Dataset Information

Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection.

ABSTRACT:

Background

A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic and mucosal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods

Twenty-six unvaccinated adults with confirmed coronavirus disease 2019 (COVID-19) were followed for 6 months with 3 collections of blood, nasal secretions, and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutralizing and binding antibody responses were respectively evaluated by pseudovirus assays and multiplex bead arrays.

Results

Neutralizing antibody responses to SARS-CoV-2 were detected in serum and respiratory samples for 96% (25/26) and 54% (14/26), respectively, of infected participants. Robust binding antibody responses against SARS-CoV-2 spike protein and S1, S2, and receptor binding (RBD) domains occurred in serum and respiratory nasal secretions, but not in stool samples. Serum neutralization correlated with RBD-specific immunoglobulin (Ig)G, IgM, and IgA in serum (Spearman ρ = 0.74, 0.66, and 0.57, respectively), RBD-specific IgG in respiratory secretions (ρ = 0.52), disease severity (ρ = 0.59), and age (ρ = 0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (ρ = 0.42) and IgA (ρ = 0.63).

Conclusions

Sustained antibody responses occurred after SARS-CoV-2 infection. Notably, there was independent induction of IgM and IgA binding antibody and neutralizing responses in systemic and respiratory compartments. These observations have implications for current vaccine strategies and understanding SARS-CoV-2 reinfection and transmission.

SUBMITTER: Wright PF

PROVIDER: S-EPMC8903457 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection.

Wright Peter F PF Prevost-Reilly Alejandra C AC Natarajan Harini H Brickley Elizabeth B EB Connor Ruth I RI Wieland-Alter Wendy F WF Miele Anna S AS Weiner Joshua A JA Nerenz Robert D RD Ackerman Margaret E ME

The Journal of infectious diseases 20220901 7

<h4>Background</h4>A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic and mucosal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.<h4>Methods</h4>Twenty-six unvaccinated adults with confirmed coronavirus disease 2019 (COVID-19) were followed for 6 months with 3 collections of blood, nasal secretions, and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutral ...[more]

PMID: 35188974

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Project description:BackgroundMucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, we have a limited understanding about the antibodies present on the nasal mucosal surfaces.MethodsIn this study, we evaluated SARS-CoV-2 mucosal antibodies following previous infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 143 individuals, which include convalescent, vaccinated, or breakthrough infections.FindingsWe detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. Depletion of IgA antibodies in nasal fluids resulted in a tremendous reduction of neutralization activity against SARS-CoV-2, indicating that IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against SARS-CoV-2 was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants.InterpretationIn summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates higher titers of binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies.FundingThe work was funded by the COVID-19 National Research Program 78 (grant number 198412) of the Swiss National Science Foundation.

Project description:BackgroundThe impact of previous SARS-CoV-2 infection on the systemic immune response during tuberculosis (TB) disease has not been explored.MethodsAn observational, cross-sectional cohort was established to evaluate the systemic immune response in persons with pulmonary tuberculosis with or without previous SARS-CoV-2 infection. Those participants were recruited in an outpatient referral clinic in Rio de Janeiro, Brazil. TB was defined as a positive Xpert-MTB/RIF Ultra and/or a positive culture of Mycobacterium tuberculosis from sputum. Stored plasma was used to perform specific serology to identify previous SARS-CoV-2 infection (TB/Prex-SCoV-2 group) and confirm the non- infection of the tuberculosis group (TB group). Plasmatic cytokine/chemokine/growth factor profiling was performed using Luminex technology. Tuberculosis severity was assessed by clinical and laboratory parameters. Participants from TB group (4.55%) and TB/Prex-SCoV-2 (0.00%) received the complete COVID-19 vaccination.ResultsAmong 35 participants with pulmonary TB, 22 were classified as TB/Prex-SCoV-2. The parameters associated with TB severity, together with hematologic and biochemical data were similar between the TB and TB/Prex-SCoV-2 groups. Among the signs and symptoms, fever and dyspnea were significantly more frequent in the TB group than the TB/Prex-SCoV-2 group (p < 0,05). A signature based on lower amount of plasma EGF, G-CSF, GM-CSF, IFN-α2, IL-12(p70), IL-13, IL-15, IL-17, IL-1β, IL-5, IL-7, and TNF-β was observed in the TB/Prex-SCoV-2 group. In contrast, MIP-1β was significantly higher in the TB/Prex-SCoV-2 group than the TB group.ConclusionTB patients previously infected with SARS-CoV-2 had an immunomodulation that was associated with lower plasma concentrations of soluble factors associated with systemic inflammation. This signature was associated with a lower frequency of symptoms such as fever and dyspnea but did not reflect significant differences in TB severity parameters observed at baseline.

Dataset Information

Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection.

Background

Methods

Results

Conclusions

Publications

Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection.

Similar Datasets

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