Cochrane is producing a series of reviews to help decision makers respond to the COVID-19 pandemic and is keeping these up to date as new evidence emerges. In October 2020, we published our second update of the review of convalescent plasma and hyperimmune immunoglobulin and we asked its lead author, Khai Li Chai from Monash University in Australia, to tell us about the latest findings.
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 and is keeping these up to date as new evidence emerges. In October 2020, we published our second update of the review of convalescent plasma and hyperimmune immunoglobulin and we asked its lead author, Khai Li Chai from Monash University in Australia, to tell us about the latest findings.
Khai Li: Convalescent plasma and hyperimmune immunoglobulin, which come from patients who have recovered from the infection, have been used to treat a variety of infections, including during 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 in these conditions.
For COVID-19, the hope is that convalescent plasma will treat the 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. Although convalescent plasma and hyperimmune immunoglobulin treatment are thought to be generally safe, adverse events can occur, as with any transfusion of blood products. So it’s important to know whether they are an effective and safe treatment for people with COVID-19.
Our living systematic review is bringing together the available research evidence to try to assess this.
We searched for studies from anywhere in the world, with patients with any stage of COVID-19, and were looking for a range of effects on a variety of patient outcomes, including survival, clinical improvement, quality of life and adverse events. In this update, we have included 19 studies of convalescent plasma, two of which are randomised trials and eight are non-randomised studies with a control group. The other nine studies did not include a control group but provided information on possible side effects. In total, more than 38,000 people have been included in the studies reported to date, with about 36,000 receiving convalescent plasma. There were no studies of hyperimmune immunoglobulin reported yet.
To assess the effects of convalescent plasma, we focused on the randomised trials. In these, participants in the control group received standard care at the time of treatment but without convalescent plasma. Considering the two trials, there was insufficient evidence to determine whether convalescent plasma affected the risk of death in hospital but they do suggest that convalescent plasma may decrease the need for breathing support. However, our confidence in this is low.
Turning to the safety outcomes, for which we also used the data from the non-randomised trials, we could only assess this for the people treated with convalescent plasma, because none of the included studies reported safety data for the control group. There were some severe adverse events that could be related to convalescent plasma, including death, allergic reactions or respiratory complications; but the limited information available to date means that there is not enough evidence to determine whether convalescent plasma therapy causes serious unwanted events and our confidence in the evidence is also low.
In summary, the information from the studies that were available in mid-August 2020 means that we remain uncertain about the effectiveness and safety of convalescent plasma for people with COVID-19. Despite extensive searching, we were only able to include low-certainty evidence. There were two published, randomized trials, both of which had stopped early. One because of containment of the disease at the study location and the other because of the detection of antibodies to SARS-CoV-2 in participants at baseline. Participants received a range of other treatments alongside convalescent plasma, and some had underlying health problems; so we cannot know whether the reported effects were due to convalescent plasma, another treatment, or simply the natural course of their COVID-19.
We urgently need the results of more, high-quality, randomised trials that were powered for important clinical outcomes such as mortality and intensive care support; and we know that this field of research is rapidly changing. There are 140 on-going studies, of which over 70 are randomised trials, and we will continue to update this Cochrane Review as a ‘living systematic review’. This will ensure that it reflects the most current, available evidence and we are already aware of two randomised trials, published as preprints. However, our quick assessment of these have shown that they would not change our current, overall conclusions and we will wait to consider them more fully in the next update.
Monaz: If you’d like to read this systematic review, and to watch for further updates as the results of more of the ongoing studies become available, just go online to Cochrane Library dot com and search 'plasma and COVID-19'.