The good news is that the risk of developing long COVID has dropped significantly since the pandemic began, and new research suggests that this drop is largely due to COVID-19 vaccines. The bad news is that the risk of developing this post-acute infectious syndrome remains significant.
At the beginning of the pandemic, about 10% of people with COVID-19 developed long COVID. Now, the risk of getting long COVID among vaccinated people has dropped to about 3.5% (primary series). That’s a significant decrease, but more than 1.3 million Americans still get infected with SARS-CoV-2 every day. “If you do the math, 3-4% of those is a huge number that will be added to the roster as potential long COVID patients,” said Ziyad Al-Ali, MD, director of research and development services at the Veterans Affairs St. Louis Healthcare System and lead author of the study.
The study also found that COVID-19 vaccination plays a key role in reducing long COVID cases. The researchers published their findings July 17 in the New England Journal of Medicine.
The FDA recently approved an improved COVID-19 vaccine, and the findings are an important reminder to get vaccinated this fall. “We’ve been educating patients that the goal of the COVID vaccine is to keep them from being hospitalized and to keep them from dying,” says Scott Roberts, MD, assistant professor of infectious diseases at Yale University School of Medicine, who was not involved in the study. “We need to continue to communicate that an added benefit of the vaccine is that it may also prevent long COVID in the future.”
With each new variant, the number of long-term COVID-19 cases drops
For their study, Dr. Al-Ali’s team utilized a database within the VA to identify approximately 450,000 veterans infected with SARS-CoV-2, as well as healthy controls. They divided this cohort into era-specific groups based on SARS-CoV-2 variants: pre-Delta (unvaccinated), Delta era (unvaccinated), Delta era (vaccinated), Omicron era (unvaccinated), and Omicron era (vaccinated). They followed each group for a year to determine which groups were at highest risk of developing Long COVID symptoms. The researchers found that the rate of new Long COVID cases decreased with each variant, with significantly fewer cases in the vaccinated cohort.
The research team then conducted an analysis to determine the reason for the decline in Long COVID cases observed from the pre-Delta to Omicron era. They found that about 70% of the decline was due to vaccination. There are several reasons why vaccines can prevent Long COVID, says Dr. Al-Ali. First, vaccines reduce the risk of severe acute infections that lead to an increased risk of Long COVID. They also help the body’s immune system eliminate the virus more quickly, reducing the chance of residual viral particles remaining. Viral persistence is one of multiple hypotheses that researchers have made as the cause of Long COVID. “This really means that maintaining vaccination rates is likely a key factor in curbing Long COVID,” says Dr. Al-Ali.
The remaining 30% were related to changes in the virus’ characteristics — in other words, as SARS-CoV-2 evolves, it may have changed in ways that made people less susceptible to developing long COVID.
Interestingly, while the overall risk of Long COVID is reduced, the researchers found that unvaccinated people are more likely to develop metabolic disorders such as diabetes and dyslipidemia (abnormal levels of fats in the blood) and gastrointestinal disorders after COVID compared to the earlier group. “There are large cohorts in the U.S. with metabolic disorders who may be at particular risk for becoming sicker with COVID,” Dr. Roberts says. “This needs to be investigated in more detail.”
How will the risk of Long COVID continue to evolve?
Long COVID has afflicted 400 million people worldwide, and experts estimate the disease has an economic impact of as much as $1 trillion annually, according to a recent review including Dr. Al Ali and Sterling Professor of Immunobiology Akiko Iwasaki, PhD. The latest research raises the question of whether SARS-CoV-2 will continue to evolve and one day make the risk of Long COVID so small that it can be ignored. Experts don’t know yet, Dr. Al Ali says. “It’s theoretically possible, but so far it’s doubtful.”
According to the findings, the risk of Long COVID is not constant. It may continue to decline, but if more people refrain from vaccination, the risk may rebound. Scientists need to continue to monitor SARS-CoV-2 and its evolution to understand how the risk patterns of Long COVID change with it. Dr. Al-Ali’s team plans to conduct long-term studies to determine how Long COVID affects different organ systems. In the meantime, continuing vaccination will be crucial to reduce an individual’s risk, he said.
“If Long COVID was a child, it would be kindergarten age,” he said. “It’s still very young and very new, and there’s a lot to learn.”
Isabella Bachman is an associate editor and writer at the Yale School of Medicine.
Final words from Lisa Sanders, MD:
Many of my patients ask me whether they should continue to get vaccinated if they are not at high risk for severe illness. They point out that for many people, the virus seems to cause illness worse than a cold, but not as bad as the flu. It is true that hospitalization and death rates have dropped dramatically from their peaks four years ago. Part of the reason is the virus itself, which continues to change over time. But a large part of the reason is vaccination, which has contributed to the decline in both deaths and hospitalizations.
In fact, for people at the lowest risk of complications from the virus (based on age and the absence of chronic conditions that increase the risk of SARS-CoV-2 infection), I would argue that the most important reason to continue to vaccinate is to reduce the chance of getting Long COVID. No matter who asks me, I tell them I’m not scared of COVID, but I am terrified of Long COVID. So I’m grateful to the authors of this New England Journal of Medicine study that quantified the reduction in risk and incidence of Long COVID, thanks in large part to vaccination. The illness in people who get COVID usually clears up in a week or less. For the 3-4% of people whose illness is made worse by Long COVID, the road is much longer. In one study, up to 60% of people who got Long COVID still had significant symptoms almost a year and a half later. About 40% were unable to return to their previous productivity levels. The fact that the vaccine can reduce both the risk of COVID and the risk of Long COVID is a strong argument for continuing to vaccinate annually now and for the foreseeable future.
Read other articles from Long COVID Dispatches here:
If you would like to share your Long COVID experience for consideration on this blog (under a pseudonym), please contact us at LongCovidDispatches@yale.edu and, if space allows, it may appear in a future post.
The information provided in Yale Medicine content is for general informational purposes only. It should not be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the independent advice of your health care provider with any questions you may have regarding a medical condition.
