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Vaccines likely to reduce risk of long COVID, experts say, but by how much?

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As more details emerge about the long-term effects of COVID-19, experts say vaccination is likely to have protective benefits against long COVID, also known as post-acute sequelae SARS-CoV-2 infection (PASC). But an important question that has yet to be answered is exactly how much protection it offers.

“The collective evidence is all pointing towards the fact that vaccines are reducing the risk of developing long COVID,” Dr. Kieran Quinn told CTVNews.ca in a telephone interview Wednesday. Quinn is a clinician scientist at the University of Toronto and Sinai Health System, leading a large research program studying long COVID.

A study recently published in the Nature Medicine journal discovered that COVID-19 vaccination resulted in a 15 per cent reduction in the risk of developing long COVID. Long COVID is when symptoms of an initial COVID-19 infection persist for longer than about 12 weeks after infection. As part of the study, researchers looked at nearly 34,000 people who experienced breakthrough infections, and compared their data with control groups made up of millions of people. The data was pulled from health-care databases belonging to the United States Department of Veterans Affairs.

This number is not as high as what some other research has suggested. An earlier study stemming from the United Kingdom showed that vaccines resulted in a 50 per cent reduction in the risk of developing long COVID in adults, though it involved self-reported data gathered from fewer people. While some may find the latest data disappointing, Quinn said, it’s still a “positive sign” that vaccines play a role in protecting against long COVID.

“We're talking about over 550 million COVID infections around the world, and depending on which estimates you believe in, somewhere between 20 and 40 per cent of people develop some long-term, persisting consequences of their acute COVID infection,” he said. “If vaccination reduces the risk of developing these lingering symptoms by 15 per cent … that's 30 million people who have been helped by their vaccines.”

LIMITATIONS IN RESEARCH

One of the limitations of the study stemming from the U.S. is that there’s no clear breakdown of the underlying health conditions of those involved, said Dr. Dale Kalina, an infectious disease physician at Joseph Brant Hospital in Burlington, Ont. Being aware of the different types of diseases or medical conditions a person has can indicate how well their immune system will respond to vaccination, he said.

Without these details, it’s difficult to tell exactly how much protection might be gained against long COVID if someone is vaccinated, Kalina said.

“If you have certain comorbidities, particularly as we age … you would expect that the immune response to the vaccine isn't as strong, so you would expect that vaccines wouldn't work as well against acute COVID [infection],” Kalina told CTVNews.ca in a telephone interview Wednesday. “I would expect that that could be extended out to symptoms of long COVID as well, but we don't know that from this study.”

Additionally, with the Veterans Affairs population made up of mostly men, this was also reflected in the cohort observed as part of the study. As a result, the data isn’t necessarily applicable to the general population, said Dr. Brian Conway, an infectious disease expert and medical director of the Vancouver Infectious Diseases Centre.

“These are American veterans, largely older males who have more comorbidities and who have chosen to engage in care as a result of whatever illness they might have, such as COVID,” he told CTVNews.ca in a telephone interview Wednesday. “So you're selecting for people who have a higher risk of complications.”

It’s also important to take into account research suggesting that long COVID has a disproportionate impact on women compared to men. A study recently published in the Journal of Women’s Health revealed that women with long COVID exhibited more symptoms than men suffering from the condition. With emerging evidence that the female sex is a risk factor for developing long COVID, more research is needed to determine what impact vaccination will have on this group, Quinn said.

Still, Conway said it is likely that younger, healthier populations will reap even greater benefits from vaccines when it comes to protection against long COVID. This is because they don’t carry the same risk factors capable of resulting in long-term consequences from COVID-19, Conway said, such as old age and underlying health conditions.

“The fact that in a population that is, to me, at higher risk of long COVID, they were able to show a benefit of the vaccine of any magnitude is very promising that in a healthier population, vaccines will have even more benefit in reducing the risk of long COVID,” Conway said. “Although the data are not yet there to prove that.”

While the U.S. study does not stipulate how many COVID-19 vaccine doses each person involved had received, both Quinn and Conway said that those with three doses of the vaccine, for example, would be better protected and less likely to develop long COVID compared to those who had only received two doses.

Previous studies comparing the effectiveness of two and three doses of COVID-19 vaccines show that three doses offer increased protection against symptomatic illness and severe outcomes as a result of Omicron infection. With vaccination reducing a person's chances of getting infected with COVID-19, and the odds of being hospitalized or dying from infection, it is likely to reduce the risk of developing long COVID as well, said Quinn.

“By reducing your risk of getting infected at all and your risk of getting severe infection leading to hospitalization or intensive care unit admission, this might reduce your risk of long COVID overall,” he said.

WHAT WE KNOW (AND DON’T KNOW) ABOUT LONG COVID

While researchers are still nailing down the exact cause of long COVID, some underlying factors being studied include damage from the original course of infection, an abnormal immune response to the virus and pockets of SARS-CoV-2 that may linger in the body after acute COVID-19 infection.

Emerging evidence points to the possibility that even after acute infection, viral particles can persist in the gut, resulting in symptoms such as diarrhea, Quinn said. It’s possible that current vaccines don’t adequately address this outcome and that another form of treatment may be needed altogether to minimize the impact. It’s also not known whether a severe case of COVID-19 will necessarily increase a person’s chances of developing long COVID.

“We still don't fully understand the mechanisms by which long COVID develops, and until you understand what the root cause of a problem is, you can't expect that any treatments are going to necessarily target any one of those,” Quinn said. “Vaccination only targets some elements of what causes long COVID.”

Different health agencies also have varying definitions of what is considered long COVID. The World Health Organization (WHO) defines long COVID, or the post-COVID-19 condition, as symptoms that persist at least three months after the onset of SARS-CoV-2 infection. In cases of long COVID, symptoms “cannot be explained by an alternative diagnosis,” WHO says. The Public Health Agency of Canada has a similar definition for long COVID.

Meanwhile, according to the U.S. Centers for Disease Control and Prevention, “at least four weeks after infection is the start of when post-COVID conditions could first be identified.”

“That's a difference of eight weeks,” Quinn said. “That’s a huge period of time, and that’s going to affect the numbers overall, substantially.”

Additionally, there are a wide range of symptoms associated with long COVID, said Conway. In fact, as many as 203 symptoms have been associated with the condition, according to a study published in The Lancet in 2021. Most of these symptoms fit into three different categories, which include fatigue, reduced respiratory capacity – such as shortness of breath – and issues with memory. According to experts, the fact that these symptoms are rather generalized makes it increasingly tough to detect and treat long COVID.

“The symptoms are nebulous,” said Kalina. “[They’re] likely reflective of phenomena that we see across the infectious disease world, where conditions lead to a post-infectious inflammatory state that is very poorly defined.”

Despite how much remains unknown about long COVID, studies such as this one help to paint a clearer picture of what treatment should look like, Quinn said.

“All of this, I hope, is going to inform how to treat [long-COVID patients], health policy interventions and how to organize our health-care system to be able to deliver high-quality care for people with the post-COVID condition,” he said.

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