COVID-19 is frequently associated with a coagulopathy with severe consequences. The mechanisms leading to a pro-coagulant state in these patients is multifactorial, including tissue destruction and inflammatory mechanisms. Based on the analysis of publicly available interactomes, we propose that SARS-CoV-2 infection causes a deficiency in C1 esterase inhibitor (C1-INH), a pathogen-specific mechanism that may help explain the pro-coagulant state in COVID-19 patients.