“I really felt back to myself,” the 34-year-old Brooklyn therapist said, “to a way that I didn’t think was possible when I was really sick.”
“The only thing that we can safely assume is that an unknown proportion of people who acquire SARS-CoV-2 have long-term symptoms,” said Steven Deeks, an infectious-disease physician at the University of California at San Francisco. “We know the questions. We have no answers. Hard stop.”
Those questions include: If long-haulers are suffering from immune systems that went awry and never reset, why would vaccines — which rev up the immune system — help some of them? Are reservoirs of coronavirus hiding in the body? Are some long-haulers experiencing a placebo effect from the vaccine? Or does the disease simply take longer to run its course in some people?
U.S. clinicians and researchers have yet to come to a consensus on even a definition for long-haul covid-19. They do not know how many people have it, what all the symptoms may be or who tends to develop problems that persist or begin after the virus is cleared.
A December workshop held by the National Institutes of Health that began grappling with those issues suggested that 10 percent to 30 percent of people infected with the coronavirus suffer some long-term symptoms. And on Feb. 23, NIH announced that it would spend more than $1.1 billion over four years to study the effects of long-term covid-19.
But there is little guidance about vaccination for people suffering through extended battles with the disease, other than medical authorities’ instruction that everyone in the United States should be immunized. Diana Berrent, founder of Survivor Corps, an online organization of people with long-term covid-19 symptoms, said many members of the group were initially hesitant to comply for fear that the vaccine would create more havoc with their immune systems.
One tiny study released Monday but not yet submitted for peer review concluded that people with long-term symptoms who get vaccinated are more likely to see their problems resolve or not worsen than people who have not been vaccinated. But the research out of the University of Bristol in England compared only 44 vaccinated patients against 22 unvaccinated ones and was designed to determine whether the vaccines were safe for people with long-haul covid-19.
The authors said it is possible that the act of getting the vaccine influenced the patients’ recall of symptoms, what they described as a “a placebo/nocebo effect.”
When Survivor Corps informally surveyed its members recently, 216 people said they felt no different after vaccination, 171 said their conditions improved and 63 reported that they felt worse, Berrent said.
Eisenberg, who said she had a mild case of covid-19 last summer, doesn’t believe the placebo theory fits because she had no expectation that the vaccine would help with her debilitating symptoms. She was immunized because tests did not detect antibodies to the virus in her blood and she was terrified that she could be reinfected. She received her second shot of the Moderna vaccine on Feb. 5.
“I didn’t expect the vaccine to do this,” she said. “It is possible. The mind is a very powerful thing.”
Rebecca Neff, 61, an information technology manager at a mortgage company, thinks she caught a fairly severe case of covid-19 last March in Los Angeles and has been paying the price ever since. Although she was never tested and never hospitalized, she has experienced chronic gastrointestinal problems, shortness of breath, fatigue and brain fog. Her hair fell out and her teeth loosened, she said.
Neff, who recently moved to Frisco, Tex., said she consistently measured the oxygen level in her blood with a fingertip pulse-oximeter and found it to be two or three points below normal for many months. Stress would trigger flare-ups, she said, as would wine and some foods. Her dreams were “more bizarre” than she has ever experienced.
One shot of Pfizer’s vaccine on March 8 has changed all that, she said.
“My head is clearer in the last week than it’s been the whole entire year,” she said. “So even though I felt better, I didn’t realize how much I was off.”
Akiko Iwasaki, an immunologist at Yale University, said that immunization is likely to reduce the chances of long-term covid-19, based on evidence that shows that vaccines help prevent the disease.
“Vaccines will generate good antibody and T-cell responses. They have been already shown to significantly reduce infection, both symptomatic and asymptomatic,” she said.
Iwasaki said she understands that it can be “a bit scary to get the vaccine when you are already feeling ill from long covid. However, more people appear to benefit from the vaccine than get worse with the vaccine.” She stressed that the benefit of vaccination outweighs the risks, and that vaccines also “will greatly reduce the risk of reinfection.”
Michael S. Saag, a professor of medicine and infectious disease at the University of Alabama at Birmingham who took part in the NIH workshop, said he, too, is trying to make sense of the conflicting signals.
“I’m looking at that disorder as a potential overreaction to the SARS-Cov-2 virus, and stimulating [patients’ immune systems] further could make them worse,” he said. “I’m intrigued and puzzled by the reports and curious to see whether this pans out to be real and, if so, why is it happening.”
Several theories have emerged, although researchers have barely begun to explore them.
Deeks noted that people who are infected with varicella zoster, the virus that causes chickenpox and shingles, may harbor the pathogen in their nervous systems for years. The Centers for Disease Control recommends that people in their 50s be vaccinated against it. That offers a potential comparison with the coronavirus vaccine; the varicella zoster immunization “doesn’t prevent new infections but takes care of the infection that’s there,” he said.
The coronavirus vaccine could be triggering an immune response sufficient to eliminate any viral holdouts. “You put one and one together and you can say, ‘Okay, you know, this is plausible,’ ” Deeks said.
In a few cases, the virus persisted in small intestine cells at low levels for weeks or even months. Mehandru said he does not know whether a lingering infection in the intestine could contribute to long-term symptoms. He emphasized that more work needs to be done, such as determining whether people who have long-term symptoms also have infected intestinal cells. All of the biopsied patients in the study who had virus in their cells at four months were asymptomatic.
But he said it is plausible that viral remnants in the gut could lead to a “low degree of inflammation, which could drive some of the features associated with persistence of symptoms. This is the speculation.”
In a post on the blog Elemental, Iwasaki proposed three reasons vaccines might improve people’s symptoms: T cells, boosted by the vaccine, could eliminate a viral reservoir; a heightened immune response could clear any lingering virus fragments; or the vaccine may “divert autoimmune cells,” if long-lasting symptoms are the result of an inappropriate autoimmune response.
These are all working hypotheses.
“We will try some animal models to test this,” she said, “but my hope is that more and more people will be engaged in this research.”
Saag said the clues remind him most of long-term Lyme disease, “because there we know the infectious organism . . . is long gone, and the organism seems to have triggered a persistent hyperactive immune syndrome.”
Eisenberg is confident that her health is returning to normal. She is taking on more clients, working out and cleaning her house again. She still feels occasional nerve pain in her feet, but is seeing a doctor to resolve it.
Best of all, she can fall asleep without medication.
“Even the brain fog has gone away to a point where I didn’t know how bad I had brain fog,” she said.