A Randomized Trial of Convalescent Plasma for COVID-19—Potentially Hopeful Signals

Abstract

Convalescent plasma for the treatment of infectious diseases has been used since the early 20th century and was associated with reduced mortality during the 1918 influenza, 1 2003 SARS, 2 and 2009 influenza H1N1 3 pandemics. However, most published studies of these diseases were case series and retrospective comparisons of treated and nontreated individuals. Consistent with this, several uncontrolled case series of convalescent plasma use in patients with coronavirus disease (2019) COVID-19 have suggested a possible benefit. 4-6 Given encouraging historical precedents and the absence of proven SARS-CoV-2 (severe acute respiratory disease coronavirus 2) antiviral therapies, convalescent plasma therapy has been proposed as a treatment option for COVID-19. 7 The availability of clinical information generated from randomized clinical trials is therefore of substantial importance given that the world remains in the grip of the COVID-19 epidemic and convalescent plasma is currently in use in many countries, including the US. In their article in JAMA, Li et al 8 present findings from the first randomized clinical trial of convalescent plasma therapy for patients with COVID-19 conducted in China. In contrast to most other reports of convalescent plasma use in past epidemics, this study is noteworthy in that it used a randomized trial design and well-characterized plasma units with a high titer of antibody to SARS-CoV-2. It was an important accomplishment to conduct a carefully controlled trial during a pandemic with an entirely new highly contagious disease that stressed health systems in an unprecedented way. However, the authors report that because the COVID-19 outbreak in China was being contained while the trial was ongoing and new cases were unavailable for enrollment, the trial was terminated before it reached its targeted original sample size of 200 patients; only 103 were enrolled (for whom randomization was stratified by disease severity). Consequently, the study was underpowered and many comparisons between the convalescent plasma group and the control group were not statistically significant. In the primary analysis, based on 52 patients who were randomized to receive convalescent plasma in addition to standard treatment and 51 patients who were randomized to receive standard treatment alone (control), the primary outcome of time to clinical improvement within 28 days (defined as being discharged alive or having a reduction of 2 points on a 6-point disease severity scale) was 2.15 days shorter (95% CI, −5.28 to 0.99 days) in the intervention

Convalescent plasma therapy: Helpful treatment of COVID‐19 in a kidney transplant recipient presenting with severe clinical manifestations and complex complications

“…2,3 However, only a very limit evidences has been showed it is effective in COVID-19 treatment. 4,5 Here, we describe the first successful recovery of case of COVID-19 in a KTR treated with convalescent plasma therapy.…”

Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

“…We previously demonstrated that passive transfer of monoclonal antibodies against SARS-CoV-2 S protein reduced viral titers and pathology in the lungs in a mouse model of SARS-CoV-2 (3). Monoclonal antibodies engineered from neutralizing antibodies, initially identified from convalescent COVID-19 patients, have been advanced as potential antiviral therapeutics (4)(5)(6), and early results from convalescent plasma use in patients indicate a protective effect of antibodies against SARS-CoV-2 (7)(8)(9)(10). While early results are promising, the antibody titer conferring protection remains unclear and the role of neutralizing antibodies in protection has not been fully elucidated (11).…”

A rapidly adaptable biomaterial vaccine for SARS-CoV-2

“…Many strategies to combat COVID-19 are currently being implemented; among them include contact tracing, convalescent plasma therapy, anti-viral drug therapy, and vaccine development (6)(7)(8)(9). Here, we focus on vaccine development.…”