Remdesivir for COVID-19 and acute kidney injury: disproportionality analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. AIM: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. METHOD: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. RESULTS: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. CONCLUSION: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic.

Obesity or increased body mass index and the risk of severe outcomes in patients with COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: To assess the effect of obesity or a high body mass index (BMI) on the risk of severe outcomes in patients with coronavirus disease 2019 (COVID-19). METHODS: Studies on the relationship between BMI or obesity and COVID-19 since December 2019. The odds ratio (OR) and weighted mean difference (WMD) with their 95% confidence intervals (CIs) were used to assess the effect size. RESULTS: BMI was significantly increased in COVID-19 patients with severe illness (WMD: 1.18; 95% CI: 0.42-1.93), who were admitted to an intensive care unit (ICU) (WMD: 1.46; 95% CI: 0.96-1.97), who required invasive mechanical ventilation (IMV) (WMD: 2.70, 95% CI: 1.05-4.35) and who died (WMD: 0.91, 95% CI: 0.02-1.80). In Western countries, obesity (BMI of ≥30 kg/m2) increased the risk of hospitalization (OR: 2.08; 95% CI: 1.22-3.54), admission to an ICU (OR: 1.54; 95% CI: 1.29-1.84), need for IMV (OR: 1.73, 95% CI: 1.38-2.17), and mortality (OR: 1.43; 95% CI: 1.17-1.74) of patients with COVID-19. In the Asian population, obesity (BMI of ≥28 kg/m2) increased the risk of severe illness (OR: 3.14; 95% CI: 1.83-5.38). Compared with patients with COVID-19 and a BMI of <25 kg/m2, those with a BMI of 25-30 kg/m2 and ≥30 kg/m2 had a higher risk of need for IMV (OR: 2.19, 95% CI: 1.30-3.69 and OR: 3.04; 95% CI: 1.76-5.28, respectively). The risk of ICU admission in patients with COVID-19 and a BMI of ≥30 kg/m2 was significantly higher than in those with a BMI of 25-30 kg/m2 (OR: 1.49; 95% CI: 1.00-2.21). CONCLUSION: As BMI increased, the risks of hospitalization, ICU admission, and need for IMV increased, especially in COVID-19 patients with obesity. ETHICS AND DISSEMINATION: This systematic review and meta-analysis does not require an ethics approval as it does not collect any primary data from patients.

Drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19: a disproportionality analysis of U.S. food and drug administration adverse event reporting system (FAERS) data.

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59-3.46), 3.16 (2.68-3.73), and 5.39 (4.63-6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15-5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09-6.94), and compared with remdesivir (3.85; 3.03-4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.