An artist’s impression of red blood cells flowing through a vein. Image: Narupon Promvichai/pixabay.
Researchers in China have been experimenting with using blood plasma from patients who have recovered from COVID-19 as a possible way to treat severely ill COVID-19 patients. In a new study published in the Proceedings of the National Academy of Science, clinicians reported that convalescent plasma therapy improved the outcomes of ten patients with severe cases of COVID-19.
“It’s consistent with what I’m hearing from other places,” Michael Joyner, a physiologist at Mayo Clinic who is leading a convalescent plasma clinical trial in the US and wasn’t involved in the study from China, told The Wire Science.
In convalescent plasma therapy, a dose of antibody-containing plasma obtained from the blood of recovered individuals is transferred to persons with the disease in order to treat it. It’s an experimental therapy going back a hundred years, having found use – to different efficacies – in the treatment of the Spanish flu as well as, more recently, the 2009 H1N1 influenza, SARS and MERS viruses.
Convalescent plasma could shorten the duration of a COVID-19 illness or render it less dangerous. The therapy can be administered at different stages: after exposure to a known carrier but before infection to boost immunity, and to critically and non-critically ill patients to improve their outcomes.
At the moment, while researchers are exploring a number of experimental therapies and drugs, regulatory bodies have not approved any specific antiviral agents to treat COVID-19. Convalescent plasma is one of three immune-based options that may be able to tackle COVID-19 (the other two are hyperimmune serums and intravenous immunoglobulin products, which comprise antibodies against other human coronaviruses that may respond against the SARS-CoV-2 virus as well). However, convalescent plasma is easier to give even at the level of a single institution compared to the other options, which may require assistance from pharmaceutical companies.
“This is the second encouraging case series in critically ill patients from China, but we definitively need phase 3 randomised controlled trials to assess the clinical benefit of convalescent plasma therapy,” Daniele Focosi, a transfusion specialist at Pisa University Hospital, Italy, who is involved in a multi-centre clinical trial for convalescent plasma and was not associated with the Chinese study, told The Wire Science.
Yet another study published in the Journal of the American Medical Association reported that five patients who were receiving mechanical ventilation and were then administered convalescent plasma therapy had recovered from the disease. Compared to phase 3 clinical trials, phase 2 trials are conducted in smaller groups to check for efficacy and safety, and have already proven during “previous pandemics that convalescent plasma is safe and partially effective.”
In the newest study, the researchers recruited ten patients – six male, four female – at three hospitals in China. At a median time of 16.5 days from the beginning of their respective infections, the patients were administered 200 ml of convalescent plasma obtained from former COVID-19 patients. In addition, all patients also received antiviral agents and supportive care.
The donors were tasked with supplying plasma four days after their discharge from hospital and the collected blood product was treated to ensure the absence of any virus. The very high titres of antibodies needed for convalescent plasma therapy can only be drawn from patients that have had a bad case of the condition soon after their discharge, Focosi added.
Within three days, the patients all showed robust improvements across several clinical symptoms, including cough, fever, shortness of breath and chest pain. Eight of the ten patients had been receiving some form of ventilation or oxygenation, and showed lower dependence post-transfusion. A number of immunological and other parameters also improved following transfusion.
Within seven days, radiological scans showed that lung damage was reduced to different extents in the patients. Moreover, the viral load in seven patients who had had viraemia, which is the presence of virus particles in blood, was imperceptible seven days after the transfusion even as the researchers recorded high levels of antibodies. Except for one patient, who developed a facial red spot, none displayed any adverse side effects either.
The team did compare their results in these 10 patients to a control group of 10 patients who had been matched for gender, age and the severity of their COVID-19 infection, but the antiviral and supportive care administered was not necessarily similar across patients or even within each of the two groups.
“In this sort of brief report, all you can try to do is match the controls you have to the cases,” Joyner said. “When there are larger numbers [of participants], more extensive case control studies with better matching will be available and more insights about recovery will be available.”
While all patients showed significant recovery across the board, with three even being discharged (while the remaining seven were well on their way to full recoveries), researchers agreed that more extensive randomised controlled trials are needed to assess the efficacy of the therapy, and pave its way for widespread use. Such trials could also help lock down the best dosage and time of transfusion.
Currently, there are more than 20 clinical trials using convalescent plasma being conducted worldwide.
Sukanya Charuchandra has written for The Scientist, Johns Hopkins Magazine and Firstpost. Her writing interests feature biology, medicine and archaeology.