During the early stages of the COVID-19 pandemic, plasma-based therapies were a low-hanging fruit that held the potential of yielding effective treatments — and even vaccine candidates — against this then-unknown virus as they could be moved from bench to bedside fast.
This approach, which was first used as a treatment in the late 1800s, makes use of plasma derived from the blood of people who have recovered from the infection, which is rich in antibodies against the virus. The plasma-derived treatment is then injected into an uninfected individual as a vaccine or an infected person to help fight the infection.
“But some initial preclinical studies showed that in certain situations, some SARS-CoV-1 vaccine candidates could make the infection worse,” says Dr Ruklanthi de Alwis, a then-senior research fellow from the Viral Research and Experimental Medicine Centre at SingHealth Duke-NUS (ViREMiCS).
This happens when antibodies in the plasma that are supposed to fight the virus go rogue and enhance the viral infection instead.
“And because we’ve been studying the mechanisms that make these antibodies go turncoat, we wrote this mini-review about the good and bad of this kind of approach,” explains de Alwis, who wrote the review together with Professor Ooi Eng Eong from Duke-NUS’ Emerging Infectious Diseases Programme and co-director of ViREMiCS.
Drawing on their experience of working with antibodies in all kinds of diseases including dengue where antibodies can switch sides when people are re-infected, they summarised what was known then, what to look out for and how to mitigate this risk in a review article published in the journal eBioMedicine.
They concluded that because of the nature of the data available, the risks appeared to be low, an assessment they would subsequently confirm.
“In terms of antibody-dependent enhancement, we did not see that in subsequent SARS-CoV-2 preclinical studies,” says de Alwis.
Looking back at the role that plasma-based interventions would end up playing, de Alwis says that early hopes of an effective plasma therapy were quickly dashed.
“It still holds true for monoclonal antibodies. If given very early on in an infection, they can be protective against severe disease,” she says. “But plasma therapy, unfortunately, has not shown a lot of protection from disease.”