A Convincing Case for Convalescent Plasma Treatment of COVID-19

Providing convalescent plasma in early treatment of COVID-19 reduced risk for hospitalization by half, in a placebo-controlled study of over 1000 outpatients at multiple US sites, coordinated by investigators at Johns Hopkins, Baltimore, MD..

Study lead author David Sullivan, MD, Departments of Molecular Microbiology and Immunology at Johns Hopkins Medicine and Department of Epidemiology, Johns Hopkins Bloomberg School of Medicine, described COVID-19 convalescent plasma (CCP) as the only antibody therapy that "keeps up with SARS COV-2 variants", in a statement released by Johns Hopkins.

"As the changing, often unpredictable landscape of the COVID-19 pandemic demands multiple treatment options--especially in low- and middle-income nations where frontline therapies, such as vaccines and monoclonal antibodies, may not be readily available--our study provides solid evidence that antibody-rich convalescent plasma should be part of the outpatient arsenal," Sullivan stated.

Sullivan and colleagues noted that while data on CCP treatment from randomized clinical trials (RCT) are limited and mixed, there have been indications that benefit is more likely when CCP with high antibody titer to SARS-CoV-2is provided early after symptom onset.

To obtain RCT data with those conditions, the investigators randomized 1181 participants ≥18 years of age testing positive for SARS-CoV-2 to receive either CCP or placebo control plasma within 9 days of symptom onset, regardless of their risk factors or vaccine status. The study enrollment period was between June 3, 2020 to October 1, 2021. The primary outcome was cumulative COVID-19 related hospitalizations, with secondary measures of disease severity by ICU admission, invasive mechanical ventilation, or death in hospital.

Among participants receiving the CCP transfusion, 17 of 592 (2.9%) required hospitalization, compared to 37 of 589 (6.3%) who received the placebo control plasma, corresponding to a 54% risk reduction. The investigators found that this outcome did not change after analysis for covariates. Hospital oxygen was required by 12 of those in the CCP group and 26 in the control group.All 3 post-hospitalization deaths were in the control plasma group.

The investigators acknowledged several limitations in the study, including that standards of care and available therapies changed throughout the study period. Targeted monoclonal antibody products became available in late November 2020, which increasingly reduced those eligible for CCP.I n addition, they noted that as vaccine utilization increased, the frequency of study hospitalizations decreased. In fact, they halted the trial after enrolling over 90% of their initial target due to declining hospitalization among enrolled participants.

The evidence of benefit from early treatment with CCP was strong, however, and the investigators assert that it has important public health implications, especially in resource-constrained settings.

"With early administration of high-titer SARS-COV-2 convalescent plasma reducing outpatient hospitalizations by more than 50%, our findings suggest that this is another effective treatment for COVID-19 with the advantages being low cost, wide availability and rapid resilience to the evolving SARS-CoV-2," study co-lead author Kelly Gebo, MD, MPH, Department of Medicine, Division of Infectious Diseases, Johns Hopkins, indicated in the released statement.

Sullivan added that they had shared the findings with the FDA and the WHO. "We hope that both organizations will see the value of convalescent plasma for outpatients based on the strength of our study, the largest randomized clinical tiral of its kind to date," he said.

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