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Convalescent plasma could still be a crucial coronavirus treatment, says an immunology professor.
Plasma is donated by recovered patients, providing an injection of virus-fighting antibodies.
"Most patients - even in very poor countries - can make plasma," Dr. Arturo Casadevall said.
The rise of contagious coronavirus variants has led to fears that they can both evade existing vaccines as well as authorized treatments like monoclonal antibodies.
Former President Donald Trump received an experimental batch of monoclonal antibodies from the pharmaceutical company Regeneron last October, crediting it with his recovery. The Food & Drug Administration issued an emergency-use authorization soon after.
But such treatment was targeting the original virus, leading many experts to fear that existing treatments could also prove less effective in the face of new variants.
Dr. Arturo Casadevall, chair of the molecular microbiology and immunology department at Johns Hopkins Bloomberg School of Public Health, is less gloomy. Even if vaccines ultimately prove less effective against variants, he told Insider, there may still be a way to help patients infected with these strains, both in the US and the developing world.
Convalescent plasma, donated by people who've recovered from the virus and then injected into those with active infections, provides antibodies generated by the donor's immune system. It's a strategy that's been used for decades - it was even used a century ago in the 1918 flu pandemic - and in August 2020 was authorized for emergency use by the Food and Drug Administration to treat COVID-19.
Convalescent plasma is similar to monoclonal antibody therapies, which are lab-developed drugs that follow the same approach, offering an infusion of proteins designed to recognize and target a particular threat. But unlike its manufactured cousins, new batches of plasma do not require a potentially lengthy regulatory review before they can be put to use.
"One thing about convalescent plasma is that it needs no development," Casadevall said. "If you were to make a vaccine, you have to develop it. If you want to make monoclonal antibodies, you have to develop it. With convalescent plasma, all you need are patients who are recovered and you have a therapy."
In the coming months, Casadevall predicts, patients who have recovered from various coronavirus variants will have donated enough convalescent plasma that (in theory) a patient should be able to go to a hospital and receive a treatment tailored to the variant affecting them.
"That is a future where we continue to use plasma because I think the virus is going to continue to generate new variants," Casadevall said. Plasma could also offer a backstop while vaccine formulas are tweaked to better protect people against variants.
"Even if we defeat the current variants," he added, "more are coming."
But is it just another hydroxychloroquine?
But anecdotal evidence isn't enough, and recent studies have yielded mixed results.
In the fall, a study published in the New England Journal of Medicine found little difference in the death rates of hospitalized patients in Argentina who received convalescent plasma and those who received a placebo. This prompted one comparison, from the University of Minnesota's Center for Infectious Disease Research and Policy, to hydroxychloroquine, the antimalarial drug once touted by Trump as a miracle cure (the FDA revoked the drug's emergency use authorization last summer).
More recently, researchers at Oxford University found that plasma made "no significant difference" in the life-or-death outcomes of hospitalized patients. And in the US, the National Institutes of Health halted a clinical trial involving plasma, saying that while the treatment didn't hurt, it also doesn't seem to provide serious benefits for those suffering from mild cases of COVID-19.
And then there was the case study of a British man who received plasma and experienced a number of viral mutations before he passed away, leading some to speculate that the treatment, when given to the seriously ill, could be responsible for producing new variants.
But most studies are focusing on a test population that is already hospitalized.
Casadevall believes the timing is everything. "One of the things we know about antibody therapies is that they work best when given early," he said. "You need to ask the question: When did they give it relative to the symptoms?"
In another study published last month in The New England Journal of Medicine, one group of Argentine doctors achieved far better outcomes, they said, by treating patients with convalescent plasma "within 72 hours after the onset of mild COVID-19 symptoms."
Wait too long, and plasma can appear no more effective than a placebo.
Johns Hopkins is conducting two clinical trials to investigate whether administering antibodies early is effective. The trials are double-blind, meaning neither the paid volunteers nor medical professionals know whether they are using plasma or a placebo. One group will include people who have tested positive and just begun showing symptoms, while the other will be people who have been exposed to the virus but are not yet symptomatic, an effort to see plasma can stave off any sign of infection altogether.
The studies are being conducted at 20 medical centers across the US and within the Navajo Nation, but it is not yet known when results will be published.
If antibody therapies work, poorer nations could benefit
Although three effective vaccines are authorized and being distributed in the US, less wealthy countries are not inoculating people at anywhere near the same pace. In Guatemala, Honduras, and the Philippines, less than 0.1% of the population has received a single dose, compared to at least 20% in the US and 34% in the UK. That raises questions of equity - whether the developed world is hoarding vaccines - and also jeopardizes the entire trajectory of the pandemic, since the more the virus spreads uncontrolled, the higher the likelihood of new variants emerging.
Convalescent plasma could help here, too, Casadevall said. Not by preventing COVID-19, but by treating it so that many hospitalizations and deaths are avoided.
"Most of humanity is struggling to get vaccines. But humanity - most patients, even in very poor countries - can make plasma," Casadevall said. "So if we learn how to use it, and we get really good protocols for how to make them work, then what I would like to see is that information rapidly disseminated. Because it could really make a difference in some of these countries that are going to get very hard hit."
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