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SARS-CoV-2 infection of thymus induces loss of function that correlates with disease severity.
Rosichini, Marco; Bordoni, Veronica; Silvestris, Domenico Alessandro; Mariotti, Davide; Matusali, Giulia; Cardinale, Antonella; Zambruno, Giovanna; Condorelli, Angelo Giuseppe; Flamini, Sara; Genah, Shirley; Catanoso, Marialuigia; Del Nonno, Franca; Trezzi, Matteo; Galletti, Lorenzo; De Stefanis, Cristiano; Cicolani, Nicolò; Petrini, Stefania; Quintarelli, Concetta; Agrati, Chiara; Locatelli, Franco; Velardi, Enrico.
  • Rosichini M; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Bordoni V; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Cellular Immunology Laboratory, INMI L Spallanzani - IRCCS, Rome, Italy.
  • Silvestris DA; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Mariotti D; Cellular Immunology Laboratory, INMI L Spallanzani - IRCCS, Rome, Italy.
  • Matusali G; Virology Laboratory, INMI L Spallanzani - IRCCS, Rome, Italy.
  • Cardinale A; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Zambruno G; Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Condorelli AG; Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Flamini S; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Genah S; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Catanoso M; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
  • Del Nonno F; Pathology Unit, INMI L Spallanzani - IRCCS, Rome, Italy.
  • Trezzi M; Cardiac Surgery Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Galletti L; Cardiac Surgery Unit, Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • De Stefanis C; Pathology Unit, Core Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Cicolani N; Confocal Microscopy Core Facility, Research Center, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Petrini S; Confocal Microscopy Core Facility, Research Center, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Quintarelli C; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Department of Clinical Medicine and Surgery, University of Naples Federico II, Rome, Italy.
  • Agrati C; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Cellular Immunology Laboratory, INMI L Spallanzani - IRCCS, Rome, Italy.
  • Locatelli F; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy.
  • Velardi E; Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address: enrico.velardi@opbg.net.
J Allergy Clin Immunol ; 151(4): 911-921, 2023 04.
Article in English | MEDLINE | ID: covidwho-2235011
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Lymphopenia Type of study: Prognostic study Limits: Humans Language: English Journal: J Allergy Clin Immunol Year: 2023 Document Type: Article Affiliation country: J.jaci.2023.01.022

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Lymphopenia Type of study: Prognostic study Limits: Humans Language: English Journal: J Allergy Clin Immunol Year: 2023 Document Type: Article Affiliation country: J.jaci.2023.01.022