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

Sarah Chapman blogs about a 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 last updated on 20th May 2021.

Page last updated 18 October 2021.

A Cochrane rapid review (updated in May 2021) with 13 studies and 48,509 participants shows that convalescent plasma has little to no benefit for the treatment of people with moderate to severe COVID‐19. The effects of convalescent plasma for treating people with mild COVID‐19 or who have no symptoms are uncertain. The review is being regularly updated as a ‘living systematic review’, based on weekly searches for new evidence. The authors found about 130 ongoing, unpublished and recently published studies and will update the review with evidence from these studies soon.

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, updated on 20th May 2021, 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.

This has led some researchers to consider plasma as a potential 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 latest news (20 May 2021)

This review is being updated as a ‘living systematic review’. The authors search for new evidence every week and update the review when they identify relevant new evidence.

In May 2021, the review was updated for the fourth time. Thankfully, we now have much more reliable evidence than we had previously. The review now includes 13 studies with 48,509 participants, of whom 41,880 received convalescent plasma. Twelve of these studies are randomized controlled trials – the most reliable form of study. All but one of the studies included participants with moderate to severe COVID‐19. The studies mainly took place in hospitals, in countries all over the world. The review authors only found studies that investigated plasma – none investigated hyperimmune immunoglobulin.

Plasma as a treatment for people with moderate to severe COVID‐19

Compared to placebo or standard care, convalescent plasma makes little to no difference to:

  • the chance of dying from any cause up to 28 days after treatment.
  • the improvement of patients’ condition in terms of needing less breathing support, neither for people needing any breathing support before the start of treatment, nor for the people who were ventilated at the beginning of the study.
  • the worsening of patients’ condition.

Convalescent plasma may make little to no difference to unwanted effects. However, only eight studies reported unwanted effects and they measured and reported their results very differently, so there is still uncertainty about potential harms.

None of the studies reported information about quality of life.

Plasma as a treatment for people with mild COVID19

The review authors only found one study with 160 participants that assessed people with mild COVID‐19. As such, the potential benefits and risks of plasma as a treatment for people with mild COVID-19 remain uncertain.

Increasing certainty that plasma has little to no benefit for treating people with moderate to severe COVID-19

The latest update of this review has brought increasing certainty. We can now be confident that convalescent plasma has little or no benefit as a treatment for people with moderate to severe COVID‐19. However, the effects of convalescent plasma for treating people with mild COVID‐19 or who have no symptoms remain uncertain.

More studies under way…

The authors found about 130 ongoing, unpublished and recently published studies. They will update the review with evidence from these studies as soon as possible. Hopefully, new evidence may answer the remaining questions.

Read an interview with Vanessa Piechotta, the lead author of the review.

There is a Cochrane Clinical Answer for this Review: What are the effects of convalescent plasma for people with moderate to severe COVID‐19?


What about antibodies made in a laboratory?

Plasma contains naturally-produced antibodies, but antibodies can also be made in a laboratory, from cells taken from people who have recovered from the disease. These can be made to target only one specific protein – in this case, a protein on the virus that causes COVID‐19. These are called ‘monoclonal antibodies’. They attach to the COVID‐19 virus and stop it from entering and reproducing in human cells. This may help to fight the infection. It is thought that they might cause fewer unwanted effects than convalescent plasma, which contains a variety of different antibodies.

A Cochrane Review SARS‐CoV‐2‐neutralising monoclonal antibodies for treatment of COVID‐19 (published September 2021) explored the potential benefits and harms of laboratory-made monoclonal antibodies. It included 6 studies with 17,495 people (some of whom were hospitalised, others were not).

Overall, the “current evidence insufficient to draw meaningful conclusions” about whether monoclonal antibodies are an effective and safe treatment for COVID-19. However, there are 36 ongoing studies which will hopefully address this uncertainty.

For more information, you can listen to this Cochrane podcast: Are laboratory-made, COVID-19-specific monoclonal antibodies an effective treatment for COVID-19?

Read these Cochrane Clinical Answers:


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.

References:

Burch J and Tort. For adults with asymptomatic or mild COVID‐19, what are the effects of SARS‐CoV‐2‐neutralising monoclonal antibodies (alone or combined)? Cochrane Library, Cochrane Clinical Answers, 07 September 2021. Web. 14 October 2021. https://www.cochranelibrary.com/cca/doi/10.1002/cca.3724/full

Burch J and Tort. For adults hospitalized with moderate to severe COVID‐19, what are the effects of SARS‐CoV‐2‐neutralising monoclonal antibodies (alone or combined)? Cochrane Library, Cochrane Clinical Answers, 06 September 2021. Web. 14 October 2021. https://www.cochranelibrary.com/cca/doi/10.1002/cca.3819/full

Cochrane. Updated Cochrane living review investigates the use of convalescent plasma to treat people with COVID-19. Cochrane.org, 20 May 2021. Web. 26 May 2021. Available from: https://www.cochrane.org/news/updated-cochrane-living-review-investigates-use-convalescent-plasma-treat-people-covid-19

Kreuzberger N. Are laboratory-made, COVID-19-specific monoclonal antibodies an effective treatment for COVID-19? Cochrane Library, Cochrane Podcasts, 22 September 2021. Web. 14 October 2021. https://www.cochrane.org/podcasts/10.1002/14651858.CD013825.pub2

Kreuzberger  N, Hirsch  C, Chai  KL, Tomlinson  E, Khosravi  Z, Popp  M, Neidhardt  M, Piechotta  V, Salomon  S, Valk  SJ, Monsef  I, Schmaderer  C, Wood  EM, So-Osman  C, Roberts  DJ, McQuilten  Z, Estcourt  LJ, Skoetz  N. SARS‐CoV‐2‐neutralising monoclonal antibodies for treatment of COVID‐19. Cochrane Database of Systematic Reviews 2021, Issue 9. Art. No.: CD013825. DOI: 10.1002/14651858.CD013825.pub2. Accessed 18 October 2021. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013825.pub2/full

Piechotta  V, Iannizzi  C, Chai  KL, Valk  SJ, Kimber  C, Dorando  E, Monsef  I, 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 2021, Issue 5. Art. No.: CD013600. DOI: 10.1002/14651858.CD013600.pub4. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600.pub4/full

Sarah Chapman has nothing to disclose.



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

1 Comments on this post

  1. Seeing as the antibodies in people who have recovered from Coronavirus, whether they were very ill or whether they were asymptomatic should be found in the plasma, maybe we should consider making vaccines out of the blood of people who have recovered, the same way they have used horses and eggs to build vaccines for other conditions.

    It may be a bit late when someone is already sick to be able to see the difference. People are not knock-off rats, so it’s hard to get a good comparison, especially when hospitals are overworked. Conditions such as hyperglycemia upon entering the hospital would have to be matched, and which combination of ApoE genes.

    What about using convalescent plasma on healthcare workers and others who have an exposure to COVID-19, such as the San Jose Kaiser Permanente first responders?

    Deborah E Barges / Reply

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