Early Fluvoxamine Reduces the Risk for Clinical Deterioration in Symptomatic Outpatients with COVID-19: A Real-World, Retrospective, before–after Analysis

Abstract

Fluvoxamine, a selective serotonin reuptake inhibitor with anti-inflammatory properties, has gained attention as a repurposed drug to treat COVID-19. We aimed to explore the potential benefit of fluvoxamine on outpatients with early SARS-CoV-2 infection. We performed a retrospective study of fluvoxamine adult outpatients with symptomatic COVID-19 disease of early onset (<5 days), in the context of an infectious diseases private practice, between September–December 2021, in Greece. Patients with disease duration ≥5 days, dyspnea and/or hypoxemia with oxygen saturation <94% in room air and pregnancy were excluded from the analysis. In total, 103 patients, 54 males/49 females with a median age of 47 years (39–56), were included in this study. Patient characteristics were balanced before and after the introduction of fluvoxamine. Two patients in the fluvoxamine arm (3.8%; 95% CI 0.4–13) had clinical deterioration compared to 8 patients in the standard of care group (16%; 95% CI 7.2–29.1, p < 0.04). After controlling for age, sex, body mass index > 30 and vaccination status, fluvoxamine was independently associated with a lower risk of clinical deterioration (adj. OR 0.12; 95% CI 0.02–0.70, p < 0.02). Adding on fluvoxamine to treatment for early symptomatic COVID-19 patients may protect them from clinical deterioration and hospitalization, and it is an appealing low-cost, low-toxicity option in the community setting and warrants further investigation.

A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications

“…All the studies identified for this meta-study scored one or higher and were therefore deemed eligible for meta-analysis. Four of the studies scored below five 28 , 29 , 32 , 35 .…”

“…A Ugandan study of fluvoxamine showed that it was significantly associated with reduced mortality but did not decrease time spent in hospital 31 . A small open-label study in Greece investigated fluvoxamine as part of a real-world, retrospective, before–after analysis, and the results also indicated that it reduced the risk of clinical deterioration in COVID-patients (3.8% of fluvoxamine-treated patients and 16% standard care patients experienced clinical deterioration (OR 0.12; 95% CI 0.02–0.70, p < 0.02) 32 .…”

Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19

“… [46] , [47] , [48] Similarly, several, [49] , [45] though not all [50] , [51] , [52] prospective, randomized, controlled investigations into the potential therapeutic effects of fluvoxamine in outpatients with acute COVID-19, have suggested evidence of benefit. A number of other investigators have been interested in the evaluating whether SSRIs prevent COVID-19, exert a treatment effect in acute infection or lower early mortality after acute COVID-19 [53] , [54] , [55] , [56] , [57] , and a recent uncontrolled study including 95 patients with PASC treated with SSRI therapy has been published [58] , but to our knowledge, ours is the first study to suggest a diminished risk of the development of Long COVID in patients receiving SSRIs at baseline (i.e., prior to SARS-CoV-2 infection). Although an immunological basis for this observation has been postulated, we acknowledge the possibility that the findings in the current study may reflect non-immunological effects of SSRIs.…”

Antidepressants for prevention of severe COVID-19, Long COVID and outlook for other viral diseases

“…This assumption is supported by the results of a large retrospective study exploring the effects of AD on COVID-19 severity and mortality ( N = 25 034) ( 4 ). Also bearing in mind the assumed mechanisms of action, which make the major effect in particular at the beginning of the infection plausible, the current evidence suggests that the earlier the AD were administered to patients exposed to SARS-CoV-2 or showing first mild-to-moderate COVID-19 symptoms, the more favorable was the outcome regarding SARS-CoV-2 infection rates, COVID-19 severity and related mortality ( 7 , 17 ). On the other hand, AD seemed to have no relevant impact when they were added to the standard treatment of a full-blown COVID-19 pneumonia ( Table 1 ) ( 8 , 11 ).…”