High-titre plasma reduces mortality risk in non-ventilated hospitalised COVID-19 patients

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Among patients hospitalised with coronavirus disease 2019 (COVID-19) who were not receiving mechanical ventilation, transfusion of plasma with higher anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)G antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels, finds a study published in The New England Journal of Medicine.

“We found no such relationship (between antibody level and the risk of death) among patients with COVID-19 who were receiving mechanical ventilation,” wrote Michael J Joyner, MD, Mayo Clinic, Rochester, Minnesota, and colleagues. “In addition, patients who received plasma within 3 days after receiving a diagnosis of COVID-19 had a lower risk of death than those who received transfusions later in the disease course.”

The retrospective study included 3,082 patients hospitalised with COVID-19 from 680 acute care facilities across the US. Overall, 61% of the patients were men, and 69% were younger than 70 years of age. The cohort was stratified into three groups according to anti-SARS-CoV-2 IgG antibody levels based on signal-to-cutoff ratios: low (<4.62), medium (4.62 to 18.45), or high (>18.45). Patients in these three groups were generally similar in terms of demographic characteristics, risk factors associated with severe COVID-19, and concomitant use of therapeutic agents for COVID-19. The primary outcome was death within 30 days after the transfusion of convalescent plasma.

Overall, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titre group, 549 of 2,006 patients (27.4%) in the medium-titre group, and 166 of 561 patients (29.6%) in the low-titre group. Study data showed that patients in the high-titre group had a lower relative risk of death within 30 days after transfusion than patients in the low-titre group (relative risk, 0.75; 95% confidence interval [CI], 0.61-0.93). Additional analyses with adjustment for patient demographic characteristics (age, weight status, and race) and clinical characteristics (receipt of invasive mechanical ventilation, use of concomitant therapeutics, and hypoxemia) showed a similar association.

Among patients who were not receiving mechanical ventilation, death within 30 days after plasma transfusion occurred in 81 of 365 patients (22.2%) in the low-titre group, 251 of 1,297 patients (19.4%) in the medium-titre group, and 50 of 352 patients (14.2%) in the high-titre group. Meanwhile, among patients who were receiving mechanical ventilation, death within 30 days after plasma transfusion occurred in 80 of 183 patients (43.7%) in the low-titre group, in 277 of 666 patients (41.6%) in the medium-titre group, and in 64 of 158 patients (40.5%) in the high-titre group. In both subgroups, the characteristics of the patients were well balanced across the three antibody-titre groups.

In the fully adjusted relative risk regression model, the lower risk of death within 30 days after plasma transfusion in the high-titre group than in the low-titre group was observed among patients who were not receiving mechanical ventilation before transfusion (relative risk, 0.66; 95% CI, 0.48-0.91). No effect on mortality was observed among patients who received mechanical ventilation before transfusion (relative risk, 1.02; 95% CI, 0.78-1.32).

Additionally, the researchers found the unadjusted mortality within 30 days after transfusion was lower among patients who received a transfusion within 3 days after receiving a diagnosis of COVID-19 (point estimate, 22.2%; 95% CI, 19.9-24.8) than among those who received a transfusion 4 or more days after the diagnosis of COVID-19 (point estimate, 29.5%; 95% CI, 27.6-31.6).

“These data show that 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,” the authors noted. “Our findings are also consistent with aggregate data from observational studies and randomised trials of convalescent plasma as well as with historical evidence regarding antibody therapy for infectious diseases.”

“Our data and those from other studies provide support for the use of anti–SARS-CoV-2 antibody assays as an indicator of the potency of COVID-19 convalescent plasma,” the authors added.