Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19

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

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti–SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti–SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti–SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti–SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.)