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

Nikaïa Smith,Jérôme Hadjadj,Timothée Bruel,Solen Kernéis,Amine Ghozlane,Nader Yatim,Benjamin Terrier ,Hugo Mouquet,Ludivine Grzelak,Pedro Gonçalves ,Darragh Duffy,Sarah H Merkling,Frédéric Rieux‐Laucat ,Vincent Bondet,Hélène Péré ,Vincent Rouilly,Olivier Schwartz,Maxime Beretta,Cyril Planchais,Bruno Charbit,James P Di Santo

doi:10.1038/s41590-021-01028-7

Abstract

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.

Highlights

(SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes
Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and with spike-specific neutralizing antibodies
Nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities

Summary

Introduction

(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. Clinical manifestations following SARS-CoV-2 infection are highly variable, ranging from asymptomatic or mild symptoms to severe pneumonia that can progress to acute respiratory distress syndrome[1]. It is still unclear whether disease progression is related to the viral infection itself, to the host immune response, to host comorbidities or to a combination of these different factors[2]. One severe clinical manifestation in patients with COVID-19 is an extensive systemic immune reaction triggered by the excessive production of inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1 alpha (MIP-1α/CCL3), IL-6, tumor necrosis factor (TNF)

Methods

Results

Conclusion