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

Rebillard, R.-M.; Charabati, M.; Grasmuck, C.; Filali-Mouhim, A.; Tastet, O.; Brassard, N.; Daigneault, A.; Bourbonniere, L.; Balthazard, R.; Carmena Moratalla, A.; Carpentier Solorio, Y.; Farzam-kia, N.; Fournier, A. P.; Gowing, E.; Jamann, H.; Lemaitre, F.; Mamane, V. H.; Thai, K.; Cailhier, J.-F.; Chomont, N.; Finzi, A.; Chasse, M.; Durand, M.; Arbour, N.; Kaufmann, D. E.; Prat, A.; Larochelle, C.

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 provides novel 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 novel candidate molecules to investigate from a therapeutic perspective.