Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study
Bruce J Kirenga, Levicatus Mugenyi, Marina Sánchez-Rico, Henry Kyobe, Winters Muttamba, Raymond Mugume, Eliya Mwesigwa, Ezra Kalimo, Vicky Nyombi, Ivan Segawa, Loryndah Olive Namakula, Rogers Sekibira, Wilberforce Kabweru, Rosemary Byanyima, Hellen Aanyu, Pauline Byakika-Kibwika, Henry G Mwebesa, Nicolas Hoertel, William Bazeyo
Molecular Psychiatry, doi:10.1038/s41380-023-02004-3
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; χ 2 = 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.
AUTHOR CONTRIBUTIONS Concept and design: BJK; Funding acquisition: BJK and WB; Acquisition of data: RM, EM, EK, VN, LON, RS, WK and HA; Administrative, technical, or material support: WM, IS, HK, RB and HGM; Supervision: BJK and WM; Critical revision of the manuscript: BJK, LM, MSR, NH, WM, PBK and WB; Statistical analysis: BJK, LM, MSR and NH.
COMPETING INTERESTS NH is an inventor on a patent application related to methods of treating COVID-19 (FIASMA antidepressants), filled by Assistance Publique-Hopitaux de Paris in France. The other authors have no conflicts of interest related to this work to declare.
ETHICAL APPROVAL Compassionate use approval of fluvoxamine for the treatment of COVID-19 was obtained from the Ministry of Health of Uganda (clearance reference no. ADM.180/O1 dated 2nd January 2022). All patients were informed that this medication was under evaluation by health authorities. Patients willing to be treated with this medication gave verbal informed consent. All data used in this study were collected as part of routine care.
ADDITIONAL INFORMATION Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41380-023-02004-3. Correspondence and requests for materials should be addressed to Bruce J. Kirenga. Reprints and permission information is available at http://www.nature.com/ reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and..
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