An interim analysis published in The American Journal of Pathology indicates that treatment of coronavirus disease 2019 (COVID-19) with high anti-receptor binding domain (RBD) IgG titer convalescent plasma, transfused within 72h of hospital admission, reduces mortality at 28 days post-transfusion.
Eric Salazar, Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, and colleagues, are conducting an ongoing prospective, propensity score-matched study assessing convalescent plasma versus standard care to treat severe and/or critical COVID-19 disease. Their interim analysis looked at data from eight Houston Methodist hospitals from March 28 to July 6, 2020.
Patients were transfused with one or two units of convalescent plasma, with the second included if the patient experienced worsening of their condition, although limited plasma inventory early in the study meant a second unit was not always available. All plasma was donated by recovered and healthy COVID-19 patients who had been asymptomatic for more than 14 days, with donors ranging in age from 18-65 years.
Only patients who had outcome data available 28 days post-transfusion (cases) and 28 days post-admission (controls) were analyzed. The authors said that of 316 transfused patients, 136 met the 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, body mass index (BMI), comorbidities, and baseline ventilation requirement 48h from admission, and in a second matching analysis, ventilation status at day 0.
Relative to non-transfused patients, transfused patients generally were younger, predominantly male, had a higher BMI, lower rates of comorbidities, a higher requirement for supplemental oxygen, and higher inflammatory marker concentrations. Use of steroids, azithromycin, and tocilizumab was more common among the transfused cohort, but use of remdesivir was not.
Most transfused patients (242/316; 76%) received only one unit of convalescent plasma, and most received an initial or sole unit with anti-RBD IgG titer of ≥1:1350 (284/316; 90%), while 22 patients received a unit with an anti-RBD IgG titer >1:150 but <1:1350, and 8 patients with anti-RBD IgG titer of <1:150. For those given a second unit of convalescent plasma, 70 (70/74; 95%) received a unit with an anti-RBD IgG titer ≥1:1350, and 4 (4/74; 5%) with an anti-RBD IgG titer >1:150 but <1:1350.
Results showed a lower probability of death within 28 days in the transfused cohort relative to propensity score-matched controls, although the difference did not reach statistical significance. According to the authors, the decreased mortality reached significance (P = 0.047) when only patients who received a plasma transfusion with an anti-RBD IgG titer of ≥1:1350 (high titer) within 72h of hospital admission were considered.
Risk of overall mortality, and mortality within 28 days in non-transfusion patients, was significantly higher when compared with patients who received plasma transfusion with an anti-RBD IgG titer of ≥1:1350 (high titer) within 72h of hospital admission [RR 7.53 (95% CI 1.12, 50.46); P = 0.04] and [RR 5.92 (95% CI 0.90, 38.84); P = 0.06], respectively. There was no reduction in the risk of mortality within 28 days or mortality with no time constraints when patients were transfused >72h after admission [RR 0.89 (95% CI 0.24, 3.30); P = 0.86] and [RR 0.81 (95% CI 0.25, 2.69); P = 0.74], respectively.
Meanwhile, an analysis comparing outcomes in subgroups of transfused patients rather than to matched controls showed findings consistent with transfusion earlier in the hospital stay. Specifically, compared to those who received plasma transfusion within 72h, pa