Sarah Chapman blogs about the latest Cochrane A rapid review is a simplified systematic review that can be done in a few weeks to produce timely evidence for decision-making. 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 A Living Systematic Review is a systematic review which is continually updated, incorporating relevant new evidence as it becomes available., 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 In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 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 Something done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. 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). Randomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group). Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. 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 A trial in which a group (the ‘intervention group’) is given a intervention being tested (for example a drug, surgery, or exercise) is compared with a group which does not receive the intervention (the ‘control group’)., 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 The ability of an intervention (for example a drug, surgery, or exercise) to produce a desired effect, such as reduce symptoms. and Refers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. 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.
The evidence is all assessed as being low- or The certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate. Concerns about factors such as bias can reduce the certainty of the evidence. Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty. Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find out more here: https://training.cochrane.org/grade-approach, 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.
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.
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.