A review of the evidence on convalescent plasma therapy

By Dr. Brit Cooper-Jones

On March 11, 2020, the World Health Organization declared COVID-19 to be a global pandemic. Given the magnitude of this public health crisis and the fact that there are currently no known effective drug treatments or vaccines for COVID-19, there is great interest in exploring other potential treatment options such as convalescent plasma.

And what exactly is convalescent plasma? It is an intervention where plasma (the liquid portion of blood that excludes red blood cells, white blood cells, platelets, and other cellular components) is collected from a recovered COVID-19 patient and then transferred into a patient with an active infection. The theory is that the COVID-19 antibodies (the disease-specific immune molecules) from the recovered individual could help facilitate the recovery of the patient who is actively infected.

Convalescent plasma has been used to treat other types of infections in the past, such as diphtheria, scarlet fever, pertussis and the Spanish flu. However, as promising as the treatment might sound, it isn’t without risks. Because the treatment requires a blood transfusion (from the recovered individual to the patient with an active COVID-19 infection), all of the risks associated with blood transfusions also come into play here (e.g., anaphylaxis, transfusion related lung injury, transfusion associated circulatory overload, transmission of infections). Therefore, it becomes a matter of determining how effective and safe the treatment is, whether the benefits outweigh the risks, and which situations (if any) may warrant the use of convalescent plasma as a treatment for COVID-19.

Currently in Canada there is one clinical trial underway investigating the use of convalescent plasma for the treatment of COVID-19 – the CONCOR-1 trial. This trial is including patients from over 50 hospitals across Canada, and preliminary results are expected to be available at the end of October 2020. But until then, is there other research we can draw upon to better understand the potential effectiveness and safety of convalescent plasma for COVID-19? To help answer this question, the health care community turned to CADTH – an independent agency that finds, assesses, and summarizes the research on drugs, medical devices, tests, and procedures – to find out what the evidence says.

According to CADTH’s recently published report on this topic, the evidence on the effectiveness of convalescent plasma therapy for the treatment of COVID-19 is currently still in the early stages. CADTH identified one randomized controlled trial and two non-randomized studies that compared the clinical effectiveness of convalescent plasma to the current standard of care. While the studies showed some potential promise with convalescent plasma (e.g., two studies reported higher rates of viral clearance, one study suggested a lower mortality rate [but the other two studies found no difference in mortality], and one study showed that patients survived longer with convalescent plasma), the quality of evidence was overall too low to draw any firm conclusions.

The main limitations with the current body of evidence are the lack of high-quality clinical trials and the high risk of bias (due to the study designs; the small sample sizes; and the fact that both the patients who received convalescent plasma and those who didn’t all received standard care, making it difficult to discern if an improvement in health status was the result of convalescent plasma therapy or of another treatment). With regards to safety, the studies reported a total of two non-severe adverse events in patients who received convalescent plasma (out of a total of 53 patients) – but again, the limitations of the study designs and small sample sizes must be considered.

At the current time, while convalescent plasma shows promise as a treatment for COVID-19, additional high-quality research is needed to better inform decisions around its use. Fortunately, many clinical trials further investigating convalescent plasma therapy for COVID-19 are currently underway around the globe. Appendix 6 in CADTH’s report outlines the details of these trials. CADTH will also continue to update its convalescent plasma review monthly as a “living review” to ensure that it continues to reflect the latest evidence as it emerges.

Finally, if convalescent plasma were to be implemented in a more widespread way in the future, additional implementation considerations would need to include: the availability and eligibility criteria for donors; the prioritization and eligibility criteria for recipients (since availability of convalescent plasma is anticipated to be a barrier); the economic and budgetary impacts; and ethical, equity, and safety considerations.

Subscribe to New at CADTH (cadth.ca/subscribe) to stay updated on CADTH’s latest reports, including updates to the convalescent plasma review.

If you would like to learn more about CADTH, visit cadth.ca, follow us on Twitter @CADTH_ACTMS, or speak to a Liaison Officer in your region: cadth.ca/Liaison-Officers

Dr. Brit Cooper-Jones, MD is a Knowledge Mobilization Officer at CADTH.