Distinct systemic and mucosal immune responses to SARS-CoV-2

Nikaïa Smith (1) , Pedro Goncalves (2) , Bruno Charbit (3) , Ludivine Grzelak (4, 5) , Maxime Beretta (6) , Cyril Planchais (6) , Timothée Bruel (4) , Vincent Rouilly (7) , Vincent Bondet (1) , Jérôme Hadjadj (8, 9) , Nader Yatim (1) , Helene Pere (10) , Sarah Merkling (11) , Solen Kernéis (12, 13, 14) , Frederic Rieux-Laucat (8) , Benjamin Terrier (9) , Olivier Schwartz (4) , Hugo Mouquet (6) , Darragh Duffy (1, 3) , James Di Santo (2)

1 Immunologie Translationnelle - Translational Immunology lab
2 Immunité Innée - Innate Immunity
3 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
4 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
5 USPC - Université Sorbonne Paris Cité
6 Immunologie humorale - Humoral Immunology
7 Datactix
8 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
9 APHP-CUP - National Referral Center for Rare Systemic Autoimmune Diseases [Paris, France]
10 HEGP - Hôpital Européen Georges Pompidou [APHP]
11 IVI - Interactions Virus-Insectes - Insect-Virus Interactions
12 Hôpital Cochin [AP-HP]
13 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
14 EMAE - Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials

Coordinated local mucosal and systemic immune responses following SARS-CoV-2 infection protect against COVID-19 pathologies or fail leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and 16S bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct COVID-19 patients during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. In contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microrganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.

Keywords: Covid-19; cytokines; mucosal immunity; systemic immunity

Domains: Immunology

Nikaïa Smith, Pedro Goncalves, Bruno Charbit, Ludivine Grzelak, Maxime Beretta, et al.. Distinct systemic and mucosal immune responses to SARS-CoV-2. 2021. ⟨pasteur-03244398⟩