Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19.

Claudia Gomes,Kun Qian,Kelly A Crotty,Kimon V Argyropoulos,Ana Rodriguez,Jill Buyon,David C Lee,Lawrence Hsu Lin,Nubia Catalina Tovar,Peter Izmirly,Paolo Cotzia,Huilin Li,Robert Clancy,Maria Fernanda Yasnot-Acosta,Marisol Zuniga

doi:10.26508/lsa.202101180

Abstract

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

Highlights

Infections trigger immune responses that target pathogen antigens, but frequently they induce potent autoimmune responses that are characterized by high levels of antibodies recognizing a variety of host antigens (Rivera-Correa & Rodriguez, 2018)
We observed that COVID-19 patients had significantly higher average levels of circulating anti-RBCL, anti-PS, and anti-DNA than controls, with 36% of patients testing positive for anti-RBCL (Fig 1A–C)
Patients with systemic lupus erythematosus (SLE), an autoimmune disorder which frequently results in increased levels of anti-DNA antibodies (Pisetsky, 2016), showed higher levels of all autoantibodies, especially of anti-DNA than COVID-19 patients

Summary

Introduction

Infections trigger immune responses that target pathogen antigens, but frequently they induce potent autoimmune responses that are characterized by high levels of antibodies recognizing a variety of host antigens (Rivera-Correa & Rodriguez, 2018). In COVID-19, autoantibodies are found in high levels in a large proportion of hospitalized patients with severe disease (Woodruff et al, 2020 Preprint; Zhou et al, 2020; Wang et al, 2021) and have been associated with the development of autoimmune pathologies (Ehrenfeld et al, 2020), such as thrombocytopenia (Zulfiqar et al, 2020), hemolytic anemia (Lazarian et al, 2020), Guillain–Barre (Toscano et al, 2020), and anti-phospholipid (Zhang et al, 2020; Zhou et al, 2020) syndromes. Autoantibodies against the lung protective protein Annexin-A2 correlated with patient mortality in COVID-19, suggesting a detrimental effect of certain autoantibody specificities in patients (Zuniga et al, 2021)

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Results

Conclusion