Adverse drug events in hospitalized COVID-19 patients: a pharmacovigilance perspective on ICU management and fentanyl exposure.

BACKGROUND: Pharmacovigilance is the science and practice aimed at detecting, assessing, understanding, and preventing adverse drug events (ADEs). During the COVID-19 pandemic, a wide range of medications - suchasantivirals, corticosteroids, anticoagulants, immunomodulators, and sedatives - were used during respiratorysupport. Reports of hepatotoxicity, cardiotoxicity, renal impairment, and neurological effects underscored the need for systematic safety monitoring. Since 2012, our research group has been monitoring the clinical use of various prescriptions at the National Institute of Infectious Diseases in Brazil. In this study, we aimed to evaluate factors associated with adverse drug events in hospitalized COVID-19 patients,with emphasis on ICU management practices, polypharmacy and fentanyl exposure. METHODS: This observational study was conducted between March and September 2021 and included patients with a positive molecular test for SARS-CoV-2. Sociodemographic characteristics, including age, sex, educational level, and family income, as well as medical history such as hypertension, diabetes, obesity, dyslipidemia, fever, cough, dyspnea, and anosmia, were collected. Clinical data on hospitalizations, commonly prescribed medications, length of stay in intensive care units, vaccination status, oxygen supplementation, type of respiratory support, deaths, and oxygen saturation were also recorded. All adverse reactions were classified using a validated algorithm and standard terminology, and patients were followed until discharge or death. Data were initially collected on paper forms and subsequently entered into an electronic data capture platform. Associations between patient characteristics, treatments, and adverse reactions were analyzed using Poisson regression, with statistical significance set at p-value < 0.05. RESULTS: Among 113 patients, 110 experienced at least one adverse event, totaling 411 events. The mean age was 56.5 years; 54.9% were male, 53.1% had hypertension, 28.3% had diabetes, 22.2% had received at least one vaccine dose, and 17.7% died. Higher rates of adverse events were observed among intubated patients and those who received fentanyl, which is commonly used during the intubation process. CONCLUSIONS: In this study, intubation and fentanyl use were associated with higher rates of ADEs. These findings should be interpreted cautiously given the severity of illness, ICU sedation practices, and the possibility of confounding by indication. Therefore, active pharmacovigilance strategies may contribute to improved medication safety in critically ill populations.