Thymosin-α-1 plasma levels measured after acute SARS-CoV-2 infection are associated with the severity of infection

Abstract

Thymalfasin, the synthetic form of Thymosin-α-1 (Tα1), which is a thymic peptide hormone with immunomodulatory properties, has been used in the treatment of severe cases of COVID-19, with inconclusive results. Plasma concentrations of Tα1 in COVID-19 patients have never been measured, nor have they been linked to the severity of COVID-19. The cohort included unvaccinated SARS-CoV-2-infected subjects. Subjects were classified into asymptomatic or mildly-symptomatic (AM group, n  = 20) and moderate to severe symptomatology (MS group, n  = 49). Blood samples were collected one to two months after diagnosis, with comparable timing across study groups. Biochemical parameters, inflammatory soluble biomarkers, immune subsets, thymic output, PBMC relative leukocyte-telomere-length (rLTL) and plasma Tα1 levels were determined. Specific IgG-antibodies were quantified and microneutralization assays against wild-type and omicron BA.1 variants were also performed. The AM group tended to be younger and to include a higher proportion of females and higher CD4 T-cell levels, although these differences did not reach statistical significance. Lower specific antibody titers ( p  < 0.001), as well as neutralizing antibodies ( p  = 0.002 for the wild-type variant), were observed in the AM group, despite having higher total (IgA + IgG + IgM) immunoglobulin levels ( p  = 0.001). Plasma cytokine levels differed between groups, with a distinct profile observed in the AM group compared to the MS group. Higher Tα1 plasma levels were found in the AM group ( p  = 0.003), being strongly correlated with IgG levels (rho = 0.434; p  < 0.001). Thymic output and PBMC rLTL did not differ between study groups. Our data suggest a potential immunomodulatory role of Tα1 in the context of SARS-CoV-2 infection and COVID-19 and support further investigation into its potential role in this context.