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

  • J Clin Invest. 2021 Apr 15;131(8):e145853. doi: 10.1172/JCI145853.
Rose-Marie Rébillard  1  2 ,  Marc Charabati  1  2 ,  Camille Grasmuck  1  2 ,  Abdelali Filali-Mouhim  2 ,  Olivier Tastet  2 ,  Nathalie Brassard  2 ,  Audrey Daigneault  2 ,  Lyne Bourbonnière  2 ,  Sai Priya Anand  2  3 ,  Renaud Balthazard  1  2 ,  Guillaume Beaudoin-Bussières  2  4 ,  Romain Gasser  2  4 ,  Mehdi Benlarbi  2  4 ,  Ana Carmena Moratalla  1  2 ,  Yves Carpentier Solorio  1  2 ,  Marianne Boutin  2  4 ,  Negar Farzam-Kia  1  2 ,  Jade Descôteaux-Dinelle  2  4 ,  Antoine Philippe Fournier  1  2 ,  Elizabeth Gowing  1  2 ,  Annemarie Laumaea  2  4 ,  Hélène Jamann  1  2 ,  Boaz Lahav  2 ,  Guillaume Goyette  2 ,  Florent Lemaître  1  2 ,  Victoria Hannah Mamane  1  2 ,  Jérémie Prévost  2  4 ,  Jonathan Richard  2  4 ,  Karine Thai  1  2 ,  Jean-François Cailhier  2  5 ,  Nicolas Chomont  2  4 ,  Andrés Finzi  2  3  4 ,  Michaël Chassé  2  5 ,  Madeleine Durand  2  5 ,  Nathalie Arbour  1  2 ,  Daniel E Kaufmann  2  5 ,  Alexandre Prat  1  2 ,  Catherine Larochelle  1  2
Affiliations
  • 1. Department of Neuroscience, Université de Montréal, Montreal, Quebec, Canada.
  • 2. Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
  • 3. Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
  • 4. Department of Microbiology, Infectious Diseases and Immunology, and.
  • 5. Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
PMID: 33635833 DOI: 10.1172/JCI145853
Abstract

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.

Keywords
Adaptive immunity; COVID-19; Innate immunity.
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