Thymalfasin increases the number of lymphocytes and attenuates inflammatory reaction significantly.
Severe or critical COVID-19 pneumonia is the key factor threatening the life of COVID-19 patients, and even those survivors may have adverse health consequences such as pulmonary fibrosis, hypoxia, thrombosis and fatigue, seriously affecting their quality of life. It is therefore necessary to conduct explorative research on the prevention of severe pneumonia. Anti-viral drugs and anti-inflammatory glucocorticoids are routine selections of the clinicians. Although these drugs have definite therapeutic effects in most cases, some cases of common COVID-19 infection would still progress to severe pneumonia. In addition, these therapeutic measures are passive to the human body. More importantly, elderly patients may have thymic tissue degeneration, reduced output of lymphocytes and immune aging due to other metabolic reasons [6]. In addition, lymphocyte exhaustion or even inflammatory storm may occur in elderly patients. For these reasons, researchers have tried to prevent common COVID-19 infection from progressing to severe pneumonia and change the prognosis by enhancing the anti-viral immune function of lymphocytes, activating the anti-viral function of immune cells and regulating the immune response of the human body [7]. Thymosin is a polypeptide hormone that regulates the production of T cells which can promote differentiation of T lymphocytes and enhance their anti-viral activity. It has been repeated applied to treat patients with COVID-19 in recent years. Thymalfasin is a drug with good tolerance. However, the actual therapeutic efficacy of Thymalfasin remains unclear. To fight against viral infection and reduce inflammatory damage, we have tried using Thymalfasin as an adjuvant therapy to treat patients with non-severe COVID-19 infection in our hospital from 2022 to 2023. An overview of the medical records of the therapeutic efficacy of Thymalfasin in 105 subjects in the present study revealed no occurrence of significant Thymalfasin-associated adverse effects. In addition, Thymalfasin was found to have positive therapeutic effects in improving the thymic function as represented by the increased number of lymphocytes and the decreased level of CRP and inflammatory reaction.
Liu et al [8] reported that thymosin could reverse T cell exhaustion and restore immune reconstruction by promoting thymic output during the severe COVID-19 infection period, especially in COVID-19 patients with the circulating CD8 + T cells or CD4 + T cell count < 400/µL or 650/µL, who could obtain more benefits from thymosin treatment. Our findings are consistent with their results. Some experimental studies [9] revealed that COVID-19 infection induced temporary but severe thymic atrophy and selective exhaustion of CD4+/CD8 + thymocytes, and increased the level of apoptosis in adult BALB/c mice. Therefore, the use of Thymalfasin plays an important role in promoting restoration of the T lymphocyte output function in the thymic tissue. Other studies found that the number of T effector cells was reduced markedly in COVID-19 patients with severe comorbidities [10], suggesting that the decreased number of T cells may be the main reason for the reduced number of lymphocytes and also the reason for the increased severity of COVID-19. The important role of T cells in eradicating viruses highlights the therapeutic significance of thymosin drugs. Yu et al [11] also reported that thymosin could promote the proliferation of T effector cells in vitro and attenuate lymphocytopenia in COVID-19 patients. Matteucci et al [12] reported that the expression of genes related to the transduction and expression of cytokine signals was upregulated in COVID-19 patients, and treatment with thymosin drugs reduced the expression of cytokines and inhibited the activation of lymphocytes in vitro. All these findings provide a foundation for the rational use of thymosin drugs in COVID-19, though further clinical studies are required to support the conclusion. Several recent cohort studies [11, 12, 13] demonstrated that thymosin could reduce the mortality rate of patients with severe COVID-19 infection by reversing lymphocytopenia and restoring the function of the exhausted T cells. Despite the positive effects of thymosin drugs in the treatment of COVID-19, the sample size of currently available studies is relatively small and therefore clinical studies with larger samples are required to provide more support.
Thymalfasin is an independent factor for preventing common COVID-19 from progressing to severe pneumonia through multiple protective mechanisms.
It was found in our study that the inflammatory level decreased more quickly, and the length of hospital stay was shorter in COVID-19 patients who used Thymalfasin as compared with those in the control group. Multivariate Cox model analysis showed that the use of Thymalfasin promoted negative conversion of the COVID-19 antigen, and that the lime of negative conversion in elderly patients was longer than that in younger patients. The use of Thymalfasin was an independent factor of preventing progression of common COVID-19 to severe pneumonia. All these findings suggest that Thymalfasin can not only promote the T cell output function of the thymic tissue but also enhance anti-viral immunity, alleviate inflammatory damage to the human body and promote rehabilitation. Inflammation-related immune impairment is the pathological foundation of viral infections, and anti-virus, anti-inflammation and organ protection are the important foundation in the treatment of viral infections. Previous studies found that thymosin drugs could inhibit the inflammatory/activated state of monocytes in the treatment of COVID-19 by reducing the release of proinflammatory mediators such as TNF-α, IL-6 and IL-8, and promote the generation of anti-inflammatory cytokines such as IL-10 [14]. Some experimental studies [14, 15] demonstrated that thymosin drugs could regulate actin polymerization, and play their role by acting as anti-inflammatory molecules, antioxidants, and wound-healing and angiogenesis accelerators. In COVID-19 BALB/c mouse models established by using the CoV-MHV-A59 virus, researchers found that thymosin drugs could balance the host immune response, and attenuate virus-induced inflammatory pathologic injury by inhibiting virus replication, and reducing the level of CRP and inflammatory mediators, thus promoting organ repair and increasing the survival rate of the mice infected with the MHV-A59 virus. These findings will provide a basic mechanism for further use of thymosin drugs in the treatment of COVID-19 and other coronal virus-associated diseases [15]. There are different reports about the protective value in COVID-19 patients, which we believe may be due to the different timing of using thymosin drugs. Thymosin drugs may have the ability of regulating immune responses to SARS-CoV-2 infection during the viremia phase by affecting the activities of T cells, NK cells and dendritic cells, regulating the generation of cytokines, and avoiding progression to cytokine storm, thus preventing evolution to severe COVID-19. By the time of progression of common COVID-19 infection to severe or critical pneumonia, inflammatory storm has occurred. The therapeutic effect of thymosin drugs used at this moment is minimal [16, 17, 18]. Thymosin drugs may have the ability of COVID-19 induced immune damage during the reactive phase of COVID-19 infection to prevent it from progressing to a cytokine storm [19]. In the SARS-CoV-2 pandemic setting, thymosin drugs can be used to prevent the occurrence of severe COVID-19 pneumonia in patients with relatively low autoimmune function such as elderly people, patients complicated with severe underlying diseases and advanced cancer patients [20–24].