQR) PR (96.0 [84.0-104.5] pulsations/min vs 105.0 [100.0-115.0] pulsations/min, P < .02) and RR (22.0 [20.0-25.0] breaths/min vs 26.0 [24.0-29.0] breaths/min, P < .05).
This cohort study among infants and young children in Italy found that the use of facial masks was not associated with significant changes in SaO2 or PETCO2, including among children 24 months and younger. These results suggest that using surgical masks among children may be safe during the COVID-19 pandemic, especially with schools reopening.
Source: Lubrano R, Bloise S , Testa A , et al. Assessment of respiratory function in infants and young children wearing face masks during the COVID-19 pandemic. JAMA Netw Open. 2021;4(3):e210414.

Respiratory and Psychophysical Sequelae Among COVID-19 Patients After Hospital Discharge

A prospective cohort study involving a consecutive series of patients 18 year and older (n=238, median age 61 years, 59.7.% men) hospitalized with severe acute respiratory coronavirus 2 from March 1 to June 29, 2020 indicates that at 4 months after discharge, respiratory, physical, and psychological sequelae were common.
The study took place in an academic hospital in Northern Italy. At 3 to 4 months after discharge, study participants underwent standard pulmonary function testing. Physical performance was assessed using the Short Physical Performance Battery, and the presence of posttraumatic stress (PTS) symptoms was assessed by administering the Impact of Event Scale-Revised. At the end of follow-up, more than half of the study population still had DLCO less than 80% of expected. When a more stringent threshold of less than 60% of expected was applied, the proportion of patients with severe impairment decreased to 15%. Thus, a significantly impaired diffusion persisted in a sizable proportion of survivors of COVID-19. Some degree of motor impairment was observed in 53.8% of the study population. Different factors that may explain this observation include lung damage, circulatory limitation, muscle weakness, critical illness neuropathy, and myopathy. Regarding psychological health, clinically relevant PTS symptoms were observed in 17% of patients, in line with other studies. Additionally, about 5% of patients who were discharged after COVID-19 treatment died within a few weeks after discharge. Finally, dyspnea persisted in approximately 10% of patients who reported experiencing it during the acute phase of COVID-19 indicating the presence of residual symptoms of disease.
The authors conclude that a significant proportion of patients hospitalized for COVID-19 still reported a high proportion of symptoms associated with COVID-19 up to 4 months after hospital discharge, with reduced exercise tolerance being the most common. In COVID-19 survivors respiratory and physical functional impairment may impact psychological health and residual lung injury may be associated with reduced quality of life. Although age is a major factor associated with COVID-19–related mortality, 4 months after hospital discharge, there was not a higher residual symptomatic burden in the older patients in this study.
Source: Bellan M, Soddu D, Balbo PE, et al. Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge. JAMA Netw Open. 2021;4(1):e2036142.

Pregnancy Outcomes and COVID-19

An observational cohort study of maternal and neonatal outcomes in women with and without severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) was conducted from March 18 through August 22, 2020, at Parkland Health and Hospital System in Dallas, Texas. This is a high-volume prenatal clinic system and public maternity hospital, allowing for 252 SARS-CoV-2–positive and 3122 negative pregnant women tested in outpatient and inpatient settings to be included in the study. The objectives were to evaluate adverse outcomes related to SARS-CoV-2 infection in pregnancy and to describe clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes. The primary outcome was a composite of preterm birth, severe preeclampsia, or cesarean delivery for abnormal fetal heart rate for deliveries after 20 weeks of gestation. Maternal illness severity, neonatal infection, and placental abnormalities were evaluated.
Of 3374 pregnant women (mean [SD] age, 27.6 [6] years) tested for SARS-CoV-2 who delivered during the study period, 252 tested positive for SARS-CoV-2 and 3122 tested negative. No differences existed in age, parity, body mass index, or diabetes among women with or without SARS-CoV-2. No difference existed in the composite primary outcome (52 women [21%] vs 684 women [23%]; relative risk, 0.94; 95% CI, 0.73-1.21; P = .64). Early neonatal SARS-CoV-2 infection occurred in 6 of 188 tested infants (3%), born mostly to asymptomatic or mildly symptomatic women. There were no placental pathologic differences according to illness severity. Maternal illness at first presentation was asymptomatic or mild in 239 women (95%), and 6 of those women (3%) developed severe or critical illness. Fourteen women (6%) were hospitalized for COVID-19.
The authors concluded that in a large, single-institution cohort study, SARS-CoV-2 infection during pregnancy was not associated with adverse pregnancy outcomes. Neonatal infection may be as great as 3% and appears to occur mostly among asymptomatic or mildly symptomatic women. Placental abnormalities were not linked to disease severity, and hospitalization rates were similar to rates among nonpregnant women.
Source: Adhikari EH, Moreno W, Zofkie AC, et al. Pregnancy outcomes among women with and without severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAMA Netw Open. 2020;3:e2029256.

Clinical Outcomes in Patients with Heart Failure Hospitalized with COVID-19

An analysis of a large, administrative U.S. health care database indicates patients with heart failure (HF) hospitalized with COVID-19 were at high risk for complications, with nearly one in four dying during hospitalization.
Among 1,212,153 patients identified with history of HF in the Premier Healthcare Database, 132,312 patients were hospitalized from April 1, 2020, to September 30, 2020. Those hospitalized included 23,843 patients (18.0%) with acute HF, 8,383 patients (6.4%) with COVID-19, and 100,068 patients (75.6%) with other reasons. Hospitalization with COVID-19 was associated with greater odds of in-hospital mortality as compared with hospitalization with acute HF; 24.2% compared to 2.6% respectively. Among patients with HF hospitalized with COVID-19, male gender, morbid obesity, advanced age, diabetes, and kidney disease were associated with greater odds of in-hospital mortality. The authors conclude that “Dedicated and innovative efforts surrounding education and infection control are needed for this high-risk population as the pandemic continues to evolve.”
Source: Bhatt AS, Jering KS, Vaduganathan M, et al. Clinical outcomes in patients with heart failure hospitalized with COVID-19. JACC Heart Fail. 2021;9:65-73.

Assessment of Immunological Memory to COVID-19

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. In this study, researchers aimed to fill gaps in our basic understanding of immune memory after COVID-19. Researchers analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, researchers observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
Source: Source: Dan JM, MateusJose, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021, Jan 6.

Risk Factors Associated with In-Hospital Mortality in Patients With COVID-19

To describe the characteristics of patients with COVID-19 treated in US hospitals and to determine the risk factors associated with in-hospital mortality, a cohort study of 64,781 patients in 592 acute care hospitals during April and May 2020 was performed. Patient characteristics were reported by inpatient/outpatient and survival status. Risk factors associated with death included patient characteristics, acute complications, comorbidities, and medications.
Of the 64,781 patients COVID-19 patients reviewed, 29,479 [45.5%] were outpatients and 35,302 [54.5%] were inpatients. The median (interquartile range [IQR]) age was 46 (33-59) years for outpatients and 65 (52-77) years for inpatients; 31,968 (49.3%) were male, 25,841 (39.9%) were White, and 14,340 (22.1%) were Black. In-hospital mortality was 20.3% (7164 patients) among inpatients. A total of 5625 inpatients (15.9%) required invasive mechanical ventilation, and 6849 (19.4%) were admitted to the intensive care unit (ICU). Median (IQR) inpatient length of stay (LOS) was 6 (3-10) days. Median (IQR) ICU LOS was 5 (2-10) days. Frequent acute complications for inpatients were acute respiratory failure (19,706 [55.8%]), acute kidney failure (11,971 [33.9%]), and sepsis (11,910 [33.7%]). Older age was the risk factor most greatly associated with death (age ≥80 years vs 18-34 years: odds ratio [OR], 16.20; 95% CI, 11.58-22.67; P < .001). Treatment with statins (OR, 0.60; 95% CI, 0.56-0.65; P < .001), angiotensin-converting enzyme inhibitors (OR, 0.53; 95% CI, 0.46-0.60; P < .001), and calcium channel blockers (OR, 0.73; 95% CI, 0.68-0.79; P < .001) was associated with lower odds of death. Compared with patients not treated with hydroxychloroquine or azithromycin, patients treated with both azithromycin and hydroxychloroquine had greater odds of death (OR, 1.21; 95% CI, 1.11-1.31; P < .001).
In this study, the authors found that COVID-19 was associated with a high rate of ICU admissions and in-hospital mortality. Use of statins, angiotensin-converting enzyme inhibitors, and calcium channel blockers was associated with lower odds of death. The authors concluded that evaluating the potential benefits of unproven treatments such as hydroxychloroquine and azithromycin will require randomized trials.
Source: Rosenthal N, Cao Z, Gundrum J, et al. Risk factors associated with in-hospital mortality in a US national sample of patients with COVID-19. JAMA Netw Open. 2020;3(12):e2029058.

COVID-19 In-patients at High Risk of Readmission for 10 Days Post-discharge

The first week and a half are especially dangerous for discharged COVID-19 patients, who face an increased risk of ongoing health problems, trips back to the hospital, and death.
In this study, 18.5% of COVID-19 patients died during their initial hospitalization. In those who were discharged, COVID-19 patients had a 40% to 60% higher risk of ending up back in the hospital or dying in the first 10 days after discharge, compared with similar patients treated at the same hospitals during the same months for heart failure or pneumonia. In the first two months, 9% of the COVID-19 patients who survived hospitalization had died, and almost 20% had suffered a setback that sent them back to the hospital.
The researchers compared post-hospital outcomes for nearly 2,200 veterans who survived their hospitalization at 132 VA hospitals for COVID-19 this past spring and early summer. Outcomes were evaluated for almost 1,800 similar patients who survived a hospital stay for pneumonia (unrelated to COVID-19), and 3,500 who survived a heart failure-related stay, during the same time.
In all, the 2,179 COVID-19 patients spent a total of 27,496 days in the hospital, and the 354 veterans who were readmitted spent a total of 3,728 additional days in the hospital. All but 5% of the patients were male, and half were Black, which is not nationally representative but focuses on 2 high-risk groups. But within the veterans studied, the only factor that made a significant difference in outcomes was age; about half of veterans in their 70s and 80s died in the 60 days after leaving the hospital.
The most common reasons listed for rehospitalization were COVID-19, cited in 30% of patients, and sepsis seen in 8.5%. Over 22% of the readmitted veterans went to an intensive care unit. By the end of 60 days, the COVID-19 patients’ overall risk of readmission or death was lower than that for the other 2 serious conditions.
Source: Donnelly JP, Wang XQ, Iwashyna TJ, Prescott HC. Readmission and death after initial hospital discharge among patients with COVID-19 in a large multihospital system. JAMA. 2020, DSec 14.

Diagnosis-Wide Analysis of Covid-19 Complication: An Exposure-Crossover Study

An exposure-crossover study of over 70,000 patients with COVID-19 confirmed and provided risk estimates for numerous complications of COVID-19. The study objective was to analyze all diagnoses associated with COVID-19, to identify those that could be complications of the disease, and to present both the risk and relative odds of any complications identified. The study used United States health claims data to compare the frequency of all International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis codes that occurred before and after the onset of the COVID-19 pandemic.
The more common and expected complications identified included viral pneumonia, respiratory failure, kidney failure, and sepsis. Less common complications identified included disseminated intravascular coagulation, pneumothorax, myocarditis, and rhabdomyolysis, although the overall risk for most of these complications were comparatively low. The authors conclude that “Understanding the full range of associated conditions can aid in prognosis, guide treatment decisions and better inform patients as to their actual risks for the variety of COVID-19 complications reported in the literature and media.”
Source: Murk W, Gierada M, Fralick M, Weckstein A, et al. Diagnosis-wide analysis of COVID-19 complications: an exposure-crossover study. CMAJ. 2020, Dec 7.

Public health & COVID-19

Media Consumption on Public Knowledge on COVID-19

A recent study assessing people’s knowledge of the coronavirus in the earliest stages of the pandemic has found that people who trust television and Facebook to provide accurate news about the coronavirus pandemic are less knowledgeable about COVID-19.
In this study, 5,948 adults in Pennsylvania were surveyed between March 25-31, 2020. The respondents answered questions about where they got their COVID-19 news, and which news sources they trusted most. They were then given 15 statements about COVID-19 and asked if they thought the statements were true or false, and how confident they were in their answer.
The results showed that the most trusted news sources were government websites (42.8%), followed by television (27.2%), and health system communications (9.3%). There was a clear relationship between where people got their news from, and their knowledge of coronavirus. For example, participants who said that their most trusted source of information was government health websites were more likely to correctly answer COVID- 19 questions than other groups, while people whose most trusted source was television news were less likely to correctly answer COVID-19 questions.
In addition, the rise of social media has changed the way people around the world keep up with current events, with studies showing that up to 66% of people in the US rely on social media for news. Respondents who selected Facebook as either their single most trusted source or as an additional information source were less likely to answer knowledge questions correctly.
According to the authors, these findings highlight the importance of considering where people get their news from when designing public health interventions. For example, basic virus-prevention guidance and messaging such as stay at home, wash your hands, wear a mask, and socially distance can only work if understood. Effective communication remains a critical element of successfully managing a pandemic response.
Source: Sakya SM, Van Scoy LJ, Garman JC, et al. The impact of COVID-19-related changes in media consumption on public knowledge: results of a cross-sectional survey of Pennsylvania adults. Cur Med Res Opin, 2021, Apr 11.

The Seen and the Unseen: Race and Social Inequities Affecting Kidney Care

In this Perspectives article, the authors discuss how “…policies and social conditions, institutional contexts, social contexts and relationships, and physical contexts, social factors serve as fundamental influences on the health of people and communities,” emphasizing that:
Race is one of the most powerful sociopolitical constructs in the United States because of its omnipresence and entrenchment in racialized policies, norms, and practices. US racial categorizations were directly conceived and influenced through a centuries-long political system in which Black and other individuals have been historically enslaved, disenfranchised, marginalized, and treated unequally through systemic means that remain “baked in” to our daily lives.
The authors further explain how this systemic construct affects peoples’ health and well-being, namely, unequal access to promoters of good health, including education, employment, health care, living conditions, and wealth.
Restricted fundamental opportunities and resources have led to poorer access to health care; lower health literacy; greater exposure to resource-constrained neighborhood environments; greater exposure to the trauma of police violence and incarceration; and a greater burden of poverty, food, and housing insecurity for racial and ethnic minorities and other socially disadvantaged individuals.
Adding to this assault on health promotion among racial and ethnic minorities, the authors point out that health care professionals’ implicit or explicit bias/racism during patient-clinician interactions and their inadequate consideration of these social factors may further promote health inequities. They also explain that healthcare professionals often do not consider how these “contextual, non-biologic factors affect health and health behaviors.”
Ultimately, the authors highlight how systemic racism and social biases contribute to inequities in the care of patients with chronic kidney disease (CKD), while offering recommendations on how to address these issues, such as dismantling systemically racist policies and practices that impede access to CKD care, and creating clinical care models that address patients’ social contexts. They conclude that initial efforts to eradicate racism and bias in CKD care must include “…sustained strategies that are continually tracked, evaluated, and revised.”
Source: Boulware LE, Mohottige D. The Seen and the unseen: race and social inequities affecting kidney care. Clin J Am Soc Nephrol. 2021, Jan 13.

Alcohol Consumption Sharply Rises During COVID-19 Pandemic

Adults in the United States have increased their consumption of alcohol during the shutdown triggered by the coronavirus pandemic.
A research letter detailed the results of a national survey of 1,540 adults and found the overall frequency of alcohol consumption increased by 14% among adults over age 30, compared to the same time last year. The increase was 19% among all adults aged 30 to 59, 17% among women (with 41% reporting heavy drinking episodes of 4 or more drinks within a couple of hours), and 10% among non-Hispanic white adults.
According to the authors, the alcohol spike seen among women, younger adults, and non-Hispanic white adults highlights the need for primary care providers, behavioral health providers, and family members to be aware of the risks of increased alcohol use and heavy drinking during the pandemic.
The findings also suggest that future research should examine whether increases in alcohol use persist as the pandemic continues, and whether psychological and physical well-being are subsequently affected.
Source: Pollard MS, Tucker JS, Green HD. Changes in adult alcohol use and consequences during the COVID-19 pandemic in the US. 2020;3:e2022942.

Community-Level Disparities of COVID-19 in Large US Metropolitan Areas

In this cross-sectional study, researchers examined the association of neighborhood race/ethnicity and poverty with COVID-19 infections and related deaths in urban US counties, hypothesizing disproportionate burdens in counties with a larger percentage of the population belonging to minority racial/ethnic groups and a higher rate of poverty. This study is among the first to investigate such associations in US metropolitan areas.
Counties were grouped by US Office of Management and Budget–defined combined statistical areas (CSAs). Information regarding county-level poverty rates and median household income was obtained from the 2018 US Census Small Area Income and Poverty Estimates Program.Of 158 counties, 81 (51.3%) were considered less-poverty counties and 77 (48.7%), more-poverty counties.
In more-poverty counties, those with substantially non-White populations had an infection rate nearly 8 times that of counties with substantially White populations (RR, 7.8; 95% CI, 5.1-12.0) and a death rate more than 9 times greater (RR, 9.3; 95% CI, 4.7-18.4).
Among both more-poverty and less-poverty counties, those with substantially non-White or more diverse populations had higher expected cumulative COVID-19 incident infections compared with counties with substantially White or less-diverse populations (e.g., more diverse counties with less poverty: RR, 3.2; 95% CI, 2.3-4.6).
While the excess burden of both infections and deaths was experienced by poorer and more diverse areas, racial and ethnic disparities in COVID-19 infections and deaths existed beyond those explained by differences in income.
Source:Adhikari S, Pantaleo N, Feldman J, et al. Assessment of Community-Level Disparities in Coronavirus Disease 2019 (COVID-19) Infections and Deaths in Large US Metropolitan Areas. JAMA. 2020, Jul 28.

Genomic Surveillance of COVID-19 in a Healthcare Setting

A study examined the use of rapid COVID-19 sequencing combined with detailed epidemiological analysis to investigate health-care associated COVID-19 infections and inform infection control measures.In this prospective surveillance study, rapid COVID-19 nanopore sequencing from PCR-positive diagnostic samples were set up and collected from a hospital in Cambridge, UK, and random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. Researchers established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. Between March 13 and April 24, 2020, researchers collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. 1000 samples were sequenced producing 747 high-quality genomes.
Researchers combined epidemiological and genomic analysis of the 299 patients and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. Results were fed back to clinical, infection control and hospital management teams, leading to infection-control interventions and informing patient safety reporting.
The authors report the establishment of real-time genomic surveillance of COVID-19 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled them to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections.
Source: Meredith L, Hamilton W, Warne B, et al. Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study. Lancet. 2020, 14 Jul 14.

Asymptomatic Transmission: The Achilles’ Heel of Current Strategies to Control Covid-19

At first, public health authorities focused on the symptom similarities between COVID-19 and the SARS outbreak in 2003, such as high genetic relatedness, transmission primarily through respiratory droplets, and the frequency of lower respiratory symptoms (fever, cough, and shortness of breath), with both infections developing a median of five days post exposure.
Based on these similarities, public health officials used interventions that had proved effective in 2003 such as “symptom-based case detection and subsequent testing to guide isolation and quarantine.” While this initial approach was justified, in hindsight, Monica Gandhi et al, recognize that the results “strongly demonstrate that our current approaches are inadequate.”
The authors noted that, “despite the deployment of similar control interventions, the trajectories of the two epidemics have veered in dramatically different directions.” After eight months, SARS-CoV-1 virus was well contained and had infected around 8,100 people worldwide with outbreaks limited to specific geographic areas.
With the number of COVID-19 cases surging, the authors conclude there is “clear evidence that COVID-19 transmissions from asymptomatic people and the eventual need to relax current social distancing practices argue for broadened COVID-19 testing to include asymptomatic persons in prioritized settings” such as skilled nursing facilities, prisons, mental health facilities, and homeless shelters.
Source: Gandhi M, Yokoe DS, Havlir, DV. Asymptomatic transmission, the Achilles' heel of current strategies to control Covid-19.N Engl J Med. 2020;382:2158-2160.

Prevalence of Asymptomatic COVID-19 Infection

It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing COVID-19 pandemic.A review and analysis of available studies on asymptomatic COVID-19 infection found that asymptomatic persons seem to account for approximately 40% to 45% of COVID-19 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography, indicating that the absence of COVID-19 symptoms in persons infected with SARS-CoV-2 might not necessarily imply an absence of harm, although more research is needed in this area.The authors also concluded that the focus of testing programs for COVID-19 should be substantially broadened to include infected persons who do not have symptoms.
Source: Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review.Ann Intern Med. 2020, 3 Jun.

Reduction of COVID-19 secondary transmission in households by face mask use, disinfection, and social distancing

A retrospective cohort study of 335 people in 124 families with at least one laboratory confirmed COVID-19 case indicates the effectiveness of mask use, disinfection, and social distancing in preventing COVID-19. The overall secondary transmission rate in households was 23%. Facemasks were 79% effective and disinfection was 77% effective in preventing transmission. In contrast, close frequent contact in the household increased the risk of transmission 18 times.
In the univariate analysis, wearing a mask after illness onset was significant, but in multivariate analysis, only wearing it before symptom onset was effective. Viral load is highest in the two days before symptom onset and on the first day of symptoms and up to 44% of transmission is during the pre-symptomatic period in settings with substantial household clustering. This study showed that social distancing within the home is effective and having close contact (within 1 meter or 3 feet, such as eating around a table or sitting together watching TV) is a risk factor for transmission. The study also provides evidence of effectiveness of chlorine or ethanol-based household disinfection in areas with high community transmission.
The results of this study may be informative for families of high-risk groups such as health workers, quarantined individuals, or situations where cases of COVID-19 can be managed at home.
Source: Wang Y, Tian H, Zhang L, et al. Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China. BMJ Glob Health. 2020 May 5.

Early Spread of COVID-19 in New York City

COVID-19 is the cause of one of the largest non-influenza pandemics of this century. Phylogenetic analysis of 84 distinct COVID-19 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. The study also found evidence for community transmission of COVID-19 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
Early introductions by cases that were identified based on their known travel histories did not seed the larger community clusters, suggesting that their early quarantine and hospitalization were effective in curtailing further spread. However, the study shows that the COVID-19 epidemic in NYC was mainly sourced from untracked transmission between the US and Europe, with limited evidence of direct introductions from China where the virus originated.
Source: Gonzalez-Reiche A, Hernandez M, Sullivan M, et al. Introductions and Early Spread of SARS-CoV-2 in the New York City Area. Science. 2020 May 29.

Reducing Spread of COVID-19 Transmission through Aerosol and Droplets

Aerosol transmission of viruses must be acknowledged as a key factor leading to the spread of infectious respiratory diseases. Evidence suggests that COVID-19 is silently spreading in aerosols exhaled by highly contagious infected individuals with no symptoms. Owing to their smaller size, aerosols may lead to higher severity of COVID-19 because virus-containing aerosols penetrate more deeply into the lungs. It is essential that control measures be introduced to reduce aerosol transmission. A multidisciplinary approach is needed to address a wide range of factors that lead to the production and airborne transmission of respiratory viruses, including the minimum virus titer required to cause COVID-19; viral load emitted as a function of droplet size before, during, and after infection; viability of the virus indoors and outdoors; mechanisms of transmission; airborne concentrations; and spatial patterns. Masks and testing are necessary to combat asymptomatic spread in aerosols and droplets.
Source: Prather P, Wang C, Schooley R. Reducing Transmission of SARS-CoV-2. Science. 2020 May 27.

Mental health & COVID-19

Impact of COVID-19 on the Mental Health of Healthcare Workers

More than a year into the COVID-19 pandemic, a majority of frontline health care workers say the crisis is taking a toll on their mental health, including about 3 in 10 who either received mental health services or thought they needed them directly as a result of the pandemic, according to a, according to a national survey.
Most (62%) frontline health care workers say that worry and stress related to the pandemic has negatively affected their mental health, the survey of all frontline health care workers shows. About 8 in 10 frontline health care workers say concerns about being exposed to COVID-19 at work and exposing others in their household have been sources of stress during the past year.
For about 3 in 10 frontline health workers, the mental health challenges led them to obtain mental health care or medications (13%) or to think that they needed such services but didn’t get them (18%).
About 1 in 6 frontline health care workers (16%) say they tested positive for COVID-19 at some point during the pandemic.
Source: Kaiser Family Foundation. KFF/Post survey reveals the serious mental health challenges facing frontline health care workers a year into the COVID-19 pandemic. 2021, Apr 6.

Alcohol Dependence during COVID-19 Lockdowns

A cross sectional study of 5,931 individuals indicates that over a 6-month period, hazardous alcohol use and likely dependence increased month-by-month for those under lockdowns compared to those not under restrictions.
Between April and September 2020, the researchers collected 5,931 cross sectional responses to the Alcohol Use Disorders Identification Test (AUDIT), divided across six data collections taken approximately one month apart. The AUDIT is a brief 10-item questionnaire with scores ranging from 0 to 40, that focuses on hazardous alcohol consumption. Greater alcohol consumption was associated with younger age, male gender, and primary job loss due to COVID-19, with job loss during the pandemic having the greatest impact. The greatest increase in high-risk drinking over the course of the pandemic occurred mainly among individuals who were under lockdowns or stay-at-home restrictions, meaning those confined to their homes with other family members who were doing the same. Since this study did not follow individuals longitudinally, these findings only point to changes in population prevalence over time as the pandemic unfolds, not the effects of prolonged lockdowns on individual-level changes over time, which suggests the need for longitudinal studies to further inform appropriate policies for lockdowns.
The authors conclude that “this increase in harmful alcohol use and related behaviors is likely to have prolonged adverse psychosocial, interpersonal, occupational, and health impacts as the world attempts to recover from the pandemic crisis.”
Source: Killgore WDS, Cloonan SA, Taylor EC, et al. Alcohol dependence during COVID-19 lockdowns. Psychiatry Res. 2021;296:113676.

Depression Levels in the US during the COVID-19 Pandemic

COVID-19 and the associated social distancing and lockdown restrictions are expected to have substantial and enduring mental health effects. In this study, researchers aimed to assess depression levels before and during the COVID-19 pandemic in the United States. The findings indicate that there is likely to have been a rise in depression since during the COVID-19 pandemic. A particularly large increase in depression among young adults is a cause for concern, according to the authors.
The Patient Health Questionnaire-2 (PHQ-2) brief screening instrument was used to detect probable depression in two nationally representative surveys of US adults. Pre-pandemic levels of depression were assessed (5,075 adults) from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Depression was assessed in March (N = 6,819) and April 2020 (N = 5,428) in the Understanding America Study, a representative sample of the US population.
The percentage of US adults with depression increased significantly from 8.7% in 2017–2018 to 10.6% in March 2020 and 14.4% in April 2020. Statistically significant increases in depression levels were observed for all population subgroups examined with the exception of those aged 65+ years and Black participants. Young adults (aged 18–34) experienced a marked increase in depression of 13.4 percentage points that was larger than any other age group. Additional analyses of depression trends in NHANES from 2007/2008–2017/2018 showed that the substantial increase in depression in April 2020 was unlikely to be due to typical year-to-year variation.
The findings suggest that depression levels have risen substantially during the COVID-19 pandemic and reinforce recent findings indicating that young adults may be particularly vulnerable to the mental health effects of the pandemic, according to the authors.
Source: Daly M, Sutin AR, Robinson E. Depression reported by US adults in 2017-2018 and March and April 2020. J Affect Disord. 2020;278;131-135.

The Implications of COVID-19 for Mental Health and Substance Use

The COVID-19 pandemic and the resulting economic recession have negatively affected many people’s mental health and created new barriers for people already suffering from mental illness and substance use disorders.
A report by the Kaiser Family Foundation found that mid-July, 53% of adults in the United States reported that their mental health has been negatively impacted due to worry and stress over the coronavirus. This is significantly higher than the 32% reported in March.
Many adults are also reporting specific negative impacts on their mental health and wellbeing, such as difficulty sleeping (36%) or eating (32%), increases in alcohol consumption or substance use (12%), and worsening chronic conditions (12%), due to worry and stress over the coronavirus. As the pandemic wears on, ongoing and necessary public health measures expose many people to experiencing situations linked to poor mental health outcomes, such as isolation and job loss, according to the report.
Researchers also found that that a significantly higher share of households experiencing income or job loss reported that worry or stress over the coronavirus outbreak caused them to experience at least one adverse effect, such as difficulty sleeping or eating, increases in alcohol consumption or substance use, and worsening chronic conditions, on their mental health and wellbeing compared to households with no lost income or employment (59% vs. 46%, respectively).
Source: Panchal N, Kamal R, Orgera K, et al. The Implications of COVID-19 for Mental Health and Substance Use. Kaiser Family Foundation. 2020, Aug 21.

Impact of COVID-19 on Mental Health in the General Population

The COVID-19 pandemic has led to unprecedented hazards to mental health globally. A systematic search found that relatively high rates of symptoms of anxiety (6.33% to 50.9%), depression (14.6% to 48.3%), post-traumatic stress disorder (7% to 53.8%), psychological distress (34.43% to 38%), and stress (8.1% to 81.9%) are reported in the general population during the COVID-19 pandemic in China, Spain, Italy, Iran, the US, Turkey, Nepal, and Denmark. Risk factors associated with distress measures include female gender, younger age group (≤40 years), presence of chronic/psychiatric illnesses, unemployment, student status, and frequent exposure to social media/news concerning COVID-19.
The authors concluded that the COVID-19 pandemic is associated with highly significant levels of psychological distress that, in many cases, would meet the threshold for clinical relevance. Mitigating the hazardous effects of COVID-19 on mental health is an international public health priority.
Source: Xiong J, Lipsitz O, Nasri F, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020, Aug 8.

Short and Long-term Mental Health Effects of COVID-19

Most people with severe coronavirus infections (ie, SARS, MERS, and COVID-19) appear to recover without experiencing mental illness. However, recent studies indicate delirium is not uncommon in hospitalized patients in the acute stages of severe SARS, MERS, and COVID-19 illness.
Analysis of data from two studies that systematically assessed common symptoms of patients hospitalized with SARS and MERS found that confusion occurred in 28% (36/129) of patients, suggesting delirium was common during acute illness. There were also frequent reports of low mood (42/129; 33%), anxiety (46/129; 36%), impaired memory (44/129; 34%), and insomnia (34/208; 12%) during the acute stage.
Twelve studies focusing on COVID-19 note a similarity, with evidence of delirium (confusion in 26/40 intensive care unit patients, 65%; agitation in 40/58 ICU patients, 69%; and altered consciousness in 17/82 patients who subsequently died, 21%) while acutely ill.
In the longer-term, the analysis suggests that SARS and MERS survivors may be at increased risk for mental illnesses such as depression, anxiety, fatigue, and post-traumatic stress disorder in the months and years following discharge from hospital.
While previous coronavirus outbreak data and analyses may provide insights, they cannot be deemed exact predictors of psychiatric complication prevalence in severely ill COVID-19 patients. On the other hand, there is value in recognizing that delirium in acute-stage COVID-19 patients may be a precursor to a several long-term mental illnesses.
Source: Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psych. 2020 May 18.

The Impact of COVID-19 on Mental Wellbeing

A national poll indicates that Americans have stress and anxiety caused by the COVID-19 pandemic, which is having an effect of people’s physical and mental health. Among the findings, nearly half of Americans (48%) are anxious about the possibility of getting COVID-19 coronavirus, and 62% are anxious about the possibility of family and loved ones getting COVID-19 coronavirus. Most (59%) feel COVID-19 coronavirus is having a serious impact on their day-to-day lives. Considering these findings, APA CEO and Medical Director Saul Levin, M.D., M.P.A. emphasizes the need to maintain self-care and manage stress. Clear consistent communications on how to prevent the spread of COVID-19 is also important.
Source: American Psychiatric Association. New Poll: COVID-19 Impacting Mental Well-Being: Americans Feeling Anxious, Especially for Loved Ones; Older Adults are Less Anxious.

Mental Health and the COVID-19 Pandemic

Public health emergencies may affect the health, safety, and well-being of both individuals and communities. Extensive research in disaster mental health has established that emotional distress is ubiquitous in affected populations — a finding certain to be echoed in populations affected by the COVID-19 pandemic. Health care workers have an important role in addressing these emotional outcomes as part of the pandemic response. Health care systems will also need to address the stress on individual workers.
Source: Pfefferbaum B, North CS. Mental Health and the Covid-19 Pandemic. N Engl J Med. 2020 Apr 13.

Natural Mood Regulation and Depression

Periods of lockdown during the COVID-19 pandemic are likely to exacerbate problems with mood regulation. Situations in which personal choices of activities are constrained, such as during times of social isolation and lockdown, natural mood regulation is impaired potentially leading to depression.
A study from Taquet et al suggests a new target for treating and reducing depression is supporting natural mood regulation. This study looked at 58,328 participants from low-, middle-, and high-income countries, and compared people with low mood or a history of depression with those of high mood. In a series of analyses, the study investigated how people regulate their mood through their choice of everyday activities and how they are more vulnerable to depression when their ability to choose activities is restricted.
According to the authors, these research findings open the door to new opportunities for developing and optimizing treatments for depression, which could potentially be well adapted to treatments in the form of smartphone apps and made available to a large population that lacks access to existing treatments.
Source: Taquet M, Quoidbach J, Gross JJ, Saunders KEA, Goodwin GM. Mood homeostasis, low mood, and history of depression in 2 large population samples. JAMA Psychiatry. April 22, 2020.

Mental Health of Health Care Workers

A cross-sectional survey-based study of 1257 health care workers in 34 hospitals in China found that participants reported experiencing significant psychological burden. The study found that a considerable proportion of participants reported symptoms of depression (50.4%), anxiety (44.6%), insomnia (34.0%), and distress (71.5%). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers.
Source: Lai J, Ma S, Wang Y, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020;3:e203976.

Research on COVID-19 treatments

Delaying Second COVID Vaccine Dose May Prevent Deaths: Simulation Modeling Study

Both the Pfizer and Moderna COVID-19 vaccines in a standard two dose schedule are highly effective at preventing symptomatic infections and death. But immunity worldwide remains low, partly owing to low vaccination rates. The longer it takes to effectively vaccinate the global population, increases the risk of vaccine resistant strains developing. This has led to calls to prioritize single dose vaccination for as many people as possible, even if this means delaying a second dose beyond the studied time frame.
The objective of this study was to measure the impact of delayed second dose vaccine policies on infections, hospital admissions, and deaths compared with the current on-schedule two dose regimen. Using a simulation model based on a “real-world” sample population of 100,000 adults, researchers ran a series of scenarios to forecast potentially infectious interactions under different conditions over a six-month period. These included varying levels of vaccine efficacy and administration rates, and varying assumptions as to whether the vaccine prevents transmission and serious symptoms or only prevents serious symptoms, including death. They also examined the impact of delaying second doses for those younger than 65, but not before fully vaccinating older people.
The study replicated the simulations several times and used that data to estimate different population-level outcomes. For example, for a first dose efficacy of 80% and a daily vaccine administration rate of 0.1%, 0.3% and 1% of the population, the estimated total mortality per 100,000 for the delayed versus standard second-dose administration were 402 versus 442, 204 versus 241, and 86 versus 50, respectively.
The results suggest that under specific conditions a decrease in cumulative mortality, infections, and hospital admissions can be achieved when the second vaccine dose is delayed. The delayed second dose strategy is optimal for vaccination rates at or lower than 0.3% population per day if the vaccine efficacy from one dose is 80% or greater. In addition, the delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested, resulting in absolute cumulative mortality reductions up to an estimated 48 per 100,000.
Source: Romero-Brufau S, Chopra A, Ryu A J, et al. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study. BMJ. 2021;373:n1087.

Ivermectin and Mild COVID-19

A double-blind, randomized trial was performed at a single site in Cali, Colombia to determine if ivermectin is an effective treatment for mild COVID-19. A total of 476 adult patients with mild disease and symptoms for 7 days or less, either at home or in-patient, were enrolled between July 15 and November 30, 2020 and followed up through December 21, 2020. Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). The primary outcome was time to symptom resolution within 21-days.
Among 400 patients randomized in the primary analysis, the median time to symptom resolution was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for symptom resolution, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By 21 days, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) given placebo. The most common serious adverse event was multiorgan failure, which occurred in 4 patients, with 2 from each group.
Among adults with mild COVID-19, 5-day treatment with ivermectin, as compared with placebo, did not significantly improve the time to symptom resolution. The results do not support using ivermectin to treat mild COVID-19, although larger trials may elucidate the effects of ivermectin on other clinically relevant outcomes.
Source: López-Medina E, López P, Hurtado IC, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults with Mild COVID-19: A Randomized Clinical Trial. JAMA. 2021;325:1426–1435.

Aspirin Use for CVD and the Likelihood of COVID-19 Infection

Researchers recently published study results that evaluated whether pre-infection treatment with daily low-dose aspirin (75 mg) might have a potential beneficial effect on COVID-19 susceptibility and disease duration. Data from 10,477 people who had been tested for COVID-19 during the first COVID-19 wave in Israel from February 1, 2020 to June 30, 2020 was collected and analyzed.


The retrospective population-based cross-sectional study found that aspirin use to avoid the development of cardiovascular diseases in healthy individuals was associated with a 29% lower likelihood of COVID-19 infection, as compared to aspirin non-users. The proportion of patients treated with aspirin was significantly lower among the COVID-19-positive individuals, as compared to the COVID-19-negative ones. In addition, patients who had been treated with aspirin were less likely to develop COVID-19 infection than those who were not.


The authors observed an inverse association between the likelihood of COVID-19 infection, disease duration and mortality, and aspirin use for primary prevention.


Source: Merzon E, Green I, Vinker S, et al. The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection. FEBS J. 2021, Feb 23.

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Impact of COVID-19 Vaccination on Asymptomatic Infection

A retrospective cohort study of consecutive, asymptomatic adult patients (n=39,156) within a large US healthcare system indicates COVID-19 vaccination with an mRNA-based vaccine was associated with a reduced risk of developing asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening.


This real-world study included patients (mean age 54 years, 52.5% female) at several Mayo Clinic locations who underwent pre-procedural and pre-surgical SARS-CoV-2 molecular testing within 48-72 hours of their procedure, between December 17, 2020 to February 8, 2021. The primary exposure was vaccination with at least one dose of the Pfizer or Moderna SARS-C0V-2 vaccines prior to molecular screening. The primary outcome was relative risk of a positive SARS-CoV-2 molecular test. The study showed that 3.2% of the unvaccinated patients were positive, compared to 1.4% of those who had received a vaccine. After adjusting for confounding variables, the adjusted relative risk of asymptomatic infection comparing vaccinated versus unvaccinated was 0.35 (95% CI 0.26-0.47).


The authors conclude that “The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.”


Reference: Tande AJ, Pollock BD, Shah ND, et al. Impact of the COVID-19 vaccine on asymptomatic infection among patients undergoing pre-procedural COVID-19 molecular screening. Clin Infect Dis. 2021 Mar 10.

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Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine

A study examining the response of the first vaccine dose in persons with previous COVID-19 found that a single dose of mRNA vaccine elicited rapid immune responses in seropositive participants, with postvaccination antibody titers that were similar to or exceeded titers found in seronegative participants who received two vaccinations.


The study included 110 participants from the longitudinal PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) study. SARS-CoV-2 spike IgG was measured with the use of a previously two-step enzyme-linked immunosorbent assay and expressed as area under the curve (AUC).


Repeated sampling after the first dose indicates that the majority of seronegative participants had variable and relatively low SARS-CoV-2 IgG responses within 9 to 12 days after vaccination. In contrast, participants with SARS-CoV-2 antibodies at baseline before the first vaccine injection rapidly developed uniform, high antibody titers within days after vaccination.


The antibody titers of vaccinees with preexisting immunity were 10 to 45 times as high as those of vaccinees without preexisting immunity at the same time points after the first vaccine dose (e.g., 25 times as high at 13 to 16 days) and also exceeded the median antibody titers measured in participants without preexisting immunity after the second vaccine dose by more than a factor of 6. The study supports further investigation as to whether a single dose of mRNA vaccine provides effective protection in seropositive persons.


Source: Krammer F, Srivastava K, Alshammary H, et al. Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine. N Engl J Med. 2021, Mar 10.

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Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected with SARS-CoV-2

A study of those previously infected with SARS-CoV-2 indicates that a single dose of mRNA vaccine resulted in a higher antibody titer response and neutralization in 14 days compared with Ab-negative volunteers.
Of the 151 health care workers previously enrolled in a serosurvey study, conducted from July to August 2020, 59 volunteers enrolled based on stratification into 3 groups: 17 in the SARS-CoV-2 IgG-antibody negative (Ab-negative); 16 in the IgG-positive asymptomatic COVID-19 (asymptomatic); and 26 in the IgG-positive with history of symptomatic COVID-19 (symptomatic). The median age and gender were 38 years and 71% female for the Ab-negative, 40 years and 75% female for the asymptomatic, and 38 years and 88% female for the symptomatic Participants received either the Pfizer-BioNTech or Moderna vaccine. Blood was drawn at days 0 (base-line), 7, and 14 postvaccination in December 2020 and January 2021. At 0, 7, and 14 days, median reciprocal half-maximal binding titers were higher in each of the asymptomatic (208, 29364, and 34033) and symptomatic (302, 32301, and 35460) groups compared with the Ab-negative group (<50, <50, and 924) (P< .001 for each). At 0 and 14 days, median reciprocal ID99 virus neutralization titers of each of the asymptomatic (80 and 40960) and symptomatic (320 and 40960) groups were higher than the Ab-negative group (<20 and 80) (P< .001 for each).
The authors conclude that “Given the ongoing worldwide vaccine shortages, the results inform suggestions for a single-dose vaccination strategy for those with prior COVID-19 or placing them lower on the vaccination priority list.”
Source: Saadat S, Tehrani ZR, Logue J, et al. Binding and neutralization antibody titers after a single vaccine dose in health care workers previously infected with SARS-CoV-2. JAMA. 2021 Mar 1.

FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine

The U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the third vaccine for the prevention of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for use in people 18 years of age and older.
This decision was based on the totality of scientific evidence, including data from Phase 3 data that demonstrated the vaccine was 85% effective in preventing severe disease across all regions studied, and showed protection against COVID-19 related hospitalization and death, beginning 28 days after vaccination.
Overall, the vaccine was approximately 67% effective in preventing moderate to severe/critical COVID-19 occurring at least 14 days after vaccination and 66% effective in preventing moderate to severe/critical COVID-19 occurring at least 28 days after vaccination. Additionally, the vaccine was approximately 77% effective in preventing severe/critical COVID-19 occurring at least 14 days after vaccination and 85% effective in preventing severe/critical COVID-19 occurring at least 28 days after vaccination.
The single-dose vaccine is estimated to remain stable for two years at -4°F (-20°C), and a maximum of three months at routine refrigeration at temperatures of 36-46°F (2 to 8°C). The vaccine uses adenovirus type 26 (Ad26) to deliver a piece of the DNA that is used to make the distinctive “spike” protein of the SARS-CoV-2 virus.
Source: US FDA. FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine. 2021, Fen 27.

Real-world Effectiveness of COVID-19 Vaccine

Researchers analyzed one of the world’s largest integrated health record databases to examine the effectiveness of the Pfizer vaccine against COVID-19. This observational study provides the first large-scale peer-reviewed evaluation of the effectiveness of a COVID-19 vaccine in a nationwide mass-vaccination setting. The study was conducted in Israel, which currently leads the world in COVID-19 vaccination rates.
The results of this study validate and complement the previously reported findings of the Pfizer/BioNTech Phase-III randomized clinical trial, which focused on symptomatic infections, and which, with 21,720 vaccinated individuals, could not precisely assess vaccine effectiveness against severe disease in the fully vaccinated.
The study took place from December 20, 2020, the launch of Israel’s national vaccination drive to February 1, 2021. It coincided with Israel’s third and largest wave of coronavirus infection and illness, during which the B.1.1.7 variant gradually became the dominant strain in the country for new infections.
Researchers reviewed data from 596,618 vaccinated individuals aged 16 and over (of whom approximately 170,000 were aged 60+). These individuals were carefully matched with 596,618 unvaccinated individuals based on an extensive set of demographic, geographic and health-related attributes associated with risk of infection, risk of severe disease, health status and health seeking behavior. Individuals were assigned to each group dynamically based on their changing vaccination status (approximately 85,000 individuals moved from the unvaccinated cohort into the vaccinated cohort during the study). Multiple sensitivity analyses were conducted to ensure that the estimated vaccine effectiveness was robust to potential biases.
The results show that in fully vaccinated individuals (7 or more days after the second dose), the risk of symptomatic COVID-19 decreased by 94% compared with the unvaccinated, while the risk of severe disease decreased by 92%. In the period immediately preceding the second dose (days 14-20 after the first dose), vaccine effectiveness was lower, but still substantial – the risk of symptomatic COVID-19 decreased by 57% in vaccinated individuals, and the risk of severe disease by 62%. While there was insufficient data to provide an estimate on the reduction in mortality in those who received 2 doses, data from 21-27 days after the first dose points to a substantial reduction in mortality as well.
The authors reported that this vaccine is highly effective against symptomatic COVID-19, one week after the second dose. The study results are similar to those reported in the previously published clinical trial, despite the challenges inherent in a mass-vaccination setting.
Source: Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Eng J Med. 2021, Feb 24.

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

A phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States to study the efficacy and safety of the mRNA-1273 COVID-19 vaccine, which is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of SARS-CoV-2. The study showed that the vaccine showed 94.1% efficacy at preventing COVID-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified, according to the authors.
The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic COVID-19 illness was confirmed in 185 participants in the placebo group and in 11 participants in the mRNA-1273 group; vaccine efficacy was 94.1%. Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe COVID-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.
Source: Baden L, El Sahly H, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384:403-416.

Initial Phase Three Results of Two Adenoviral-Vector COVID-19 Vaccine Candidates

Initial Phase 3 results for two adenoviral-vector COVIID-19 vaccine candidates were announced.
A vaccine, called Ad.26.COV2.S or JNJ-78436725 appears to be safe and effective at preventing moderate and severe COVID-19 in adults, according to an interim analysis of Phase 3 clinical data. The interim analysis assessed 468 cases of symptomatic COVID-19 among 44,325 adult volunteers in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, and the United States. The investigational vaccine was reportedly 66% effective at preventing the study’s combined endpoints of moderate and severe COVID-19 at 28 days post-vaccination among all volunteers, including those infected with an emerging viral variant. Geographically, the level of protection for the combined endpoints of moderate and severe disease varied: 72% in the United States; 66% in Latin American countries; and 57% in South Africa, 28 days post-vaccination. The vaccine was also shown to be to 85% effective overall in preventing severe disease and demonstrated complete protection against COVID-19 related hospitalization and death as of day 28. The vaccine requires a single injection and can be stored in a refrigerator for months. The vaccine is a recombinant vector vaccine that uses a human adenovirus to express the SARS-CoV-2 spike protein.
Another vaccine, called ChAdOx1 nCoV-19 or AZD1222 showed that vaccine efficacy is higher at longer prime-boost intervals, and that a single dose of the vaccine is 76% effective from 22- to up to 90-days post vaccination. The primary analysis for efficacy was based on 17,177 participants accruing 332 symptomatic cases from the UK, Brazil and South Africa trials. The reported effect of dosing interval on efficacy is pronounced, with vaccine efficacy rising from 54.9% with an interval of less than six weeks to 82.4% when spaced 12 or more weeks apart. The analysis also showed the potential for the vaccine to reduce asymptomatic transmission of the virus, based on weekly swabs obtained from volunteers in the UK trial. The data showed that PCR positive readings were reduced by 67% after a single dose, and 50% after the two dose regimen, supporting a substantial impact on transmission of the virus. The vaccine uses a replication-deficient chimpanzee viral vector based on a weakened version of an adenovirus contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body. The vaccine can also be stored at normal refrigerated conditions.
Johnson & Johnson: J&J Announces Single-Shot Janssen COVID-19 Vaccine Candidate Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial.
NIH: Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released.
AstraZeneca: COVID-19 Vaccine AstraZeneca confirms 100% protection against severe disease, hospitalisation and death in the primary analysis of Phase III trials.
University of Oxford: Oxford coronavirus vaccine shows sustained protection of 76% during the 3-month interval until the second dose.

Kidney disease & COVID-19

AKI and Advanced Kidney Disease in the COVID-19 Pandemic: Proceedings From a NKF Symposium

The NKF held a 2-part continuing medical education live virtual symposium to address the multiple challenges of COVID-19 in the context of advanced CKD. This concise review addresses major findings of the symposium along with certain updates regarding vaccinations since then. These findings include: (1) severe COVID-19 infection has been associated with AKI, (2) it is essential to prevent and actively manage AKI to decrease mortality in these critically ill patients, (3) management of patients with advanced kidney disease should be geared toward minimizing their risk for exposure while making sure they are receiving adequate treatments, and (4) patients with kidney disease, especially ones in advanced stages, should be prioritized for vaccination.
Source: Hirsch JS, Ikizler TA, Sharma S, Mohammed A. Acute Kidney Injury and Advanced Kidney Disease in the COVID-19 Pandemic: Proceedings From a National Kidney Foundation Symposium. 2021 Apr 17.

Proteinuria and Outcomes in Hospitalized COVID-19 Patients

A single-center retrospective study found that proteinuria is very frequent among patients admitted for COVID-19 and may precede AKI. Urine protein-creatinine ratio ≥1 g/g at admission was strongly associated with poor kidney and patient outcomes.
The study’s objective was to describe the features of proteinuria measured within 48 hours following admission among patients with COVID-19 admitted in a tertiary care hospital in France. Its association with initiation of dialysis, intensive care unit admission, and death were also evaluated.
Among 200 patients with available data, urine protein-creatinine ratio at admission was ≥1 g/g for 84 (42%), although kidney function was normal in most patients, with a median serum creatinine of 0.94 mg/dl (interquartile range, 0.75–1.21). Median urine albumin-creatinine ratio was 110 mg/g (interquartile range, 50–410), with a urine albumin-protein ratio <50% in 92% of patients. Urine protein-creatinine ratio ≥1 g/g was associated with initiation of dialysis (OR, 4.87; 95% CI, 2.03 to 13.0; P<0.001), admission to the intensive care unit (OR, 3.55; 95% CI, 1.93 to 6.71; P<0.001), and death (OR, 3.56; 95% CI, 1.90 to 6.54; P<0.001).
Source: Karras A, Livrozet M, Lazareth H. Proteinuria and clinical outcomes in hospitalized COVID-19 patients: a retrospective single-center study. Clin J Am Soc Nephrol. 2021. Feb 23.

CKD: A Key Risk Factor for Severe COVID-19

Since January 2020, key risk factors for severe coronavirus disease 2019 (COVID-19) include diabetes, hypertension, and cardiovascular disease. A year later, there is realization that hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89] but kidney disease is.
In fact, dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent 3 of the 4 comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is even higher than the risk associated with diabetes mellitus (aHR range 1.31-1.95, depending upon glycemic control) or chronic heart disease (aHR 1.17).
CKD is the most prevalent risk factor for severe COVID-19 and mortality appears to be different in patients with CKD as compared to the general population. This article defines essential action points, one of which advocates the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
Source: ERA-EDTA Council; ERACODA Working Group. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA. Nephrol Dial Transplant. 2021;36(1):87-94.

COVID-19 Antibody Point-of-Care Testing in Dialysis and Kidney Transplant Patients

A number of serological tests for IgG against SARS-CoV-2 are now commercially available including multiple lateral flow immunoassays (LFIA) which have the advantage of being inexpensive and easy to use, without the reliance on laboratory facilities.
This study included 60 patients (40 hemodialysis and 20 kidney transplant recipients) with SARS-CoV-2 infection confirmed by viral RT-PCR testing, and 88 historic negative-control samples (collected prior to September 2019). The study found that symptomatic dialysis and transplant patients commonly develop an immune response against SARS-CoV-2 infection which can be detected using a LFIA.
The study found that 56/58 (96.6%) patients (38/39 hemodialysis and 18/19 transplant) tested positive for SARS-CoV-2 IgG. 5/7 (71.4%) of patients who were negative on preliminary testing, had detectable IgG when retested, >21 days post diagnosis. The median time to first and second tests after diagnosis were 17 (15-20) and 35 (30-39) days respectively. Calculation of test characteristics gave a sensitivity of 96.6% (95% CI 88.3%-99.4%) and specificity of 97.7% (95% CI 92.0-99.6%)
Used diligently, a LFIA could be utilized to help screen dialysis populations or confirm exposure on a patient level, especially in facilities where laboratory resources are limited, according to the authors.
Source: Prendecki M, Clarke C, McKinnon T, Thomas DC, McAdoo SP Willicombe M. SARS-CoV-2 Antibody Point-of-Care Testing in Dialysis and Kidney Transplant Patients With COVID-19. Kidney Medicine. 2020. Dec 3.

Prevalence of AKI in Patients Hospitalized with COVID-19 Infection

COVID-19 may be associated with high rates of acute injury (AKI) and kidney replacement therapy (KRT), potentially overwhelming healthcare resources. The objective of this study was to determine the pooled prevalence of AKI and KRT among hospitalized patients with COVID-19. The study found that AKI complicated the course of nearly 1 in 3 patients hospitalized with COVID-19. The risk of AKI was higher in critically ill patients with a substantial number receiving KRT at rates higher than the general ICU population.
A systematic review and meta-analysis analyzed data from 53 published and 1 preprint study, which comprised 30,657 hospitalized patients with COVID-19. Data on AKI were available for 30,639 patients (n=54 studies), and the receipt of KRT for 27,525 patients (n=48 studies). The pooled prevalence of AKI was 28% (95% CI 22% to 34%; I2=99%), and the pooled prevalence of KRT was 9% (95% CI 7% to 11%; I2=97). The pooled prevalence of AKI among patients admitted to the ICU was 46% (95% CI 35% to 57%, I2=99%) and 19% of all ICU patients with COVID-19 (95% CI 15% to 22%; I2=88%) commenced KRT.
Since COVID-19 will be a public health threat for the foreseeable future, these estimates should help guide KRT resource planning, according to the authors.
Source: Silver SA, Beaubien-Souligny W, Shah PS, Meraz-Munoz A, Wald R, Harel Z. The Prevalence of Acute Kidney Injury in Patients Hospitalized With COVID-19 Infection: A Systematic Review and Meta-analysis. Kidney Medicine. 220, Dec 8.

AKI in Hospitalized Patients with COVID-19

The aim of this retrospective, observational study was to determine the frequency of AKI and dialysis requirement, AKI recovery and mortality among hospitalized COVID-19 patients within a New York City health system. The study found that that AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.
The study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI.
Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on post-hospital follow-up.
Source: Chan L, Chaudhary K, Saha A, et al. AKI in hospitalized patients with COVID-19. J Am Soc Nephrol. 2020, Sep 3.

Kidney Disease or Injury Increases Mortality Risk for COVID-19 Patients in ICU

COVID-19 patients in intensive care units (ICUs) who have chronic kidney disease (CKD) or those who develop acute kidney injury (AKI) as a result of developing COVID-19 are at increased risk of mortality.
In this study, researchers examined the association between AKI and CKD with clinical outcomes in 372 patients with COVID-19 admitted to 4 regional ICUs in the United Kingdom between March 10 and July 23, 2020. The average patient age was 60 years, 72% were male, and 76% of patients were of Black, Asian, and minority ethnic (BAME) background.
A total of 216 (58%) patients had some form of kidney impairment (45% developed AKI during their ICU stay, while 13% had pre-existing CKD), while 42% had no CKD or AKI. The patients who developed AKI had no history of serious kidney disease before their ICU admission (confirmed by blood tests at hospital admission or from medical records).
Overall, patients with no AKI or CKD had a mortality of 21% (32/156 patients). COVID-19 patients with new onset AKI had a mortality of 48% (81/168) and mortality for patients with pre-existing CKD (Stages 1-4) was 50% (11/22). In patients with end-stage kidney failure (ie, CKD stage 5), where they already required regular out-patient dialysis, mortality was 47% (9/19). Mortality was highest in COVID-19 patients with kidney transplants, with 6 out of 7 patients (86%) dying, highlighting that these patients are an extremely vulnerable group.
Renal replacement therapy (RRT) rates were also evaluated and out of 216 patients with any form of kidney impairment, 121 (56%) patients required RRT. Of the 48 survivors who needed dialysis for the first time during their ICU stay, 9 patients (19%) had to continue with dialysis after discharge from ICU, suggesting COVID-19 may lead to chronic kidney problems.
The reasons for the increased mortality in patients with kidney problems are not clearly understood. There are several theories, including that the COVID-19 virus causes endotheliitis, an inflammation of the blood vessels in the kidneys, which is similar to the damage COVID-19 is known to cause in the lungs. Other reports have suggested that there could be direct kidney injury from the cytokine-induced immune system inflammatory response and also death of kidney tissue related to multi-organ failure caused by COVID-19.
Source: Gasparini M, Khan S, Patel JM, et al. Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID‐19: a multicentre observational study. Anaesthesia. 2020, Oct 15.

Outcomes among Patients Hospitalized With COVID-19 and AKI

A retrospective cohort study investigates the survival and kidney outcomes of patients hospitalized with COVID-19 and acute kidney injury (AKI). The study included patients (age ≥18) hospitalized with COVID-19 at 13 hospitals in metropolitan New York, between March 1, 2020 – April 27, 2020, and followed until hospital discharge. The study found that AKI in hospitalized patients with COVID-19 was associated with significant risk for death.
Among 9657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1000 patient-days. The incidence rates of in-hospital death among patients without AKI, with AKI not requiring kidney replacement therapy (AKI non-KRT) and with AKI receiving KRT (AKI-KRT) were 10.8, 31.1 and 37.5/1000 patient-days, respectively. The risks of in-hospital death for patients with AKI-non KRT and AKI-KRT were greater than among those without AKI (HR 5.6 [95% CI 5.0-6.3] and HR 11.3 [95% CI 9.6 - 13.1], respectively).
After adjusting for demographics, comorbidities, and illness severity, the risk of death remained higher among those with AKI non-KRT and AKI-KRT compared to those without AKI. Among patients with AKI non-KRT who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI-KRT who survived, 30.6% remained on dialysis at discharge, and pre-hospitalization CKD was the only independent risk factor associated with needing dialysis at discharge.
Source: Ng J, Hirsch J, Hazzan A, et al. Outcomes among patients hospitalized with COVID-19 and acute kidney injury. Am J Kidney Dis. 2020, Sep 19.

Pre-existing Kidney Disease and COVID-19 Admitted to ICUs

Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. A study examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. The study found that that having pre-existing kidney disease was associated with higher in-hospital mortality rates, with the strength of this association varying by degree of baseline kidney dysfunction.
4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease).
More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44).
The authors conclude that the findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population.
Source: Flythe JE, Assimon MM, Tugman MJ, et al. Characteristics and outcomes of individuals With pre-existing kidney disease and COVID-19 admitted to intensive care units in the United States. Am J Kidney Dis. 2020, Sep 19.

suPAR and AKI in Patients with COVID-19

Researchers in an observational study found patients with COVID-19 experience elevated levels of soluble urokinase receptor (suPAR), an immune-derived pathogenic protein that is strongly predictive of kidney injury.
According to the study authors, suPAR levels of 352 patients were tested upon admission to the hospital for COVID-19 infection. A quarter of the patients developed acute kidney injury (AKI) while hospitalized, and their median suPAR levels were more than 60% higher than those other patients.
In addition, the risk of needing dialysis was increased 20-fold in patients with the highest suPAR levels. Overall, median suPAR levels for these hospitalized patients with severe COVID-19 were almost 3 times higher than levels found in healthy people.
The authors concluded that measuring suPAR levels of COVID-19 patients upon hospital admission will provide an important risk stratification tool with respect to patient outcomes such as intubation or kidney failure and identify patients with higher risk of running a more severe COVID-19 course.
These findings require further study to determine whether suPAR is a cause of COVID-19 associated AKI. If so, can AKI in COVID-19 infected patients be prevented by keeping plasma suPAR levels low? This hypothesis is supported by the study findings, which showed COVID-19 infected patients with a suPAR level below 4.6 ng/ml did not require dialysis. A newly developed and specific suPAR apheresis device is about to enter a clinical pilot trial where this scenario will be tested.
Source: Azam TU, Shadid HR, Blakely P, et al and International Study of Inflammation in COVID-19. Soluble urokinase receptor (SuPAR) in COVID-19–related AKI. J Am Soc Nephrol. 2020, Sep 21.
In Press.

Dialysis & COVID-19

Humoral Response to the BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis

This study aimed to assess the humoral response following vaccination with the BNT162b2 vaccine in patients on maintenance hemodialysis and the factors associated with it. The study found that although most patients on maintenance hemodialysis developed a substantial humoral response following the BNT162b2 vaccine, it was significantly lower than controls. Age was an important factor in the humoral response, regardless of chronic medical conditions.
The study included 56 patients on maintenance hemodialysis (dialysis group) and a control group composed of 95 health care workers. All participants had received two doses of the BNT162b2 vaccine. The serology testing was done using Quant II IgG anti-Spike SARS-CoV-2 assay by Abbott a median of 30 days after receipt of the second dose of the vaccine.
All subjects in the control group developed an antibody response compared with 96% (54 of 56) positive responders in the dialysis group. The IgG levels in the dialysis group (median, 2900; interquartile range, 1128–5651) were significantly lower than in the control group (median, 7401; interquartile range, 3687–15,471). There was a significant inverse correlation of age and IgG levels in both groups. The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; 95% confidence interval, 1.08 to 1.20; P=0.004) and for the dialysis group compared with the control group (odds ratio, 2.7; 95% confidence interval, 1.13 to 7.51; P=0.05).
Source: Grupper A, Sharon N, Finn T, et al. Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis. Clin J Am Soc Nephrol. 2021 Apr 6.

Experience with SARS-CoV-2 BNT162b2 mRNA Vaccine in dialysis patients

This study investigated dialysis patients and a control group who had completed 2 doses of vaccination with the mRNA BNT162b2 vaccine for anti–spike protein antibody response and observed them for up to 10 weeks. A total of 160 chronic dialysis patients (127 hemodialysis and 33 peritoneal dialysis patients) and 132 control group persons were analyzed. The study’s main findings are (i) a lower response rate to the vaccine, (ii) a lower anti–spike antibody level, and (iii) a higher rate of COVID-19 infection after vaccination in the dialysis group. The study found a lower anti–spike antibody response rate in dialysis patients compared with a control group representative of the general population.
A total of 90% of the dialysis group and 100% of the control group were positive for anti–spike antibodies (P < 0.0001). The median level of anti–spike antibody was 116.5 arbitrary unit (AU)/ml (IQR, 66–160 AU/ml) in the dialysis group and 176.5 AU/ml (IQR, 142–235 AU/ml) in the control group (P < 0.001). In the dialysis group, in patients aged ≥75 years, the median anti–spike antibody level was 99.5 AU/ml (IQR, 28.75–139.5 AU/ml), and in patients aged <75 years, the median level was 122 AU/ml (IQR, 72.8–167.0 AU/ml; P = 0.035)
Source: Yanay NB, Freiman S, Shapira M, et al. Experience with SARS-CoV-2 BNT162b2 mRNA vaccine in dialysis patients. Kidney Int. 2021, Apr 20.

Seroprevalence of antibody to S1 spike protein following vaccination against COVID-19 in patients receiving hemodialysis: a call to arms

A cohort of 94 maintenance hemodialysis patients in the United Kingdom were studied for their antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein 28 days after the first dose of either the Pfizer-BioNTech vaccine (BNT162b2) or the Oxford-AstraZeneca vaccine (AZD1222) vaccine.
The mean time between vaccination and antibody testing was 27.8 ± 4.2 days. SARS-CoV-2 neutralizing antibodies against the receptor binding domain of the S1 spike protein were detected in 75 patients (79.8%) and were not detected in 19 patients (20.2%).
The median antibody level was 2.4 [interquartile range, 8.8] relative light units. Patients with detectable antibodies were younger than those without detectable antibodies (60.2 ± 11.6 years vs. 69.8 ± 11.8 years; P = 0.002). Immunosuppressed patients were less likely to have detectable antibodies than patients who were not immunosuppressed (50% vs. 83.3%; χ2 [1, N = 94] = 6.2; P = 0.013). Patients previously infected with COVID-19 were more likely to have detectable antibodies than those without a history of COVID-19 infection (100% vs. 74.3%; χ2 [1, N = 94] = 6.436; P = 0.011). There was no difference in detectability of antibodies within the cohort between females and males (84.2% vs. 76,8%; χ2 [1, N = 94] = 0.77; P = 0.4); the presence or absence of diabetes (86% vs. 74.5%; χ2 [1, N = 94] = 1.9; P = 0.17); or race (Asian, 85.1%; White, 68.6%; Black, 90%; mixed, 100%; other, 100%; χ2 [1, N = 94] = 4.7; P = 0.32).
No differences were found between patients who received the Pfizer-BioNTech vaccine or the Oxford-AstraZeneca vaccine (81.8% vs. 70.6%; χ2 [1, N = 94] = 1.089; P = 0.3).
These results are consistent with data on other populations, but the authors stress that because of the small numbers in this study, they should be viewed only as hypothesis-generating, and that the presence or absence of antibodies 28 days after the first vaccine dose does not indicate either protection or absence of protection from COVID-19.
These data were published to highlight the urgent, international need for professional organizations, clinicians, and all stakeholder to work together to study the factors that influence the immune response following vaccination against COVID-19 in this vulnerable hemodialysis population.
Source: Billany RE, Selvaskandan H, Adenwalla SF, et al. Seroprevalence of antibody to S1 spike protein following vaccination against COVID-19 in patients receiving hemodialysis: a call to arms. Kidney Int. 2021 Apr 20.

Durability of Humoral Immune Response to SARS-CoV-2 in Symptomatic Hemodialysis Patients

A study on humoral immune response to SARS-CoV-2 among survivor hemodialysis patients found that symptomatic COVID-19 disease confers higher and durable anti-SARS-CoV-2 spikes IgG titers then those in asymptomatic chronic hemodialysis patients. In addition, these Abs titers were not lower when compared to COVID-19 symptomatic health care staff members.
Between March 9th to April 6th 2020, 210 hemodialysis patients were studied. Fifty-six (27%) of them were positive to SARS-CoV-2 nasopharyngeal swabbing (NPS) while 154 (73%) did not. Among those with positive NPS, 29 patients (52%) were COVID-19 symptomatic (CoV-sympt) and 27 (48%) remained COVID-19 asymptomatic (CoVasympt). Twenty-six CoV-sympt patients were treated as inpatients because of severe symptoms (fever and interstitial pneumonia), while 3 with mild symptoms were treated as outpatients. Within the inpatients CoV-sympt group, 13 (50%) died and 13 (50%) recovered (one of them refused to continue HD and was lost to follow-up) while all 3 CoV-sympt outpatients recovered. Eleven members (26%) of the HD health care staff had positive NPS and symptomatic for SARS-CoV-2 infection in the same period; they were all treated as outpatients.
The authors concluded that this information may be of importance to assess the usefulness of a vaccination campaign among these patients.
Source: La Milia V, Tonolo S, Luzzaro F, et al. The humoral immune response to SARS-CoV-2 mounts and is durable in symptomatic hemodialysis patients. Nephrol Dial Transplant. 2021, Feb 19.

The Urgent Need to Vaccinate Dialysis Patients against COVID-19

This editorial aims to highlight both the catastrophic risks of infection with SARS-CoV-2 and of subsequent death from COVID-19 in dialysis patients and the current failure to recognize these risks when considering priorities for COVID-19 vaccination. People receiving dialysis treatment for end-stage kidney disease have specific circumstances that lead to an increased risk of SARS-CoV-2 infection. Patients on dialysis should be prioritized, as they are at much greater risk of acquiring COVID-19, and once infected their risk of death due to COVID-19 is substantially greater. People receiving maintenance dialysis report profound psychosocial stress related to the pandemic and anxiously await vaccination. National and regional stakeholders can advocate for priority access to vaccination for dialysis patients and assist efficient implementation of a vaccine program that will protect the most vulnerable: those on dialysis.
Source: Francis A, Baigent C, Ikizler TA, Cockwell P, Jha V. The urgent need to vaccinate dialysis patients against severe acute respiratory syndrome coronavirus 2: a call to action. Kidney International. 2021, Feb 11.

Serologic Assessment of COVID-19 in a Belgian Hemodialysis Facility

Data concerning the dynamics of anti–SARS-CoV-2 antibodies in patients on hemodialysis (HD) are scarce. This prospective studied analyzed the onset and evolution over 3 months of anti–SARS-CoV-2 antibodies in a cohort of adult patients on in-center maintenance HD.
The study included all patients on in-center maintenance HD at Cliniques Universitaires Saint-Luc, Brussels, Belgium. On March 19th (day 0), a 77-year-old man presented with cough and fever (patient 1) and had a positive real-time reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 (1) on a nasopharyngeal swab. Since then, the use of surgical face masks by all staff members and all patients on HD has become mandatory, as long as they are in the facility. Between March 19th and April 6th, seven additional symptomatic patients (patients 2–8) were diagnosed with COVID-19 by RT-qPCR. On April 6th and 7th, all asymptomatic patients (n=90) were screened by RT-qPCR, and two (patients 9 and 10) were found to be positive.
The study found that almost all patients on maintenance HD with COVID-19 developed specific antibodies within the first month after symptom onset. However, a regular titer decrease was observed from 30 days after seroconversion through the following 3 months.
The authors noted that if confirmed in larger cohorts, the findings suggest that cross-sectional studies of seroprevalence in HD units may underestimate the actual rates of prior infections, except in recent months. Additionally, the decline of titers suggests that the efficacy of a vaccine in this specific population may be temporary if the level of antibodies predicts protection. Serologic monitoring may thus be needed to determine the timing of boosters after a vaccine is available, according to the authors.
Source: Labriola L, Scohy A, Seghers F, et al. A Longitudinal, 3-Month Serologic Assessment of SARS-CoV-2 Infections in a Belgian Hemodialysis Facility. Clin J Am Soc Nephrol. 2020 Nov 18.

Dialysis Care during the COVID-19 Pandemic

This review discusses dialysis patients' care during COVID-19, addressing measures for patient and health care personnel protection and care of dialysis patients with suspected or confirmed COVID-19. There is a scarcity of real-world data regarding hemodialysis patients and COVID-19. The atypical presentation and higher risks of transmission and mortality warrant specific protocols for caring dialysis patients with COVID-19. In this time of a public health emergency, it is essential to prevent transmission and use evidence-based medicine in caring for dialysis patients to avoid any interruption in their usual care.
Source: Verma A, Patel AB, Tio MC, Waikar SS. Caring for Dialysis Patients in a Time of COVID-19. Kidney Med. 2020, Oct 14.

Impact of the COVID-19 Pandemic on Commercial Airlines: Implications for the Kidney Transplant Community

Many deceased-donor and living-donor kidney transplants (KTs) rely on commercial airlines for transport. However, the COVID-19 pandemic has drastically impacted the commercial airline industry. To understand potential pandemic-related disruptions in the transportation network of kidneys across the United States, national flight data was used to compare scheduled flights during the pandemic versus 1-year earlier, focusing on organ procurement organization (OPO) pairs between which kidneys historically most likely traveled by direct flight (High-Volume by direct Air transport OPO Pairs, HVA-OPs).
Across the US, there were 39% fewer flights in April 2020 versus April 2019. Specific to the kidney transportation network, there were 65.1% fewer flights between HVA-OPs, with considerable OPO-level variation (IQR 54.7%-75.3%, range 0%-100%). This translated to a drop in median number of flights between HVA-OPs from 112 flights/week in April 2019 to 34 in April 2020 (p<0.001), and a rise in wait time between scheduled flights from 1.5 hours in April 2019 (IQR 0.76-3.3) to 4.9 hours in April 2020 (IQR 2.6-11.2) (p<0.001).
Fewer flights and longer wait times can impact logistics as well as cold ischemia time. The findings motivate an exploration of creative approaches to KT transport as the impact of this pandemic on the airline industry evolves.
Source: Strauss AT, Cartier D, Gunning BA, et al. Impact of the COVID-19 pandemic on commercial airlines in the United States and implications for the kidney transplant community. Am J Transplant. 2020, Aug 29.

COVID-19 Incidence and Course of Illness: French National Cohort of Dialysis Patients

A study of the dialysis population in France (n=48,669) indicates a relatively low frequency of COVID-19 among dialysis patients in contrast to what was expected. The prevalence of COVID-19 varied from less than 1% to 10% between regions. Of the 1,621 (3.3%) infected patients reported on the French national ESRD REIN registry from March 16, 2020 to May 4, 2020, 344 died (21%). The mortality of patients admitted to the ICU was higher (34%) in comparison to patients who were not admitted to the ICU (15.5%).
The risk of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Mortality in diagnosed cases was associated with the same causes as in the general population including higher age, hypoalbuminemia, and the presence of an ischemic heart disease. Home dialysis was associated with a lower probability of being infected. The authors note that “despite relatively low incidence, maintenance dialysis patients with COVID-19 have high mortality due to similar risk factors observed in the general population.”
Source: Cécile C, Florian B, Carole A, et al., in the name of the French REIN registry, Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients. Kidney Int. 2020, Aug 25.

Estimating Shortages in Capacity to Deliver CKRT during the COVID-19 Pandemic

During the COVID-19 pandemic, New York encountered shortages in continuous kidney replacement (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis (AKI 3D). To inform planning for current and future crises, mathematical models were used to study estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. The models projected nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation (IHME) model, the Harvard Global Health Institute model, and published literature. The study included data on US patients hospitalized during the initial wave of the COVID-19 pandemic (02/06/2020 to 08/04/2020).
Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval: 910-1,568) machines, and shortages in 6 states at peak resource utilization. In sensitivity analyses, varying assumptions around (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of AKI 3D requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3-8 states (933-1,282 machines) and 4-8 states (945-1,723 machines), respectively. In the best-case and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines).
The authors concluded that several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. The– while based on limited data on CKRT demand and capacity – suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.
Source: Reddy YNV, Walensky RP, Mendu ML, Green N, Reddy KP. Estimating shortages in capacity to deliver continuous kidney replacement therapy during the COVID-19 pandemic in the United States. AJKD. 2020, Jul, 27.

Kidney transplant & COVID-19

Antibody Response to COVID-19 mRNA Vaccine Series in Transplant Recipients

A prospective cohort study of 658 transplant recipients (168 were kidney transplant recipients) who received 2 doses of SARS-CoV-2 mRNA vaccine indicates most patients had detectable antibody responses after the second dose. Patients that did not have a response after the first dose had low antibody levels. Those receiving antimetabolite maintenance immunosuppression were less likely to respond.
Transplant recipients without prior confirmed COVID-19 completed the 2-dose SARS-CoV-2-mRNA vaccine series between December 16, 2020, and March 13, 2021 and were followed up through April 13, 2021. Overall, of the 658 participants, 98 (15%) had measurable antibody response after dose 1 and dose 2; 301 (46%) had no antibody response after dose 1 or dose 2; and 259 (39%) had no antibody response after dose 1, but subsequent antibody response after dose 2. Among 473 receiving antimetabolites compared to 185 not receiving antimetabolites: antibody response after dose 1 and dose 2 was 38 (8%) and 60 (32%), no antibody response after dose 1 or dose 2 was 268 (57%) and 33 (18%), and no antibody response after dose 1 but subsequent antibody after dose 2 was 167 (35%) and 92 (50%), respectively.
The authors conclude that “Although this study demonstrates an improvement in antispike antibody responses in transplant recipients after dose 2 compared with dose 1, these data suggest that a substantial proportion of transplant recipients likely remain at risk for COVID-19 after 2 doses of mRNA vaccine. Future studies should address interventions to improve vaccine responses in this population, including additional booster doses or immunosuppression modulation.”
Source: Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021 May 5.

COVID-19 Outcomes for Patients on Immunosuppressive Drugs on Par with Non-Immunosuppressed Patients

Newly reported data shows people taking immunosuppressive drugs to prevent organ transplant rejection or to treat inflammatory or autoimmune diseases do not fare worse than others on average when they are hospitalized with COVID-19.
Estimates suggest that there are approximately 10 million immunocompromised people in the US alone. Suppression of the immune system has been considered a potentially major risk factor for severe and fatal COVID-19 because it could allow the SARS-CoV-2 virus to spread unchecked in the body. At the same time, there have been anecdotal reports of immunosuppressed people who experienced only mild COVID-19 or even no symptoms at all—suggesting that immunosuppressive drugs might have a protective effect by preventing the inflammatory storm sometimes associated with severe COVID-19.
In this study, researchers analyzed the records of 2,121 hospitalized COVID-19 patients seen at the Johns Hopkins Medicine medical system in Baltimore, MD, and Washington, DC, from March 4 to August 29, 2020. Five percent (108 patients) of the total COVID-19 cases could be classified as immunosuppressed because they were taking an anti-inflammatory drug such as prednisone or an anti-rejection drug such as tacrolimus after organ transplant.
The researchers found COVID-19 patients who were immunosuppressed prior to their COVID-19 hospitalization did not, on average, have worse COVID-19 outcomes – such as longer length of stay in the hospital, death in hospital, or use of a ventilator – compared to their counterparts who were not immunosuppressed.
These results were obtained after using statistical methods to account for differences between the groups in factors such as age, sex, and non-COVID-19 disease burden that might have skewed the analysis. But even the raw, unadjusted analysis found no statistical association between worse COVID-19 outcomes and immunosuppression status.
The authors concluded that there is no indication that people taking immunosuppressive drugs for other diagnosed conditions should be concerned that their medication increases their risk for severe COVID-19.
Source: Andersen KM, Mehta HB, Palamuttam N, et al. Association between chronic use of immunosuppresive drugs and clinical outcomes from coronavirus disease 2019 (COVID-19) hospitalization: a retrospective cohort study in a large US health system. Clin Infect Dis. 2021. Jan 7.

COVID-19 Outcomes in Patients Waitlisted for Kidney Transplantation and Kidney Transplant Recipients

A study of 56 waitlisted patients (mean age 60 years, 66% male) and 80 kidney transplant recipients (mean age 57 years, 70% male) diagnosed with COVID-19 between March 13 to May 20, 2020 indicates that waitlisted patients were more likely to require hospitalization (82% vs. 65%) and were at a higher risk of mortality (34% vs.16%). Intubation was required in 29% of waitlisted patients and 31% of transplant patients and was linked with a very poor prognosis. Waitlist status, age, and male sex were independently associated with mortality. Most patients who died were male (84% waitlist, 100% transplant).
Waitlisted and transplanted patients frequently have comorbidities associated with increased risk and worsened prognosis of COVID-19. However, waitlisted patients do not have the health benefits gained by transplantation, which may account for their worse outcomes with COVID-19 infection. ESKD patients also have impaired immune function due to their uremic state. The authors conclude that “COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk.”
Source: Craig-Schapiro R, Salinas T, Lubetzky M, Abel BT, et al. COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients. Am J Transplant. 2020, Oct 12.
<a data-cke-saved-href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/ajt.16351 target=" href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/ajt.16351 target=" _blank"="">Access study

Back-to-School Safety Guidelines for Pediatric Solid Organ Transplant Recipients

Throughout the COVID-19 pandemic, pediatric solid organ transplant (SOT) recipients have been categorized as high-risk due to their use of immunosuppressive medications, frequent presence of additional medical issues, and elevated risk for more severe outcomes from other viral respiratory infections. While there is no specific evidence that pediatric SOT recipients fare worse from COVID-19, parents of children with SOT may be concerned about school starting in just a few weeks.
A group of pediatric infectious disease experts from across the United States was convened to develop back-to-school safety guidelines for SOT recipients.
The consensus statements are grouped into 3 areas: 1) SOT patient-specific risk factors, 2) community transmission and public health responses, and 3) school-related interventions. A number of questions were addressed on topics of interest to parents, caregivers, and healthcare providers, such as masking, virtual learning, and infection prevention measures.
The panel fully supports efforts to allow all children to safely return to in-person education this academic year and have provided recommendations for transplant patients, families, and providers to help meet this goal.
Source: Downs KJ, Danziger-Isakov LA, Cousino MK, et al. Return to school for pediatric solid organ transplant recipients in the United States during the COVID-19 pandemic: expert opinion on key considerations and best practices. J Pediatric Infect Dis Soc. 2020, Aug 4.

COVID-19 in Kidney Transplant Recipients: A Single-Center Report from Belgium

A prospective single-center cases series included 22 kidney transplant recipients diagnosed with COVID-19 infection out of a cohort of 1,200 kidney transplant recipients at a center in Belgium.
Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients.
Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n=3), moderate (n=8), extensive (n=1), severe (n=2), and critical (n=1) involvement. Immunosuppression reduction was initiated in all patients.
Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died.
The authors noted that the clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.
Source: Devresse A, Belkhir L, Vo B, et al. COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium.Kidney Medicine. 2020. 15, Jun.

Kidney Transplantation Safety during the COVID-19 Pandemic: A Simulation Study

A simulation study was conducted to quantify the benefit/harm of kidney transplantation in the context of various COVID-19 scenarios. The study compared immediate-kidney transplantation scenarios versus delay-until-after-pandemic scenarios for different patient phenotypes. A calculator was implemented, and machine learning approaches were used to evaluate the important aspects of the modeling.
The simulation suggests that even after weighing the potential risks of COVID-19 infection, kidney transplantation still provides survival benefit to transplant candidates in most scenarios. If local resources allow, it might be reasonable to continue kidney transplantation unless evidence emerges of extremely high case fatality rates of COVID-19 among recipients.
Source: Massie A, Boyarsky B, Werbel W, et al. Identifying scenarios of benefit or harm from kidney transplantation during the COVID-19 pandemic: a stochastic simulation and machine learning study. Am J Transplant. 2020 Jun 9.

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.


Dietary Advice in HD Patients: Impact of a telehealth approach during the COVID-19 pandemic

The purpose of this study was to assess the effect of a telehealth-delivered nutritional intervention via telephone in maintenance hemodialysis (HD) patients during the coronavirus outbreak. The results suggest that telehealth-delivered dietary interventions can improve the clinical and nutritional parameters of HD patients.
This was a multicenter, observational, prospective, and longitudinal study of 156 patients undergoing maintenance HD from 15 dialysis units conducted during the COVID-19 pandemic. Patients were assigned to receive dietary counseling through a phone call, according to their biochemical and nutritional parameters. Dry weight, intradialytic weight gain percentage (%IDWG), body mass index, potassium, phosphorus, calcium, calcium/phosphorus product, normalized protein catabolic rate, albumin, and hemoglobin were recorded at baseline and one month after nutrition counseling.
The study found that the prevalence of hyperkalemia and hyperphosphatemia decreased significantly after dietary advice. A statistically significant reduction in serum potassium and phosphorus levels was observed in patients receiving counseling for hyperkalemia and hyperphosphatemia. In addition, there was a statistically significant decrease in the prevalence of hypophosphatemia. Researchers also observed a significant decrease in %IDWG, although no statistically significant differences were detected in patients with high %IDWG.
Source: Valente A, Jesus J, Breda J, et al. Dietary advice in hemodialysis patients: Impact of a telehealth approach during the COVID-19 pandemic. J Ren Nutr. 2021, May 5.

Vitamin D Deficiency May Increase Risk for COVID-19

Vitamin D is a known immune system booster and vitamin D supplementation has previously been shown to lower the risk of viral respiratory tract infections. A retrospective study of patients tested for COVID-19 found an association between vitamin D deficiency and an increased risk of coronavirus infection.
Researchers evaluated 489 University of Chicago Medicine patients whose vitamin D level was measured within a year before being tested for COVID-19. Patients who had untreated vitamin D deficiency (<20ng/ml) were almost twice as likely to test positive for the COVID-19 coronavirus compared to patients who had sufficient levels vitamin D.
Vitamin D deficiency is common in the United States with 50% of adults having insufficient levels of the nutrient. Vitamin D deficiency rates are higher in African Americans, Hispanics, and people living in areas like Chicago where there is limited winter sun exposure.
The authors emphasize the importance of experimental studies to determine whether vitamin D supplementation can reduce the risk, and potential severity, of COVID-19. They also highlight the need for additional studies and determining appropriate strategies for the most effective vitamin D supplementation in specific populations.
Source: Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open. 2020;3:e2019722.

Obesity Linked to Higher Risk for COVID-19 Complications & Limited Vaccine Efficacy

Obesity is associated with several underlying risk factors for COVID-19, including hypertension, heart disease type 2 diabetes, and chronic kidney and liver disease, as well as an increased likelihood of developing more severe complications from the virus.
Roughly 40% of people living in the United States are obese, and the pandemic’s resulting lockdown has made it more difficult for people to achieve or sustain a healthy weight. Economic hardships and food insecurity have increased unhealthy food consumption resulting in greater population obesity and complications in patients with COVID-19.
Researchers from the University of North Carolina at Chapel Hill reviewed immunological and biomedical data on COVID-19 patients and found that those with obesity (BMI >30) were at a greatly increased risk for hospitalization (113%), more likely to be admitted to an intensive care unit (74%), and had a higher risk of death (48%) from the virus.
Previous studies have shown the influenza vaccine is less effective in adults with obesity. The authors are concerned that the efficacy of a future COVID-19 vaccine may also be limited in obese adults and should be viewed as a modifying factor in vaccine testing.
Source: Popkin BM, Du S, Green WD, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obesity Reviews. 2020;1-17.

Guidance & Strategies for Clinicians to Optimize Care in the ICU

The society of Critical Care Medicine (SCCM) and the American Society for Parenteral and Enteral Nutrition (ASPEN) have published guidelines on Nutrition Support for Critically Ill Patients with COVID-19 Disease. Relevant key recommendations include estimating protein/calorie needs; timing of nutrition delivery; route, tube placement and method of nutrition delivery; nutrition dose, advancing to goal, and adjustments; formula selection; monitoring nutrition tolerance; nutrition for the patient undergoing prone positioning; and nutrition therapy during extracorporeal membrane oxygenation.
In addition to general key recommendations for enteral and parenteral nutrition for this patient population, there are recommendations for AKI as follows:
  • Recommendation # 9A With AKI requiring CRRT dose protein at 2.0-2.5 gm/kg/d
  • Recommendation # 9B Monitor and replace micronutrients in AKD on CRRT (especially zinc, iron, selenium, Vit D, Vit C)
Faculty: Stephen McClave, MD, and Mary Rath, RDN, CSNC, LD
Provider: Abbott Nutrition Institute (ANHI) https://anhi.org/resources/podcasts-and-videos/nutrition-care-of-the-covid-19-patient-series
Nutrition Therapy in the patient with COVID-19 Disease Requiring ICU Care, SCCM and ASPEN – updated April 1, 2020

Selenium Status and Outcome Of COVID-19

A population-based retrospective analysis in 17 cities outside of Hubei, China indicates that the COVID-19 cure rate was significantly associated with selenium status, as measured by the amount of selenium in hair. These data are consistent with evidence of the antiviral effects of selenium from previous studies in other viral infections including HIV. While it is important not to overstate this finding, this data indicates the need for further research regarding the role selenium may play in COVID-19 that may help to guide ongoing public-health decisions.
Note: There are currently no recommendations for selenium supplementation in patients with CKD. The current Recommended Dietary Allowance (RDA) for selenium is 55mcg/d for men and women. Whether similar amount of intake is recommended in various stages of CKD and maintenance dialysis is unknown.
Source: Jinsong Z, Taylor EW, Bennett K, et al. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr. 2020 Apr 28.

Vitamin D Deficiency and Severe COVID-19

An observational study on 186 consecutive patients hospitalized with COVID-19 found that patients with severe COVID-19 show lower median serum 25(OH)D and a higher percentage of vitamin D deficiency at intake than a season/age-matched reference population. The correlation between vitamin D deficiency and the need for hospitalization due to COVID-19 was only seen in male patients. In males but not females, the percentage of vitamin D deficient patients also increased with more advanced COVID-19 disease stage as measured by CT. The data indicates a strong statistical correlation between the degree of vitamin D deficiency and severity of COVID-19 lung disease.
Source: De Smet D, De Smet K, Herroelen P, Gryspeerdt S. Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics. MedRxiv. 2020 May 5.

NKF Advocacy during the COVID-19 pandemic

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

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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Sharon Pearce
Senior Vice President, Government Relations