Reply: Correspondence on Fluvoxamine Treatment of Patients with Symptomatic COVID-19.

Dear Editor:

We are grateful for the thoughtful comments [1] and appreciate the opportunity to respond to them. We provided our response below.

The correspondence article in this journal presents a recent meta-analysis of randomized clinical trials on fluvoxamine for the early treatment of coronavirus disease 2019 (COVID-19) [2], which included three randomized trials: STOP COVID 1 [3] and 2, and TOGETHER trial [4]. This meta-analysis results showed that patients receiving fluvoxamine compared with placebo had a 31.0% risk reduction in clinical deterioration or hospitalization (risk ratio [RR]: 0.69; 95% confidence interval [CI]: 0.54 – 0.88). In this meta-analysis, the TOGETHER trial (weight, 87.4%) with 1,497 patients was heavily weighted. The main difference between the TOGETHER trial and our study is the inclusion criteria of enrolled patients. In the TOGETHER trial, enrolled patients had at least one criterion for high risk; diabetes, systemic arterial hypertension requiring at least one medication, known cardiovascular diseases, symptomatic lung diseases, smoking, obesity, having had a transplant, chronic kidney disease, immunosuppressive therapy, history of cancer or aged 50 years or older. However, we enrolled adult patients admitted to a community treatment center, who usually had no or minimum comorbidities [5]. We excluded patients with severe underlying lung diseases, chronic liver diseases, congestive heart failure, chronic kidney disease, or those who were immunocompromised. As a result, 59.6% of patients had no preexisting medical conditions in our study. Therefore, we suggest that the discrepancy between our study and the others may have been associated with underlying diseases of the patients.

One of three trials included in the meta-analysis was STOP COVID 2, which was a follow-up study of STOP COVID 1 and included 547 patients [2]. Although this trial was stopped due to operational futility with increasing vaccination rates and an overall decrease in the events, they could not demonstrate statistically significant difference in clinical deterioration between patients with fluvoxamine and placebo (RR: 0.88; 95% CI: 0.42 – 1.81). Therefore, we believe routine fluvoxamine treatment for every patient may not be helpful and selecting high-risk patients is needed in further larger-scale studies in the future.