Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors
Katie L. Kunze, Patrick W. Johnson, Noud van Helmond, Jonathon W. Senefeld, M. Petersen, Stephen A. Klassen, Chad C. Wiggins, Allan M. Klompas, Katelyn A. Bruno, John R. Mills, Elitza S. Theel, Matthew Buras, Michael A. Golafshar, Matthew A. Sexton, Juan C. Diaz Soto, Sarah E. Baker, John R.A. Shepherd, Nicole Verdun, Peter Marks, Nigel Paneth, DeLisa Fairweather, R. Scott Wright, Camille M. van Buskirk, Jeffrey L. Winters, James R. Stubbs, Katherine A. Senese, Michaela C. Pletsch, Zachary A. Buchholtz, Robert F. Rea, Vitaly Herasevich, Emily R. Whelan, Andrew J. Clayburn, Kathryn F. Larson, Juan G. Ripoll, Kylie J. Andersen, Elizabeth R. Lesser, Matthew N.P. Vogt, Joshua J. Dennis, Riley J. Regimbal, Philippe R. Bauer, Janis E. Blair, Arturo Casadevall, Rickey E. Carter, Michael J. Joyner
Abstract
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.