Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors

Kunze, Katie L.; Johnson, Patrick W.; van Helmond, Noud; Senefeld, Jonathon W.; Petersen, Molly M.; Klassen, Stephen A.; Wiggins, Chad C.; Klompas, Allan M.; Bruno, Katelyn A.; Mills, John R.; Theel, Elitza S.; Buras, Matthew R.; Golafshar, Michael A.; Sexton, Matthew A.; Diaz Soto, Juan C.; Baker, Sarah E.; Shepherd, John R. A.; Verdun, Nicole C.; Marks, Peter; Paneth, Nigel S.; Fairweather, DeLisa; Wright, R. Scott; van Buskirk, Camille M.; Winters, Jeffrey L.; Stubbs, James R.; Senese, Katherine A.; Pletsch, Michaela C.; Buchholtz, Zachary A.; Rea, Robert F.; Herasevich, Vitaly; Whelan, Emily R.; Clayburn, Andrew J.; Larson, Kathryn F.; Ripoll, Juan G.; Andersen, Kylie J.; Lesser, Elizabeth R.; Vogt, Matthew N. P.; Dennis, Joshua J.; Regimbal, Riley J.; Bauer, Philippe R.; Blair, Janis E.; Casadevall, Arturo; Carter, Rickey E.; Joyner, Michael J.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.