Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19)

Abstract

Immunopathology may play a significant role in the pathogenesis of Coronavirus-Induced Disease-19 (COVID-19). Immune-mediated tissue damage could result from development of rapid autoimmune responses, characterized by production of self-reactive autoantibodies. In this study, we tested specimens from acutely ill patients hospitalized with COVID-19 for autoantibodies against nuclear, vasculitis-associated, and phospholipid antigens. Detectable autoantibodies were present in 30% of the patients in our cohort, with the majority of reactive specimens demonstrating antibodies to nuclear antigens. However, antinuclear antibodies were only weakly reactive and directed to single antigens, as is often seen during acute infection. We identified strongly reactive antibodies to nuclear antigens only in patients with a prior history of autoimmune disease. In our cohort, the prevalence of antiphospholipid antibodies was low, and we did not detect any vasculitis-associated autoantibodies. We found similar levels of inflammatory markers and total immunoglobulin levels in autoantibody positive versus negative patients, but anti-SARS-CoV-2 antibody levels were increased in autoantibody positive patients. Together, our results suggest that acute COVID-19 is not associated with a high prevalence of clinically significant autoantibody responses of the type usually associated with autoimmune rheumatic disease.

Keywords: Antinuclear antibody; Antiphospholipid antibody; Autoantibody; COVID-19; SARS-CoV-2.

Fig. 1

Antigens Targeted by Autoantibodies in COVID-19 Patients. The Venn diagram and table illustrate the number of patients with autoantibody combinations against nuclear and phospholipid antigens. Two patients had a history of systemic lupus erythematosus (denoted by superscript letters a and b). Patient a was also positive for Sm and SmRNP.

Fig. 2

The Presence of Autoantibodies is Not Associated with Markers of Inflammation. Laboratory values for patients without history of autoimmune disorders who were negative for all autoantibodies assessed in this study (Neg) versus positive for at least one autoantibody (Pos). Autoantibodies were classified using the manufacturer’s suggested thresholds for each assay. Box-and-whisker plots show median and 25th to 75th percentiles; whiskers indicate minimum and maximum values. No laboratory values were found to be statistically different between groups using the Mann–Whitney U test.

Fig. 3

The Presence of Autoantibodies is Not Associated with Levels of Total IgG, IgG subclasses or IgM. Levels of total antibody classes (IgG and IgM) and subclasses (IgG1, IgG2, IgG3, IgG4) were measured for autoantibody negative (Neg, n ​= ​43) versus positive (Pos, n ​= ​14) specimens from patients without history of autoimmune disorders. Box-and-whisker plots show median and 25th to 75th percentiles; whiskers indicate minimum and maximum values. No antibody levels were found to be statistically different between groups using the Mann–Whitney U test.

Fig. 4

Increased anti-SARS-CoV-2 Antibodies in Autoantibody Positive Patients. Levels of anti-SARS-CoV-2 IgG were measured for autoantibody negative (Neg, n ​= ​43) versus positive (Pos, n ​= ​14) specimens. The dotted line indicates the manufacturer’s suggested threshold for positivity. Mean±SEM is shown. ∗p ​= 0.0086 using the Mann–Whitney U test.