Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients

Claudia Matteucci; Antonella Minutolo; Emanuela Balestrieri; Vita Petrone; Marialaura Fanelli; Vincenzo Malagnino; Marco Ianetta; Alessandro Giovinazzo; Filippo Barreca; Silvia Di Cesare; Patrizia De Marco; Martino Tony Miele; Nicola Toschi; Antonio Mastino; Paola Sinibaldi Vallebona; Sergio Bernardini; Paola Rogliani; Loredana Sarmati; Massimo Andreoni; Sandro Grelli; Enrico Garaci

doi:10.1093/ofid/ofaa588

Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients

Open Forum Infect Dis. 2020 Dec 5;8(1):ofaa588. doi: 10.1093/ofid/ofaa588. eCollection 2021 Jan.

Authors

Claudia Matteucci¹, Antonella Minutolo¹, Emanuela Balestrieri¹, Vita Petrone¹, Marialaura Fanelli¹, Vincenzo Malagnino^{2

3}, Marco Ianetta^{2

3}, Alessandro Giovinazzo¹, Filippo Barreca^{2

3}, Silvia Di Cesare^{2

4}, Patrizia De Marco⁵, Martino Tony Miele¹, Nicola Toschi^{6

7}, Antonio Mastino^{8

9}, Paola Sinibaldi Vallebona^{1

8}, Sergio Bernardini¹, Paola Rogliani^{1

5}, Loredana Sarmati^{2

3}, Massimo Andreoni^{2

3}, Sandro Grelli^{1

10}, Enrico Garaci^{11

12}

Affiliations

¹ Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
² Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
³ Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome, Italy.
⁴ Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Childrens' Hospital-Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy.
⁵ Respiratory Medicine Unit, University Hospital Policlinico Tor Vergata, Rome, Italy.
⁶ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
⁷ Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Institute of Translational Pharmacology, National Research Council, Rome, Italy.
⁹ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
¹⁰ Virology Unit, Policlinic of Tor Vergata, Rome, Italy.
¹¹ University San Raffaele, Rome, Italy.
¹² IRCCS San Raffaele Pisana, Rome, Italy.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is characterized by immune-mediated lung injury and complex alterations of the immune system, such as lymphopenia and cytokine storm, that have been associated with adverse outcomes underlining a fundamental role of host response in severe acute respiratory syndrome coronavirus 2 infection and the pathogenesis of the disease. Thymosin alpha 1 (Tα1) is one of the molecules used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancer.

Methods: In this study, we captured the interconnected biological processes regulated by Tα1 in CD8+ T cells under inflammatory conditions.

Results: Genes associated with cytokine signaling and production were upregulated in blood cells from patients with COVID-19, and the ex vivo treatment with Tα1-mitigated cytokine expression, and inhibited lymphocyte activation in a CD8+ T-cell subset specifically.

Conclusion: These data suggest the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.

Keywords: SARS-CoV-2; Thymosin alpha 1; cytokine storm; enrichment analysis; immune modulation.