Cross-reactive humoral immune responses against seasonal human coronaviruses in COVID-19 patients with different disease severities

Abstract

Background We evaluated the cross-reactive antibody response against seasonal human coronaviruses (HCoVs) according to disease severity in patients with COVID-19 in Japan. Methods We analyzed 194 paired-collected serum samples from 97 patients with COVID-19 (mild, 35; severe, 62) on admission and during convalescence. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 and four seasonal HCoVs (HCoV-NL63, -229E, -OC43, and -HKU1) were detected by enzyme-linked immunosorbent assays. Results There was no difference in optical density (OD) values for seasonal HCoVs on admission between the severe and mild cases. In addition, a specific pattern of disease severity-associated OD values for HCoVs was not identified. A significant increase of OD values from admission to convalescence for HCoV-HKU1and -OC43 IgG-S and HCoV-NL63 and -229E IgG-N was observed in the severe cases. Significant differences were observed between the mild and severe cases for HCoV-HKU1 and -OC43 IgG-S OD values during convalescence. Correlations were found between the fold-change of HCoV-OC43 IgG-S OD values with the fold-change of SARS-CoV-2 IgG-S OD values and C-reactive protein, lactate dehydrogenase, and lymphocyte levels. Conclusions There was no association between the antibody titer of seasonal HCoVs in the early phase of COVID-19 and disease severity.

Long-Term, CD4+ Memory T Cell Response to SARS-CoV-2

“…Similarly, Loyal et al were able to show that pre-existing spike-cross-reactive T cells were activated after COVID-19 mRNA vaccination and showed signs similar to a secondary immune response ( 32 ). Contrasting studies that measured a high degree of cross-reactivity between SARS-CoV-2 and HCoV, however, found no correlation between HCoV reactivity and increased COVID-19 immunity ( 33 , 34 ). This is in line with other studies showing that HCoV-specific antibody titers increased in convalescent individuals but did not correlate with increased SARS-CoV-2 titers or protection ( 35 – 37 ).…”

Pre-Existing Cross-Reactive Antibody Responses Do Not Significantly Impact Inactivated COVID-19 Vaccine-Induced Neutralization

“…Also, Focosi et al showed an association between previous humoral immunity to NL63 and 229E and worse clinical outcome in COVID-19 patients (21). Other studies have suggested that pre-existing immunity to sCoVs may not be related to COVID-19 severity or protection at all (17,27,35). Currently, few studies have provided evidence for an impact of pre-existing cross-reactive antibodies on inactivated COVID-19 vaccineinduced neutralization.…”

“…Additionally, T cell-mediated anti-SARS-CoV-2 responses were found in unexposed human, indicating a cross-reaction between human CoVs and SARS-CoV-2 (10)(11)(12)(13)(14). Accumulating evidence suggests that pre-existing humoral immunity to sCoVs may play a role in the specific anti-SARS-CoV-2 antibody responses (15), but this possibility is controversial (16,17). Some studies showed that elevated levels of pre-existing antibodies against sCoVs, specifically OC43 and HKU1, were associated with a less severe course of COVID-19, suggesting a protective effect of prior exposure to sCoVs (18)(19)(20).…”

Projecting the SARS-CoV-2 transition from pandemicity to endemicity: Epidemiological and immunological considerations

“…However, it remains largely unclear in which ways circulating HCoV antibodies affect the SARS-CoV-2 immune response [ 85 – 87 ]. Several other studies have indicated that B cell [ 88 ] and T-cell responses mounted against a lifetime of exposures to HCoVs can cross-react with SARS-CoV-2 [ 70 , 89 ], yet there is no known cross-protective effect for B cells [ 85 , 90 ] and the protective role of the T-cell response remains unclear.…”