A new large-scale study provides some of the strongest evidence yet that vaccines reduce the risk of developing persistent or long-term Covid.
Scientists looked at people infected in the United States during the first two years of the pandemic and found that the percentage of vaccinated people who developed long-term Covid was much lower than the percentage of unvaccinated people who did.
Medical experts have previously said that vaccines can reduce the risk of long Covid, largely because they help prevent severe illness during the infectious period and people with severe infections are more likely to have long-term symptoms.
But many individuals with mild infections also develop long-term Covid, and the study, published Wednesday in The New England Journal of Medicine, found that vaccination did not eliminate all risk of developing the disease, which continues to affect millions of people in the United States.
“There was a residual risk of long-term Covid among vaccinated individuals,” Clifford Rosen, a senior scientist at MaineHealth Research Institute who was not involved in the study, wrote in an accompanying editorial. Because of this, Rosen added, new cases of long-term Covid “may continue unabated.”
The study evaluated the medical records of millions of patients in the Department of Veterans Affairs health care system. It involved nearly 450,000 people who had COVID-19 between March 1, 2020, and Jan. 31, 2022, and about 4.7 million people who were not infected during that time.
The veteran study population was significantly less diverse than the general U.S. population. Nearly three-quarters of the participants were white, about 91 percent were male, and their median age was 64.
Researchers analyzed medical records to estimate the percentage of COVID patients who had long COVID a year after becoming infected. The lowest rate of long COVID in the study, 3.5 percent, occurred among vaccinated people who became infected during the later study period, between mid-December 2021 and January 2022.
That compares with a rate of 7.8 percent for unvaccinated patients in the study who were infected during the same period.
“We found that much of the decline is attributable to vaccination,” said study senior author Ziyad Al-Aly, the chief of research and development at the St. Louis Veterans Affairs Health Care System and a clinical epidemiologist at Washington University in St. Louis.
Still, he said, “vaccine efficacy declines significantly over time, and people are not keeping up with annual vaccinations.”
He added: “We cannot have it all. We cannot say that Covid has gone down in the long term thanks to vaccines and then abandon vaccination. This will lead to a rise in cases again.”
To rule out other possible causes, the researchers looked at comparisons between uninfected people who developed similar symptoms, Al-Aly said.
For example, key symptoms of long Covid, such as fatigue and brain fog, can also affect patients with cancer and other conditions, so the authors subtracted the rate of those symptoms in the uninfected population from the rate in infected people to calculate the percentage attributable to long Covid, he said.
The study covered the period between the initial emergence of the coronavirus and the arrival of two increasingly contagious variants — delta and omicron — after the rollout of vaccines. The authors compared outcomes between vaccinated and unvaccinated patients, but did not calculate a rate for the two groups together.
Researchers found that among unvaccinated people infected between June 19 and Dec. 18, 2021, when delta was the dominant variant, the rate of long-haul Covid a year later declined slightly to 9.5 percent from 10.4 percent among those infected in the first 15 months of the pandemic.
The rate declined further—to 7.8 percent—among unvaccinated people infected between December 19, 2021, and January 31, 2022, during the Omicron surge.
Among vaccinated people who had become infected, rates of long Covid were markedly lower. Differences in variants and other aspects of the delta and omicron variants’ lifespans played a role, the authors said, but they attributed about 72% of the decline to the vaccines.
About 5.3 percent of those infected during the delta variant period had long-term COVID a year later, and 3.5 percent of those infected during the omicron variant period did.
“This is lower than in previous phases, but it is not low,” Al-Aly said. “Multiplied by the huge number of people who continue to get infected and reinfected, 3.5 percent per 100 infected adults will translate into millions of additional cases of long Covid.”
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The researchers did not look at later time periods, but a recent survey by the Centers for Disease Control and Prevention reported that about 5.3 percent of U.S. adults — about 13.7 million people — currently have long COVID.
The authors noted that long-term COVID symptoms across most categories, including cardiovascular and renal problems, decreased during the first two years of the pandemic, but gastrointestinal, metabolic and musculoskeletal problems increased during the Omicron variant era in unvaccinated people, likely reflecting changes in the virus and other factors.
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