SARS-CoV-2 infection of thymus induces loss of function that correlates with disease severity - 05/04/23
![](/templates/common/images/mail.png)
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : COVID-19, SARS-CoV-2, immunodeficiency, thymus, T cells, thymic epithelial cells
Abbreviations used : ACE2, βTREC, cjKREC, CK1, CK5, COVID-19, cTEC, DEGs, EpCAM, hTEC, ICU, KREC, LCMV, mTEC, sjKREC, sjTREC, TEC, SARS-CoV-2, TREC, UEA1
Plan
E.V. was supported by grants from the Amy Stelzer Manasevit Research Program, the Italian Association for Cancer Research (AIRC), and the Italian Ministry of Health (“Ricerca Corrente”). F.L. was supported by grants from AIRC (Special Program Metastatic disease: The Key Unmet Need in Oncology 5 per mille 2018 Project Code 21147 and Accelerator Award 2017 INCAR), Ministero dell’Istruzione dell’Università e della Ricerca (grant PRIN ID 2017 WC8499_004), and the Italian Ministry of Health (grant RF-2016-02364388). S.F and S.G. were supported by the AIRC fellowship for Italy. The study was also supported by the European Virus Archive - GLOBAL funded by European Union's Horizon 2020 research and innovation programme (grant agreement no. 871029). |
|
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 151 - N° 4
P. 911-921 - avril 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.