In rare cases, coronavirus vaccines may cause Long Covid–like symptoms
In late 2020, Brianne Dressen began to spend hours in online communities for people with Long Covid, a chronic, disabling syndrome that can follow a bout with the virus. “For months, I just lurked there,” says Dressen, a former preschool teacher in Saratoga Springs, Utah, “reviewing post after post of symptoms that were just like my own.”
Dressen had never had COVID-19. But that November, she’d received a dose of AstraZeneca’s vaccine as a volunteer in a clinical trial. By that evening, her vision blurred and sound became distorted—“I felt like I had two seashells on my ears,” she says. Her symptoms rapidly worsened and multiplied, ultimately including heart rate fluctuations, severe muscle weakness, and what she describes as debilitating internal electric shocks.
A doctor diagnosed her with anxiety. Her husband, Brian Dressen, a chemist, began to comb the scientific literature, desperate to help his wife, a former rock climber who now spent most of her time in a darkened room, unable to brush her teeth or tolerate her young children’s touch.
As time passed, the Dressens found other people who had experienced serious, long-lasting health problems after a COVID-19 vaccine, regardless of the manufacturer. By January 2021, researchers at the National Institutes of Health (NIH) began to hear about such reports and sought to learn more, bringing Brianne Dressen and other affected people to the agency’s headquarters for testing and sometimes treatment.
The research was small in scale and drew no conclusions about whether or how vaccines may have caused rare, lasting health problems. The patients had “temporal associations” between vaccination and their faltering health, says Avindra Nath, clinical director at the National Institute of Neurological Disorders and Stroke (NINDS), who has been leading the NIH efforts. But “an etiological association? I don’t know.” In other words, he does not know whether vaccination directly caused the subsequent health problems.
NIH’s communications with patients faded by late 2021, though Nath says the work continues behind the scenes. The pullback caused bewilderment and dismay among patients who spoke with Science, who said the NIH researchers were the only ones helping them. Now, a small number of other researchers worldwide is beginning to study whether the biology of Long Covid, itself still poorly understood, overlaps with the mysterious mechanisms driving certain postvaccine side effects.
More discrete side effects connected to COVID-19 vaccines have been recognized, including a rare but severe clotting disorder that occurs after the AstraZeneca and Johnson & Johnson vaccines and heart inflammation, documented after the messenger RNA (mRNA) vaccines manufactured by Pfizer and Moderna. Probing possible side effects presents a dilemma to researchers: They risk fomenting rejection of vaccines that are generally safe, effective, and crucial to saving lives. “You have to be very careful” before tying COVID-19 vaccines to complications, Nath cautions. “You can make the wrong conclusion. … The implications are huge.” And complex and lingering symptoms like Dressen’s are even more difficult to study because patients can lack a clear diagnosis.
At the same time, understanding these problems could help those currently suffering and, if a link is nailed down, help guide the design of the next generation of vaccines and perhaps identify those at high risk for serious side effects. “We shouldn’t be averse to adverse events,” says William Murphy, an immunologist at the University of California, Davis. In November 2021 in The New England Journal of Medicine, he proposed that an autoimmune mechanism triggered by the SARS-CoV-2 spike protein might explain both Long Covid symptoms and some rare vaccine side effects, and he called for more basic research to probe possible connections. “Reassuring the public that everything is being done, researchwise, to understand the vaccines is more important than just saying everything is safe,” Murphy says. Like others, he continues to urge vaccination.
A touchy topic
Long Covid research also brought the Dressens to Nath. In January 2021, Brian Dressen sought help from Nath, who had been studying Long Covid. Nath responded quickly and asked Brianne Dressen to join an ongoing study he leads on the natural history of inflammatory diseases of the nervous system.Dozens more patients describing postvaccine complications found their way to Nath and Farinaz Safavi, an NINDS neurologist. “I promise you we will report your issue and other cases we are reviewing now,” Safavi wrote to Danice Hertz in March 2021. Hertz, a retired gastroenterologist who lives in Southern California, had developed debilitating side effects after one dose of the Pfizer vaccine. Senior officials at the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention, and Pfizer, among others, were copied on the email, which Hertz shared with Science.
Over the first half of 2021, Nath and Safavi invited Brianne Dressen and others to NIH for testing and, in some cases, short-term treatment, for example with high-dose steroids or intravenous immunoglobulin (IVIG), which can quell or modulate immune responses. The patients spent at least several days undergoing neurological, cardiac, and other tests, including lumbar punctures and skin biopsies.
The NIH researchers were “trying to help people,” says a health care worker whose symptoms began after the Pfizer vaccine, one of four people in the study who spoke to Science. Nath says 34 people were enrolled on the protocol, 14 of whom spent time at NIH; the other 20 shipped their blood samples and in some cases cerebrospinal fluid.
As time passed, however, the patients say the NIH scientists pulled back. A September visit Brianne Dressen had scheduled for additional neurologic testing was converted to a telemedicine appointment. In December, Nath asked her to stop sending patients his way. “It is best for such patients to receive care from their local physicians,” he wrote to her.
For patients, the silence from NIH was distressing, especially as they struggled to find care elsewhere. The scientists “took the data and left us hanging,” says a person who traveled to NIH in the spring of 2021. “I have no treatment, I have no idea what’s happening to my body.” Physicians, several patients said, had nothing to offer and sometimes even declared the symptoms imagined.
Nath told Science NIH facilities are not equipped to treat large numbers of patients long-term. Says the health care worker of the effort: “It’s too much for two people at the NIH to do.”
The NIH data, which documented the patient cases, haven’t been reported yet. Two top medical journals declined to publish a case series of about 30 people, which Nath first submitted in March 2021. Nath says he understands the rejection. The data weren’t “cut and dried; it was observational studies.” This month, the scientists submitted a case series of 23 people to a third publication, and Nath says his group has submitted an amendment to a Long Covid protocol to include patients with postvaccine side effects.
Science contacted regulators and vaccinemakers about any information they’d gleaned on these side effects. A Pfizer spokesperson wrote, “We can confirm it’s something we’re monitoring.” Moderna, AstraZeneca, and Johnson & Johnson all said they take side effects seriously and share reports they receive with regulators. An FDA spokesperson said the agency “continues to maintain a strong focus on monitoring the safety of the COVID-19 vaccines,” while the European Medicines Agency notes it “is taking steps to use real-world data from clinical practice to monitor the safety and effectiveness of COVID-19 treatments and vaccines.”
Other researchers note the scientific community is uneasy about studying such effects. “Everyone is tiptoeing around it,” Pretorius says. “I’ve talked to a lot of clinicians and researchers at various universities, and they don’t want to touch it.”
Rest of the article can be read here: AAAS
