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. 2023 Jan;95(1):e28134.
doi: 10.1002/jmv.28134. Epub 2022 Sep 16.

COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity

Wei Jiang  1   2   3 , Douglas Johnson  1   3 , Ruth Adekunle  2   3 , Hughes Heather  2   3 , Wanli Xu  4 , Xiaomei Cong  4 , Xueling Wu  5 , Hongkuan Fan  6   7 , Lars-Magnus Andersson  8   9 , Josefina Robertson  8   9 , Magnus Gisslén  8   9
Affiliations

COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity

Wei Jiang et al. J Med Virol. 2023 Jan.

Abstract

Coronavirus disease 2019 (COVID-19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre-existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID-19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self-antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID-19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus-2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti-type I IFN autoantibodies or neutralizing anti-type I IFN activity of plasma samples from the two patient groups. Increased anti-type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)-229E and HCOV-NL63 spike proteins were associated with mild disease outcome. COVID-19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long-term humoral immunity against HCOV-22E and HCOV-NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life-threatening COVID-19 is critical to reducing mortality and morbidity.

Keywords: COVID-19; SARS-CoV-2; autoantibodies; autoantibodies against type I interferons.

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Conflict of interest statement

Competing interests. The authors declare no competing financial and non-financial interests.

Figures

Figure 1
Figure 1
A. Plasma IgM levels in healthy controls and patients presenting with or without lymphopenia. B. Plasma IgG levels in healthy controls and patients presenting with or without lymphopenia.
Figure 1
Figure 1
A. Plasma IgM levels in healthy controls and patients presenting with or without lymphopenia. B. Plasma IgG levels in healthy controls and patients presenting with or without lymphopenia.
Figure 2
Figure 2
A. Plasma levels of IgGs against different subtypes of type I IFNs in the three study groups. B-C. Plasma levels of IgGs against different subtypes of type II and III IFNs in the three study groups. D. The effect of plasma samples from patients on STAT1 responses to IFN-α in PBMCs in vitro.
Figure 2
Figure 2
A. Plasma levels of IgGs against different subtypes of type I IFNs in the three study groups. B-C. Plasma levels of IgGs against different subtypes of type II and III IFNs in the three study groups. D. The effect of plasma samples from patients on STAT1 responses to IFN-α in PBMCs in vitro.
Figure 2
Figure 2
A. Plasma levels of IgGs against different subtypes of type I IFNs in the three study groups. B-C. Plasma levels of IgGs against different subtypes of type II and III IFNs in the three study groups. D. The effect of plasma samples from patients on STAT1 responses to IFN-α in PBMCs in vitro.
Figure 3
Figure 3
A-B. Plasma IgG levels against SARS-CoV-2 proteins and non-SARS-CoV-2 viral proteins in the three study groups. C. Correlations between plasma levels of antibodies and lymphocyte counts in patients.
Figure 3
Figure 3
A-B. Plasma IgG levels against SARS-CoV-2 proteins and non-SARS-CoV-2 viral proteins in the three study groups. C. Correlations between plasma levels of antibodies and lymphocyte counts in patients.
See this image and copyright information in PMC

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