Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

Abstract

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity and detect phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. Among others, viral infections have been proposed to trigger the production of aPL while mostly being considered non-pathogenic. Yet, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that select non-criteria aPL are enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effect models suggest an association of aPL to prothrombin (PT) with the strength of the antibody response against SARS-CoV-2 and further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity and aPL against PT in patients with SARS-CoV-2.

Autoantibodies in COVID-19 correlate with anti-viral humoral responses and distinct immune signatures

“…Similarly, recent reports found increased anti-viral humoral responses in autoantibody-positive individuals during acute COVID-19, although the interrelation remained unclear. 16,19,22 Interestingly, following COVID-19 mRNA vaccination in systemic lupus erythematosus (SLE) patients, higher humoral responses positively correlated with anti- dsDNA antibodies, 39 supporting our findings of increased S1-specific IgA production in ANA- positive individuals following vaccination. These findings indicate an inherent capacity of ANA-positive individuals to mount more robust antibody responses upon antigen challenge.…”

“…[10][11][12] Other acute or chronic viral infections have been associated with autoimmune responses, which have been proposed to arise by molecular mimicry, epitope spreading or bystander activation. 13 Various autoantibodies have been described in association with COVID-19, including antinuclear antibodies (ANA), [14][15][16][17][18][19][20] anti-neutrophil cytoplasmic antibodies (ANCA), 15,16,21 antiphospholipid antibodies, 5,8,14,17,19,22 and antibodies targeting different extracellular antigens. 11,16 While the presence of different autoantibodies has been associated with severe COVID-19 and worse outcome, 11,15,[17][18][19] it remains unclear to what extent autoantibodies are triggered by acute infection, even though transient autoreactivity and new development of autoantibodies have been suggested in a subgroup of COVID-19 patients.…”

Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma

“…However, the individual immune responses to any given virus are highly variable and can translate into different efficacies of viral clearance. Several studies have investigated antibodies generated during SARS-CoV-2 infection in the contexts of the immune system ( 3 , 4 , 5 , 6 , 7 , 8 Preprint ), antibody cross-reactivity ( 9 ), disease prevalence in certain geographical areas ( 10 , 11 Preprint , 12 Preprint ), and the temporal evolution of the antibody response on the population level ( 10 , 11 Preprint , 12 Preprint ). Furthermore, multiple ongoing studies focus on the applicability of antibodies for therapeutic purposes ( 13 ), including plasmapheresis ( 14 , 15 , 16 , 17 , 18 ), which may be a promising therapeutic strategy ( 18 ).…”

Microfluidic Affinity Profiling reveals a Broad Range of Target Affinities for Anti-SARS-CoV-2 Antibodies in Plasma of COVID-19 Survivors

“…However, the individual immune responses to any given virus are highly variable and can translate into different efficacies of viral clearance. Several studies have investigated antibodies generated during SARS-CoV-2 infection in the contexts of the immune system 3–8 , antibody cross-reactivity 9 , disease prevalence in certain geographical areas 10–12 , and the temporal evolution of the antibody response on the population level 10–12 . Furthermore, multiple ongoing studies focus on the applicability of antibodies for therapeutic purposes 13 , including plasmapheresis 14–18 , which may be a promising therapeutic strategy 18 .…”