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

Bellet, Marina Maria; Renga, Giorgia; Pariano, Marilena; Stincardini, Claudia; D’Onofrio, Fiorella; Goldstein, Allan L.; Garaci, Enrico; Romani, Luigina; Costantini, Claudio

doi:10.1016/j.intimp.2023.109949

Cited by 6 publications

(4 citation statements)

References 29 publications

(41 reference statements)

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“…In our investigation, α-thymosin, as a non-specific T cell activator, demonstrated a higher probability of improving both survival and HRQoL over 2 months. The observed discrepancies between studies could be attributed to differences in disease severity among patients [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

et al. 2023

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Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a Bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL), and disability in 1082 severely and critically ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 2023. Results: Among 1082 patients (mean age, 78.0 years, 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24–0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44–1.14]) compared with the control. IL-6 receptor antagonist, baricitinib and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR > 0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06–2.50]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71–2.16]). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

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Section: Discussionmentioning

confidence: 99%

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

et al. 2023

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“…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][21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Early use of Thymalfasin prevents progression of common COVID-19 infection to severe pneumonia

Wang¹,

Wang²,

Fei³

et al. 2023

Preprint

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Introduction Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. Whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to explore the clinical value of Thymalfasin in preventing COVID-19 progression to severe pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital. Methods The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels. Results The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients. Conclusion Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms. However, it is necessary to grasp the timing of treatment to achieve better therapeutic effects. The present study demonstrated that use of Thymalfasin within a week of confirmed diagnosis of COVID-19 infection could offer greater clinical efficacy.

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“…Tα1 is, indeed, endowed with a plethora of immunoregulatory activities ( 39 , 64 , 65 ), which include: (1) Maturation, activation and prevention of apoptosis of various immune cells, such as T and B lymphocytes and Natural Killer cells, via different signaling pathways, including TLRs ( 36–40 , 47–49 ); (2) Activation of CD8 + T cells for cross-priming in antitumor and antiviral responses, via transcriptional regulation of MHC class I expression ( 40 ) and immunostimulation ( 66 , 67 ); (3) Activation of innate immune cells for antimicrobial activity ( 68 ); (4) Activation of antigen presenting function of different dendritic cells subsets via selective TLR stimulation for immunity and tolerance in infection and antitumor immunity ( 47–49 , 52 , 53 ); (5) Regulation of cytokines for increased production of interferon-γ (IFN-γ), IFN-α, interleukin-2 (IL-2), IL-6, and IL-10 and decreased production of inflammatory IL-1β and TNF-α via different receptor signaling pathways ( 37–39 , 47–49 , 69 , 70 ); (6) Induction of immune tolerance via the activation of the tolerogenic IDO1 pathway ( 52 , 53 ); (7) Metabolic activity via the AhR/IL-22 axis and the control of lipid peroxidation in experimental metabolic disorders ( 54 , 71 ); (8) Metabolic regulation of the oxidative/anti-oxidative stress pathways in preclinical murine and human preclinical settings ( 50 , 51 ); (9) Direct antitumor activity via PTEN-mediated apoptosis ( 37 ) and other mechanisms ( 67 ), including suppression of migration via inhibition of STAT3-MMP2 signaling ( 41 ). Overall, it appears that Tα1 is capable of a multifaceted, pleiotropic immune activation, resulting in apparently opposing effects on the immune system, an activity that points to its context-dependent activity, as long suggested ( 39 ).…”

Section: Tα1 In Physiologymentioning

confidence: 99%

“…Tα1 has been investigated as an adjuvant therapy for viral, bacterial, and fungal infections ( 33 , 66 , 79 , 80 ). It has been used to treat a variety of illnesses, including chronic hepatitis B and C, ( 81–83 ), acquired immune deficiency syndrome ( 84 ), bacterial and mold pneumonia ( 33 ), sepsis ( 85 , 86 ), and, most recently, COVID-19 ( 80 , 87–103 ).…”

Section: Tα1 In Medicinementioning

confidence: 99%

Phenotypic drug discovery: a case for thymosin alpha-1

Garaci,

Paci,

Matteucci

et al. 2024

Front. Med.

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Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host–microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework.

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

Cited by 6 publications

References 29 publications

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

Early use of Thymalfasin prevents progression of common COVID-19 infection to severe pneumonia

Phenotypic drug discovery: a case for thymosin alpha-1

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