Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors

Abstract

Treatment and prevention of coronavirus disease 2019 (COVID-19) have attempted to harness the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) including the development of successful COVID-19 vaccines and therapeutics (e.g., Remdesivir, convalescent plasma [CP]). Evidence that SARS-CoV-2 exists as quasispecies evolving locally suggests that immunological differences may exist that could impact the effectiveness of antibody-based treatments and vaccines. Regional variants of SARS-CoV-2 were reported in the USA beginning in November 2020 but were likely present earlier. There is available evidence that the effectiveness of CP obtained from donors infected with earlier strains in the pandemic may be reduced when tested for neutralization against newer SARS-Cov-2 variants. Using data from the Expanded Access Program to convalescent plasma, we used a gradient-boosting machine to identify predictors of 30-day morality and a series of regression models to estimate the relative risk of death at 30 days post-transfusion for those receiving near sourced plasma (defined as plasma transported ≤ 150 miles) vs. distantly sourced plasma (> 150 miles). Our results show a lower risk of death at 30 days post-transfusion for near sourced plasma. Additional analyses stratified by disease severity, time to treatment, and donor region further supported these findings. The results of this study suggest that near sourced plasma is superior to distantly sourced plasma, which has implications for interpreting the results of clinical studies and designing effective treatment of COVID-19 patients as additional local variant are likely to emerge.

Resistance of SARS‐CoV‐2 beta and gamma variants to plasma collected from Canadian blood donors during the spring of 2020

“…There was also no Delta construct for the pseudovirus assay system. This study was limited to Canadian blood donors 20 . Specimens were also collected from routine blood donors and not qualified convalescent plasma donors in Canada 7 .…”

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

“…Convalescent plasma is also adaptable to changing conditions. As variant SARS-CoV-2 strains continue to emerge, convalescent plasma donated by survivors of infections with variant strains represents an immediately deployable therapeutic for patients identified with a variant infection, whereas other immune therapies may require (re)development to more specifically target new viral strains ( 16 – 19 ).…”

“…Pooling these available survival data demonstrated a 11% relative improvement in 28-day survival associated with convalescent plasma compared to control (88 vs. 79%) ( Figure 2B ). While the effect of convalescent plasma on mortality was found to be statistically significant in only two RCTs ( 42 , 71 ), it is important to highlight that signals of efficacy have emerged despite several limitations, including trials that (i) were underpowered due to declining local infection rates and early termination ( 27 , 43 ), (ii) transfused convalescent plasma units with unknown or low anti-SARS-CoV-2 antibody levels ( 30 ), (iii) transfused severely ill patients that had progressed to severe COVID-19 ( 11 , 27 ), and (iv) used prepositioned plasma units, which may not have accounted for SARS-CoV-2 variants ( 18 , 19 ). Transfusion of low antibody titer plasma to patients with severe COVID-19 reduces the opportunity to achieve the survival benefit associated with convalescent plasma.…”

A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia

“…Given recent large, randomized studies that have not shown benefit in general hospitalized cohorts, it is important to put the positive result of our study in context. This study has several unique characteristics that may have contributed to the demonstrated benefit, including the early administration of two units of locally sourced, plasma in a highly comorbid, majority antibody seronegative population [29,30]. In addition, we employed a sensitive primary outcome measure enabling a composite characterization of clinical status [31].…”