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Convalescent plasma – a once-celebrated treatment for Covid-19 that has largely fallen out of favor – does work well for people who are immune-compromised, according to a study published Thursday.
The report in the journal JAMA Network Open analyzed the results of nine studies and found that immune-compromised Covid-19 patients were 37% less likely to die if they got convalescent plasma, an antibody-rich blood product from people who’d recovered from the virus.
Although it’s legal to use convalescent plasma to treat Covid patients who are immune-compromised, as inpatients or outpatients, government guidelines are neutral about whether the treatment works, so some hospitals offer it but others do not.
“Our concern is that many patients who need [convalescent plasma] are not getting it,” said Dr. Arturo Casadevall, an infectious disease expert at Johns Hopkins University and a co-author of the new study. “This is really important because these people can be treated, and they could have better outcomes with this material if we can just get the word out.”
He said it’s to everyone’s advantage to treat immune-compromised patients quickly.
Immune-compromised people sometimes have “smoldering Covid” for months because they lack the antibodies to fight it off, which gives the virus plenty of opportunities to mutate in the person’s body.
“These immune-compromised patients are essentially variant factories,” said Dr. Michael Joyner, an anesthesiologist at the Mayo Clinic and another study co-author. “And you do not want a bunch of people running around out there making weird variants.”
There are about 7 million immune-compromised people in the US, and treating them if they contract Covid-19 has proved challenging.
Many of them can’t take the antiviral drug Paxlovid because it interferes with other medicines they take.
Monoclonal antibodies, once popular for prevention and treatment for this group, aren’t used anymore because coronavirus variants have changed over time. One of the advantages of convalescent plasma is that as long as it’s been donated recently, there’s a high likelihood it will have antibodies to currently circulating variants, according to advocates for the treatment.
But the National Institutes of Health’s Covid-19 treatment guidelines say there’s not enough evidence to recommend either for or against the use of convalescent plasma in people with compromised immune systems.
Three times last year – in May, August and December – Casadevall, Joyner and dozens of other doctors from Harvard, Stanford, Mayo, Columbia and other academic medical centers wrote emails to scientists at the National Institutes of Health, sending them research materials and urging them to revise the guidelines. They say they have not received a response.
Joyner said he’s “frustrated” with the NIH’s “bureaucratic rope-a-dope,” calling the agency’s guidelines a “wet blanket” that discourages doctors from trying convalescent plasma on these people.
Some patient advocates say they’re angry.
“This lack of response to the researchers is infuriating,” said Janet Handal, co-founder of the Transplant Recipient and Immunocompromised Patient Advocacy Group.
Several large randomized clinical trials on the general population, including one in India and one in the UK, have found that convalescent plasma did not reduce Covid-19 deaths or prevent severe illness, and the treatment is no longer authorized in the US for people who have healthy immune systems.
The nine studies analyzed in the new report are much smaller and looked only at immune-compromised patients.
Dr. Peter Horby, a professor at the University of Oxford and the co-principal investigator of the large UK study, said that a large randomized clinical trial should be done on immune-compromised patients before clinical practice guidelines for this group are changed.
He said that support for convalescent plasma to treat Covid-19 has been based on “an emotional feeling that something had to be done.”
“We’ve seen time and again that people’s beliefs and emotions about what works can be wildly wrong, and so the best thing to do is to evaluate these things properly in trials,” he said.
At the beginning of the pandemic, there was great enthusiasm for convalescent plasma as Covid-19 survivors sought to save lives, donating antibodies against the virus to people who were sometimes at death’s door.
In August 2020, the US Food and Drug Administration granted emergency use authorization for the treatment, but some questioned whether it was politically motivated and whether the data really showed that it worked.
Then, the large clinical trials suggested convalescent plasma didn’t work.
“We didn’t see a benefit,” said Horby, director of Oxford’s Pandemic Sciences Institute.
But there was one exception.
Horby said his study did find “some evidence of some benefit” in Covid-19 patients who had not developed antibodies against the virus. This would most likely include immune-compromised patients because their faulty immune systems don’t always generate antibodies the way they should, even after infection.
When this group of patients received convalescent plasma, Horby said, they had a slightly shortened hospital stay and a slightly lower risk of ending up on a ventilator compared with similar patients who did not receive convalescent plasma.
Joyner and Casadevall, the Mayo and Hopkins doctors, point to that finding – and a similar one in a large trial in Australia, Canada, the UK and the US, as well as results of smaller studies – as an indication that convalescent plasma is worth trying in immune-compromised patients.
Immune-compromised patients who catch Covid-19 can get convalescent plasma relatively easily if they’re patients at Hopkins, Mayo or several other medical centers.
But many other people might have a difficult time accessing it.
It took Bernadette Kay of Manhattan Beach, California, months to get it, and she had to be “relentless” and call in the help of several “angels” in New York, Maryland, Minnesota and California to finally make it work.
Kay, 64, who has a compromised immune system because of a drug she takes for rheumatoid arthritis, got Covid-19 in July. She took two monoclonal antibodies, as well as remdesivir and Paxlovid – twice. But she still tested positive on and off for months and had fatigue, congestion and headaches.
“I felt like half a person,” she said. “I was not an able-bodied person. I was disabled because of lack of energy. It feels dark – a heavy feeling in your forehead and your face.”
Kay said she saw several doctors and none of them suggested convalescent plasma. That’s where her first angel came in: her daughter, who had signed her up for the Transplant Recipient and Immunocompromised Patient Advocacy Group.
That group, as well as the CLL Society, an advocacy organization for cancer patients, have been helping immune-compromised people when they get infected with Covid-19, connecting them with experts and offering guidance on how to arrange to have the plasma ordered.
Kay says Handal, the co-founder of the immune-compromised patients’ group, was her second angel, because she pointed her to angels No. 3 and 4: Joyner, the Mayo doctor, and Dr. Shmuel Shoham, an infectious disease expert at Hopkins.
Joyner and Shoham pointed Kay to her fifth angel: Chaim Lebovits, a businessman, leader in the New York’s Hasidic Jewish community and co-founder of the Covid Plasma Initiative.
Lebovits reached out to a hospital and blood bank near Kay that could procure the plasma once a doctor ordered it. Kay then reached out to six local doctors, most of them infectious disease experts, inquiring about convalescent plasma, but she didn’t make any progress.
“I think they thought it was quack medicine,” she said.
By this time, it was November, four months after she initially tested positive for Covid. She sought out a seventh doctor, sending him information from plasma experts, including a slide presentation by Joyner and Casdevall. She said that doctor, after conferring with someone at the blood bank that Libovits had suggested, agreed to order the plasma.
That’s where her sixth angel came in: Robert Simpson, vice president for hospital services at the San Diego Blood Bank, who arranged to have the blood flown in from Stanford University Medical Center.
“Robert watched the flight on Flight Tracker and had a courier waiting to bring it to the hospital,” Kay said, adding that she calls her angels collectively her “circle of love.”
Two to three weeks after her infusion, she began to feel better. She tested negative on January 4 and has continued to feel well and test negative since then.
“My energy level is back to normal. I don’t feel like half a person,” she said.
She said she’ll never know for sure exactly what spurred her recovery, but “I think it was plasma that made the difference, because in six months, nothing else made a difference.”
Kay, who works in health care, said most other people wouldn’t have known how to navigate the system like she did or might have given up in frustration.
“With the help of Janet [Handal] and her team of scientists, I’ve been able to get where I am today,” she said. “But it was not easy. This was driven by my bullheaded advocacy, because that’s who I am. I think I’m a total anomaly. No one has the persistence that I have.”
Joyner said that while he and his colleagues wait for a response from their emails to the NIH, they’ve formed the National Covid-19 Convalescent Plasma Project, and they have a phone meeting every Thursday night to discuss their progress.
“We’ve encountered many roadblocks,” said Dr. Liise-anne Pirofski, chief of the Division of Infectious Diseases at the Albert Einstein College of Medicine. “It’s just not viewed as part of the Covid-19 treatment armamentarium, and it should be.”
Pirofski, Joyner and Casadevall say they receive no financial benefit from convalescent plasma. They think one reason convalescent plasma isn’t more widely used is that there isn’t a pharmaceutical company spending money to advocate for it.
Handal, who runs the Facebook group for people who are immune-compromised, said that after she sent several emails to the NIH, agency scientists wrote back, inviting her and other leaders of her group to a meeting next week.
She plans to tell them that they need to review their Covid-19 plasma guidelines and fund more research on the coronavirus and the immune-compromised, as they have few treatment options and so often isolate at home with their families to avoid the virus.
“It is unconscionable that the NIH has let stand for months its guideline on Covid convalescent plasma, which says there is not enough information to make a recommendation, while we who are immune-compromised see our treatments dwindle,” she said. “The NIH needs to speak to the clinician researchers who are experts, prioritize the immune-compromised and fund the research needed to keep us safe.”