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

Abstract

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.).

Figure 1. Participation in the Covid-19 Convalescent Plasma Expanded-Access Program.

A choropleth map shows the number of cumulatively enrolled patients in the expanded-access program within each state of the contiguous United States. The choropleth map does not show data from noncontiguous U.S. locations, including registered facilities in Puerto Rico, Hawaii, Alaska, Guam, and the Northern Mariana Islands.

Figure 2. Relative Risk of Death within 30 Days after Convalescent Plasma Transfusion.

Forest plots of the relative risks of death associated with medium versus low antibody levels (Panel A) and high versus low antibody levels (Panel B) are shown. The subgroups are 12 mutually exclusive categories of the time period of the study in 2020, patient age, and ventilator support in patients who received transfusions of convalescent plasma. Shown are the estimated relative risks of death among patients who received convalescent plasma with IgG signal-to-cutoff ratios in the range of 4.62 to 18.45 (medium titer) or more than 18.45 (high titer), as compared with the relative risks among those who received plasma with IgG signal-to-cutoff ratios below 4.62 (low titer). The pooled estimates from all the subgroups are based on the Mantel–Haenszel estimator. Table S5 provides the sample sizes and number of deaths in each subgroup. 𝙸 bars indicate 95% confidence intervals.