Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection

Area of Science:

• Immunology
• Virology
• Epidemiology

Background:

• Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) causes significant morbidity, but factors preventing symptomatic disease are not fully understood.
• Endemic human coronaviruses (HCoV) circulate globally, and their interaction with SARS-CoV-2 immunity warrants investigation.

Purpose of the Study:

• To investigate the impact of pre-existing severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptomatic disease development following initial SARS-CoV-2 exposure.
• To assess the role of mucosal and systemic immunity in mitigating SARS-CoV-2 infection symptoms.

Main Methods:

• Analysis of saliva and plasma antibody reactivity to HCoVs and SARS-CoV-2 antigens in longitudinal and cross-sectional cohorts.
• Determination of neutralizing activity against SARS-CoV-2 variants (Wuhan, Alpha, Delta, Omicron BA.2).
• Correlation of antibody responses with symptomatic versus asymptomatic SARS-CoV-2 infection.

Main Results:

• Pre-existing HCoV-S1 antibody reactivity was associated with significantly higher SARS-CoV-2 antibody responses in both plasma and saliva.
• Asymptomatic individuals exhibited higher pre-existing HCoV-S1 activity and SARS-CoV-2 reactivity in mucosal samples.
• Saliva neutralization activity showed modest but broad cross-reactivity against multiple SARS-CoV-2 variants.

Conclusions:

• Pre-existing HCoV immunity, particularly mucosal responses, significantly contributes to limiting symptomatic SARS-CoV-2 disease, even if not preventing infection.
• These findings support the development of pan-coronavirus vaccines that induce robust mucosal immune responses.
• Understanding HCoV-SARS-CoV-2 interplay is crucial for predicting future zoonotic coronavirus transmissions.