SARS-CoV-2 infection of thymus induces loss of function that correlates with disease severity

Marco Rosichini, Veronica Bordoni, Domenico Alessandro Silvestris, Davide Mariotti, Giulia Matusali, Antonella Cardinale, Giovanna Zambruno, Angelo Giuseppe Condorelli, Sara Flamini, Shirley Genah, Marialuigia Catanoso, Franca Del Nonno, Matteo Trezzi, Lorenzo Galletti, Cristiano De Stefanis, Nicolò Cicolani, Stefania Petrini, Concetta Quintarelli, Chiara Agrati, Franco LocatelliEnrico Velardi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Background: Lymphopenia, particularly when restricted to the T-cell compartment, has been described as one of the major clinical hallmarks in patients with coronavirus disease 2019 (COVID-19) and proposed as an indicator of disease severity. Although several mechanisms fostering COVID-19–related lymphopenia have been described, including cell apoptosis and tissue homing, the underlying causes of the decline in T-cell count and function are still not completely understood. Objective: Given that viral infections can directly target thymic microenvironment and impair the process of T-cell generation, we sought to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on thymic function. Methods: We performed molecular quantification of T-cell receptor excision circles and κ-deleting recombination excision circles to assess, respectively, T- and B-cell neogenesis in SARS-CoV-2–infected patients. We developed a system for in vitro culture of primary human thymic epithelial cells (TECs) to mechanistically investigate the impact of SARS-CoV-2 on TEC function. Results: We showed that patients with COVID-19 had reduced thymic function that was inversely associated with the severity of the disease. We found that angiotensin-converting enzyme 2, through which SARS-CoV-2 enters the host cells, was expressed by thymic epithelium, and in particular by medullary TECs. We also demonstrated that SARS-CoV-2 can target TECs and downregulate critical genes and pathways associated with epithelial cell adhesion and survival. Conclusions: Our data demonstrate that the human thymus is a target of SARS-CoV-2 and thymic function is altered following infection. These findings expand our current knowledge of the effects of SARS-CoV-2 infection on T-cell homeostasis and suggest that monitoring thymic activity may be a useful marker to predict disease severity and progression.
Lingua originaleEnglish
pagine (da-a)911-921
Numero di pagine11
RivistaJournal of Allergy and Clinical Immunology
Volume151
DOI
Stato di pubblicazionePubblicato - 2023

Keywords

  • COVID-19
  • SARS-CoV-2
  • T cells
  • immunodeficiency
  • thymic epithelial cells
  • thymus

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