Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study

Abstract

BackgroundThymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy.MethodsWe performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome.ResultsAll crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1–2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4–2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1–14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1–3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate.ConclusionTα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.

COVID-19 and beyond: Reassessing the role of thymosin alpha1 in lung infections

“…A meta-analysis on 1498 COVID-19 patients, including the three studies mentioned before [6] , [7] , [9] and a fourth retrospective study that reported a high risk for fatal outcome in patients treated with different immunoregulatory treatments, including thymosin [10] , concluded that there was no significant correlation between Tα1 treatment and mortality, although a beneficial effect was not excluded in specific subgroups of patients [11] . Another study also reported a worsening of condition upon Tα1 treatment with specific reference to the non-recovery rate [12] . Besides mortality, a retrospective study on 25 severe and critical COVID-19 patients reported an increase in lymphocyte count after one week of Tα1 treatment [13] .…”

Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

“… 172 It has been reported that thymosin alpha 1 (Tα1) effectively reduces mortality associated with severe COVID‐19, however the effect of Tα inn restoring T Lymphocyte counts is controversial. 173 , 174 The safety of Tα1 in the treatment of COVID‑19 was also investigated in clinical trials (NCT04487444, NCT04428008). Another option is immunoglobulin, which regulates cytokine responses and immune cell functions and has been reported to show clinical benefit in severe sepsis patients.…”

“…With an emergency use of thymosin, the symptoms and lung imaging improved significantly in a COVID‐19 patient 172 . It has been reported that thymosin alpha 1 (Tα1) effectively reduces mortality associated with severe COVID‐19, however the effect of Tα inn restoring T Lymphocyte counts is controversial 173,174 . The safety of Tα1 in the treatment of COVID‑19 was also investigated in clinical trials (NCT04487444, NCT04428008).…”

Efficacy of thymosin-α-1 in patients with COVID-19: A systematic review and meta-analysis

“…Afterwards, 14 papers were excluded from our study for the following reasons: no full text available, invalid assignment, incomplete data, no accurate outcomes, previously published meta-analyses. Ultimately, 9 studies were included in our metaanalysis [18][19][20][21][22][23][24][25][26] (Figure 1).…”