Negative Prognostic Associations of Selective Serotonin Reuptake Inhibitors Use in Hospitalized COVID-19 Patients and Potential Contribution of Cardiovascular Comorbidities

Abstract

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of Coronavirus disease 2019 (COVID-19), a very contagious systemic disease dominantly affecting the respiratory tract. Recent findings oppose earlier suggestions that selective serotonin reuptake inhibitors (SSRI) might be protective during acute SARS-CoV-2 infection, prompting the current study. Patients and methods: The institutional registry of a tertiary referral center was retrospectively evaluated for SSRI use and associated clinical outcomes among hospitalized COVID-19 patients with mostly severe and critical disease. Results: Among 1558 patients, there were 78 (5%) exposed to SSRI during hospitalization. SSRI users in comparison to non-users did not significantly differ in their demographic characteristics, comorbidity profile or the severity of COVID-19 symptoms and associated inflammatory response at admission. In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher risks of death, mechanical ventilation, intensive care unit treatment, and bacteremia, whereas no significant relationship with risks of venous, arterial thrombosis, and major bleeding was present. Patients with less severe initial COVID-19 presentation, lower inflammatory burden, higher platelet count, lower cumulative comorbidity burden, presence of hyperlipidemia, atrial fibrillation, chronic heart failure and non-exposed to acetylsalicylic-acid had higher mortality associated with SSRI use. Conclusions: Findings of the current study validate findings of higher mortality but also report higher tendency for respiratory deterioration, intensive care unit treatment, and bacteremia associated with SSRI use among hospitalized COVID-19 patients. These findings also suggest the potential contribution of cardiovascular comorbidities to detrimental clinical course of SSRI exposed patients.