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This review combines phenotypic, functional, and transcriptomic findings to explain the disruption of NK cell subsets in COVID\u201019. Flow cytometry studies have shown generalised lymphopenia and a significant reduction in the CD56bright and CD56\n                    <jats:sup>dim<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    subsets. This change is linked to an increase in the CD56\n                    <jats:sup>dim<\/jats:sup>\n                    CD16\n                    <jats:sup>\u2212<\/jats:sup>\n                    and CD56\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    populations, which correlate with disease severity. At the molecular level, there is an imbalance between activating and inhibitory receptors. This includes increases in NKG2A, PD\u20101, and LAG\u20103, along with decreases in NKp30, NKp46, and NKG2D. These findings are consistent with an exhausted phenotype and weakened cytotoxicity. Single\u2010cell RNA sequencing (scRNA\u2010seq) studies have identified an increase in proliferative, cytotoxic, and platelet\u2010associated CD56\n                    <jats:sup>dim<\/jats:sup>\n                    NK subpopulations in severe cases and a reduction of CD56\n                    <jats:sup>bright<\/jats:sup>\n                    cells. Transcriptomic profiling showed that upregulation of interferon\u2010stimulated genes (ISGs) and inflammatory pathways driven by STAT1\/3, NF\u2010\u03baB activation, and transforming growth factor\u2010beta (TGF\u2010\u03b2) signalling suppresses NK effector functions. Collectively, these findings suggest a model in which progressive NK cell dysfunction may be associated with the immunopathogenesis of COVID\u201019. The integration of multi\u2010omic and phenotypic approaches provides a comprehensive view of NK cell responses to SARS\u2010CoV\u20102 and suggests potential biomarkers and therapeutic targets to restore NK cell antiviral activity.\n                  <\/jats:p>","DOI":"10.1111\/sji.70115","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:05:09Z","timestamp":1776229509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding\n                    <scp>NK<\/scp>\n                    Cell Subset Dysregulation in\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 Infection: Phenotypic, Functional, and Transcriptomic Insights Into\n                    <scp>COVID<\/scp>\n                    \u201019 Pathogenesis"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2512-8257","authenticated-orcid":false,"given":"Marlyn D.","family":"Sep\u00falveda","sequence":"first","affiliation":[{"name":"Grupo Inmunovirolog\u00eda, Facultad de Medicina Universidad de Antioquia, UdeA  Medell\u00edn Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0062-6444","authenticated-orcid":false,"given":"Walter D.","family":"Cardona Maya","sequence":"additional","affiliation":[{"name":"Grupo Reproducci\u00f3n, Facultad de Medicina Universidad de Antioquia, UdeA  Medell\u00edn Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-8738","authenticated-orcid":false,"given":"Wildeman","family":"Zapata\u2010Builes","sequence":"additional","affiliation":[{"name":"Grupo Infettare, Facultad de Medicina Universidad Cooperativa de Colombia  Medell\u00edn Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0885-1320","authenticated-orcid":false,"given":"Paula A.","family":"Velilla","sequence":"additional","affiliation":[{"name":"Grupo Inmunovirolog\u00eda, Facultad de Medicina Universidad de Antioquia, UdeA  Medell\u00edn 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