In a large retrospective study of critically ill COVID‑19 patients, giving thymosin‑alpha‑1 did not lower the chance of dying within 28 days. After matching patients to balance other factors, mortality was almost the same whether they got the peptide or not. A tiny hint of benefit showed up only in men, but the effect was weak and not seen in any other groups.

Thymosin α1 therapy was commonly used in patients with coronavirus disease 2019 (COVID-19), while its impact on outcomes and which patients could benefit from thymosin α1 therapy were uncertain. Patients with COVID-19 from 19 designated hospitals between January 1 to February 29, 2020 were included, and the main exposure of interest was administration of thymosin α1. The primary outcome was 28-day mortality. Propensity score matching (PSM) was used to account for baseline confounders, cluster analysis and Cox proportional hazard model was used to account for subgroup analysis. A total of 771 patients were included, and 327/771 (42.4%) patients received thymosin α1 therapy. The 28-day mortality in thymosin group was significantly lower than that in control group (41.3% vs. 60.6%, p < 0.001). After PSM 522 patients were included in analysis and the 28-day mortality in thymosin α1 group and control group were 51.0% and 52.9% respectively, with no significant difference. In subgroup analyses, the association between thymosin α1 therapy and 28-day mortality appeared to be stronger among male patients (HR 0.673, 95% CI 0.454-0.998; p = 0.049). There were no benefits of thymosin α1 in 28-day mortality in other subgroups. There were two phenotypes after cluster analysis, but no benefits of thymosin α1 were shown in phenotype 1 (HR 0.823 95% CI 0.581-1.166; p = 0.273) and phenotype 2 (HR 1.148 95% CI 0.710-1.895; p = 0.442). There was no association between use of thymosin α1 and decreased mortality in critically ill COVID-19 patients. Subgroups analysis and phenotype analysis also showed no differences on mortality after thymosin α1 therapy.