Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience

Abstract

Importance: Passive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. Objective: To explore potential signals of efficacy of COVID-19 convalescent plasma. Design: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma. Setting: Multicenter, including 2,807 acute care facilities in the US and territories. Participants: Adult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. Intervention: Transfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. Results: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. Conclusions and Relevance: The relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma. Trial Registration: ClinicalTrials.gov Identifier: NCT04338360

Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID19 Patients

“…To this end, investigators from the Mayo Clinic's COVID-19 Expanded Access Program (EAP) performed an exploratory analysis on the efficacy of CP as a therapeutic agent using data from over 35,000 transfusions. (20) Although the study showed uncertainty as to the statistical significance of effect, the authors noted that patients transfused with high antibody titer CP units, quantified by the Ortho IgG assay, showed a notable reduction in the odds ratio of mortality at both 7 and 30 days after transfusion. These data support the assertion that antibody quantification of CP units using high dynamic range HSTA assays may further improve therapeutic options for COVID-19 and, perhaps, future pandemic responses.…”

Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID-19 Patients

“…the extent to which three widely available SARS-CoV-2 HTSAs correlated to nAb activity as well as to on November 5, 2020 by guest http://jcm.asm.org/ Downloaded from each other, providing the clinical and scientific community with a comprehensive overview of clinical serology test performance. To this end, investigators from the Mayo Clinic's COVID-19 Expanded AccessProgram (EAP) performed an exploratory analysis on the efficacy of CP as a therapeutic agent using data from over 35,000 transfusions (20). Although the study showed uncertainty as to the statistical significance of effect, the authors noted that patients transfused with high antibody titer CP units, quantified by the Ortho IgG assay, showed a notable reduction in the odds ratio of mortality at both 7 and 30 days after transfusion.…”

Convalescent plasma for COVID-19: male gender, older age and hospitalisation associated with high neutralising antibody levels, England, 22 April to 12 May 2020

“…At the time of a second wave of the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1], effective antiviral therapies and vaccines are not yet available for clinical use [2,3]. Convalescent plasma collected from recovered COVID-19 patients has been suggested a safe and probably effective treatment in some nonrandomised studies [4][5][6][7][8][9][10][11]. As the efficacy of such therapy is most probably associated with the presence of high levels of neutralising antibody in the donated plasma, we investigated the clinical and demographic factors that are predictive of high titres in convalescent plasma donors.…”