Tα1 tied to significantly lower mortality in severe COVID-19 patients
A study in Clinical Infectious Diseases has shown that thymosin alpha 1 (Tα1) supplement was associated with significantly reduced mortality in patients with severe coronavirus disease 2019 (COVID-19). Specifically, researchers said Tα1 was able to improve and restore T-cell counts in COVID-19 patients with severe lymphocytopenia, as well as reverse T-cell exhaustion and induce immune reconstitution by promoting thymus output during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Investigators retrospectively analysed the medical records of 76 patients with COVID-19, aged from 21 to 92 years, who were admitted into two hospitals in Wuhan, China, from December 2019 to March 2020. Only severe or critical COVID-19 patients with at least 10 days' hospitalization were included in the study. All subjects received antiviral and antibacterial treatment during hospitalisation, while glucocorticoid and oxygen inhalation were also very common.
Based on whether they received once-daily subcutaneous injections of Tα1 for at least 7 consecutive days, enrolled patients were categorized as "treatment group" (n=36) or "non-treatment group" (n=40), with the primary endpoint being recovery or death. In addition, thymus output in peripheral blood mononuclear cells (PBMCs) from patients was measured by T-cell receptor excision circles (TREC), while levels of T-cell exhaustion markers PD-1 and Tim-3 on CD8+ T cells were detected by flow cytometry.
Results showed that the death rate among patients in the treated group was significantly lower than in the untreated group (11.11% vs. 30%, p=0.044), "suggesting Tα1 supplement can reduce mortality," wrote Yueping Liu, General Hospital of the Central Theater Command, Wuhan, Hubei province, China, and colleagues. Two patients in the treatment group underwent non-invasive mechanical ventilation, versus 11 in the non-treatment group. In addition, 9 of the 11 cases in the control arm underwent subsequent invasive mechanical ventilation owing to hypoxia, whereas none in the treatment arm were intubated.
In order to determine whether Tα1 can restore T-cell numbers in COVID-19 patients with severe lymphocytopenia, researchers next focused on 34 cases that had a recording of T-cell numbers on admission and who underwent 7 continuous days of Tα1 treatment. Results showed that Tα1 supplement effectively restored T-cell numbers in cases with CD8+ or CD4+ counts lower than 400/μL or 650/μL, respectively. However, patients whose T-cell numbers were higher than these levels gained no benefits from Tα1 treatment. The authors also noted that Tα1 "dramatically" increased the counts of CD8+ and CD4+ T cells in patients over 60 years old, and cases with hypertension or cardiovascular disease comorbidities.
Finally, researchers conducted PD-1/Tim-3 analysis using peripheral blood samples from 22 enrolled patients, including 12 from the Tα1-treatment group and 10 from the non-treatment group. Findings here showed that Tα1 effectively down-regulated both PD-1 and Tim-3 on CD8+ T cells in cases with Tα1 treatment, compared to the non-treatment group. Tα1-treated patients also manifested significantly higher TREC levels than untreated controls, "suggesting Tα1 has the capacity to enhance thymus output," the authors said.
They noted that limitations of the study include the issue of normalization of TREC levels among individuals, there being no specific guidelines as to how to normalize circulating TREC copies, as well as the fact that they only investigated PD-1 and Tim-3 on CD8+ T cells. "Though our results should be interpreted with caution, it does give a clue to the treatment of COVID-19 patients and future similar studies," the authors said. They also pointed out that "to enhance immunity,…medical support team members from all over [China] got Tα1 injection before being deployed to Hubei Province, and no infectious cases were reported till now, suggesting Tα1 might have the potential to prevent SARS-CoV-2 infection."