Thymosin-α1 in lung health and COVID-19: immune rescue, anti-inflammatory action and recovery

Description of the potential effects of Thymosin-α1 based on the literature. (This is not a product description, disclaimer at the bottom of the page)

Thymosin-α1 (Tα1) is an immune-regulating peptide that has been shown to have therapeutic effects in a variety of lung diseases and infections caused by SARS-CoV-2. In the respiratory system, it consistently promotes immunity, providing more effective control of pathogens and tumours, while reducing harmful inflammation. 

Clinical studies in exacerbations of chronic obstructive pulmonary disease (COPD), patients ventilated in the intensive care unit, post-tracheostomy care, severe pneumonia with sepsis and lung cancer treated with chemotherapy or radiotherapy indicate that Tα1 is associated with improved gas exchange and lung function, fewer or delayed infections, faster recovery in the intensive care unit, protection against treatment-induced lymphocyte decline and lower rates of radiation pneumonitis. These benefits were achieved without introducing new safety risks. Mechanistic studies of airway cells and immune cell populations support these results, demonstrating that Tα1 can upregulate ACE2/ACE activity, rebalance monocyte and dendritic cell activation, downregulate key inflammatory signals such as TNF-α, IL-6 and IL-8, and restore T-cell function by increasing CD4⁺ and CD8⁺ cells while reducing markers of exhaustion.

In COVID-19, thymosin-α1 (Tα1) has shown beneficial supportive effects at different stages of the disease. In critically ill patients, short treatment cycles are associated with lower mortality within 28 days and better oxygenation, especially in the elderly, those with low lymphocyte counts or other high-risk conditions. In milder cases, Tα1 shortens the time to virus elimination and hospital stay. Preliminary results on long-term COVID suggest that it may help restore naïve lymphocyte reserves, and preliminary data on prophylaxis in dialysis patients suggest a good safety profile and possible protection against severe outcomes.

Thymosin-α1 (Tα1) in human lung disease

Clinical studies have demonstrated the therapeutic potential of thymosin-α1 (Tα1) in the treatment of a wide range of respiratory disorders. Human studies suggest that Tα1 can enhance immune function, reduce inflammation, promote lung regeneration and improve treatment outcomes in conditions such as chronic obstructive pulmonary disease (COPD), lung cancer, pneumonia, tuberculosis, sepsis-related lung damage and lung damage associated with cancer treatment.

Restores immune balance in lung cancer

The addition of thymosin-α1 (Tα1) may help to rebalance the immune system in people with lung cancer. Shi et al (2024) conducted a case-control study comparing 50 patients with non-small cell lung cancer (NSCLC) with 50 healthy individuals. They found that the patients had significantly higher levels of immune suppressor cells known as HLA-DR-CD14-CD33⁺ myeloid-derived suppressor cells (MDSCs) compared to healthy controls (1.70 ± 0.52% vs 0.51 ± 0.15%, P < 0.05). After thymalfascin administration, the number of these tumour suppressor cells decreased significantly both in the tumour tissue (1.65 ± 0.43% to 1.15 ± 0.50%, P < 0.05) and in the bloodstream (1.70 ± 0.52% to 0.59 ± 0.18%, P < 0.05). These results indicate that Tα1 may reduce tumour-induced immunosuppression and help restore a more balanced immune environment conducive to tumour control [1].

Improves long-term results of tuberculosis treatment 

Adding thymosin-α1 (Tα1) to standard therapy for tuberculosis (TB) may improve long-term outcomes for patients who also have diabetes. Wu et al (2022) conducted a randomised trial involving 120 people with pulmonary TB and diabetes, comparing multidrug TB chemotherapy with and without Tα1. After six months, both groups showed similar rates of sputum conversion, lesion absorption and cavity closure. However, after 12 months, the group receiving Tα1 achieved significantly higher success in all three measures (all P < 0.05). Importantly, immunological studies showed that Tα1 increased the number of infection-fighting cells, such as CD3⁺ cells, CD4⁺ cells and natural killer (NK) cells, while decreasing the number of CD8⁺, Th17 and Treg cells. Cytokines also changed to a more strongly protective (Th1) profile, with lower levels of IL-4 and TNF-α and higher levels of IL-2 and IFN-γ. Side effects were comparable in both groups, indicating that Tα1 is a safe and effective long-term immune booster in patients with TB and diabetes [2].

Accelerates recovery and improves breathing in COPD

Thymosin-α1 (Tα1) may accelerate recovery and improve lung function during acute exacerbations of chronic obstructive pulmonary disease (COPD). In a meta-analysis of 39 clinical trials involving 3329 participants, Cao et al (2024) found that adding Tα1 to routine therapy was more effective than standard care alone. Respiratory tests improved significantly: FEV₁ increased by +0.29 L (95% CI 0.26-0.32) and the FEV₁/FVC ratio increased by +6.24% (95% CI 3.83-8.65). In addition, blood oxygen levels increased by +7.24 mmHg (95% CI 3.42-11.07) and carbon dioxide levels decreased by -5.85 mmHg (95% CI -9.38 to -2.33). Immunity also improved, with CD4⁺ cell counts increasing by +7.54 and the CD4⁺/CD8⁺ ratio improving (both P < 0.001). In addition, hospital stay was reduced by approximately 5.4 days (MD -5.39; 95% CI -7.82 to -2.97). In conclusion, these results show that Tα1 helps to restore breathing capacity, enhance immunity and reduce recovery time during COPD exacerbations [3].

Helps prevent future exacerbations of COPD

The use of thymosin-α1 (Tα1) along with standard care may reduce the risk of repeat exacerbations of COPD. Zheng et al (2008) studied 80 people with COPD and randomly assigned them to receive routine care or Tα1 injections (1.6 mg subcutaneously every other day for 10 doses). Tα1-treated patients experienced fewer exacerbations, shorter exacerbation periods and stronger immune responses, including improved CD4 cell counts and a healthier CD4/CD8 balance. Although changes in lung function were not the main focus of this study, the lower relapse rate suggests that Tα1 may help prevent future COPD attacks [4].

Protects immunity and improves chemotherapy outcomes

Thymosin-α1 (Tα1) may help to maintain immune defences and improve the efficacy of chemotherapy in advanced lung cancer. Salvati et al (1996) conducted a controlled phase II study involving 22 patients with advanced non-small cell lung cancer (NSCLC). They compared chemotherapy with ifosfamide alone with ifosfamide given in combination with low doses of interferon-α and Tα1. The group receiving the combination achieved a higher tumour response rate (33% versus 10%), a significantly longer time before tumour progression (P = 0.0059) and significantly less blood toxicity (no grade 3/4 events versus 50% in the group receiving chemotherapy alone). Importantly, immune cells, such as CD4⁺, CD8⁺ and NK cells, remained stable when using Tα1 in combination with interferon-α, whereas there was a sharp decline in patients receiving chemotherapy alone. These results suggest that Tα1 supports immune health and allows for more effective and better tolerated cancer treatment [5].

Protects lungs and immune cells in case of lung cancer

Thymosin-α1 (Tα1) may reduce treatment-related lung damage and protect immune cells during combined chemotherapy and radiotherapy. Liu et al (2022) conducted a phase II study, GASTO-1043, involving 69 patients with inoperable locally advanced non-small cell lung cancer (LA-NSCLC), comparing them with 69 matched controls. Patients received weekly injections of Tα1, starting on day one of concurrent chemoradiotherapy (CCRT) and continuing for two months after treatment. The CCRT regimen consisted of weekly docetaxel 25 mg/m² and nedaplatin 25 mg/m², with radiation doses of 51 Gy in 17 fractions or 40 Gy in 10 fractions, followed by a booster dose of 15-24 Gy. The addition of Tα1 reduced the risk of moderate to severe radiation pneumonitis (36.2% vs 53.6%, p = 0.040), prevented late mild pulmonary scarring (0% vs 3.7%) and reduced severe lymphopenia from 62.1% to 19.1% (p < 0.001). Importantly, the lowest lymphocyte count remained higher for Tα1 (0.51 vs 0.30 k/µL, p < 0.001) and dangerously high C-reactive protein (CRP ≥100 mg/L) levels were less common (13.8% vs 29.7%, p = 0.029). The gut microflora profiles remained stable. In conclusion, the results of this study show that Tα1 safely reduces lung inflammation and preserves immune strength during intensive chemoradiotherapy [6].

Delays pneumonia associated with mechanical ventilation and speeds recovery in the intensive care unit

Short daily treatments with thymosin-α1 (Tα1) may help critically ill patients recover faster, while reducing the risk of early complications. Zhang et al (2015) conducted a randomised trial involving 52 ventilator-connected patients, comparing standard care with and without Tα1 (1.6 mg subcutaneously once daily for seven days). Although the total number of cases of ventilator-associated pneumonia (VAP) was similar in both groups, pneumonia developed later in Tα1-treated patients (p < 0.05). In addition, these patients spent fewer days on mechanical ventilation and in the intensive care unit (both p < 0.05). At three and seven days, their immune systems showed faster recovery, with higher numbers of infection-fighting cells (CD3⁺ and CD4⁺), a healthier CD4⁺/CD8⁺ balance, stronger monocyte activity (HLA-DR) and lower procalcitonin levels (all p < 0.05). In conclusion, this means that, even without a reduction in the total number of pneumonia cases, Tα1 helped patients to recover immune function and leave the intensive care unit faster [7].

Improves breathing and relieves airway inflammation in COPD

Adding thymosin-α1 (Tα1) to standard treatment may help people with chronic obstructive pulmonary disease (COPD) to recover better during exacerbations. Jia et al (2015) conducted a randomised trial involving 84 patients hospitalised for acute exacerbations of COPD (AECOPD). Participants received subcutaneous Tα1 for four weeks or placebo along with routine therapy. Those treated with Tα1 had better blood oxygen (PaO₂) and carbon dioxide (PaCO₂) levels (both p < 0.01) and better lung function on spirometry compared to baseline and placebo. Immunological studies also showed higher CD4⁺ cell levels, improved CD4⁺/CD8⁺ balance and higher IFN-γ, while harmful immune signals such as IL-4, IL-8 and leukotriene B4 decreased (all p < 0.05-0.01). These results suggest that Tα1 may alleviate airway inflammation, enhance immune function and improve breathing during COPD exacerbations [8].

Reduces lung infections and inflammation after tracheotomy

Daily administration of thymosin-α1 (Tα1) may help control lung infection and reduce inflammation in high-risk patients in the intensive care unit after tracheotomy. Huang et al (2006) randomly assigned 42 critically ill patients who had undergone tracheotomy to a group receiving 1.6 mg Tα1 subcutaneously once daily for seven days or to a group receiving saline. Those given Tα1 had fewer lung infections and significantly lower levels of white blood cells, C-reactive protein (CRP), TNF-α and IL-6 (all p < 0.05). These results indicate that Tα1 helps to regulate immune responses and protect against serious infections in this vulnerable group [9].

Strengthens infection control and accelerates recovery in cases of severe pneumonia with septicaemia

Adding thymosin-α1 (Tα1) to early treatment may help patients with severe pneumonia and sepsis recover faster and better fight infection. Chen et al (2022) studied 81 patients who all received standard early care and intravenous Xuebijing herbal extract. They compared Xuebijing alone with Xuebijing in combination with Tα1 (subcutaneous injections; the exact schedule was not fully described). Patients who received Tα1 showed faster improvement in vital signs such as body temperature, respiratory rate, heart rate and white blood cell count (all p < 0.05). In addition, blood gasometry results improved, lower carbon dioxide levels (PaCO₂) and better acid-base balance were recorded. Markers of inflammation, including IL-6, TNF-α and CRP, fell more steeply, while bacterial elimination and overall treatment response were higher (both p < 0.05). These results suggest that the addition of Tα1 may accelerate recovery and enhance infection control in severe pneumonia with sepsis [10].

Thymosin-α1 (Tα1) in experimental models of lung disease

Preclinical studies using a wide range of animal models have shown that thymosin-α1 (Tα1) can modulate immune responses, reduce inflammation and protect lung structure and function. These studies highlight its potential to prevent or reduce tissue damage, promote repair and restore respiratory function in a variety of lung diseases. It may help the immune system to fight cancer after it has been weakened by chemotherapy. Garaci et al (1990) tested a three-step approach on mice: a single high dose of cyclophosphamide (200 mg/kg) to inhibit tumour defence mechanisms, followed by Tα1 (200 µg/kg daily for four days) and two days later interferon-α/β (3 × 10⁴ IU/mouse). This sequence led to almost complete tumour shrinkage, significantly longer survival and a strong reactivation of natural killer (NK) cells, which are key tumour-killing immune cells. Tumours became densely packed with immune cells, and when NK cells were blocked, the benefits disappeared. These results show that Tα1 can restore strong anti-tumour immunity after chemotherapy [11]. In addition, Mao (2023) summarised clinical evidence showing that Tα1 can improve survival after lung and liver cancer surgery, protect the immune system during chemoradiotherapy in advanced lung cancer and possibly enhance the effect of modern immunotherapies such as checkpoint inhibitors, while reducing gut-related side effects. Importantly, Tα1 works by converting tumour-supportive immune cells into active fighters, turning 'cold' tumours into more immune-responsive targets and enhancing T-cell-induced anti-tumour responses [12].

Furthermore, it can help patients stay healthy and better tolerate cancer therapy by protecting multiple organs. Bellet et al (2021) showed in disease models that Tα1 repairs the intestinal barrier, balances intestinal and systemic immunity, protects the liver and pancreas and improves metabolic health. Although not a direct cancer study, such effects may help people undergoing cancer therapy to avoid complications and maintain treatment strength [13]. In another study, Kharazmi-Khorassani and Asoodeh (2019) treated lung cancer cells (A549) with thymosin-α1 (Tα1) at a concentration of 3-48 µg/ml for 24 hours. This slowed their growth and movement, reduced the levels of harmful oxidative molecules and enhanced natural antioxidant enzymes (catalase, SOD and GPx) without inducing cell death. These findings suggest that Tα1 may reduce the aggressiveness of cancer cells, helping them to cope more effectively with oxidative stress [14].

Clinical trials confirm that thymosin-α1 (Tα1) is a safe and helpful adjunct to standard lung cancer treatments. Liu and Lu (2023) found that adding Tα1 to chemotherapy or chemoradiotherapy improves overall survival and reduces the risk of infection. When used after surgery, it accelerates the regeneration of the immune system and prolongs the time to tumour recurrence. Tα1 achieves this by enhancing anti-tumour immunity, increasing the number of T cells that kill tumour cells and making tumours more sensitive to immune attack. It can also reduce treatment-related side effects, helping patients to continue therapy and benefit more from modern drugs such as immune checkpoint inhibitors [15]. In addition, it may help reduce lung damage caused by chest irradiation without increasing the risk of death. Yu et al (2011) conducted a 24-week study in mice, comparing three groups: no irradiation, irradiation only, and irradiation plus Tα1. Mice in the Tα1 group received 1.6 mg/kg once daily subcutaneously. Mortality rates remained similar in the radiotherapy-only group and the group receiving radiotherapy in combination with Tα1 (2/10 versus 3/14 at weeks 23-24). However, there was an accumulation of fluid around the lungs (pleural effusion) in the radiotherapy-only group that did not occur in the Tα1-treated group. At both weeks 8 and 24, Tα1 reduced lung protein leakage, total immune cell infiltration and neutrophil accumulation compared with radiotherapy alone. In addition, Tα1 increased macrophage presence at week 8 and decreased lung fibrosis scores later in the study. These results suggest that Tα1 may attenuate inflammation and reduce scarring after thoracic radiotherapy without affecting survival [16].

Moreover, it can significantly increase the efficacy of chemotherapy and immunotherapy when used sequentially. Mastino et al (1992) tested a combination approach in mice with Lewis lung cancer. Animals received a single high dose of cyclophosphamide (200 mg/kg), followed by thymosin-α1 (Tα1) (200 µg/kg per day for four days) and, two days later, interleukin-2 (IL-2). Neither Tα1 nor IL-2 used alone, or even in combination with chemotherapy, produced the same results as giving both drugs after chemotherapy. The full sequence completely removed tumours in many mice, prolonged survival and induced a strong tumour-killing immune response with intense infiltration of lymphocytes inside the tumours. Removal of CD4, CD8 or natural killer (NK) cells or complete immune suppression eliminated the benefit, showing that these immune cells were essential for success [17].

In SARS-CoV-2 infection, thymosin-α1 (Tα1) may affect how SARS-CoV-2 enters airway cells. Zhang et al (2022) used human airway cell models and found that Tα1 reduced ACE2 protein, a major entry receptor for viruses such as SARS-CoV-2, in a dose-dependent manner (p < 0.001). It also reduced angiotensin levels (1-7), maintaining stable levels of other ACE-related proteins, but overall ACE activity was reduced. These findings suggest that Tα1 may help to limit viral entry into the respiratory system by modulating the ACE/ACE2 pathway [18]. In addition, it shows potential to inhibit the formation and spread of cancer. Moody (2007) tested daily administration of Tα1 (0.4 mg/kg subcutaneously) in several cancer models. In A/J mice exposed to chemical urethane-induced lung cancer, Tα1 reduced the number of lung tumours by 15-45% and slowed the growth of tumour cells in laboratory experiments. In breast cancer models, including rats exposed to NMU and transgenic mice with SV40-induced tumours, daily administration of Tα1 improved survival and reduced tumour burden in both hormone-dependent and hormone-independent cancers. These results indicate that Tα1 may act both directly on tumour cells, slowing their growth, and indirectly, enhancing immune immunity to prevent tumour formation and growth [19].

Thymosin-α1 (Tα1) provides long-term cancer prevention benefits. Moody et al (2000) conducted another long-term study in A/J mice using urethane (400 mg/kg by injection) to induce lung tumours, followed by daily administration of Tα1 (0.4 mg/kg). The number of tumours decreased by approximately 45% after 2.5 months, 40% after 3 months and 17% after 4 months compared to the control group. Tα1 also increased white blood cell levels, suggesting a stronger immune response. Interestingly, natural Tα1-like peptides were detected in both normal and tumour lung tissue, suggesting the existence of an inbuilt defence system in the lung. Taken together, these results show that Tα1 can provide long-term cancer prevention by enhancing immunity and acting directly on the lung environment [20].

Thymosin-α1 (Tα1) in the treatment of COVID-19

Thymosin-α1 (Tα1) appears to rebalance the excessive immune response observed in COVID-19, while helping patients recover faster and avoid severe disease progression. Matteucci et al (2020) studied the blood cells of people with confirmed COVID-19 to understand how Tα1 affects immune activation. They focused on CD8⁺ T cells, which in COVID-19 showed strong overexpression of inflammation-related genes, creating a 'cytokine storm' pattern. When these cells were treated with Tα1 in the laboratory, the expression of inflammatory genes decreased and the overactivity of a subset of CD8⁺ type " " cells decreased. This suggests that Tα1 can restore a healthier immune balance under the extreme inflammatory stress observed with COVID-19 [21]. Based on this immunomodulatory effect, clinical studies have shown that Tα1 can improve outcomes for hospitalised patients. Wang et al (2023) conducted a retrospective analysis of 338 patients with moderate COVID-19 pneumonia, some of whom received standard care alone, while others received thymalfascin (synthetic Tα1) along with standard treatment. Those who received Tα1 had a shorter hospital stay (p < 0.01), faster relief of fever and fatigue and smaller areas of pneumonia on CT scans (p < 0.05). In addition, blood tests showed lower inflammatory markers (CRP and PCT). Multivariate analysis confirmed that thymalfascin independently reduced the risk of disease progression to severe pneumonia and helped patients clear the virus more quickly, especially younger adults [22].

It also shows benefit for patients suffering from the most severe forms of COVID-19. Wu et al (2020) studied 334 critically ill patients in eight hospitals in China. Participants received Tα1 at a dose of 1.6 mg subcutaneously once daily or every 12 hours for more than five days along with standard care. Importantly, mortality at 28 days was significantly lower with Tα1 (P = 0.016), while mortality at 60 days was unchanged. Patients in the highest risk group, such as those over 64 years of age or those showing poor indicators such as very low lymphocyte counts ( 3, APACHE II > 7) benefited the most. In these groups, Tα1 reduced the risk of death at 28 days (HR 0.11, p = 0.013) and improved oxygenation (PaO₂/FiO₂, p = 0.036). Survivors tended to stay longer in hospital, reflecting improved survival in the critical phase [23]. Similarly, Liu et al (2020) evaluated 76 patients with severe COVID-19 in two hospitals in Wuhan and found that Tα1 reduced mortality (11.11% vs 30.00%, p = 0.044). It also restored lymphocyte levels, especially in elderly patients and those with very low lymphocyte counts at baseline. Tα1 increased the number of CD8⁺ and CD4⁺ T cells, decreased the levels of depletion markers (PD-1 and Tim-3) on CD8⁺ cells and increased the number of T cell receptor excision circles (TRECs), a sign of new T cell production in the thymus. Those with very low CD8⁺ (<400/µl) or CD4⁺ (<650/µl) cell counts benefited most. Taken together, these results suggest that Tα1 not only alleviates dangerous inflammation, but also helps rebuild infection-fighting cells, improving survival and recovery in severe and critical cases of COVID-19 [24].

In addition, it may help patients with a mild course of COVID-19 shed the virus more quickly and leave the hospital, even if it does not appear to prevent disease worsening or death. Huang et al (2021) analysed 1388 patients with a non-severe course of COVID-19, of whom 232 (16.7%) received thymosin-α1 (Tα1) along with standard care, and 1156 (83.3%) received standard care alone. After adjusting for baseline risk factors, there were no significant differences between groups in terms of progression to severe disease (2.17% vs 2.71%) and death (0.54% vs 0%). However, patients treated with Tα1 shed virus for a shorter time (median 13 vs 16 days, p = 0.025) and had a shorter hospital stay (14 vs 18 days, p < 0.001). In contrast, duration of symptoms and antibiotic use showed no significant differences. These results suggest that, although Tα1 does not prevent the worsening of the mild course of COVID-19 or reduce mortality, it may accelerate viral eradication and hospital discharge, potentially reducing the burden on health systems [25]. It may help lower the risk of early death and reduce inflammation in patients hospitalised with COVID-19. Wang et al (2022) studied 95 patients admitted to Wuhan Third Hospital between 31 January and 4 March 2020. Of these, 31 received Tα1 after admission and 64 did not. At day 28, the mortality rate was 35.5% in the Tα1 group compared to 28.1% in the control group. Although the initial Kaplan-Meier survival curves only showed a trend towards improvement, multivariate Cox analysis showed a significant survival advantage for Tα1 (HR 0.15, 95% CI 0.04-0.55, p = 0.004) and further weighted analysis confirmed improved 28-day survival (HR 0.45, 95% CI 0.25-0.84, p = 0.012). Factors associated with higher risk of death included older age, chronic kidney disease, low lymphocyte count at baseline and methylprednisolone use. For other outcomes, the number of days without mechanical ventilation and lymphocyte recovery were similar, but C-reactive protein (CRP) levels fell more with Tα1, showing an anti-inflammatory effect. The dosing regimen was not described in detail. In conclusion, these results suggest that Tα1 may improve early survival and reduce inflammation in hospitalised patients with COVID-19, even if it does not shorten mechanical ventilation time or accelerate lymphocyte recovery [26].

In addition, thymosin-α1 (Tα1) appears to precisely regulate the immune response to SARS-CoV-2 without reducing T-cell activity, and its effect is consistent across age groups. Espinar-Buitrago et al (2023) conducted an in vitro study using immune cells from both elderly (60-90 years) and younger donors. They found that α1Thy (Tα1) increased activation markers (CD40, CD80, TIM-3) and stimulated TNF-α production in plasmocytoid dendritic cells (pDCs). In mixed cultures, in which dendritic cells activated T cells with viral peptides, α1Thy reduced overall inflammatory cytokine production, but preserved T cell function and multi-cytokine responses. It also decreased CD40L levels on CD8⁺ T cells and increased PD-1 levels on CD4⁺ T cells, helping to fine-tune activation levels. Importantly, these effects were similar in both older and younger donors, demonstrating that age did not limit the ability of Tα1 to restore immune balance. These findings confirm that Tα1 may be a potential therapeutic option or vaccine enhancer in COVID-19, including in the elderly [27]. Additionally, it may help repair the long-term immune damage observed in the acute sequelae of SARS-CoV-2 (PASC or long-term COVID). Minutolo et al (2023) analysed blood cells from individuals with long-term COVID, a condition characterised by loss of naïve T and B cells, expansion of memory T cells and continuous activation of the immune system. When these cells were treated with Tα1 ex vivo, the pool of naïve lymphocytes was restored and the excessive growth of memory T cells was reduced. These effects were strongest in individuals who had severe acute COVID-19 and required respiratory support. Clinical observations linked these immunological changes to improvements in both systemic and psychiatric symptoms of long-term COVID. Furthermore, these results are consistent with reports that Tα1 reduces mortality and hospitalisation time in acute COVID-19 by restoring T-cell immunity. In conclusion, the results suggest that Tα1 may help correct long-term immune dysregulation in PASC and may be valuable as a therapy beyond the acute phase of infection [28].

It also appears to accelerate immune reconstitution and may improve outcomes for patients with severe COVID-19 and reduced lymphocyte counts. Shehadeh et al (2023) conducted a prospective, open-label, randomised pilot study involving 49 hospitalised COVID-19 patients with hypoxaemia and lymphocytopenia. Participants were randomly assigned to receive standard care alone or standard care combined with thymalfascin (synthetic Tα1). Although the overall clinical recovery rate was not statistically significant, the trends were in favour of Tα1: among those requiring low-flow oxygen at baseline, the subdistribution hazard ratio (sHR) for clinical recovery was 1.48 (95% CI 0.68-3.25), and among those receiving high-flow oxygen it was 1.28 (95% CI 0.35-4.63). Importantly, patients receiving low-flow oxygen and treated with Tα1 had a 3.84-fold increase in CD4⁺ T-cell counts from day 1 to day 5 compared to the control group (p = 0.01), indicating a more rapid return of immunity. There were nine serious adverse events in the Tα1 group, but none of these were drug-related. Thus, although these results are exploratory and small in scale, they suggest that Tα1 may safely promote T-cell regeneration and contribute to better clinical outcomes in COVID-19 hypoxaemic and immunocompromised patients, which requires confirmation in larger studies [29].

Other studies have shown that thymosin-α1 (Tα1) may reduce the risk of death in moderate to severe COVID-19, although its effect on ventilation and hospital stay remains unclear. Soeroto et al (2023) conducted a systematic review and meta-analysis of eight studies on people with moderate to severe or critical COVID-19. The pooled data showed lower mortality with Tα1 compared with standard care (RR 0.59, 95% CI 0.37-0.93, p = 0.02), despite high inter-study variability (I² = 84%). In contrast, Tα1 did not significantly reduce the need for mechanical ventilation (RR 0.83, 95% CI 0.48-1.44, p = 0.51) or shorten hospital stay (mean difference +2.32 days; not statistically significant). Further analysis suggested that the mortality benefit may depend on factors such as study size and patient gender. Dosage and schedules varied significantly between studies. Overall, these results suggest that Tα1 is associated with fewer deaths, but shows inconsistent results in terms of ventilation use and length of hospital stay, highlighting the need for large, high-quality randomised trials to clarify its role and optimal dosing [30]. In addition, it shows early promise as a prophylactic option for long-term haemodialysis patients, who are a group at particular risk of severe COVID-19. Tuthill et al . (2023) conducted a randomised pilot study involving 194 dialysis patients, allocating them to a group receiving thymalfascin (Tα1) at a dose of 1.6 mg subcutaneously twice weekly for eight weeks or to a group not receiving Tα1. Participants were followed up for four months after treatment. By July 2022, there were three deaths in the Tα1 group, compared with seven in the control group, and serious complications of COVID-19 occurred slightly less frequently (five vs seven cases). Most participants were already vaccinated (91 Tα1; 76 control). Preliminary results suggested a potential survival benefit and lower disease severity with Tα1, with no new safety concerns. At the time of writing, definitive results on antibody response and long-term outcomes were still awaited. In conclusion, these preliminary data suggest that prophylactic use of Tα1 is well tolerated and may help protect high-risk dialysis patients from severe COVID-19 [31].

Dosage of thymosin-α1 (Tα1) in lung disease and COVID-19

In the COVID-19 and SARS-CoV-2 studies reviewed, whenever the clinical dose of thymosin-α1 (Tα1) was administered, it was 1.6 mg per subcutaneous (SC) injection, and the schedule was adjusted according to clinical conditions. In a multicentre cohort of critically ill patients with COVID-19, Tα1 was administered at 1.6 mg SC once daily (q.d.) or every 12 hours (q12h) over five days. In a randomised pilot prophylaxis study in patients on long-term haemodialysis, the dosing regimen was 1.6 mg SC twice weekly for eight weeks. 

The dosing of thymosin-α1 (Tα1) in COVID-19 was generally consistent with published studies. Most acute treatment protocols used a dose of 1.6 mg administered once or twice daily as part of short treatment cycles. In contrast, prophylactic or maintenance regimens for high-risk populations, such as patients on long-term dialysis, typically used a dose of 1.6 mg twice a week for several weeks. This regimen reflects the way Tα1 is tailored to different clinical needs, with a higher frequency in acute disease and a lower, fixed dose in prophylaxis or immune support.

Disclaimer

This article has been written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We are not suggesting the use of chemical reagents on humans - this is prohibited by law, for a product to be used for treatment it must be registered as a medicine. The information contained in the text is based on available scientific research and is not intended as medical advice or to promote self-medication. The reader should consult with a qualified health professional for all health and treatment decisions.

References

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