Human genetic and immunological determinants of SARS‐CoV‐2 and Epstein–Barr virus diseases in childhood: Insightful contrasts
Open Access
- 26 March 2023
- journal article
- review article
- Published by Wiley in Journal of Internal Medicine
- Vol. 294 (2), 127-144
- https://doi.org/10.1111/joim.13628
Abstract
There is growing evidence to suggest that severe disease in children infected with common viruses that are typically benign in other children can result from inborn errors of immunity or their phenocopies. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a cytolytic respiratory RNA virus, can lead to acute hypoxemic COVID-19 pneumonia in children with inborn errors of type I interferon (IFN) immunity or autoantibodies against IFNs. These patients do not appear to be prone to severe disease during infection with Epstein-Barr virus (EBV), a leukocyte-tropic DNA virus that can establish latency. By contrast, various forms of severe EBV disease, ranging from acute hemophagocytosis to chronic or long-term illnesses, such as agammaglobulinemia and lymphoma, can manifest in children with inborn errors disrupting specific molecular bridges involved in the control of EBV-infected B cells by cytotoxic T cells. The patients with these disorders do not seem to be prone to severe COVID-19 pneumonia. These experiments of nature reveal surprising levels of redundancy of two different arms of immunity, with type I IFN being essential for host defense against SARS-CoV-2 in respiratory epithelial cells, and certain surface molecules on cytotoxic T cells essential for host defense against EBV in B lymphocytes.Keywords
Funding Information
- Vetenskapsrådet
- Cancerfonden
- Howard Hughes Medical Institute
- Rockefeller University
- Fisher Center for Alzheimer's Research Foundation
- Meyer Foundation
- Fondation du Souffle
- Institut National de la Santé et de la Recherche Médicale
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