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Monday, June 5, 2023
June 5, 2023

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Long COVID mystery: Do vaccines help or hurt?


SAN JOSE, Calif. — After months of struggling with long COVID, 25-year-old Ibrahim Rashid was excited to be vaccinated, seeking to prevent reinfection and perhaps ease his symptoms.

To his delight, the deep fatigue, chest pain and “brain fog” suddenly lifted. But within a month, the symptoms returned with a vengeance – accompanied by a shocking loss of balance and leg strength.

“After I got the vaccine, I was having the best time of my life. I was the happiest person in the world,” said Rashid, a graduate student at the University of Chicago who once excelled at skateboarding and martial arts.

“Then it all just started roaring back,” he said. “And my walking disappeared. … One day I was reading a book underneath a tree, and I just couldn’t get up.”

He’s among the many long COVID patients who report mysterious changes in their health after they get the vaccine. Some improve; others, like Rashid, worsen.

To study the phenomenon, a new nationwide project is being launched by Yale School of Medicine scientists. Expanding on an initial pilot project of 20 patients, they hope to recruit at least 100 people to determine the influence of vaccination on symptoms that persist months after COVID-19 infection. The effort uses cutting-edge immune profiling techniques to get a snapshot of each person’s cellular reaction to the shots.

The University of California, San Francisco is also exploring reports of the varying impact of vaccines within its major study of the long-term impact of COVID-19 infections, called the LIINC project. Not enough time has passed to yield results, according Dr. Michael Peluso, an expert in the virologic and immunologic mechanisms underlying infection.

These research efforts could offer insights into long COVID, which affects an estimated 30% of people whose infection was severe enough to need treatment, according to a study at UCLA’s COVID Ambulatory Program. Long COVID is defined as a range of often disabling symptoms that can last weeks or months after infection — and can happen to anyone, even if illness was mild.

The patients’ responses to vaccination “are a clue. They offer a breadcrumb trail to the possible biological mechanisms behind long COVID,” said Diana Berrent, founder of Survivor Corps, one of the nation’s largest grassroots COVID-19 patient groups. “People with long COVID have been living in a medical desert. They are desperate for answers. They’re desperate for treatments. This will inform the next steps — coming up with treatments.”

The Yale team will collect blood and saliva samples from long COVID patients who have not yet been vaccinated. Then they’ll follow up six and 12 weeks after vaccination to monitor symptoms and collect new samples.

While preliminary results from their initial study have not yet been published, they suggest that complex immunological pathways are at play, said principal investigator Akiko Iwasaki, Yale professor of immunobiology.

“There are some clear differences in factors that you can find in the blood — before and after the vaccine,” she said.

It’s well known that vaccination can help prevent long COVID. But, until now, no one has studied the effect of vaccination on those who are already infected. (The studies focus on people who had not been vaccinated before contracting COVID-19. Researchers have not yet explored the impacts of subsequent vaccination on those who developed COVID-19 as “breakthrough cases” after vaccination.)

The startling range of reactions was first revealed in a large poll by Survivor Corps. The poll was undertaken because people with long COVID were not included in vaccine manufacturers’ trials, so the group worried about the effects of the shots on their health.

Armed with data, they approached the Yale team and proposed a research partnership. They’ve since been joined by the Patient-Led Research Collaborative, a team of people with long COVID who are experts in developing patient-scientist collaborations.

About 40% of people reported mild to full resolution of their symptoms after their first dose of the vaccine, according to the poll. This supports many anecdotal reports of improvement, according to Iwasaki.

What’s going on? Perhaps the vaccine helps the immune system fight off hidden virus that’s lingering in their bodies — clearing away these viral remnants.

If so, this would suggest that long COVID is caused by a persistent but clandestine viral infection. While the Yale team hasn’t found this cryptic virus, there are clues in shifting levels of infection-fighting interferons in the blood.

“We have heard clinical stories of people who feel improved after vaccination — and if this turns out to be true in rigorous, well-controlled studies, it provides some compelling evidence that an inadequate or dysfunctional immune response to the initial infection could contribute to long COVID,” said UCSF’s Peluso.

“However, we have also seen patients who had hoped to improve with vaccination — and thought they had — but did not really feel better over time,” he said. “Sometimes, they initially felt better but then had recurrence of their long COVID symptoms.”

About 10% to 15% of patients felt worse, the poll found. This would suggest a different theory: In some cases, the symptoms of long COVID may emerge as an autoimmune disorder.

What causes this dysfunction? It’s complicated. The same protective antibodies that fend off a virus can trigger a new and misguided antibody attack on the body, which is destructive. Research has found that some people with prior infection with the COVID-19 virus have a wide variety of these cells, called “autoantibodies,” up to six months after they have fully recovered.

“We’re now comparing the pattern before and after the vaccination to see whether that pattern of autoimmunity changes,” said Iwasaki.

The results could also offer insights into a similar condition called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Like long COVID, ME/CFS may involve a biological response that goes haywire when the body encounters certain infections or other environmental hazards.

“So many of us have complex chronic conditions already and are being vaccinated,” said J.D. Davids, a 54-year-old in Brooklyn with both long COVID and ME/CFS who became feverish, passed out and fell after his first vaccine, breaking an ankle. The incident exacerbated his symptoms, he said.

Answers may come slowly, as patient recruitment into the Yale study has been challenging. That’s because the project was started after vaccines were widely available — so it’s been hard to find people who aren’t yet immunized.

When it was time to get his third shot, Rashid was fearful. But he was more worried about a repeat COVID-19 infection.

“I was terrified to get the booster,” he recalled. At the clinic, “I was crying like a kid.”

To his surprise, the experience was completely uneventful. Afterward, his health improved for awhile, then relapsed, and is now improving again. He’s completing his studies and beginning to exercise.

“I’m climbing back,” he said. “I still believe in vaccines.”