Conclusion
Emergency Use Authorization from the U.S. Food and Drug Administration is currently being sought for two monoclonal antibody therapies for COVID-19, with others under development. It has been conclusively demonstrated that soluble ACE2 decoys can be engineered to rival the affinities of monoclonal antibodies, and provided IgG fusions confer desirable pharmacokinetics in humans, there is no reason to expect soluble ACE2 decoys cannot be as effective as monoclonals in reducing viral load in patients. Anti-SARS-CoV-2 monoclonals have received a preferential regulatory environment for clinical advancement due to an in-depth understanding of antibody biochemistry, pharmacokinetics and general toxicology. Decoy receptors will always come with additional risks related to immunogenicity and safety, and the outstanding question for the community is whether they provide truly unique benefits that outweigh those risks. The advantages of soluble ACE2 are its breadth against SARS-associated coronaviruses and its potential for alleviating COVID-19 symptoms through intrinsic enzymatic activity. We believe these advantages justify continued efforts towards advancing these proteins to the clinic.