Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19
Michael J Joyner, Rickey E Carter, Jonathon W Senefeld, Stephen A Klassen, John R Mills, Patrick W Johnson, Elitza S Theel, Chad C Wiggins, Katelyn A Bruno, Allan M Klompas, Elizabeth R Lesser, Katie L Kunze, Matthew A Sexton, Juan C Diaz Soto, Sarah E Baker, John R A Shepherd, Noud Van Helmond, Nicole C Verdun, Peter Marks, Camille M Van Buskirk, Jeffrey L Winters, James R Stubbs, Robert F Rea, David O Hodge, Vitaly Herasevich, Emily R Whelan, Andrew J Clayburn, Kathryn F Larson, Juan G Ripoll, Kylie J Andersen, Matthew R Buras, Matthew N P Vogt, Joshua J Dennis, Riley J Regimbal, Philippe R Bauer, Janis E Blair, Nigel S Paneth, Delisa Fairweather, R Scott Wright, Arturo Casadevall
New England Journal of Medicine, doi:10.1056/nejmoa2031893
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.
1026 T h e ne w e ngl a nd jou r na l o f m e dicine Convalescent plasma has also received full or conditional approval in several other countries since that time. Our analyses show that among patients with Covid-19 who were not receiving mechanical ventilation, the transfusion of plasma with high antibody levels was associated with a lower risk of death than the transfusion of plasma with low antibody levels. In addition, patients who received plasma within 3 days after the diagnosis of Covid-19 had a lower risk of death than those who received a transfusion later in the disease course. These data show that the benefit of convalescent plasma was most apparent in patients who received plasma transfusions containing higher levels of anti-SARS-CoV-2 IgG antibodies early in the disease course. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of Health and Human Services and its agencies, including the Biomedical Advanced Research and Development Authority (BARDA) and the Food and Drug Administration, as well as any other agency of the U.S. Government. As-sumptions made within and interpretations from the analysis do not necessarily reflect the position of any U.S. Government entity. Supported by a contract (75A50120C00096) from the Department of Health and Human Services, the Office of the Assistant Secretary for Preparedness and Response, and BARDA; grants (UL1TR002377)..
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{ 'given': 'Noud',
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'affiliation': [ { 'name': 'From the Departments of Anesthesiology and Perioperative '
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{ 'given': 'Nicole C.',
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'affiliation': [ { 'name': 'From 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., '
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'(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 '
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'Division of Pulmonary and Critical Care Medicine (P.R.B.), Mayo '
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{ 'ORCID': 'http://orcid.org/0000-0001-5619-4404',
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'given': 'Peter',
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'Medicine (R.F.R., K.F.L., R.S.W.), the Human Research Protection '
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{ 'given': 'Camille M.',
'family': 'van Buskirk',
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'affiliation': [ { 'name': 'From 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., '
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{ 'given': 'Jeffrey L.',
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'affiliation': [ { 'name': 'From the Departments of Anesthesiology and Perioperative '
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'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...'}]},
{ 'given': 'James R.',
'family': 'Stubbs',
'sequence': 'additional',
'affiliation': [ { 'name': 'From 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., '
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'(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 '
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'Division of Pulmonary and Critical Care Medicine (P.R.B.), Mayo '
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{ 'given': 'Robert F.',
'family': 'Rea',
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'Medicine (M.J.J., J.W.S., S.A.K., C.C.W., A.M.K., M.A.S., '
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'(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...'}]},
{ 'given': 'David O.',
'family': 'Hodge',
'sequence': 'additional',
'affiliation': [ { 'name': 'From 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 '
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'Division of Pulmonary and Critical Care Medicine (P.R.B.), Mayo '
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{ 'given': 'Vitaly',
'family': 'Herasevich',
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'affiliation': [ { 'name': 'From 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., '
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'(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 '
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{ 'given': 'Emily R.',
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'affiliation': [ { 'name': 'From the Departments of Anesthesiology and Perioperative '
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'(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 '
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'Division of Pulmonary and Critical Care Medicine (P.R.B.), Mayo '
'Clinic, Rochester, MN; the...'}]},
{ 'given': 'Andrew J.',
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{ 'given': 'Kathryn F.',
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{ 'given': 'Juan G.',
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'(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 '
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{ 'given': 'Kylie J.',
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'(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 '
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'Division of Pulmonary and Critical Care Medicine (P.R.B.), Mayo '
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{ 'given': 'Matthew R.',
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{ 'given': 'Matthew N.P.',
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{ 'given': 'Joshua J.',
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{ 'given': 'Riley J.',
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{ 'given': 'Janis E.',
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{ 'given': 'Nigel S.',
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{ 'given': 'DeLisa',
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'(J.R.M., E.S.T., C.M.B., J.L.W., J.R.S.), and Cardiovascular '
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