Vaccine reduces the risk of long Covid-19, says research, but the risk remains

VAccination lowers the chance of developing long Covid-19, according to a major new study that also found the risk of serious complications has decreased but not gone as new coronavirus variants emerged.

The study, published Wednesday in the New England Journal of Medicine, compared the health records of more than 440,000 Veterans Affairs patients infected with Covid-19 with data from more than 4 million uninfected people. The analysis found that cases of long Covid – also called PASC (post-acute sequelae or severe acute respiratory syndrome coronavirus 2) – fell among all participants during the Delta and Omicron eras of the pandemic, but fell almost twice as much among vaccinated people when the Omicron variant dominated cases.

The new data on the benefits of vaccination comes over a summer revival in Covid cases across the country, and as health officials prepare to roll out a vaccine updated against newer strains which Pfizer and Moderna said they could deliver in August.

“The study is useful in validating the suspicion that the incidence of PASC has decreased over time and in relation to new variants (this question came up yesterday in my clinic),” Hilary Goldberg, Clinical Director of Lung — and critical care medicine at Brigham and Women’s Hospital in Boston, STAT told me in an email. She was not involved in the investigation. “It is also useful in validating that vaccination is protective in preventing the development of PASC, a question that has remained somewhat unanswered,” Goldberg said.

In the unvaccinated group, 10.42 out of 100 people had developed a long Covid-19 period one year after infection at the beginning of the pandemic (before vaccines were available). In the Delta variant era (defined as June 19 to December 18, 2021), 9.51 out of 100 unvaccinated people were diagnosed with long Covid, compared to 5.34 out of 100 vaccinated people. When the current Omicron era began (December 19, 2021), the gap widened: 7.76 out of 100 unvaccinated people, but only 3.5 out of 100 vaccinated people developed long Covid.

“Vaccines clearly work, but it is also clear that they do not completely wipe out the disease,” the study’s senior author Ziyad Al-Aly said in an interview. He is chief of research at the VA St. Louis Health Care System and is also a clinical epidemiologist at Washington University in St. Louis. “What we really find important here is: yes, Covid has decreased for a long time. But it is not something we can completely ignore.”

Previous studies, incl other research from the VAto have hinted on a protective effect for vaccination, as well as on the harmful impact of severe Covid infections and pre-existing medical conditions on the chances of a later long Covid-19. Jai Marathe, assistant professor of infectious diseases at Boston University and director of the ReCOver/long COVID clinic at Boston Medical Center, points out that the new paper says the type or number of comorbidities did not appear to affect PASC.

“From a research perspective, there is a strong impetus to understand the pathogenesis of PASC given the constellation of symptoms,” he wrote to STAT. He did not participate in the NEJM paper. “If vaccination alters the immune response, we need to study this further to understand the interplay between viral infection and the immunological changes that contribute to the development of PASC.”

Al-Aly is hesitant to call this the final word on the full extent to which vaccine coverage better protects people, and urges more research. The observational study also describes how symptoms changed with the variants in unvaccinated people.

While debilitating fatigue was once a hallmark of long Covid-19, recently gastrointestinal, metabolic and, to a lesser extent, musculoskeletal problems have overtaken fatigue among the unvaccinated, with gastrointestinal and metabolic problems doubling the risk of the pre-Delta and Delta periods together. The study, conducted from March 2020 through January 2022, measured how long Covid wreaks its damage across 10 disease categories: cardiovascular, blood disorders, fatigue, gastrointestinal, renal, mental health, metabolic, musculoskeletal, neurological and pulmonary.

The long Covid risk changed not only with the variants, but also with better hospital treatment, including antiviral drugs, Al-Aly said. Vaccination may have reduced the amount of virus circulating and therefore the risk of long Covid-19 compared to 2020, but that is only a hypothesis. “Quantitatively, the risk changed dynamically over time, but also qualitatively. It suggests that each species has its own fingerprints,” he said. “Long Covid is not monolithic.”

Michael Peluso, an infectious disease physician and assistant professor of medicine at the University of California, San Francisco, said he and other doctors may be seeing evidence of the changing symptom mix. “It will make me more aware of gastrointestinal and musculoskeletal symptoms in my assessment of long Covid,” Peluso, who was not part of the study, said in an email to STAT. “We certainly see these symptoms, but I wouldn’t say they are the most prominent.

Goldberg wasn’t surprised by the symptom shift. “I find this reassuring because we expect the nature of the disease to evolve over time. If we did not see this, we might question the robustness of the data in this analysis.”

To unravel the influence of vaccination versus variant, the study authors used a statistical method called decomposition analysis to conclude that 28% of the lower long Covid incidence in vaccinated people was due to changes in the variants and improved medical care, while 72% was attributed to the improvement of the vaccines.

The study did not mention how many vaccinations a subject received, Goldberg noted. “There remain gaps in the data – a common question from patients is what the risk is of reactivation or worsening of PASC symptoms from vaccination compared to from infection,” she said. “We do not yet have enough information to answer this question, and this question often determines patients’ decision-making.”

The study’s estimate of the cumulative incidence of long-term Covid-19 is lower than a June report from the Agency for Healthcare Research and Quality published last month in JAMA that put the long reach of Covid at 7% of people who have ever had Covid-19. That’s higher than the 3% to 4% of adults in the Omicron era, but reflects the agency’s research findings as opposed to the NEJM study’s reliance on health records, Al-Aly said. Estimates of long-term Covid-19 have changed dramatically from the start of the pandemic, before agreement was reached on how to define the condition.

On Tuesday, the Centers for Disease Control and Prevention said people with disabilities are at greater risk of long Covid-19 than people without disabilities. The data shows that 11% of people with disabilities have been suffering from Covid for a long time, while only 7% of people without disabilities reported symptoms.

In other long Covid research this week a study published Wednesday in Science Translational Medicine offered an explanation for damage to the lungs leading to exhausting coughs, lung disease and shortness of breath. Researchers from the University of Virginia have shown that a signaling molecule called interferon-gamma stimulated an abnormal immune response, causing inflammation and scarring in the lungs after a Covid-19 infection. In mice, treatment with anti-interferon gamma antibodies reduced inflammation and fibrosis after recovery from their acute infections. Drugs called JAK inhibitors, including one called baricitinib that was authorized for emergency use for acute Covid-19, “may merit consideration” for treating long Covid-19, the authors wrote.

Despite advances in research and the decline in long-term Covid cases, the risk is still significant, Al-Aly and others pointed out.

“Despite the risk of long Covid-19 waning, it has not fallen to zero and we will continue to see many cases of long Covid-19 as SARS-CoV-2 continues to spread,” Peluso said. “This observation is very useful for clinicians, researchers and advocates to argue that greater long-term investment in clinical care and research will be needed to meet the scope of clinical need and ultimately solve the problem. ”

Declining vaccination rates are worrying, likely due to “Covid burnout,” Marathe said. “Living with a chronic condition like PASC can be debilitating. Therefore, educating and counseling patients and physicians to increase vaccine acceptance is a critical public health task.”

Goldberg said patients with long Covid-19 often ask her about the risks and benefits of updating their vaccination status. “This study will help guide those of us who care for patients with PASC,” she said.

Peluso praised the article’s value for answering questions patients “always” ask in the clinic. “The risk with Omicron variants may be lower than with previous variants, but it is still significant,” he said. “And getting vaccinated is still the best thing anyone can do, besides avoiding Covid, to protect themselves from developing long Covid.”

STAT’s coverage of chronic health conditions is supported by a grant from Bloomberg Philanthropies. Us financial supporters are not involved in decisions about our journalism.