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Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19
Michael J Joyner1, Rickey E Carter1, Jonathon W Senefeld1
1From the Departments of Anesthesiology and Perioperative Medicine (M.J.J., J.W.S., S.A.K., C.C.W., A.M.K., M.A.S., J.C.D.S., S.E.B., J.R.A.S., V.H., A.J.C., J.G.R., K.J.A., M.N.P.V., J.J.D., R.J.R.), Laboratory Medicine and Pathology (J.R.M., E.S.T., C.M.B., J.L.W., J.R.S.), and Cardiovascular Medicine (R.F.R., K.F.L., R.S.W.), the Human Research Protection Program (R.S.W.), and the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine (P.R.B.), Mayo Clinic, Rochester, MN; the Departments of Health Sciences Research (R.E.C., P.W.J., E.R.L., D.O.H.) and Cardiovascular Medicine (K.A.B., E.R.W., D.F.), Mayo Clinic, Jacksonville, FL; the Department of Health Sciences Research (K.L.K., M.R.B.) and the Department of Internal Medicine, Division of Infectious Diseases (J.E.B.), Mayo Clinic, Phoenix, AZ; the Department of Anesthesiology, Cooper Medical School of Rowan University, Cooper University Health Care, Camden, NJ (N.H.); the Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring (N.C.V., P.M.), and the Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore (A.C.) - both in Maryland; and the Departments of Epidemiology and Biostatistics and of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing (N.S.P.).
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.).
