Identification of SARS-CoV-2-specific immune alterations in acutely ill patients

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Rebillard, Rose-Marie | Charabati, Marc | Grasmuck, Camille | Filali-Mouhim, Abdelali | Tastet, Olivier | Brassard, Nathalie | Daigneault, Audrey | Bourbonniere, Lyne | Anand, Sai Priya | Balthazard, Renaud | Beaudoin-Bussieres, Guillaume | Gasser, Romain | Benlarbi, Mehdi | Moratalla, Ana Carmena | Carpentier Solorio, Yves | Boutin, Marianne | Farzam-Kia, Negar | Descoteaux-Dinelle, Jade | Fournier, Antoine Philippe | Gowing, Elizabeth | Laumaea, Annemarie | Jamann, Helene | Lahav, Boaz | Goyette, Guillaume | Lemaitre, Florent | Mamane, Victoria Hannah | Prevost, Jeremie | Richard, Jonathan | Thai, Karine | Cailhier, Jean-Francois | Chomont, Nicolas | Finzi, Andres | Chasse, Michael | Durand, Madeleine | Arbour, Nathalie | Kaufmann, Daniel | Prat, Alexandre | Larochelle, Catherine

Edité par CCSD ; American Society for Clinical Investigation -

Dysregulated immune profiles have been described in symptomatic patients infected with SARS-CoV-2. Whether the reported immune alterations are specific to SARS-CoV-2 infection or also triggered by other acute illnesses remains unclear. We performed flow cytometry analysis on fresh peripheral blood from a consecutive cohort of (a) patients hospitalized with acute SARS-CoV-2 infection, (b) patients of comparable age and sex hospitalized for another acute disease (SARS-CoV-2 negative), and (c) healthy controls. Using both data-driven and hypothesis-driven analyses, we found several dysregulations in immune cell subsets (e.g., decreased proportion of T cells) that were similarly associated with acute SARS-CoV-2 infection and non-COVID-19-related acute illnesses. In contrast, we identified specific differences in myeloid and lymphocyte subsets that were associated with SARS-CoV-2 status (e.g., elevated proportion of ICAM-1+ mature/activated neutrophils, ALCAM+ monocytes, and CD38+CD8+ T cells). A subset of SARS-CoV-2-specific immune alterations correlated with disease severity, disease outcome at 30 days, and mortality. Our data provide an understanding of the immune dysregulation specifically associated with SARS-CoV-2 infection among acute care hospitalized patients. Our study lays the foundation for the development of specific biomarkers to stratify SARS-CoV-2-positive patients at risk of unfavorable outcomes and to uncover candidate molecules to investigate from a therapeutic perspective.

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