Fibrosis-4 Predicts the Need for Mechanical Ventilation in a National Multiethnic Cohort of Corona Virus Disease 2019.

Simple tests of routine data are needed for those with severe acute respiratory syndrome coronavirus 2, which causes corona virus disease 2019 (COVID-19), to help identify those who may need mechanical ventilation (MV). In this study, we aimed to determine if fibrosis-4 (FIB-4) is associated with the need for MV in patients with COVID-19 and if there is an association to determine the optimal FIB-4 cutoff. This was a retrospective, national, multiethnic cohort study of adults seen in an ambulatory or emergency department setting who were diagnosed with COVID-19. We used the TriNetX platform for analysis. Measures included demographics, comorbid diseases, and routine laboratory tests. A total of 4,901 patients with COVID-19 were included. Patients had a mean age of 56, 48% were women, 42% were obese, 38% were white, 40% were black, 15% had cardiac disease, 39% had diabetes mellitus, 20% had liver disease, and 50% had respiratory disease. The need for MV was 6%. The optimal FIB-4 cutoff for the need for MV was 3.04 (area under the curve, 0.735), which had sensitivity, specificity, and positive and negative predictive values of 42%, 77%, 11%, and 95%, respectively, with 93% accuracy. When stratified by race, increased FIB-4 remained associated with the need for MV in both white and black patients. Conclusion: FIB-4 can be used by frontline providers to identify patients that may require MV.

Hepatic Steatosis, Rather Than Underlying Obesity, Increases the Risk of Infection and Hospitalization for COVID-19.

Objective: Obesity is a risk factor for SARS-COV2 infection and is often associated with hepatic steatosis. The aim of this study was to determine if pre-existing hepatic steatosis affects the risk of infection and severity for COVID-19. Design: Prospective cohort study (UK Biobank). Univariate and stepwise multivariate logistic regression analyses were performed on liver phenotypic biomarkers to determine if these variables increased risk of testing positive and being hospitalized for COVID-19; then compared to previously described risk factors associated with COVID-19, including age, ethnicity, gender, obesity, socio-economic status. Setting: UK biobank study. Participants: 502,506 participants (healthy at baseline) in the UK Biobank, of whom 41,791 underwent MRI (aged 50-83) for assessment of liver fat, liver fibro-inflammatory disease, and liver iron. Positive COVID-19 test was determined from UK testing data, starting in March 2020 and censored in January 2021. Primary and Secondary Outcome Measures: Liver fat measured as proton density fat fraction (PDFF%) MRI and body mass index (BMI, Kg/m2) to assess prior to February 2020 using MRI of the liver to assess hepatic steatosis. Results: Within the imaged cohort (n = 41, 791), 4,458 had been tested and 1,043 (2.49% of the imaged population) tested positive for COVID-19. Individuals with fatty liver (≥10%) were at increased risk of testing positive (OR: 1.35, p = 0.007) and those participants with obesity and fatty liver, were at increased risk of hospitalization with a positive test result by 5.14 times (p = 0.0006). Conclusions: UK Biobank data revealed obese individuals with fatty liver disease were at increased risk of infection and hospitalization for COVID-19. Public policy measures and personalized medicine should be considered in order to protect these high-risk individuals.

The Fibrosis-4 Index Is Associated With Need for Mechanical Ventilation and 30-Day Mortality in Patients Admitted With Coronavirus Disease 2019.

The Fibrosis-4 Index (FIB-4), developed to predict fibrosis in liver disease, was used to identify patients with coronavirus disease 2019 who will require ventilator support as well as those associated with 30-day mortality. Multivariate analysis found obesity (odds ratio [OR], 4.5), diabetes mellitus (OR, 2.55), and FIB-4 ≥2.67 (OR, 3.09) independently associated with need for mechanical ventilation. When controlling for ventilator use, sex, and comorbid conditions, FIB-4 ≥2.67 was also associated with increased 30-day mortality (OR, 8.4 [95% confidence interval, 2.23-31.7]). Although it may not be measuring hepatic fibrosis, its components suggest that increases in FIB-4 may be reflecting systemic inflammation associated with poor outcomes.

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.