Convalescent plasma to treat people with COVID-19: the evidence so far

Sarah Chapman blogs about the latest Cochrane rapid review produced in response to the COVID-19 pandemic, looking at the evidence on convalescent plasma as a possible treatment for COVID-19. This blog discusses a living systematic review, which was updated for the second time on 12 October 2020.

With an urgent need for evidence to help those making health decisions in these unparalleled times, one of the things Cochrane is doing in response is to produce rapid reviews. These are simplified systematic reviews that can be done in a few weeks to produce timely evidence for decision-making. The latest of these, published on 14 May (updated 10 July), brings together the evidence on convalescent plasma as a possible treatment for people with COVID-19.

What is convalescent plasma?

Plasma is a liquid that makes up about half of your blood volume. After a person has recovered from an infection (this is the convalescent bit), their blood contains antibodies that help fight infection. Some people who have fully recovered from an infection can donate plasma (as with blood donation, there are reasons why they might not be able to). Randomized trials are being done to investigate the potential benefits or harms of using plasma from people who have recovered from COVID-19 to treat people who are currently ill with it.

Convalescent plasma has been used in the past to effectively treat infections where there were no drug treatments or vaccines, such as diptheria and polio. Evidence on whether it helps treat severe respiratory infections has been mixed and there are potential harms too, such as allergic reactions.

So this has potential as a treatment for COVID-19 but we need to know what evidence there is on the benefits and risks.

What is the evidence from the Cochrane Rapid Review?

The review authors looked for studies investigating convalescent plasma or hyperimmune immunoglobulin (prepared from convalescent plasma) for people with COVID‐19, without any limits on age, ethnicity, gender or disease severity.

The disappointing news…

In the first version of this review (May 2020), there were only 8 studies to include, with 32 people who received convalescent plasma. As well as there being very few people in the studies, they weren’t randomized controlled trials, which would give us more reliable evidence. None of the studies compared people receiving convalescent plasma with people who did not. There were other problems with the studies too, and the review authors note that it’s not possible to know whether the results reflect the natural history of the disease (the course the illness would take in an individual without treatment), the convalescent plasma treatments, or other treatments they were having at the same time.

The evidence here was assessed by the review authors as being ‘very low certainty’ and the bottom line is that the effectiveness and safety of convalescent plasma treatment for people with COVID-19 remain uncertain.

But that’s not the end of the story. This review is being updated as a ‘living systematic review’, searching for new evidence every month and adding it to the review. We hope to see more reliable results as this evidence is added.

The latest news (12 October 2020)

Since writing this blog, the review has been updated twice, most recently on 12 October 2020. It now includes 19 studies with 38,160 people; over 36,000 of them received convalescent plasma. Two of the studies are randomized controlled trials (RCTs). These RCTs involved just 189 people in total, of whom 95 received convalescent plasma and were compared with people receiving “standard care at time of treatment without convalescent plasma”. The trials were stopped early, one because there were no more eligible people due to containment of the epidemic in Wuhan and the other because most of the people in the trial were found to have SARS‐CoV‐2 antibodies. Two more RCTs, completed in August, are awaiting assessment by the review authors.

Continued uncertainty

The evidence is all assessed as being low- or very low-certainty, so there remain important questions about potential benefits and harms of this treatment for people with COVID-19. The review authors conclude that “we are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID‐19.” Also, despite the investigation of serious adverse events (harms) for over 20,000 people in 17 studies, because there was no control group in the studies the authors say “we are unable to assess the relative safety of convalescent plasma therapy”.

More studies under way…

The review authors also identified 138 ongoing studies, of which 73 are randomized trials. It’s clear that there is a scramble to produce evidence but is scientific rigour being sacrificed for speed? Let’s hope we get better quality studies in the next update.

On this page, which is constantly updated, you can stay informed about Cochrane content relating to the coronavirus (COVID-19) pandemic and the various related activities that Cochrane is undertaking in response.

Take-home points

we are unable to assess the relative safety of convalescent plasma therapy. Take-home points: A Cochrane rapid review with 19 studies, including two small randomized controlled trials, shows that the effectiveness and safety of convalescent plasma for people with COVID-19 are uncertain. The review authors identified 138 ongoing studies, including 73 randomized trials. This review is being regularly updated as a ‘living systematic review’, based on monthly searches for new evidence, and the results are likely to change.  Chapman S. “Convalescent plasma to treat people with COVID-19: the evidence so far”. Evidently Cochrane blog, 15 May 2020, last updated 12 October 2020.

 

Join in the conversation on Twitter with @CochraneUK @SarahChapman30 or leave a comment on the blog. Please note, we cannot give medical advice and we will not publish comments that link to commercial sites or appear to endorse commercial products.

Reference:

Chai  KL, Valk  SJ, Piechotta  V, Kimber  C, Monsef  I, Doree  C, Wood  EM, Lamikanra  AA, Roberts  DJ, McQuilten  Z, So-Osman  C, Estcourt  LJ, Skoetz  N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19: a living systematic review. Cochrane Database of Systematic Reviews 2020, Issue 10. Art. No.: CD013600. DOI: 10.1002/14651858.CD013600.pub3.

Sarah Chapman has nothing to disclose.

Page last updated 12 October 2020.



Convalescent plasma to treat people with COVID-19: the evidence so far by Sarah Chapman

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

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