Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

BACKGROUND: Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo. OBJECTIVE: Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19. METHOD: We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded. RESULTS: A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively. CONCLUSIONS AND RELEVANCE: This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.

Acute Kidney Injury Associated with Severe SARS-CoV-2 Infection: Risk Factors for Morbidity and Mortality and a Potential Benefit of Combined Therapy with Tocilizumab and Corticosteroids.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients with severe COVID-19. METHODS: We retrospectively reviewed 249 patients admitted to an intensive care unit (ICU) during the first wave of the pandemic to determine risk factors for AKI. Demographics, comorbidities, and clinical and outcome variables were obtained from electronic medical records. RESULTS: Univariate analysis revealed older age, higher admission serum creatinine, elevated Sequential Organ Failure Assessment (SOFA) score, elevated admission D-Dimer, elevated CRP on day 2, mechanical ventilation, vasopressor requirement, and azithromycin usage as significant risk factors for AKI. Multivariate analysis demonstrated that higher admission creatinine (p = 0.0001, OR = 2.41, 95% CI = 1.56-3.70), vasopressor requirement (p = 0.0001, OR = 3.20, 95% CI = 1.69-5.98), elevated admission D-Dimer (p = 0.008, OR = 1.0001, 95% CI = 1.000-1.001), and elevated C-reactive protein (CRP) on day 2 (p = 0.033, OR = 1.0001, 95% CI = 1.004-1.009) were independent risk factors. Conversely, the combined use of Tocilizumab and corticosteroids was independently associated with reduced AKI risk (p = 0.0009, OR = 0.437, 95% CI = 0.23-0.81). CONCLUSION: This study confirms the high rate of AKI and associated mortality among COVID-19 patients admitted to ICUs and suggests a role for inflammation and/or coagulopathy in AKI development. One should consider the possibility that early administration of anti-inflammatory agents, as is now routinely conducted in the management of COVID-19-associated acute respiratory distress syndrome, may improve clinical outcomes in patients with AKI.

COVID-19 induced bradyarrhythmia and relative bradycardia: An overview.

Novel coronavirus 2019 (COVID-19) has been the focus of the medical community since its emergence in December 2019 and has already infected more than 100 million patients globally. Primarily described to cause a respiratory illness, COVID-19 has been found to affect almost every organ system. Bradycardia is a newly recognized ramification of COVID-19 that still has unknown prognostic value. Studies have shown an increase in the incidence of arrhythmias, cardiomyopathies, myocarditis, acute coronary syndromes, and coagulopathies in infected patients as well as an increased risk of mortality in patients with preexisting cardiovascular disease. While the pathogenesis of bradycardia in COVID-19 may be multifactorial, clinicians should be aware of the mechanism by which COVID-19 affects the cardiovascular system and the medication side effects which are used in the treatment algorithm of this deadly virus. There has yet to be a comprehensive review analyzing bradyarrhythmia and relative bradycardia in COVID-19 infected patients. We aim to provide a literature review including the epidemiology, pathogenesis, and management of COVID-19 induced bradyarrhythmia.