Effect of remdesivir on adverse kidney outcomes in hospitalized patients with COVID-19 and impaired kidney function.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for mortality from COVID-19. Remdesivir has been shown to shorten time to recovery in patients with severe COVID-19. However, exclusion of patients with severe kidney function impairment in clinical trials has led to concerns about kidney safety of remdesivir in patients with pre-existing kidney disease. METHODS: Retrospective propensity score matched cohort study of hospitalized patients with COVID-19 admitted with estimated glomerular filtration rate (eGFR) between 15 - 60 mL/min/1.73m2. Remdesivir-treated patients were 1:1 matched to historical comparators admitted during the first wave of COVID-19 (between March-April 2020) prior to emergency use authorization of remdesivir using propensity scores accounting for factors predicting treatment assignment. Dependent outcomes included in-hospital peak creatinine, incidence of doubling of creatine, rate of kidney replacement therapy initiation and eGFR among surviving patients at day 90. RESULTS: 175 remdesivir-treated patients were 1:1 matched to untreated historical comparators. Mean age was 74.1 (SD 12.8), 56.9% were male, 59% patients were white, and the majority (83.1%) had at least one co-morbidity. There were no statistically significant differences in peak creatinine during hospitalization (2.3mg/dL vs. 2.5 mg/dL, P = 0.34), incidence of doubling of creatinine (10.3% vs. 13.1%, P = 0.48), and rate of kidney replacement therapy initiation (4.6% vs. 6.3%, P = 0.49) in remdesivir-treated patients versus matched untreated historical comparators, respectively. Among surviving patients, there was no difference of the average eGFR at day 90 (54.7 ± 20.0 mL/min/1.73m2 for remdesivir-treated patients vs. 51.7 ± 19.5 mL/min/1.73m2 for untreated comparators, P = 0.41). CONCLUSIONS: Remdesivir use in patients with impaired kidney function (eGFR between 15 - 60 mL/min/1.73m2) who present to the hospital with COVID-19 is not associated with increased risk of adverse kidney outcomes.

A Propensity Score-Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease.

Background: Remdesivir is not currently approved for patients with eGFR <30 ml/min per 1.73 m2. We aimed to determine the safety of remdesivir in patients with kidney failure. Methods: This study was a retrospective cohort study of patients with COVID-19 hospitalized between May 2020 and January 2021 with eGFR <30 ml/min per 1.73 m2 who received remdesivir and historical controls with COVID-19 hospitalized between March 1, 2020 and April 30, 2020 prior to the emergency use authorization of remdesivir within a large health care system. Patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. Adverse events and hospital outcomes were recorded by manual chart review. Results: The overall cohort included 34 hospitalized patients who initiated remdesivir within 72 hours of hospital admission with eGFR<30 ml/min per 1.73 m2 and 217 COVID-19 controls with eGFR <30 ml/min per 1.73 m2. The propensity score-matched cohort included 31 remdesivir-treated patients and 31 nonremdesivir-treated controls. The mean age was 74.0 (SD=13.8) years, 57% were women, and 68% were white participants. A total of 26% had ESKD. Among patients who were not on dialysis prior to initiating remdesivir, one developed worsening kidney function (defined as ≥50% increase in creatinine or initiation of KRT) compared with three in the historical control group. There was no increased risk of cardiac arrythmia, cardiac arrest, altered mental status, or clinically significant anemia or liver function test abnormalities. There was a significantly increased risk of hyperglycemia, which may be partly explained by the increased use of dexamethasone in the remdesivir-treated population. Conclusions: In this propensity score-matched study, remdesivir was well tolerated in patients with eGFR <30 ml/min per 1.73 m2.

The Case of the United States: The Impact of the COVID-19 Pandemic on Social Connectedness and Isolation in Low-Income Communities

Connectedness is vital for health and well-being. Families with lower socioeconomic status and of racial and ethnic minority groups experience inequities in social connections compared to families with higher income and of White race in the United States. We aimed to understand how families in lower-income neighborhoods experienced social connectedness and isolation during the COVID-19 pandemic and if and how political, economic, and other societal factors influenced social connectedness. We conducted in-depth interviews with nineteen caregivers of young children in Cincinnati, Ohio. Participants had a decreased sense of social connectedness to family and friends but also across all aspects of their lives. The current crisis has exacerbated preexisting societal conditions within the United States. We can learn from these caregivers how best to bolster social connectedness and disrupt social isolation.

Acute Kidney Injury Incidence, Recovery, and Long-term Kidney Outcomes Among Hospitalized Patients With COVID-19 and Influenza.

INTRODUCTION: Acute kidney injury (AKI) is a common complication in patients with severe COVID-19. We sought to compare the AKI incidence and outcomes among patients hospitalized with COVID-19 and with influenza. METHODS: This was a retrospective cohort study of patients with COVID-19 hospitalized between March and May 2020 and historical controls hospitalized with influenza A or B between January 2017 and December 2019 within a large health care system. Cox proportional hazards models were used to compare the risk of AKI during hospitalization. Secondary outcomes included AKI recovery, mortality, new-onset chronic kidney disease (CKD), and ≥25% estimated glomerular filtration rate (eGFR) decline. RESULTS: A total of 2425 patients were included; 1091 (45%) had COVID-19, and 1334 (55%) had influenza. The overall AKI rate was 23% and 13% in patients with COVID-19 and influenza, respectively. Compared with influenza, hospitalized patients with COVID-19 had an increased risk of developing AKI (adjusted hazard ratio [aHR] = 1.58; 95% confidence interval [CI], 1.29-1.94). Patients with AKI were more likely to die in the hospital when infected with COVID-19 versus influenza (aHR = 3.55; 95% CI, 2.11-5.97). Among patients surviving to hospital discharge, the rate of AKI recovery was lower in patients with COVID-19 (aHR = 0.47; 95% CI, 0.36-0.62); however, among patients followed for ≥90 days, new-onset CKD (aHR = 1.24; 95% CI, 0.86-1.78) and ≥25% eGFR decline at the last follow-up (aHR = 1.36, 95% CI, 0.97-1.90) were not significantly different between the cohorts. CONCLUSION: AKI and mortality rates are significantly higher in patients with COVID-19 than influenza; however, kidney recovery among long-term survivors appears to be similar.

A Novel Intelligent Computational Approach to Model Epidemiological Trends and Assess the Impact of Non-Pharmacological Interventions for COVID-19.

The novel coronavirus disease 2019 (COVID-19) pandemic has led to a worldwide crisis in public health. It is crucial we understand the epidemiological trends and impact of non-pharmacological interventions (NPIs), such as lockdowns for effective management of the disease and control of its spread. We develop and validate a novel intelligent computational model to predict epidemiological trends of COVID-19, with the model parameters enabling an evaluation of the impact of NPIs. By representing the number of daily confirmed cases (NDCC) as a time-series, we assume that, with or without NPIs, the pattern of the pandemic satisfies a series of Gaussian distributions according to the central limit theorem. The underlying pandemic trend is first extracted using a singular spectral analysis (SSA) technique, which decomposes the NDCC time series into the sum of a small number of independent and interpretable components such as a slow varying trend, oscillatory components and structureless noise. We then use a mixture of Gaussian fitting (GF) to derive a novel predictive model for the SSA extracted NDCC incidence trend, with the overall model termed SSA-GF. Our proposed model is shown to accurately predict the NDCC trend, peak daily cases, the length of the pandemic period, the total confirmed cases and the associated dates of the turning points on the cumulated NDCC curve. Further, the three key model parameters, specifically, the amplitude (alpha), mean (mu), and standard deviation (sigma) are linked to the underlying pandemic patterns, and enable a directly interpretable evaluation of the impact of NPIs, such as strict lockdowns and travel restrictions. The predictive model is validated using available data from China and South Korea, and new predictions are made, partially requiring future validation, for the cases of Italy, Spain, the UK and the USA. Comparative results demonstrate that the introduction of consistent control measures across countries can lead to development of similar parametric models, reflected in particular by relative variations in their underlying sigma, alpha and mu values. The paper concludes with a number of open questions and outlines future research directions.

Filter clotting with continuous renal replacement therapy in COVID-19.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.