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 {beta}2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by - among other factors - viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, 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 selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL to prothrombin (PT) with the strength of the antibody response against SARS-CoV-2 and that it is 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.
ABSTRACT
COVID-19 is a pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various disease conditions. The aim of this retrospective and observational pilot study was to examine the potential value of cfDNA plasma concentrations as a correlative biomarker in hospitalized COVID-19 patients. Lithium-Heparin plasma samples were obtained from twenty-one COVID-19 patients during hospitalization in the University Medical Center of Mainz, Germany, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). cfDNA plasma concentrations of COVID-19 patients ranged between 247.5 and 6346.25 ng/ml and the mean concentrations were 1831 {+/-} 1388 ng/ml ({+/-} standard deviation). Correlations were found between cfDNA levels and the occurrence of acute respiratory distress symptom (ARDS), acute kidney injury (AKI), myositis, neurological complications, bacterial superinfection and disease severity as defined by sepsis-related organ failure assessment score (SOFA) score. D-Dimer and C-reactive-protein (CRP), determined by clinical laboratory analysis, showed the highest correlations with cfDNA levels. The results of this observational study suggest that cfDNA plasma concentrations may serve as a predictive biomarker of disease severity in COVID-19. Prospective studies enrolling larger patient cohorts are ongoing to test this hypothesis.