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

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.

The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants

“…Similar results were found by Smit et al. ( 22 ) in an independent cohort. Conflicting results to Kaplonek et al.…”

The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants

“…With respect to disease outcomes, McNaughton et al [21] showed that prior immunity to seasonal coronaviruses was positively associated with fatal outcomes in individuals with severe COVID-19. Similar results were found by Smit et al [22] in an independent cohort. Conflicting results to Kaplonek et al [19] were found by Garrido et al [23], who found that S2 antibody responses were associated with greater disease severity.…”

Ratio between IgG against the spike protein of seasonal coronaviruses and SARS- CoV-2 is associated with a fatal outcome of hospitalized COVID-19 patients

“…Accordingly, memory B cell clones directed to HCoVs boosted during severe COVID-19 indeed poorly neutralize SARS-CoV-2 8 . In our cohort, we have also reported a back boost of HCoV-related anti-spike IgG in patients with severe disease, with the strongest correlation of anti-spike IgG to SARS-CoV-2 and to the Betacoronaviruses (OC43 and HKU1) seen in severely ill patients 9 . Following up on this work, we assessed neutralizing immunity and evaluated the anti-spike IgG ratio of SARS-CoV-2 to HCoVs in the same cohort, focusing on the subgroup of deceased patients in order to identify markers of a fatal disease course.…”

“…Severe disease was divided into individuals who recovered during follow-up (termed non-fatal disease) and individuals who deceased during hospitalization or up to one week after discharge (termed fatal disease). Baseline characteristics of each of these cohort groups have previously been published 9 . We then assessed the proportion of IgG that was directed against the spike protein (S-protein) of HCoVs compared to SARS-CoV-2 using a protein array that allows for parallel and quantitatively assessment of antigen-speci c IgG 9 .…”

“…Presence of heterologous immunity against HCoVs is detectable in patients with severe COVID-19 and is considered to arise due to substantial homologous epitopes embedded in the spike protein of these coronaviruses 9 . Here, using a protein microarray, we show that a fatal outcome is associated with an increased proportion of anti-spike IgG against HCoVs, at the time of hospital admission.…”