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

Rébillard, Rose-Marie; Charabati, Marc; Grasmuck, Camille; Filali-Mouhim, Abdelali; Tastet, Olivier; Brassard, Nathalie; Daigneault, Audrey; Bourbonnière, Lyne; Anand, Sai Priya; Balthazard, Renaud; Beaudoin-Bussières, Guillaume; Gasser, Romain; Benlarbi, Mehdi; Carmena Moratalla, Ana; Carpentier Solorio, Yves; Boutin, Marianne; Farzam-Kia, Negar; Descôteaux-Dinelle, Jade; Fournier, Antoine Philippe; Gowing, Elizabeth M; Laumaea, Annemarie; Jamann, Hélène; Lahav, Boaz; Goyette, Guillaume; Lemaître, Florent; Mamane, Victoria Hannah; Prévost, Jérémie; Richard, Jonathan; Thai, Karine; Cailhier, Jean-François; Chomont, Nicolas; Finzi, Andrés; Chassé, Michaël; Durand, Madeleine; Arbour, Nathalie; Kaufmann, Daniel E; Prat, Alexandre; Larochelle, Catherine

Dysregulated immune profiles have been described in symptomatic SARS-CoV-2-infected patients. 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 i) patients hospitalized with acute SARS-CoV-2 infection; ii) patients of comparable age/sex hospitalized for other acute disease (SARS-CoV-2 negative); and iii) 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 are 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 are 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 that are 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+ patients at risk of unfavorable outcome and uncover candidate molecules to investigate from a therapeutic perspective.