Thymosin Alpha-1 and COVID-19 outcomes
When an extra treatment appears in a hospital record, illness severity and timing can influence both the decision to give it and the result.
Early mortality reports
The early retrospective study of 76 people with severe COVID-19 associated Thymosin Alpha-1 with mortality of 11.11%, compared with 30.00% without it. The study also reported higher T-cell numbers in people with severe lymphocytopenia—low numbers of these immune cells—and reduced exhaustion markers on some T cells.
A multicentre retrospective study in critical illness likewise associated TA1 with lower 28-day mortality, particularly with earlier treatment. It’s easy to see why these results generated excitement. Those are clinically meaningful questions, with cell findings that supply a plausible explanation.
The treatment decisions had already been made, however. Retrospective comparisons inherit differences between the people who received additional care and those who did not. They can identify an association without establishing that the peptide caused it.
Recovery in larger cohorts
The study of 275 COVID-19 patients found no benefit in restoring CD4+ or CD8+ T-cell counts during recovery. Upper-respiratory viral clearance took longer among treated patients. That complicates the cell-recovery story suggested by the early report.
In a multicentre cohort of 2,282 patients, TA1 use was associated with a higher non-recovery rate after adjustment for confounders. The association was most pronounced with greater disease severity and later treatment. These were also observational records, so they leave uncertainty about cause.
I can’t dismiss the unfavourable associations while accepting the favourable ones at face value. The same attribution problem runs through both. Together they make a general COVID-19 benefit difficult to defend.
The pooled result
A 2022 systematic review and meta-analysis combined 9 studies covering 5,352 patients, of whom 1,152 received TA1. It found no statistically significant overall mortality reduction. Subgroup analyses suggested possible benefit in people over 60 and in severe or critical disease, requiring confirmation.
Pooling increases the amount of information, while retaining the limitations of the contributing studies. My confidence would increase with a trial that specified the population and treatment timing in advance and assigned the additional treatment at random. Selecting a hopeful subgroup after seeing the results leaves more room for chance.
Blood cells outside the body
The study of blood cells from COVID-19 patients tested TA1 ex vivo: the cells were studied outside the body. It reported reduced inflammatory cytokine release. That offers a biological lead for an immune-modulating treatment.
It supplies no direct measurement of whether a patient survived or recovered faster. For me, that cellular lead warrants a better clinical experiment. The present collection of clinical studies still gives a mixed answer, with no established broad mortality benefit.