A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.

This prospective, open-label, randomized pilot trial (NCT04487444) evaluated the preliminary efficacy and safety of thymalfasin (synthetic Thymosin-α-1, or Tα1) compared with standard of care in 49 hospitalized COVID-19 patients presenting with both hypoxemia and lymphocytopenia. The primary clinical outcome—rate of clinical recovery—was numerically higher in treated patients receiving either low-flow or high-flow baseline oxygen support, but neither difference reached statistical significance (subdistribution hazard ratios of 1.48 and 1.28, respectively, with wide confidence intervals crossing 1.0). A notable immunological finding was that treated patients on baseline low-flow oxygen had, on average, 3.84 times more CD4+ T cells on day 5 compared with day 1, versus controls (P = .01), suggesting faster T-cell reconstitution. Nine serious adverse events occurred in the treatment group but were adjudicated as unrelated to Tα1. Key limitations include the small sample size (n=49), open-label design (no blinding), and lack of statistical power to draw definitive efficacy conclusions. The authors suggest Tα1 may have a role in managing COVID-19-related immunosuppression, but larger trials are needed to confirm these preliminary findings.

Why this grade: While conducted in humans with randomization, the very small sample size (n=49), open-label design, and lack of statistically significant primary outcomes substantially limit the strength of evidence this pilot trial provides.