In the latest Captain America comic, Cap faces a fictional situation that resonates with our own: A pandemic threatens to engulf his world. Lucky for him, he's already manufacturing the cure in his veins. When Cap realizes his blood can revive the infected, he offers it up: "If my blood is the cure – then take it," he says.
In our real-life pandemic, one person's blood may not offer such a cure. But scientists are hoping that blood — blood plasma, specifically — could be a powerful weapon against the novel coronavirus. That blood doesn't even have to come a serum-infused super-soldier.
It can come from almost anyone, as long as they have beaten Covid-19.
Scientists are racing to cure the coronavirus, which at the time of writing has sickened over one million people around the world. Preclinical research on the virus is progressing at breakneck speed. Vaccines are even in clinical trials, but any vaccine may be a year or more away from actually being used. In the scramble for a treatment to fill the gap, scientists are turning to an old medical idea: convalescent plasma therapy.
When someone recovers from a disease, their blood contains antibodies, fighter cells sent by the immune system to combat the virus. Those antibodies linger in blood plasma, which can be sifted out from the blood by a process called apheresis. Blood from a donor is taken, run through a machine, then red and white blood cells are returned to the donor, leaving the plasma behind. That plasma can then be used as a treatment.
A study published Monday in Proceedings of the National Academy of Sciences adds to the growing body of work on convalescent blood plasma therapy.
Like many others published thus far, this trial does not meet the gold standard, a randomized controlled clinical trial. That said, in a sample of 10 critically ill people with confirmed Covid-19 diagnoses, the team reported that receiving 200 ml of plasma relieved symptoms as soon as three days. In 5 of the participants, levels of anti-viral antibodies increased, but in another four they did not.
"It gives me my power back to help other people."
While preliminary, the trial published this week is demonstrative of the hope this therapy holds for Covid-19. Its potential rests on the idea that the antibodies gleaned from someone who has beaten the coronavirus may then help at least one other person recover (similar to Captain America's fictional blood donation).
The concept behind convalescent plasma therapy was enough to inspire Tim Wils, a recent college graduate who works at The Julliard School.
As New York City retreated into quarantine, Wils got sick. He felt "very achy, headache, fever, digestive problems, loss of taste," he tells Inverse. Even after he recovered, he couldn't shake a feeling of helplessness. Then, he heard that he could donate his plasma after reading a New York Times story.
"I realized I'm just the kind of person who can feel helpless and hopeless in a situation like this," Wils says. "It gives me my power back to help other people, which this pandemic really stole from me."
But before you get too excited, scientists are not sure whether this treatment really works, Steven Spitalnik, co-director of Columbia University's Laboratory of Transfusion Biology, says. He is involved with the university's convalescent plasma therapy project.
The majority of research on convalescent plasma therapy and Covid-19 comes from small case reports, he tells Inverse.
"The best way, in my opinion, to use this plasma is in the context of controlled clinical trials. If what we learn ends up being therapeutically beneficial, we will have done a very good thing. I'm cautiously optimistic," he says.
Donating plasma is not the only way to help fight the coronavirus. You can give blood to a blood bank, donate masks to doctors in need, and protect yourself and others by practicing social distancing.
But the idea of donating blood plasma has offered those once sickened with Covid-19 a unique outlet for their altruism.
The big question is: Will it work?
What do we know about blood plasma?
Houston Methodist Hospital has already infused two critically ill patients with blood plasma taken from a Covid-19 survivor, a spokesperson for the hospital confirmed to Inverse. Houston was followed by Mount Sinai hospital in New York, which began similar transfusions in coronavirus patients in late March.
At Columbia, Spitalnik and his colleagues plan to infuse their first patient Sunday.
"The highest payoff may be if we used it preventatively."
Convalescent plasma therapy may be useful in three cases, explains Spitalnik. For example, it could be used as a preventative measure for someone who has been exposed to coronavirus, or to treat confirmed patients in hopes that it lessens the severity of their disease.
Then there's the so-called "Hail Mary" scenario — using it on deathly ill patients.
The best time to use such a therapy may be as early in the infection as possible, Arturo Casadevall, chair of molecular microbiology and immunology at Johns Hopkins University, tells Inverse.
Casadevall is also the leader of the National Convalescent Plasma Project, a "grassroots organization" involving by 34 scientific institutions in 17 states.
"Antibody [treatment] always works best when given earlier," Casadevall says.
"We think that as we go forward and deal with this epidemic, the highest payoff may be if we used it preventatively, or early when people get sick."
But scientists are mostly working with anecdotal evidence, stemming from the use of convalescent plasma therapy for compassionate care (to treat seriously ill coronavirus patients, who lack other options).
A March 27 letter published in the journal JAMA describes a case in which the therapy was used to treat five critically ill Covid-19 patients in China.
"They're not even studies most of the time."
After receiving transfusions, 3 patients recovered and were eventually discharged. Two were in stable condition 37 days post-transfusion.
On March 24, the Food and Drug Administration fast-tracked the use of convalescent plasma therapy for compassionate use in the United States.
"There's tremendous pressure to use this plasma for compassionate use, which is not in the context of a trial. That's fine as far as it goes, but the chances of getting useful scientific information out of compassionate use is very small, because those are uncontrolled studies," says Spitalnik.
"They're not even studies most of the time."
The only way to conclusively know if blood plasma therapies work to treat Covid-19 is to do a randomized controlled clinical trial. This is the gold standard for testing any treatment for disease. Even then, it can be tricky to determine what actually works. Not everyone's blood is the same, explains Spitalnik, nor is every donor the same.
"The variability is tremendous," he says.
The National Convalescent Plasma Project is in talks with the FDA right now regarding doing such clinical trials.
"We're hoping for an announcement soon," Casadevall says.
Look for the helpers
At Mount Sinai, they received 2,000 responses in the first few days of their blood plasma project's announcement, The New York Times reported.
Maureen LaPorte is one of the Covid-19 survivors who has tried to join the ranks of donors for the project.
LaPorte tells Inverse that she didn't have severe symptoms, but had to self-isolate from her husband and son when she tested positive for the novel coronavirus. She is still recovering, but she is already looking to the future. She found out about donating plasma to Mount Sinai via a Reddit post sent to her by her son.
"I emailed them immediately because I wanted to help the situation in any way that I could," LaPorte says.
She's not the only one. At Columbia, Spitalnik and colleagues are working through hundreds of emails from people looking to donate to their project. The National Convalescent Plasma Project has had "hundreds" of donors trying to register, too, says Casadevall.
But aside from the preliminary nature of the science, these projects need to get through some serious logistical road blocks, too.
The first and most obvious is that the donor has to have had Covid-19. There are at least 223,000 recovered patients in the world at the time of writing. But without widespread testing, it's hard to confirm cases.
Casadevall says the National Convalescent Plasma Project plans to test people to ensure they've actually had the virus before allowing any donation.
But in the United States, testing has consistently been a logjam. The Food and Drug Administration has approved an antibody test, which may be able to tell people whether they have had the virus, but the roll-out is still being worked out, Casadevall says.
In the meantime, donors continue to line up. LaPorte got a callback from Mount Sinai this week. She's eager to get moving.
"I'm looking forward to going in and having them be able to somehow use my plasma to help out people that are sicker than I ever got," she says.
Should the science pan out, the blood of coronavirus survivors may help us out of this mess. In the meantime, we have a sure-fire way to protect our communities.
Editor's Note: 4/6/20 4:52 p.m.: This story has been updated to include mention of the PNAS study on convalescent plasma therapy.