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.

Impact of COVID-related policies on gunshot wound assault hospitalizations in the United States: a statewide time series analysis.

BACKGROUND: The CDC recently reported that firearm homicide rates in the United States increased in 2020, particularly among Black/African American individuals and men 25-44 years old. It is unclear whether firearm hospitalizations also increased, and more importantly, what impact the COVID-19 pandemic and COVID-related policies had. Using the North Carolina Trauma Registry, a statewide registry of trauma admissions to eighteen North Carolina hospitals, we calculated weekly GSW hospitalization rates from 1/2019 to 12/2020, overall and stratified by race-ethnicity, age, and sex. Interrupted time-series design and segmented linear regression were used to estimate changes in weekly hospitalization rates over time after (1) U.S. declaration of a public health emergency; (2) statewide Stay-at-Home order; (3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and (4) further lifting of restrictions (Phase 2.5: Safer-at-Home). Non-GSW assault hospitalizations were used as a control to assess whether trends were observed across all assault hospitalizations or if effects were specific to gun violence. FINDINGS: Overall, 47.3% (n = 3223) of assault hospitalizations were GSW. Among GSW hospitalizations, median age was 27 years old (interquartile range [IQR] 21-25), 86.2% were male, and 49.5% occurred after the U.S. declared a public health emergency. After the Stay-at-Home order was implemented, weekly GSW hospitalization rates began increasing substantially among Black/African American residents (weekly trend change = 0.775, 95% CI = 0.254 to 1.296), peaking at an average 15.6 hospitalizations per 1,000,000 residents. Weekly hospitalization rates declined after restrictions were lifted but remained elevated compared to pre-COVID levels in this group (average weekly rate 10.6 per 1,000,000 at the end of 2020 vs. 8.9 per 1,000,000 pre-pandemic). The Stay-at-Home order was also associated with increasing GSW hospitalization rates among males 25-44 years old (weekly trend change = 1.202, 95% CI = 0.631 to 1.773); rates also remained elevated among 25-44-year-old males after restrictions were lifted in 2020 (average weekly rate 10.1 vs. 7.9 per 1,000,000). Non-GSW hospitalization rates were relatively stable in 2020. CONCLUSIONS: The COVID-19 pandemic and statewide Stay-at-Home orders appeared to have placed Black/African American residents and men ages 25-44 at higher risk for GSW hospitalizations, exacerbating pre-existing disparities. Persistent gun violence disparities must be addressed.

Effect of Stay-at-Home orders and other COVID-related policies on trauma hospitalization rates and disparities in the USA: a statewide time-series analysis.

BACKGROUND: To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home order and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex. METHODS: We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations for 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly rates of assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalizations between January 1, 2019, and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalization rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and sex. Changes in hospitalization rates were assessed after 1) USA declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home). RESULTS: There were 70,478 trauma hospitalizations in North Carolina, 2019-2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but substantial increases were only observed among Black/African American residents (weekly trend change = 1.147, 95% CI = 0.634 to 1.662) and 18-44-year-old males (weekly trend change = 1.708, 95% CI = 0.870 to 2.545). After major restrictions were lifted, assault rates decreased but remained elevated compared to pre-COVID levels. Unintentional non-MVC injury hospitalizations decreased after the USA declared a public health emergency, especially among women ≥ 65 years old (weekly trend change = -4.010, 95% CI = -6.166 to -1.855), but returned to pre-pandemic levels within several months. CONCLUSIONS: Statewide Stay-at-Home orders placed Black/African American residents at higher risk of assault hospitalizations, exacerbating pre-existing disparities. Males 18-44 years old were also at higher risk of assault hospitalization. Fear of COVID-19 may have led to decreases in unintentional non-MVC hospitalization rates, particularly among older females. Policy makers must anticipate policy-related harms that may disproportionately affect already disadvantaged communities and develop mitigation approaches.

Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). OBJECTIVE: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. METHODS: We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. RESULTS: Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8-2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4-64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6-3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3-33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. CONCLUSIONS: Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.

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.

Rise and Fall: Hydroxychloroquine and COVID-19 Global Trends: Interest, Political Influence, and Potential Implications.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to rapid research and reporting on potential preventatives and treatments for the disease, including the drug hydroxychloroquine (HCQ). Despite a lack of robust evidence to support the use of HCQ for treatment of COVID-19, it was publicly endorsed and received widespread media coverage and public interest. The purpose of this report is to describe and contextualize the surges in public interest, demand, and adoption of HCQ for treatment of COVID-19 and outline implications for future public health policy and practice. METHODS: Using national and global events and Google Trends data as a measure of public interest, we describe the timeline and trends in the emergence of, interest in, and adoption of HCQ as a treatment of COVID-19. We additionally review reports on public demand for HCQ for treatment of COVID-19 and impacts on medication access among patients with indicated uses. RESULTS: Public interest and demand for HCQ surged in the United States and globally following endorsements from public officials and enaction of policies to facilitate off-label use of HCQ for treatment of COVID-19. Surges in demand for HCQ led to multiple documented shortages and barriers to accessing HCQ treatment for patients with indicated uses for HCQ. Although there have been reversals in policies to support HCQ use for treatment of COVID-19 in some regions, others have continued or expanded recommended uses. CONCLUSION: Insights from the global response to HCQ and COVID-19 can be used to inform prudent decision-making in the future to prevent premature action and promote informed and equitable responses to promote public health.