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Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells
Yueping Liu, Yue Pan, Zhenhong Hu, Ming Wu, Chenhui Wang, Zeqing Feng, Congzheng Mao, Yingjun Tan, Ying Liu, Li Chen … Show moreAuthor Notes
Clinical Infectious Diseases, Volume 71, Issue 16, 15 October 2020, Pages 2150–2157, https://doi.org/10.1093/cid/ciaa630
Published: 22 May 2020 Article history
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Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and the mechanism of Tα1 treatment for COVID-19 patients are still unclear.
We retrospectively reviewed the clinical outcomes of 76 severe COVID-19 cases admitted to 2 hospitals in Wuhan, China, from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells from COVID-19 patients was measured by T-cell receptor excision circles (TRECs). The levels of T-cell exhaustion markers programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) on CD8+ T cells were detected by flow cytometry.
Compared with the untreated group, Tα1 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). Tα1 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, Tα1 also successfully restored CD8+ and CD4+ T-cell numbers in elderly patients. Meanwhile, Tα1 reduced PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients compared with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells were roughly parallel to the rise of TRECs.
Tα1 treatment significantly reduced mortality of severe COVID-19 patients. COVID-19 patients with counts of CD8+ T cells or CD4+ T cells in circulation less than 400/μL or 650/μL, respectively, gained more benefits from Tα1. Tα1 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome–coronavirus 2 infection.
What Are The Benefits of Thymosin Alpha 1?
Immune enhancing peptide
Helps prevent infections such as the common cold or the flu and diseases
Reduces inflammation in the body
Suppresses tumor growth
Aids in the removal of acute or chronic infections
Has antibacterial, antiviral, and antifungal properties.
Supports the eradication of unhealthy cells (including cancer growth).
Protects your cells against oxidative stress and damage.
Inhibits viral replication
Improve symptoms associated with chronic fatigue
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Thymalfasin (thymosin alpha 1 or Ta1), the active pharmaceutical ingredient in ZADAXIN® injection, is a 28-amino acid synthetic peptide, identical to natural Ta1 produced by the thymus gland. Ta1 is a biological response modifier which activates various cells of the immune system, and is therefore expected to have clinical benefits in disorders where immune responses are impaired or ineffective, including acute and chronic viral and bacterial infections, cancers, and vaccine non-responsiveness. Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic kidney disease and frequent burden of comorbidities, also have increased risk of exposure to communicable diseases as they are treated several times each week at hemodialysis centers with several other patients and clinic staff in attendance. The majority of patients are over 60 years of age and many are receiving immunosuppressive medications. Accordingly, ESRD patients are particularly susceptible to COVID-19 infection. Ta1 has been shown to be safely administered to hemodialysis patients. It is our hypothesis that a course of Ta1 administered to individuals with ESRD will reduce the rate and severity of infection with COVID-19.
Condition or disease Intervention/treatment Phase
Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic kidney disease and frequent burden of comorbidities, also have increased risk of exposure to communicable diseases as they are treated several times each week at hemodialysis centers with several other patients and clinic staff in attendance. The majority of patients are over 60 years of age and many are receiving immunosuppressive medications. Accordingly, ESRD patients are particularly susceptible to COVID-19 infection.
Thymalfasin (thymosin alpha 1, Ta1) is a naturally occurring peptide that has been evaluated for its immunomodulatory activities and related therapeutic potential in several conditions and diseases, including infectious disease and cancer. ZADAXIN, a synthetic form of Ta1, been has been used clinically in pilot studies for treatment of severe acute respiratory syndrome (SARS) and other lung infections including acute respiratory distress syndromeARDS) and chronic obstructive pulmonary disorder (COPD), as well as infections after bone marrow transplant]. Larger clinical trials have shown significant efficacy for treatment of severe sepsis and hepatitis B, along with certain cancers such as melanoma, hepatocellular, and lung cancer. Ta1 has also demonstrated improvement in response to vaccines in the elderly and in patients immunocompromised by renal disease. The beneficial clinical effects of Ta1 result from activation of toll-like receptor (TLR) 9 in dendritic and other immune system cells, resulting in augmentation of T helper (Th1) function, natural killer (NK) cell activity, and increased antibody responses to T-cell dependent antigens. Importantly, Ta1 also leads to an increase in IL-10 producing regulatory T cells, which create feedback inhibition of cytokine production, hence dampening immune response and preventing a pro-inflammatory cytokine storm.
It is our hypothesis that a course of Ta1 administered to individuals at high risk for COVID-19 infection (hemodialysis patients 60 years and older) will reduce the rate of COVID-19 infection and severity of infection with COVID-19, compared to untreated individuals in the same hemodialysis units with comparable risk. The study will also evaluate the need for hospitalization in those patients who do not become infected with COVID-19.
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Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 240 participants
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be centrally randomized to receive either study treatment drug (Ta1) or no Ta1. Randomization will be stratified by site.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Elderly Renal Dialysis Patients
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 2021
Resource links provided by the National Library of Medicine
MedlinePlus related topics: Dialysis
U.S. FDA Resources
Thymosin A1 info
Thymosin Alpha-1 is a peptide, or small protein, produced naturally by the thymus gland. The thymus is where immune cells known as T cells mature and are released when prompted to do so by the T α 1 peptide. Specifically, T α 1 has been shown to enhance the function of certain immune cells, these white blood cells play pivotal roles in the body’s defense process to anyone with a depleted immune system or suffering from an infection.
Thymosin Alpha-1 is a protein that consists of 28 amino acids. Thymosin Alpha-1 is a significant component of Thymosin Fraction 5 which is responsible for the activity in repairing immune function. Thymosin Alpha-1 plays a vital role in the control of immunity, tolerance, and inflammation. It manages immune response via an initial action on the cells of the innate immune system and thus acts as an endogenous regulator of both inflammatory and adaptive immune responses.
Thymosin Alpha-1 Benefits
Serum thymosin α 1 levels in patients with chronic inflammatory autoimmune diseases
Thymosin Alpha 1 Reduces the Mortality of Severe Corona virus 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells
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Used for clinical conditions where immune support is necessary, including:
SubQ General Dosage:
complicated immune suppression or over-activation
Warnings and Cautions
in more than 3,000 individuals treated to date, including patients with hepatocellular carcinoma, non–
small-cell lung cancer, melanoma, and hepatitis B and C. ,,,
disease, renal disease requiring hemodialysis and primary immunodeficient individuals.
edema, and rash.
therapy. When ALT flare occurs, thymosin alpha 1 should generally be continued unless signs and
symptoms of liver failure are observed.
THE AMERICAN ACADEMY OF ANTI-AGING MEDICINE 3
Thymosin alpha 1 has been used to support immunity in over 3,000 patients and in over 70 clinical studies,
either as monotherapy or in conjunction with current allopathic medicines., The lack of significant side
effects with thymosin alpha 1 is in sharp contrast to other major immune response modulators such as
IFN and IL-2, which can lead to flu-like symptoms including malaise, fever, headache, chills and pulmonary
edema (with IL-2).
Thymosin alpha 1 helps the body induce effective host-derived immune effectors and balance the Th1
/ Th2 arms of immunity. These effector cells improve various immunomodulatory properties that lead
to augmentation of T lymphocyte function, including modulation of interleukin-2 (IL-2), stimulation of
interferon-g (IFN-g) production, induction of T lymphocyte and natural killer (NK) cells and stimulation of
thymopoiesis. Ta1 has also been reported to up-regulate MHC Class I expression in antigen-presenting
cells. Additionally, Ta1 down-regulates the activity of terminal deoxynucleotide transferase (TdT) in TdT1
thymocytes, suggesting a role for Ta1 in thymocyte maturation. Ta1 has also been found to antagonize both
activation induced (anti-CD3) and glucocorticoid-induced thymocyte apoptosis. It has also been reported
that Ta1 stimulates activity of Indoleamine-2,3-Dioxygenase (IDO), leading to an increase in FoxP3 IL10 producing regulatory T cells. This increase leads to feedback inhibition of cytokine production, hence
dampening immune response to prevent a pro-inflammatory cytokine storm and possibly autoimmune
Immune senescence, considered an aging process, has been related to a gradual decline in thymus
function and thymic hormone production. The lack of thymic hormones may contribute to the decline in
immune function, particularly the T cell component. In the elderly, antibody response after vaccination
is compromised when compared to response in young. A similar diminished antibody response has been
reported in patients with end-stage renal disease (ESRD) and in hemodialysis patients. In hemodialysis
patients, this has been attributed to incompetence in T cell-mediated immune responses.
Since thymosin alpha-1 can enhance T-cell-dependent specific antibody production, Ta1 can help augment
specific vaccine responses both in the elderly or in younger subjects in situations in which there are
suboptimal quantities of immunizing antigen available.
Zadaxin (thymalfasin, SciClone Pharmaceuticals, China) is a thymosin alpha-1 peptide that has
been evaluated for its immunomodulatory activities and related therapeutic potential in several
diseases, including chronic hepatitis B and C, acquired immunodeficiency syndrome (AIDS), primary
immunodeficiency diseases, depressed response to vaccination, and cancer. Zadaxin is currently in Phase III
trials for the treatment of hepatitis C and in Phase II trials for hepatitis B in the US.
DISCLAIMER: Statements made are for educational purposes and have not been evaluated by the US Food and Drug Administration
(FDA). They are not intended to diagnose, treat, cure, or prevent any disease. Most peptides are not regulated by the FDA. Always use a
licensed Compounding Pharmacy to prepare peptide products.
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kidneys and COVID prevention
A Reappraisal of Thymosin Alpha1 in Cancer Therapy
Thymosin alpha1 (Tα1), an endogenous peptide first isolated from the thymic tissue in the mid-sixties, has gained considerable attention for its immunostimulatory activity that led to its application to diverse pathological conditions, including cancer. Studies in animal models and human patients have shown promising results in different types of malignancies, especially when Tα1 was used in combination with other chemo- and immune therapies. For this reason, the advancements in our knowledge on the adjuvant role of Tα1 have moved in parallel with the development of novel cancer therapies in a way that Tα1 was integrated to changing paradigms and protocols, and tested for increased efficacy and safety.
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of thymosin alpha-1 (TA1) are reviewed.