Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19

Abstract

Whereas the detection of antiphospholipid autoantibodies (aPL) in COVID-19 is of increasing interest, their role is still unclear. We analyzed a large aPL panel in 157 patients with COVID-19 according to the disease severity. We also investigated a potential association between aPL and extracellular DNA (exDNA, n = 85) or circulating markers of neutrophil extracellular traps (NET) such as citrullinated histones H3 (CitH3, n = 49). A total of 157 sera of patients infected by SARS-CoV-2 were collected. A large aPL panel including lupus anticoagulant, anti-cardiolipin and anti-beta-2 glycoprotein I (IgG, IgM and IgA), anti-phosphatidylethanolamine IgA, anti-prothrombin (IgG and IgM) was retrospectively analyzed according to the disease severity. We found a total aPL prevalence of 54.8% with almost half of the cases having aCL IgG. Within an extended panel of aPL, only aCL IgG were associated with COVID-19 severity. Additionally, severe patients displayed higher CitH3 levels than mild patients. Interestingly, we highlighted a significant association between the levels of aCL IgG and exDNA only in aCL positive patients with severe disease. In conclusion, we showed a significant link between aPL, namely aCL IgG, and circulating exDNA in patients with severe form of COVID-19, that could exacerbate the thrombo-inflammatory state related to disease severity.

Autoimmune complications of COVID-19 and potential consequences for long-lasting disease syndromes

“…This interaction competes with the targeted initiation of coagulation pathways and generates an apparent anticoagulant response (through steric hindrance for the binding of functional phospholipid binding proteins), although those autoantibodies are associatedwith thrombotic complications. In addition, the exacerbated inflammatory response in many Covid-19 patients generates NETosis, containing electronegative DNA complexed with histones and other blood proteins or immune complexes, contributing to increase the thrombotic risk [96] , [97] , [98] . NETosis can contribute to stimulate an autoimmune response, which worsens the disease evolution.…”

The role of NETosis in the pathogenesis of immunoinflammatory rheumatic diseases

“…Имеются данные об увеличении уровня аФЛ и маркеров нетоза у пациентов с пост-COVID-19 синдромом [225]. По данным другого исследования, у пациентов с COVID-19 увеличение концентрации IgG аКЛ и маркеров NETs (цитруллинированный гистон) ассоциируется с тяжестью COVID-19 [226]. Эти данные позволяют обсуждать значение NETs в развитии называемого «COVID-19-индуцированного АФСподобного синдрома» [227].…”

The Diagnostic, Prognostic, and Therapeutic Potential of Cell-Free DNA with a Special Focus on COVID-19 and Other Viral Infections

“…Identification of the tissue origin of cfDNA may be important for its more accurate use as a biomarker for COVID-19. Although the lung is the predominant locus of serious SARS-CoV-2 infections, multiple organs and tissues such as hematologic, cardiovascular, renal, gastrointestinal and hepatobiliary, endocrinologic, neurologic, ophthalmologic, and dermatologic systems can be affected in corresponding patients [ 68 ]. Tracking tissue sources of cfDNA is possible based on DNA methylation patterns and their comparison with the reference human methylome atlas [ 69 ].…”