SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

DOI record: { "DOI": "10.1186/s12964-024-01718-3", "ISSN": [ "1478-811X" ], "URL": "http://dx.doi.org/10.1186/s12964-024-01718-3", "abstract": "<jats:title>Abstract</jats:title><jats:p>T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While lymphocytosis indicates an active anti-viral response, lymphopenia is a sign of poor prognosis. T-cells, in essence, rarely express ACE2 receptors, making the cause of cell depletion enigmatic. Moreover, emerging strains posed an immunological challenge, potentially alarming for the next pandemic. Herein, we review how possible indirect and direct key mechanisms could contribute to SARS-CoV-2-associated-lymphopenia. The fundamental mechanism is the inflammatory cytokine storm elicited by viral infection, which alters the host cell metabolism into a more acidic state. This “hyperlactic acidemia” together with the cytokine storm suppresses T-cell proliferation and triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results in a shift from steady-state hematopoiesis to stress hematopoiesis. Even with low ACE2 expression, the presence of cholesterol-rich lipid rafts on activated T-cells may enhance viral entry and syncytia formation. Finally, direct viral infection of lymphocytes may indicate the participation of other receptors or auxiliary proteins on T-cells, that can work alone or in concert with other mechanisms. Therefore, we address the role of CD147―a novel route―for SARS-CoV-2 and its new variants. CD147 is not only expressed on T-cells, but it also interacts with other co-partners to orchestrate various biological processes. Given these features, CD147 is an appealing candidate for viral pathogenicity. Understanding the molecular and cellular mechanisms behind SARS-CoV-2-associated-lymphopenia will aid in the discovery of potential therapeutic targets to improve the resilience of our immune system against this rapidly evolving virus.</jats:p>\n <jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p>", "alternative-id": [ "1718" ], "article-number": "349", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "24 February 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "15 June 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "4 July 2024" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "<!--Emphasis Type='Bold' removed-->Ethical approval and consent to participants", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "Not applicable" }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The authors declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Shouman", "given": "Shaimaa", "sequence": "first" }, { "affiliation": [], "family": "El-Kholy", "given": "Nada", "sequence": "additional" }, { "affiliation": [], "family": "Hussien", "given": "Alaa E.", "sequence": "additional" }, { "affiliation": [], "family": "El-Derby", "given": "Azza M.", "sequence": "additional" }, { "affiliation": [], "family": "Magdy", "given": "Shireen", "sequence": "additional" }, { "affiliation": [], "family": "Abou-Shanab", "given": "Ahmed M.", "sequence": "additional" }, { "affiliation": [], "family": "Elmehrath", "given": "Ahmed O.", "sequence": "additional" }, { "affiliation": [], "family": "Abdelwaly", "given": "Ahmad", "sequence": "additional" }, { "affiliation": [], "family": "Helal", "given": "Mohamed", "sequence": "additional" }, { "affiliation": [], "family": "El-Badri", "given": "Nagwa", "sequence": "additional" } ], "container-title": "Cell Communication and Signaling", "container-title-short": "Cell Commun Signal", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 7, 4 ] ], "date-time": "2024-07-04T09:08:54Z", "timestamp": 1720084134000 }, "deposited": { "date-parts": [ [ 2024, 7, 4 ] ], "date-time": "2024-07-04T09:13:38Z", "timestamp": 1720084418000 }, "funder": [ { "DOI": "10.13039/501100003009", "award": [ "46721", "46721", "46721", "46721", "46721", "46721", "46721", "46721", "46721", "46721" ], "doi-asserted-by": "publisher", "name": "Science and Technology Development Fund" }, { "name": "The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB)." }, { "name": "Zewail City of Science & Technology" } ], "indexed": { "date-parts": [ [ 2024, 7, 5 ] ], "date-time": "2024-07-05T00:14:54Z", "timestamp": 1720138494277 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 7, 4 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 7, 4 ] ], "date-time": "2024-07-04T00:00:00Z", "timestamp": 1720051200000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 7, 4 ] ], "date-time": "2024-07-04T00:00:00Z", "timestamp": 1720051200000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s12964-024-01718-3.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s12964-024-01718-3/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s12964-024-01718-3.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2024, 7, 4 ] ] }, "published-online": { "date-parts": [ [ 2024, 7, 4 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1038/s41579-021-00573-0", "author": "WT Harvey", "doi-asserted-by": "publisher", "first-page": "409", "issue": "7", "journal-title": "Nat Rev Microbiol.", "key": "1718_CR1", "unstructured": "Harvey WT, et al. 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