Dr. Lise Estcourt and Dr. David Roberts
NHS Blood and Transplant
Convalescent plasma treatment, containing high levels of polyclonal antibody (Ab), has been used to treat severe viral pneumonia during previous pandemics. In fact, it has been used intermittently for over a century, including patients treated during the era of the Spanish Influenza pandemic in the early 20th century.1 Although, all the studies described at that time had significant methodological flaws, and none were randomised, they suggested a reduction in mortality.1
In the more recent past, convalescent plasma has been used to treat H1N1 influenza, and, more relevantly, SARS-CoV infections in 2003, with evidence of benefit in some of these studies, especially if convalescent plasma was given earlier in the course of the disease (within the first 14 days of symptoms).2
A systematic review of the evidence has shown that there is only limited information about the effectiveness and safety of convalescent plasma in people with COVID-19.3 There have been only 8 uncontrolled studies published, including a total of 32 participants. Currently there is insufficient evidence to say whether or not convalescent plasma is effective and safe in the treatment of COVID-19. We do know that there are many trials being registered and 22 randomised trials around the world had been registered on trial registries.3 Two living systematic reviews of convalescent plasma plan to start in the near future, one will assess the benefits of treating people who have been diagnosed with COVID-19 and the other will assess the benefits of preventative treatment for people at high risk of getting COVID-19.
Two large trials of are going to be conducted in the UK. Firstly, an international trial REMAP-CAP, has started in the UK and is randomising patients to several different treatments to assess whether they are beneficial to adults who are critically ill due to COVID-19. One of these randomisations is comparing convalescent plasma to standard care. We are giving two doses of convalescent plasma to patients who have recently been admitted to intensive care and assessing whether this decreases the risk of remaining on a ventilator or dying due to COVID-19. We are also assessing whether there are any potential harms of this treatment. We plan to randomise up to 2000 participants to this trial. This is an adaptive trial and if there is evidence that convalescent plasma improves outcomes for critically ill patients the trial will be stopped and then all patients admitted to intensive care will be given convalescent plasma. The trial is currently open at 10 hospitals around the country and plans to open at more than 100 intensive care units around the country.
Secondly, a UK-wide trial of convalescent plasma in all hospitalised patients with COVID-19 as part of the RECOVERY trial is planning to start in the near future. We are giving the same treatment, two doses of convalescent plasma, as in the REMAP-CAP trial. This will assess whether convalescent plasma decreases the risk of death or the need for mechanical ventilation for anyone who is hospitalised with COVID-19 and does not have a contraindication to receiving a plasma component. It will include people with COVID-19 of any age, including neonates, who are unwell enough to be admitted to hospital. We plan to randomise up to 5000 participants to this trial and open the trial at more than 200 hospitals around the UK.
We hope to have results from these trials by Spring 2021.
References
- Luke TC, Kilbane EM, Jackson JL, et al. Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment? Annals of Internal Medicine 2006;145(8):599. doi: 10.7326/0003-4819-145-8-200610170-00139
- Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The Effectiveness of Convalescent Plasma and Hyperimmune Immunoglobulin for the Treatment of Severe Acute Respiratory Infections of Viral Etiology: A Systematic Review and Exploratory Meta-analysis. Journal of Infectious Diseases 2015;211(1):80-90. doi: 10.1093/infdis/jiu396
- Valk S, Piechotta V, Chai K, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review. Cochrane Database of Systematic Reviews 2020;2020(5):[In Press]