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

Respiratory/mucosal and serum/systemic antibody responses to SARS-CoV-2 infection are distinct host defense mechanisms independently influenced by age, severity of illness, and immunoglobulin class. Stimulation of respiratory immunity will be important for SARS-CoV-2 vaccines designed to limit transmission. 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 rho = 0.74, 0.66, and 0.57, respectively), RBD-specific IgG in respiratory secretions (rho = 0.52), disease severity (rho = 0.59), and age (rho = 0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (rho = 0.42) and IgA (rho = 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.

Automated summary

Respiratory/mucosal and serum/systemic antibody responses to SARS-CoV-2 infection are distinct host defense mechanisms influenced by age, severity of illness, and immunoglobulin class. Stimulation of respiratory immunity is crucial for SARS-CoV-2 vaccines aiming to limit transmission.