CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity

• Published in: The Journal of infection 2024-12, Vol.89 (6), p.106304, Article 106304
• Main Authors: Amarilla-Irusta, Ainhoa, Zenarruzabeitia, Olatz, Sevilla, Arrate, Sandá, Víctor, Lopez-Pardo, Ainara, Astarloa-Pando, Gabirel, Pérez-Garay, Raquel, Pérez-Fernández, Silvia, Meijide, Susana, Imaz-Ayo, Natale, Arana-Arri, Eunate, Amo, Laura, Borrego, Francisco
• Format: Article
• Language: English
• Subjects: Adult; Aged; CD151; CD9; COVID-19; COVID-19 - blood; COVID-19 - immunology; Cytokines - blood; Female; Flow Cytometry; GDF-15; Humans; IL-15; Interleukin-15 - blood; Killer Cells, Natural - immunology; Lymphocyte Subsets - immunology; Male; Middle Aged; NK cells; SARS-CoV-2; SARS-CoV-2 - immunology; Severity of Illness Index; Tetraspanin 24; TGF-β
• ISSN: 0163-4453; 1532-2742; 1532-2742
• DOI: 10.1016/j.jinf.2024.106304

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of an NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151brightCD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis. •Patients with severe COVID-19 exhibit elevated levels of IL-15, PlGF and GDF-15.•Enrichment of CD151+ NK cells correlates with disease severity and IL-15 levels.•CD151+ NK cells are more activated and display a distinct receptor repertoire.•A CD151bright CD9+ NK cell subset was highly enriched in severe COVID-19.