Early transfusion of a large cohort of COVID-19 patients with high titer anti-SARS-CoV-2 spike protein IgG convalescent plasma confirms a signal of significantly decreased mortality

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 remains a global threat with few proven efficacious treatments. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 disease has emerged as a promising therapy and has been granted emergency use authorization by the U.S. Food and Drug Administration (FDA). We recently reported results from interim analysis of a propensity-score matched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing high titer anti-spike protein receptor binding domain (RBD) IgG significantly decreases mortality. We here present results from 60-day follow up of our cohort of 351 transfused hospitalized patients. Prospective determination of ELISA anti-RBD IgG titer facilitated selection and transfusion of the highest titer units available. Retrospective analysis by the Ortho VITROS IgG assay revealed a median signal/cutoff (S/C) ratio of 24.0 for transfused units, a value far exceeding the recently FDA-required cutoff of 12.0 for designation of high titer convalescent plasma. With respect to altering mortality, our analysis identified an optimal window of 44 hours post-hospitalization for transfusing COVID-19 patients with high titer convalescent plasma. In the aggregate, the analysis confirms and extends our previous preliminary finding that transfusion of COVID-19 patients soon after hospitalization with high titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality.

Convalescent plasma may be a possible treatment for COVID-19: A systematic review

“…Following removing duplicates and screening of titles and abstracts, we evaluated 153 articles in full text. Among these, we found 45 relevant articles (4RCTs, 11 controlled NRSIs, 7 non-controlled NRSIs and 23 case reports) [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] . Extracted details are presented in Table 1 (RCTs, controlled NRSIs, and non-controlled NRSIs) and table 2 (case report(series)).…”

“… No major adverse effects occurred. Eric Salazar et al [31] USA Prospective, propensity score-matched study,MC Intervention 321, control 582 Severe and/or critically ill One or two units ≤72 h(n = 321) Anti-RBD IgG titer ≥ 1:1350(n = 321) Steroids, AZM, and tocilizumab Transfusion of COVID-19 patients soon after hospitalization with high titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality. 7 CP-related AEs, 2 of which were serious AEs Livia Hegerova et al [32] Swedish Matched study,MC Intervention 20, control 20 Severe or life-threatening 1 unit Median time from hospitalization to CP was early at 2 days – Remdesivir CP use in severe and critically ill patients with COVID-19 may improve survival if given early in the course of disease.…”

“…The patients included in the study had a wide range of age distribution, ranged from 4 to 100 years old. The patients’ conditions were variable, two RCTs [21] , [24] and three controlled NRSIs [26] , [28] , [33] included moderate to severely ill patients, one RCT included less-severe patients, and the clinical symptoms of patients in the 6 controlled NRSIs met the definitions of severe or life-threatening disease [29] , [31] , [32] , [37] , [41] , [42] . One RCT [22] and 4 controlled NRSIs [27] , [34] , [35] , [40] evaluated CP therapy in critically ill individuals.…”

“…Mortality outcomes were reported in 21 of the included 22 controlled studies and non-controlled NRSIs [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [42] . The mortality outcome was evaluated from controlled studies: 4RCTs and 11NRSIs( Fig.…”

The art of the possible in approaching efficacy trials for COVID19 convalescent plasma

“…The yardstick for the assessment of therapeutic efficacy is the RCT, and in the setting of COVID-19 the five RCTs of CCP reported to date have produced inconclusive or negative results ( Table 1 ), potentially due to lack of nAb titer assessment in donated units and/or late treatment. More encouraging findings have been reported from retrospective ( Liu et al, 2020 ) or prospective ( Salazar et al, 2020a , Salazar et al, 2020b ) propensity-score-matched studies run in the US (again relying on CCP units not assessed for nAb titer), but the strength of evidence from this type of studies is lower than that from RCTs.…”