High-Antibody Convalescent Plasma Associated With Lower Mortality Among Patients With COVID-19

A comparison of 3 levels of SARS-CoV-2 immunoglobulin G in convalescent plasma, administered to patients with coronavirus disease 2019 (COVID-19), shows that 30-day mortality was lowest in the high-titer vs the low-titer group for those who did not require mechanical ventilation before the transfusion. These results recently appeared in The New England Journal of Medicine.

Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, is the virus that causes COVID-19.

“Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown,” the Mayo Clinic investigators stated when clarifying the purpose of their study.

By 30 days following transfusion, the high-titer group had the overall fewest deaths, at 22.3%, compared with the 27.4% in the medium-titer group and 29.6% in the low-titer group. Additionally, the high-tier group had a 25% lower risk of death following transfusion vs the low-titer group (relative risk [RR], 0.75; 95% CI, 0.61-0.93). No improvement or worsening was seen in the medium-titer group (RR, 1.02; 95% CI, 0.78-1.32).

And when accounting for mechanical ventilation status, a 34% lower risk of death was seen in the high-titer group vs the low-titer group (RR, 0.66; 95% CI, 0.48-0.91) for those not requiring a ventilator prior to their plasma transfusion:

• Low-titer group: 22.2% (95% CI, 18.2%-26.7%)
• Medium-titer group: 19.4% (95% CI, 17.3%-21.6%)
• High-titer group: 14.2% (95% CI, 10.9%-18.2%)

The data on those who required a ventilator show 30-day mortality rates that are double to triple those of the nonventilator patients:

• Low-titer group: 43.7% (95% CI, 36.7%-51.0%)
• Medium-titer group: 41.6% (95% CI, 37.9%-45.4%)
• High-titer group: 40.5% (95% CI, 33.2%-48.3%)

An exploratory analysis also shows that patients who needed mechanical ventilation had close to double the amount of mean (SD) days between diagnosis and convalescent plasma transfusion vs those not needing a ventilator: 5.4 (4.8) vs 10.0 (7.7) days.

The overall 30-day mortality rate was 26.9% (95% CI, 25.4%-28.5%).

The retrospective analysis covered 3082 patients enrolled in 2 study periods (April 4-May 14 and May 15-July 4, 2020), whose records contained data on the anti–SARS-CoV-2 antibody levels of the transfused plasma and 30-day mortality (the primary outcome). There were 515 patients in the high-titer group, 2006 in the medium-titer group, and 561 in the low-titer group. Most patients were between the ages of 40 and 69 years (P = .08), male (P = .14), and considered overweight or obese (P = .06). All had a laboratory-confirmed SARS-CoV-2 infection.

“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,” the authors concluded. “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.”

Possible limits to extrapolating these results are the open-label trial design and lack of randomization in the placebo group. However the authors’ data were part of the overall evidence the FDA reviewed before issuing an emergency use authorization for convalescent plasma on August 23, 2020.

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