Convalescent Plasma With Higher Antibodies Associated With Lower COVID-19 Mortality Risk

In patients hospitalized with COVID-19 and not mechanically ventilated, convalescent plasma with high titers of anti-SARS-CoV-2 immunoglobulin (Ig)G was associated with lower mortality rates, according to study results published in The New England Journal of Medicine.

In this retrospective study based on a US national registry of hospitalized adults with severe COVID-19 (ClinicalTrials.gov identifier: NCT04338360), researchers evaluated the association between anti-SARS-CoV-2 IgG antibody levels and mortality at 30 days after transfusion of convalescent plasma. Based on the 20th and 80th percentiles of the distribution for the signal-to-cut-off ratio, anti-SARS-CoV-2 IgG antibody levels were categorized as low (<4.62), medium (4.62-18.45), or high (>18.45).

The primary outcome was death within 30 days after plasma transfusion.

The final analyses included 3082 patients who received a single unit of convalescent plasma. At baseline, 61% of the patients were men, 23% were Black, 37% were Hispanic, and 67% had received a transfusion before invasive mechanical ventilation. Patients in the low, medium, and high anti-SARS-CoV-2 IgG antibody levels were similar in terms of demographics, risk factors associated with severe COVID-19, and concomitant use of therapeutics. However, compared with the other 2 groups, the percentages of patients with hypoxemia and concomitant use of hydroxychloroquine were lower in the high-titer group.

Death within 30 days post-plasma transfusion occurred in 26.9% (n=830) of all patients. Patients receiving plasma with high antibody levels had a lower risk of death than those receiving plasma with medium and low antibody levels: 22.3% (115/515), 27.4% (549/2006), and 29.6% (166/561), respectively. 

Compared with patients in the low-titer group, patients in the high-titer group had a lower relative risk (RR) of death (RR, 0.75; 95% CI, 0.61-0.93).

In patients who had not received mechanical ventilation before transfusion, those who received high titers had a lower risk of death within 30 days after plasma transfusion compared with patients who received low titers (RR, 0.66; 95% CI, 0.48-0.91). However, there was no effect on mortality among patients who had received mechanical ventilation (RR, 1.02; 95% CI, 0.78-1.32).

In addition, patients who received plasma within 3 days after receiving a diagnosis of COVID-19 had a lower risk of death (point estimate, 22.2%; 95% CI, 19.9-24.8) than those who received transfusions 4 or more days after receiving a diagnosis (point estimate, 29.5%; 95% CI, 27.6-31.6).

Using machine learning, the most important variables associated with risk of death at 30 days were age, receipt of mechanical ventilation, and anti-SARS-CoV-2 antibody level.

Reference

Joyner MJ, Carter RE, Senefeld JW, et al. Convalescent plasma antibody levels and the risk of death from Covid-19. N Engl J Med. Published online January 13, 2021. doi:10.1056/NEJMoa2031893