Abstract

A microarray-based assay to detect IgG and IgM antibodies against betacoronaviruses (SARS-CoV-2, SARS, MERS, OC43, and HKU1), other respiratory viruses and type I interferons (IFN-Is) was developed. This multiplex assay was applied to track antibody cross-reactivity due to previous contact with similar viruses and to identify antibodies against IFN-Is as the markers for severe COVID-19. In total, 278 serum samples from convalescent plasma donors, COVID-19 patients in the intensive care unit (ICU) and patients who recovered from mild/moderate COVID-19, vaccine recipients, prepandemic and pandemic patients with autoimmune endocrine disorders, and a heterogeneous prepandemic cohort including healthy individuals and chronically ill patients were analyzed. The anti-SARS-CoV-2 microarray results agreed well with the ELISA results. Regarding ICU patients, autoantibodies against IFN-Is were detected in 10.5% of samples, and 10.5% of samples were found to simultaneously contain IgM antibodies against more than two different viruses. Cross-reactivity between IgG against the SARS-CoV-2 nucleocapsid and IgG against the OC43 and HKU1 spike proteins was observed, resulting in positive signals for the SARS-CoV-2 nucleocapsid in prepandemic samples from patients with autoimmune endocrine disorders. The presence of IgG against the SARS-CoV-2 nucleocapsid in the absence of IgG against the SARS-CoV-2 spike RBD should be interpreted with caution.

Highlights

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new infectious agent that causes coronavirus disease 2019 (COVID-19)

  • Some studies have shown that preexisting immunity to seasonal human coronaviruses (HCoVs) and other respiratory viruses plays a limited role in the formation of SARS-CoV-2 humoral immune responses [9]

  • The microarray contained antigens corresponding to respiratory viruses (SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, HKU1; FluA and FluB; AdV; respiratory syncytial virus (RSV); parainfluenza virus (PIV)-1, PIV-2, and PIV-3) and type I IFNs (IFN-ω and IFN-α-2a)

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Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new infectious agent that causes coronavirus disease 2019 (COVID-19). Humoral immune responses play critical roles in protecting individuals against SARS-CoV-2 infection, through the development of antibodies. Studies have shown that the factors that can affect disease severity include preexisting immunity to seasonal human coronaviruses (HCoVs) [1], coinfection with other viruses [2], and the presence of autoantibodies against type I interferons (IFNs) [3]. Some studies have shown that preexisting immunity to seasonal HCoVs and other respiratory viruses plays a limited role in the formation of SARS-CoV-2 humoral immune responses [9]. An association between the levels of antibodies against common cold HCoVs and the symptoms of COVID-19 has been shown [10]

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