Cochrane is producing a series of reviews to help decision makers respond to the COVID-19 pandemic. In July 2020, we published our first update of the review of convalescent plasma and hyperimmune immunoglobulin and we asked its lead author, Vanessa Piechotta from the University Hospital Cologne in Germany, to tell us what they found.
Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. Cochrane is producing a series of reviews to help decision makers respond to the COVID-19 pandemic. In July 2020, we published our first update of the review of convalescent plasma and hyperimmune immunoglobulin and we asked its lead author, Vanessa Piechotta from the University Hospital Cologne in Germany, to tell us what they found.
Vanessa: Convalescent plasma and hyperimmune immunoglobulin, which come from patients who have recovered from the infection, have been used to treat a variety of infections when no other effective treatments are available. For example, they were used in previous outbreaks of severe viral respiratory infections, such as influenza and Severe Acute Respiratory Syndrome, or SARS, and have been shown to reduce the risk of death.
The hope is that convalescent plasma will treat COVID-19 disease through a process called passive immunization, by supplying virus-binding antibodies that will help clear viral particles. This is most likely to occur when treatment is given early after infection and, although convalescent plasma and hyperimmune immunoglobulin treatment are thought to be generally safe, adverse events can occur. So, it’s important to know whether they are an effective and safe treatment for people with COVID-19.
We searched for studies from anywhere in the world, including participants of any age, gender or ethnicity, who had mild, moderate or severe COVID-19. We were looking for effects on a variety of patient outcomes, including survival, clinical improvement, quality of life and adverse events; and, for this latest version of the review, we found twenty studies. One of these is a randomized trial that was stopped early because of containment of COVID-19 at the study location and there are also three non-randomized studies with a control group. The other 16 studies did not include a control group but provided information on possible side effects of convalescent plasma. In total, 5442 people were included in the studies reported to date, with 5211 of them receiving convalescent plasma. No studies of hyperimmune immunoglobulin have yet been reported.
To assess the effectiveness of convalescent plasma, we evaluated the results of studies with a control group that received standard care without convalescent plasma. Considering the identified evidence, we could not determine whether or not convalescent plasma affected the need for breathing support, the risk of death due to any cause before hospital discharge or time to death; and none of the included studies reported effects on quality of life.
We were able to assess safety outcomes only for those people treated with convalescent plasma because none of the controlled studies reported safety data for the control group. We identified some severe adverse events that might be related to convalescent plasma, including death, allergic reactions or respiratory complications; but the limited quality of the available evidence means that we are very uncertain whether or not convalescent plasma really did cause these severe adverse events.
In summary, the information from the studies that were available in early June 2020 still leaves us very uncertain about the effectiveness and safety of using convalescent plasma for people with COVID-19. Despite extensive searching, we were only able to include very low-certainty evidence. Most studies did not use reliable methods to gather their results. Furthermore, participants received a range of other treatments alongside convalescent plasma, and some had underlying health problems. We cannot know whether the reported effects were due to convalescent plasma, another treatment, or simply the natural course of the disease. This is why we urgently need the results of high-quality randomized trials, which will allow us to assess these factors.
However, this field of research is rapidly changing and we identified approximately 100 ongoing studies, of which 50 are randomized trials. We will continue to update this review, as a ‘living systematic review’, so that it reflects the most current, available evidence.
Monaz: Thanks Vanessa. If you’d like to read this systematic review, and to watch for its updates as the results of the ongoing studies become available, just go online to Cochrane Library dot com and search convalescent plasma and COVID-19'.