Infection

Do SSRIs reduce long COVID risk in patients with depression?

October 22, 2025

SSRIs may lower risk of long COVID in high-risk populations with depression, supporting further investigation into their potential protective mechanisms and informing antidepressant selection in post-COVID care.

Study details: This retrospective cohort study analyzed U.S. electronic health records from the TriNetX platform, comparing adults with depression prescribed SSRIs vs. non-SSRI antidepressants after SARS-CoV-2 infection (March 2020–December 2022). Primary outcome was long COVID diagnosis, with CDC-defined symptom-based outcomes as sensitivity analyses.

Results: Among 31,264 matched patients, SSRI use was associated with a significantly lower risk of long COVID. At 3 to 6 months, incidence was 0.63% in SSRI users vs. 1.13% in non-SSRI users (hazard ratio [HR], 95% confidence interval [CI], 0.57; 95% CI, 0.44–0.73). At 3–12 months, rates were 1.07% vs. 1.82% (HR 0.59; 95% CI, 0.49–0.72). Sensitivity analyses in 17,100 patients confirmed reduced risk of long COVID symptoms across symptom categories and pandemic periods.

Source:

Gao Z, et al. (2025, September 25). Infection. Associations of selective serotonin reuptake inhibitors and long COVID risk in patients with depression: a retrospective cohort study. https://pubmed.ncbi.nlm.nih.gov/40996671/