Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection

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, 5, 9) , Nader Yatim (1, 8, 5) , Helene Pere (10) , Sarah H. Merkling (11) , Amine Ghozlane (12) , Solen Kernéis (13, 14, 15) , Frederic Rieux-Laucat (9) , Benjamin Terrier (8, 5) , Olivier Schwartz (4) , Hugo Mouquet (6) , Darragh Duffy (1) , James P. 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 UPCité - Université Paris Cité
6 Immunologie humorale - Humoral Immunology
7 Datactix
8 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]
9 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
10 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
11 IVI - Interactions Virus-Insectes - Insect-Virus Interactions
12 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
13 Hôpital Cochin [AP-HP]
14 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
15 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (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 bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 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. By 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 microorganisms, 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.

Domains: Life Sciences [q-bio]

Nikaïa Smith, Pedro Goncalves, Bruno Charbit, Ludivine Grzelak, Maxime Beretta, et al.. Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection. Nature Immunology, 2021, ⟨10.1038/s41590-021-01028-7⟩. ⟨pasteur-03384279⟩