The treatment of patients with severe COVID-19 following SARS-CoV-2 infection remains difficult. Severe inflammatory reactions and thrombotic complications (blood clots) in particular can be life-threatening. Classic anticoagulants such as heparin often cannot prevent these complications. An evaluation of literature data shows that natural anticoagulants, known as plasma protease inhibitors, are important in the regulation of out-of-control inflammatory and coagulation processes and should be reviewed for their therapeutic benefits. The journal Biologicals reports on the results online ahead of print.