Background
COVID-19 severity is partly driven by lymphocytopenia (low lymphocyte counts) and T-cell exhaustion — characteristics associated with impaired viral clearance and cytokine storm. Thymosin Alpha-1 has known immunomodulatory properties including T-cell restoration and exhaustion reversal, making it a rationale candidate for severe COVID-19 adjunct therapy.
This open-label randomized trial was conducted at Tongji Hospital in Wuhan during the initial COVID-19 outbreak.
Methods
Open-label, randomized controlled trial. Severe COVID-19 patients (defined by WHO criteria: SpO₂ ≤93% on room air, respiratory rate ≥30, or PaO₂/FiO₂ ≤300) with lymphocytopenia (lymphocytes <1.0 × 10⁹/L).
- Treatment group (n=36): Tα1 1.6 mg SC twice daily × 5 days + standard of care
- Control group (n=40): standard of care only
Primary outcome: 28-day mortality.
Key Findings
| Outcome | Tα1 Group | Control | p-value |
|---|---|---|---|
| 28-day mortality | 11.1% (4/36) | 30.0% (12/40) | 0.037 |
| ICU duration | 8.7 days | 14.1 days | 0.03 |
| Lymphocyte count recovery | Day 7: significant | Day 14 | — |
| T-cell exhaustion markers | Reduced (PD-1, TIM-3) | No change | — |
| Adverse events | None significant | — | — |
Clinical Significance
This small but positive RCT demonstrated significant mortality reduction in severe COVID-19 with a well-tolerated peptide with an established safety record. The immunological mechanism (lymphocyte restoration, exhaustion reversal) was directly confirmed by flow cytometry data.
Tα1 is already approved in China for hepatitis and other conditions, facilitating its rapid deployment during the outbreak. The trial supported expanded use of Tα1 in COVID-19 protocols across multiple hospitals in China.
Limitations
- Open-label design (no blinding) — significant risk of bias
- Small sample (N=76)
- Single center (Tongji Hospital, Wuhan)
- Conducted during chaotic outbreak conditions; standard-of-care protocols evolving
- Not replicated in larger, blinded trials
- Short follow-up (28 days)