Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG
Eric Salazar, Paul A Christensen, Edward A Graviss, Duc T Nguyen, Brian Castillo, Jian Chen, Bevin V Lopez, Todd N Eagar, Xin Yi, Picheng Zhao, John Rogers, Ahmed Shehabeldin, David Joseph, Faisal Masud, Christopher Leveque, Randall J Olsen, David W Bernard, Jimmy Gollihar, M.D James M Musser
The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008
Coronavirus disease 2019 (COVID-19) convalescent plasma has emerged as a promising therapy and has been granted Emergency Use Authorization by the US Food and Drug Administration for hospitalized COVID-19 patients. We recently reported results from interim analysis of a propensity scoreematched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing hightiter anti-spike protein receptor binding domain (RBD) IgG significantly decreases mortality. We herein present results from a 60-day follow-up of a cohort of 351 transfused hospitalized patients. Prospective determination of enzyme-linked immunosorbent assay anti-RBD IgG titer facilitated selection and transfusion of the highest titer units available. Retrospective analysis by the Ortho VITROS IgG assay revealed a median signal/cutoff ratio of 24.0 for transfused units, a value far exceeding the recent US Food and Drug Administrationerequired cutoff of 12.0 for designation of high-titer convalescent plasma. With respect to altering mortality, our analysis identified an optimal window of 44 hours after hospitalization for transfusing COVID-19 patients with high-titer convalescent plasma. In the aggregate, the analysis confirms and extends our previous preliminary finding that transfusion of COVID-19 patients soon after hospitalization with high-titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality.
Author Contributions E.S. and J.M.M. conceived the project; E.S., P.A.C., E.A.G., D.T.N., B.C., J.C., B.V.L., T.N.E., X.Y., P.Z., J.R., A.S., D.J., and J.G. acquired data; E.S., P.A.C., E.A.G., D.T.N., B.C., J.C., and J.M.M. analyzed data; E.S., P.A.C., E.A.G., D.T.N., and J.M.M. wrote the manuscript; E.S., P.A.C., E.A.G., D.T.N., and J.M.M. prepared figures; C.L., R.J.O., D.W.B., F.M., and J.G. provided scholarly advice; all authors revised the manuscript and gave final approval for publication. J.M.M. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Supplemental Data Supplemental material for this article can be found at http://doi.org/10.1016/j.ajpath.2020.10.008.
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