COVID-19 Vaccine Protects Against “Long COVID,” Large New Study Finds

Study led by University Hospitals’ Grace McComsey, MD, underscores the importance of vaccination to combat what can be the serious health consequences of “long COVID”

People who are vaccinated against COVID-19 but still develop a breakthrough infection are still much better off than not being vaccinated, according to a large new study of more than 1.5 million American COVID-19 patients. The study, led by Grace McComsey, MD, Vice President of Research and Associate Chief Scientific Officer at University Hospitals, was published recently in the Open Forum Infectious Diseases, an official publication of the Infectious Diseases Society of America. It found that people who got the COVID-19 vaccine but still developed COVID were at significantly lower risk of post-acute symptoms of COVID or new onset of health conditions, also known as “long COVID,” when compared with those who were not vaccinated.

Grace McComsey, MD

Dr. McComsey is also the Director of the UH Clinical Research Center and Professor of Pediatrics and Medicine at Case Western Reserve University School of Medicine and holds the Rainbow Babies & Children's Foundation John Kennell Chair of Excellence in Pediatrics at University Hospitals.

This new study is one of just a few to assess the effect of COVID-19 vaccination on the long-term consequences of the disease, known medically as sequelae. It’s also the first to demonstrate a lower risk of new-onset diseases -- a reduced risk that can be linked to COVID-19 vaccination.

“In our study, vaccination against COVID-19 is associated with a lower risk of outcomes that have not been assessed in previous studies,” Dr. McComsey says. These outcomes include new onset of hypertension, diabetes, cancer, heart disease, thyroid disease and mental disorders, as well as new-onset symptoms known to be part of long-COVID syndrome like headaches, fatigue, body aches, and respiratory and gastrointestinal symptoms.

 “Long COVID” or post-acute sequelae of COVID-19 (PASC) is not uncommon in people recovering from the illness. Studies show that up to 70% of recovered patients report fatigue, persistent loss of taste or smell, shortness of breath, cough, headache, pain, and a wide array of serious complications affecting the cardiovascular, pulmonary, renal, endocrine and neurological systems.

“We're discovering more and more, that there are sequelae and damage that seem to happen, even if you're asymptomatic after COVID,” Dr. McComsey says. “Even for people who have mild COVID, they may end up with sequelae or damage and that could be either high inflammation that can cause a lot of bad things down the road or auto antibodies that cause autoimmune disease. That's why in the study we looked not only at persistent symptoms or new symptoms after COVID, but also new conditions that surfaced after COVID, like diabetes or thyroid disease.”

For the study, Dr. McComsey and her colleagues analyzed electronic medical record (EMR) data from more than 1.5 million adult COVID-19 patients from 24 health systems across the U.S, including University Hospitals Health System, both before and after COVID-19 vaccines were available. Factors included in the analysis were patients’ demographics, comorbidities, COVID vaccination, as well as symptoms and diagnoses prior to, at the time, one month and three months after COVID infection. They then compared outcomes for vaccinated patients with breakthrough COVID infection and unvaccinated patients, looking at new onset or persistent symptoms, new onset diagnoses and death.

“Differences in both 28 and 90-day risk between the vaccine and no-vaccine groups were observed for each outcome, and there was enough evidence to suggest that these differences were attributed to the vaccine,” Dr. McComsey says. “We found that at one month and at three months, whether we looked at diabetes, hypertension thyroid disease, heart disease, mental conditions, everything was way less in the people who had been vaccinated.”

Dr. McComsey currently has another study under way that may ultimately help explain why the COVID-19 vaccine seems to offer protection against “long COVID”/PASC. Funded by the National Institutes of Health as part of its “Researching COVID to Enhance Recovery” (RECOVER) Initiative, the NEO-CURE cohort study is enrolling approximately 1,000 post-COVID patients across Northeast Ohio, gathering data from patient questionnaires, but also collecting blood samples and other biologic fluids in an effort to determine markers that predict “long COVID”/PASC and understand its mechanism.

“Deep phenotyping will be done on a subset of participants, those who experience persisted or new symptoms evolved after COVID infection,” she says. Other aspects of health are also being measured, such as social determinants of health, metabolic and endocrine function, and subtle cardiac injury that may only be evident by specialized imaging.

The goal also is to assess the vaccination effect on PASC through RECOVER, which would further explain the trends in PASC seen in the real-world data of the current study.

“This prospective study will take it a step further, to try to understand what is PASC, how does it happen,” she says. “We'll be able to in in our RECOVER study see breakthrough infection vs. COVID without vaccine, and we’ll be able to tell if the observations that we made using real-world data can point to the mechanism, the reason we saw the difference between the two. Now we're in the phase of launching clinical trials in how to treat PASC and how to prevent it.”

In the meantime, Dr. McComsey says she hopes the sobering results of her new study will encourage people, especially younger people, to fight “COVID fatigue” and continue to take the threat of the virus seriously. Getting vaccinated and maintaining immunity are critical, she says.

“When you get vaccinated, you’re not only affecting the course of your acute COVID infection in terms of  less hospitalization and less death, but you’re also affecting the risk of damage that happens after COVID infection in the form of PASC, whether it's the new conditions or the persistent or new symptoms,” she says. “So it's important to get vaccinated and important to stay immune. If you get COVID after vaccination, know that you are at less risk of having bad things happen to you after COVID.”