Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 
causes COVID-19 disease. Therapeutic antibodies are being developed that 
interact with the viral spike proteins to limit viral infection of epithelium. 
We have applied a method to dramatically improve the performance of 
anti-SARS-CoV-2 antibodies by enhancing avidity through multimerization using 
simple engineering to yield tetrameric antibodies. We have re-engineered six 
anti-SARS-CoV-2 antibodies using the human p53 tetramerization domain, including 
three clinical trials antibodies casirivimab, imdevimab and etesevimab. The 
method yields tetrameric antibodies, termed quads, that retain efficient binding 
to the SARS-CoV-2 spike protein, show up to two orders of magnitude enhancement 
in neutralization of pseudovirus infection and retain potent interaction with 
virus variant of concern spike proteins. The tetramerization method is simple, 
general and its application is a powerful methodological development for 
SARS-CoV-2 antibodies that are currently in pre-clinical and clinical 
investigation.