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

Abstract

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.

Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

“…Thus, dynamic recruitment of various adaptive and innate populations mediating inflammation and antiviral function to the upper respiratory tract was observed during hospitalization with cell type numbers in convalescence that closely resembled levels measured in healthy donors. Of note, we did not observe an increase in nasal B cells in hospitalized patients, which corroborates observations that mucosal antibody levels seem reduced compared to systemic titres in hospitalized patients 12,29 .…”

Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-B.1.1.7 or B.1.1.7 SARS-CoV-2 variants

“…Whether elevated levels of cytokines at the nasopharyngeal mucosae may influence viral transmissibility or reflects differences in the kinetic or extent of viral shedding will deserve further exploration. It will be also worth determining whether cytokines are elevated in blood samples from individuals infected with B.1.1.7, since a tissue compartmentalization of SARS-CoV-2 immune responses have been recently reported, with a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes 18 .…”

“…We performed this analysis on the second Perturbed systemic production of cytokines is a hallmark of disease severity in COVD-19 patients [28][29][30][31] . It has also been reported a dysbiosis and a modification of cytokine profile at mucosal surfaces in severe patients 18 . In this previous study, performed on samples from individuals infected before B.1.1.7 spreading, cytokine responses were compartmentalized 18 samples.…”

“…It has also been reported a dysbiosis and a modification of cytokine profile at mucosal surfaces in severe patients 18 . In this previous study, performed on samples from individuals infected before B.1.1.7 spreading, cytokine responses were compartmentalized 18 samples. Examples of increased cytokines, including IFN-b, IP-10, IL-10, and TRAIL are depicted in Fig.…”

“…We measured anti-SARS-CoV-2 IgG and IgA with the sensitive flow-cytometry based S-Flow assay 17 . In a subset of 202 samples, we measured the levels of 48 cytokines, by either a bead-based multiplexed immunoassay system Luminex or the digital Elisa Simoa 18 . We also titrated infectious virus with the S-Fuse assay 19,20 .…”