Heterologous Immune Responses of Serum IgG and Secretory IgA Against the Spike Protein of Endemic Coronaviruses During Severe COVID-19

Wouter L Smit,Femke Van Vulpen,Sandhya Shrestha,Shannon La Grouw,Lenneke Van Lelyveld,Michiel Heron,Sanne Van Der Wal,Johan Reimerink,Chantal Reusken,Gert-Jan Godeke,Gijs Limonard,Steven Thijsen,Ailko Bossink,Dirk Eggink,Sophie Van Tol

doi:10.3389/fimmu.2022.839367

Abstract

Defining immune correlates of disease severity is important to better understand the immunopathogenesis in COVID-19. Here we made use of a protein microarray platform to detect IgG- and IgA-reactive antibodies in sera and saliva respectively, and assess cross-reactivity between SARS-CoV-2 and endemic coronaviruses (eCoVs). IgG responses against the full protein of spike, but not the S1 subunit, were significantly higher in convalescent sera of patients with severe disease compared to mild disease and healthy controls. In addition, we detected reactivity of secretory IgA to eCoVs in saliva of patients with severe disease, not present in patients with moderate disease or seropositive healthy controls. These heterologous immune responses are in line with non-protective cross-reactivity, and support a potential role for immune imprinting in the pathogenesis of severe COVID-19.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of symptoms known as COVID-19
Proven history of exposure to SARS-CoV-2 infection was based on serostatus as measured by the Wantai Ab ELISA, a high-validity assay for detection of SARS-CoV-2 seroconversion in mild and severe disease through detection of total immunoglobulin antibodies binding the SARS-CoV-2 receptor binding domain [17]
Patients with fatal disease primarily contributed to this correlation (R values: 0.68 and 0.79 for HCoV-HKU1 and HCoV-OC43, respectively). These results indicate that patients with severe disease, who mount high IgG anti-SARS-CoV-2 responses mount a response to endemic coronaviruses (eCoVs) of the genus Betacoronavirus, which is likely not aimed at the S1 subunit

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of symptoms known as COVID-19. A large majority of infections follows a mild or asymptomatic disease course, a proportion of individuals develop severe disease for which hospitalization and invasive ventilation is necessary. Immunopathogenic mechanisms or correlates of protection underpinning heterogeneity in host responses remain to be clarified. Heterologous humoral and cellular immune responses induced by different related viruses lead to extremely complex host-pathogen interactions of which the outcome is unpredictable [2]. Depending on the virus-host context, heterologous immunity may either be protective, ineffective or even counterproductive [3]. During sequential influenza infections or after vaccination, cross-protective immune responses have clearly been observed [4]. It is thought that antigenic drift over time could elicited a nonproductive memory recall response if the cross-reactive epitope is a non-dominant epitope [5]

Methods

Results

Conclusion