ABSTRACT
Background. Thymosin-alpha-1 (T alpha 1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. Methods. Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of T alpha 1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. Results. A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25] ) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4(+) T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to T alpha 1. Conclusions. T alpha 1 increases CD4(+) T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19.
ABSTRACT
PURPOSE: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are considered particularly susceptible to infection with SARS-CoV2 on the basis of the immunodeficiency associated with advanced age, comorbidity burden, medication use, and need for frequent visits to dialysis clinics. In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used as an adjunct to influenza vaccine. Early in the COVID-19 pandemic we speculated that administration of Ta1 to HD patients would result in reduced rate and severity of COVID-19 infection. We also hypothesized that HD patients treated with Ta1 who did become infected with COVID-19 would have a milder course of infection in terms of hospitalization rates, requirement for and length of ICU stays, requirement for mechanical ventilation, and survival. Further, we proposed that patients who avoided COVID-19 infection during the study would have decreased non-COVID-19 infections and hospitalizations compared to controls. PROCEDURES: The study launched in January 2021 and, as of July 1, 2022, 254 ESRD/ HD patients from five dialysis centers in Kansas City, MO have been screened. Of these, 194 patients have been randomized 1:1 to either Group A (1.6 mg Ta1 given subcutaneously twice weekly for 8 weeks), or Group B (control group not receiving Ta1). After the 8-week treatment period, subjects were followed for an additional 4 months and monitored for safety and efficacy. A data safely monitoring board reviewed all reported adverse effects and commented on study progress. RESULTS: To date, only 3 deaths have occurred in subjects treated with Ta1 (Group A), compared to 7 in the control (Group B). There have been 12 COVID-19 related serious adverse effects (SAEs; 5 in Group A, and 7 in Group B). The majority of patients have received a COVID-19 vaccine (91 patients in group A, and 76 patients in Group B) at various times throughout the study. Nearing completion of the study, blood samples have been collected and antibody responses to COVID-19 will be analyzed along with safety and efficacy endpoints when all subjects have completed the study.
Subject(s)
COVID-19 , Influenza Vaccines , Kidney Failure, Chronic , Humans , Aged , COVID-19/epidemiology , Thymalfasin/therapeutic use , SARS-CoV-2/genetics , COVID-19 Vaccines , Pandemics/prevention & control , RNA, Viral , Pilot Projects , Renal Dialysis , Kidney Failure, Chronic/therapy , MorbidityABSTRACT
Introduction Thymosin-α-1 (Tα1) elevates lymphocyte counts among patients with COVID-19, but its effect on reversing lymphocytopenia is unknown. Methods 24 patients treated with Tα1 and 100 patients in the control arm were included in this analysis. The incidence rate of reversing lymphocytopenia, overall and stratified by baseline oxygen support, above the threshold for classification of lymphocytopenia (i.e., Total Lymphocyte Count (TLC) < 1.5 x 109/L) and severe lymphocytopenia (i.e., TLC < 1.0 x 109/L) within 3, 5, and 7 days of treatment initiation was calculated, along with incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Results Compared with the standard of care, the rate of reversing lymphocytopenia (IRR: 2.38, 95% CI: 0.92 – 5.81) and severe lymphocytopenia (IRR: 1.57, 95% CI: 0.59 – 3.72), especially among patients with severe lymphocytopenia on high flow oxygen support (IRR: 3.64, 95% CI: 0.71 – 23.44), was greater for patients treated with Tα1 within 3 days of treatment initiation, although analyses were not significant. Conclusion Among patients with hypoxemia and lymphocytopenia, Tα1 may reverse lymphocytopenia and severe lymphocytopenia, particularly within 3 days of treatment initiation, faster than the standard of care.
ABSTRACT
BACKGROUND: Thymosin-α-1 (Tα1) may be a treatment option for COVID-19, but efficacy and safety data remain limited. METHODS: Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. RESULTS: 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low flow oxygen (subdistribution hazard ratio [SHR]: 1.48; 95% CI: 0.68-3.25) or baseline high flow oxygen (SHR: 1.28; 95% CI: 0.35-4.63), although neither were significant. Among patients with baseline low flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on Day 5 than on Day 1 (p = 0.0113). Nine serious adverse events among treated patients were deemed not related to Tα1. CONCLUSION: Tα1 increases CD4+ T cell count among patients with baseline low flow oxygen support faster than standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19.
ABSTRACT
Background. Thymosin-alpha-1 (T alpha 1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited. Methods. Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of T alpha 1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19. Results. A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25] ) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4(+) T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to T alpha 1. Conclusions. T alpha 1 increases CD4(+) T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19.
ABSTRACT
Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.