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

Am J Pathol. 2021 Jan;191(1):90-107. doi: 10.1016/j.ajpath.2020.10.008. Epub 2020 Nov 4.

Abstract

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 score-matched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing high-titer 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 Administration-required 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • COVID-19 / mortality*
  • COVID-19 / therapy*
  • Female
  • Follow-Up Studies
  • Hospitalization
  • Humans
  • Immunization, Passive
  • Immunoglobulin G / immunology*
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Propensity Score
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / immunology*
  • Treatment Outcome

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus

Supplementary concepts

  • COVID-19 serotherapy