Introduction

Viral infections have been implicated in the initiation of the autoimmune diseases. Recent reports suggest that a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. We evaluated the relationship between COVID-19 severity, prevalence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 infection specific anti-nucleocapsid (N) IgG antibodies and protective neutralizing antibody (Nab) levels.

Methods

Samples from 119 COVID-19 patients categorized based on their level of care and 284 healthy subjects were tested for the presence and persistence of antinuclear and other systemic and organ specific autoantibodies as well as SARS-CoV-2 and neutralizing antibody levels.

Results

The data shows significantly increased levels of anti RNP-A, anti-nucleocapsid and neutralizing antibody among patients receiving ICU care compared to non-ICU care. Furthermore, subjects receiving ICU care demonstrated significantly higher nucleocapsid IgG levels among the RNP-A positive cohort compared to RNP-A negative cohort. Notably, the expression of anti RNP-A antibodies is transient that reverts to non-reactive status between 20 and 60 days post symptom onset.

Conclusions

COVID-19 patients in ICU care exhibit significantly higher levels of transient RNP-A autoantibodies, anti-nucleocapsid, and SARS-CoV-2 neutralizing antibodies compared to patients in non-ICU care.

Background

The SARS-CoV-2 virus has mutated and evolved since the inception of the COVID-19 pandemic bringing into question the future effectiveness of current vaccines and antibody therapeutics. With evolution of the virus updated methods for the evaluation of the immune response in infected and vaccinated individuals are required to determine the durability of the immune response to SARS-CoV-2 variants.

Methods

We developed a multiplexed surrogate virus neutralization test (plex-sVNT) that simultaneously measures the ability of antibodies in serum to inhibit binding between angiotensin converting enzyme-2 (ACE2) and 7 SARS-CoV-2 trimeric spike protein variants, including wild type, B.1.1.7(α), B.1.351(β), P.1(γ), B.1.617.2(δ), B.1.617.1(κ), and B.1.429(ε). The assay was validated against a plaque reduction neutralization test (PRNT).We evaluated 170 samples from 97 COVID-19 patients and 281 samples from 188 individuals that received the Pfizer-BioNTech or Moderna mRNA vaccines.

Results

The plex-sVNT demonstrated >96% concordance with PRNT. Antibody neutralization activity was significantly reduced for all SARS-CoV-2 variants compared to wild type in both the infected and vaccinated cohorts. There was a decline in overall antibody neutralization activity, within both cohorts, out to 5 months post infection or vaccination, with the rate of decline being more significant for the vaccinated.

Conclusions

The plex-sVNT provides a correlative measure to PRNT and a convenient approach for evaluating antibody neutralization against SARS-CoV-2 variants. Neutralization of SARS-CoV-2 variants is reduced compared to wild type and declines over the ensuing months after exposure or vaccination within each cohort, however it is still unknown what degree of neutralizing capacity is protective.