Effectiveness of convalescent plasma therapy in severe COVID-19 patients
clinical immunology/immunity therapeutics
Authors: Duan et al. Link to paper: https://www.pnas.org/content/pnas/early/2020/04/02/2004168117.full.pdf
Key Words: Plasma therapy
1. Plasma therapy showed no severe adverse events in COVID-19 patients
2. One dose of convalescent plasma was sufficient to increase or maintain neutralising antibodies
3. Timing of therapy was important for speed of recovery
Main findings of the study
This study investigated the feasibility of treating severe COVID-19 with convalescent plasma (CP) containing neutralising antibodies. 10 patients with a range of ages, sex, symptoms, viral titres and antibody titres were given one dose of CP at a range of days post symptom onset. No severe adverse events were seen, and all patients recovered. When given CP less than 14 days after symptom onset, recovery was faster than when at more than 14 days. Symptoms diminished after CP even in patients where viral titre was already undetectable but severe symptoms remained, suggesting CP could be a valuable therapeutic.
IMPACT FOR SARS-COV2/COVID19 RESEARCH EFFORTS
Treatment of SARS-CoV2/COVID19 positive individuals
Successful treatment options for severe COVID-19 are currently limited, and there have been concerns that plasma therapy may cause adverse reactions such as antibody dependent infection enhancement (or transfer more virus). However, this paper indicates that it can be given without severe adverse events, and could be a useful therapeutic.
· Clinical Cohort study (e.g. drug trials)
STRENGTHS AND LIMITATIONS OF THE PAPER
Novelty: Shows treatment of COVID-19 with convalescent plasma therapy, which has been used for other diseases previously.
Standing in the field: Both SARS and MERS have previously been shown to be treatable with CP (whereas Ebola was not), supporting the idea that SARS-CoV2 may also be treatable, although interestingly different concentrations of neutralising antibody were needed for the different diseases.
Appropriate statistics: No statistical tests were performed in this study.
Viral model used: SARS-CoV2
Translatability: Highly translatable, if shown in more patients this could be a quick and successful treatment for severe disease.
Main limitations: This study was only performed in 10 patients who were all on various antiviral and antibacterial agents. They had all been in hospital for some days before plasma therapy was given, and it might be expected that at the time points investigated, some patients would have started to recover anyway, and develop their own neutralising antibodies (indeed, some already had them and/or had no viral load). The control group used was a random mixture of patients treated in the same hospitals and, although matched as closely as possible to the experimental group, were historic cases. It is therefore hard to draw strong conclusions on the efficacy of treatment without the ability to directly to compare to patients without CP therapy.
Due to the number of antivirals given alongside the therapy tested, it could be that these played an important part in recovery as well, either alone or in synergy with CP.
- Moreover, we cannot tell whether these patients were going to recover anyway given these antivirals or other agents (including Remdesivir)
- A clinical trial should be done to check if CP is the way forward.