Abstract: Molecular Psychiatry ARTICLE www.nature.com/mp OPEN Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study ✉ Bruce J. Kirenga1,2 , Levicatus Mugenyi 2,3, Marina Sánchez-Rico 4, Henry Kyobe 5, Winters Muttamba2,6, Raymond Mugume2, 2,7 Eliya Mwesigwa , Ezra Kalimo7, Vicky Nyombi7, Ivan Segawa 2, Loryndah Olive Namakula2,7, Rogers Sekibira2, Wilberforce Kabweru7, Rosemary Byanyima7, Hellen Aanyu 7, Pauline Byakika-Kibwika 1, Henry G. Mwebesa5, Nicolas Hoertel4,8,9 and William Bazeyo10 1234567890();,: © The Author(s) 2023 Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessivecompulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited. Molecular Psychiatry; https://doi.org/10.1038/s41380-023-02004-3