Generation of Inhibitory Autoantibodies to ADAMTS13 in Coronavirus Disease 2019

Doevelaar, A. A. N.; Bachmann, M.; Hoelzer, B.; Seibert, F. S.; Rohn, B. J.; Witzke, O.; Dittmer, U.; Brenner, T.; Paniskaki, K.; Yilmaz, S.; Dittmer, R.; Schneppenheim, S.; Babel, N.; Budde, U.; Westhoff, T. H.

Objectives: It has recently been shown that von Willebrand factor (vWf) multimers may be a key driver of immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. Design: Observational prospective controlled multicenter study. Setting: Blood samples and clinical data of patients with COVID-19 were collected regularly during hospitalization in the period from April to November 2020. Patients: 90 patients with confirmed COVID-19 of mild to critical severity and 30 healthy controls participated in this study. Measuerements and Main Results: Antibodies to ADAMTS13 occurred in 31 (34.4%) patients with COVID-19. Generation of ADAMTS13 antibodies was associated with a significantly lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p=0.0041), increased disease severity (severe or critical disease in 90% vs. 62.3%, p=0.0189), and a trend to a higher mortality (35.5% vs. 18.6%, p=0.0773). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Conclusion: The present study demonstrates for the first time, that generation of antibodies to ADAMTS13 is a frequent finding in COVID-19. Generation of these antibodies is associated with a lower ADAMTS13 activity and an increased risk of an adverse course of the disease suggesting an inhibitory effect on the protease. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.