[Background: Lymphopenia, particularly restricted to the T-cell compartment, has been described as one of the major clinical hallmarks in COVID-19 patients and proposed as a disease severity indicator. 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 SARS-CoV-2 on thymic function. Methods: We performed molecular quantification of T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) to assess, respectively, T- and B-cell neogenesis in SARS-CoV-2-infected patients. We developed in vitro culture system of primary human thymic epithelial cells (TECs) to mechanistically investigate the impact of SARS-CoV-2 on TEC function. Results: We showed that COVID-19 patients had reduced thymic function, which was inversely associated with the severity of the disease. We found that angiotensin-converting enzyme 2 (ACE2), 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 upon 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 represent a useful marker to predict disease severity and progression]

Fuente: Journal of Allergy and Clinical Immunology
Available online 8 February 2023