Microarray-based detection of antibodies against SARS-CoV-2 proteins, common respiratory viruses and type I interferons

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 pa-tients 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.

From rare disorders of immunity to common determinants of infection: Following the mechanistic thread

“…In a subsequent study, the neutralization of lower, more physiological concentrations of IFN-a and/or IFN-u (100 pg/mL, again with plasma diluted 1/10), and of IFN-b, was found to underlie 15% of critical cases, and 20% of cases in patients over the age of 80 years (Bastard et al, 2021a). These studies have been replicated in at least 26 other cohorts in the Americas, Europe, and Asia (Abers et al, 2021;Acosta-Ampudia et al, 2021;Akbil et al, 2022;Bastard et al, 2021;Busnadiego et al, 2022;Carapito et al, 2021;Chang et al, 2021;Chauvineau-Grenier et al, 2022;Eto et al, 2022;Frasca et al, 2022;Goncalves et al, 2021;Koning et al, 2021;Lamacchia et al, 2022;Lemarquis et al, 2021;Mathian et al, 2022;Meisel et al, 2021;Raadsen et al, 2022;Savvateeva et al, 2021;Simula et al, 2022;Solanich et al, 2021;Soltani-Zangbar et al, 2022;Troya et al, 2021;van der Wijst et al, 2021;Vazquez et al, 2021;Wang et al, 2021;Ziegler et al, 2021). These auto-Abs had been known for 40 years, in patients treated with recombinant IFN-a or -b (Zhang et al, 2022a), or with autoimmune conditions, such as systemic lupus erythematosus (SLE), myasthenia gravis, thymoma, autoimmune polyendocrinopathy syndrome type 1 (APS-1), immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX), or RAG1/ RAG2 hypomorphic mutations (Bastard et al, 2020(Bastard et al, , 2021d.…”