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  • A new study finds 1 in 8 people may have symptoms 3 to 5 months after having COVID-19.
  • Researchers found that many of the long-COVID symptoms in study participants were ones reported previously, such as tiredness, loss of sense of taste and/or smell, difficulty breathing and painful muscles.
  • The study was conducted before vaccines were widely available and before the rise of the infectious Omicron variant.

A new study looks at the risk of people having new or worsening symptoms 3 to 5 months after having had COVID-19.

But the study was done before widespread availability of vaccines and before the arrival of the Omicron variant.

It found one in eight people who had COVID-19 may experience new or worsening symptoms 3 to 5 months after a COVID-19 case.

Many earlier studies have tried to estimate how often symptoms linger after coronavirus infection — known as “long COVID” — with a wide range of results.

To provide a more reliable picture of the prevalence of long COVID — and its main symptoms — Dutch researchers looked at symptoms in people before and after coronavirus infection. They also compared these people to a similar group of uninfected people.

Researchers found that many of the long-COVID symptoms in study participants were ones reported previously, such as tiredness, loss of sense of taste and/or smell, difficulty breathing and painful muscles.

“These core symptoms have major implications for future research, as these symptoms can be used to distinguish between post-COVID-19 condition and non-COVID-19-related symptoms,” study author Aranka Ballering, a doctoral candidate at the University of Groningen in the Netherlands, said in a release.

They also compared to results to a control group of people who did not get COVID-19.

They found some symptoms also appeared in that group which were not related to coronavirus infection. They theorize these symptoms “may have been a result of non-infectious disease health aspects of the pandemic, such as stress caused by restrictions and uncertainty,” she added.

In the study, published August 6 in The Lancet, researchers asked over 76,000 adults to regularly fill out digital questionnaires asking about 23 symptoms commonly associated with long COVID.

The questionnaires were sent out between March 2020 and August 2021, primarily when the Alpha and earlier coronavirus variants were circulating in the Netherlands; the Delta variant appeared in the country at the end of this period.

Too few people in the study had been vaccinated during this period to enable researchers to see if vaccination impacted the risk of developing long COVID.

Over 4,200 participants had COVID-19 during the study — indicated by either a positive test or a doctor’s diagnosis. These people were matched to a control group of over 8,400 similar, but uninfected, people.

By looking at symptoms experienced by people before and after their infection, and in people who didn’t have a coronavirus infection, researchers were able to identify a core group of long-COVID symptoms.

These were chest pain, difficulty breathing, pain while breathing, painful muscles, loss of sense of taste and/or smell, tingling hands/feet, a lump in the throat, alternately feeling hot and cold, heavy arms and/or legs, and general tiredness.

The average severity of these symptoms plateaued at 3 months after infection and did not decline during the study period.

Several other symptoms occurred in people who had COVID-19, but the severity of the symptoms did not worsen 3 to 5 months after infection: headache, itchy eyes, dizziness, back pain and nausea.

Based on the differences in the rate of symptoms in people with COVID-19 and the control group, researchers estimate that 12.7% of the COVID-19 patients in the study had long-term symptoms due to coronavirus infection.

The research suggests that at the time of the study 12.7% of the general population infected with SARS-CoV-2, or about 1 in 8, were at risk of experiencing long COVID.

Because the authors looked at people’s symptoms before and after COVID-19 development and included a control group, this study provides a stronger estimate of how common long COVID is.

However, the study was done before the emergence of the highly transmissible Omicron variants and before the widespread use of COVID-19 vaccines, so the results may not apply to the situation today.

Research suggests that vaccination reduces the risk of developing long COVID.

In one study published in July 2022, Italian health care workers who had COVID-19 and had been vaccinated with two or three doses had a lower long-COVID risk compared to the unvaccinated. This research was carried out between March 2020 and April 2022, so it included periods when Delta and Omicron were circulating.

Other research published in June 2022 suggests that the risk of developing long COVID was lower with Omicron than with Delta.

However, as the authors of this paper point out, even if the risk is lower for Omicron because the variant caused such a large spike in cases, the actual number of people who develop long COVID could still be quite high.

In addition, some people may still get severe long COVID even with an Omicron infection.

“We’re definitely still seeing post-COVID cases just as severe now as they were a year ago. So it’s not as though universally the cases are less severe,” said Dr. Aaron Friedberg, a clinical assistant professor of internal medicine at the Ohio State Wexner Medical Center in Columbus.

In the medical center’s Post-COVID Recovery Program, he sees patients who have had symptoms for a minimum of 4 weeks, with some having them for 3 months to as long as 2 years.

Prior coronavirus infection may also impact the risk of developing long COVID. This, along with vaccination and other factors, make up what some call the population’s “immunity wall.”

Currently, “there’s a really high baseline level of protection in the population,” said Friedberg. “It’s pretty unusual right now for someone to get COVID and have never received a vaccine and never had COVID.”

Another limitation of the new study is that additional symptoms have been added to the long-COVID list since then, including “brain fog,” worsening of symptoms after physical or mental exertion (aka “post-exertional malaise”), and depression or anxiety.

One study published in July 2022 found that over half of hospitalized COVID-19 patients had some kind of cognitive impairment a year after being discharged from the hospital.

Future research will need to examine the prevalence of these other symptoms in people after coronavirus infection, as well as the prevalence of long COVID in children and teens, who can also have lingering symptoms.

While no treatment has been approved specifically to treat long COVID, Friedberg said doctors have had “tremendous” success — through studies and clinical experience — finding ways to address specific symptoms of long COVID.

This includes treatments such as physical therapy and rehabilitation, targeted breathing exercises, as well as treatments to manage neurologic symptoms such as chronic pain and numbness, and cognitive symptoms such as brain fog.

He recommends that people with long COVID look for a specialist to help them manage symptoms, ideally one who works as part of a multidisciplinary clinic.

Other long-COVID treatments, including ones specific for aspects of this condition, are in development.

Axcella Therapeutics, a biotechnology company in Cambridge, Mass., released preliminary results on August 2 from a Phase 2a clinical trial of its treatment for fatigue related to long COVID.

In the study, a group of 41 patients was given either the company’s special combination of six amino acids and derivatives twice a day for 28 days, or an inactive placebo on the same schedule.

People taking the amino acids showed improvements in self-reported mental and physical fatigue, compared to those taking the placebo. The treatment was also well tolerated, researchers found.

Additional clinical trials, including a larger phase 3 study, will be needed to know how much of an impact this treatment may have on patients with long COVID, and before regulatory agencies can approve the treatment.

Axcella’s trial focused on people who had long COVID symptoms for at least three months, in this case fatigue.

Dr. Margaret Koziel, Axcella’s chief medical officer, said they chose this cut-off because “studies have suggested that once you get beyond that three-month time point, you tend to get stuck in persistent symptoms. In other words, there’s very little resolution of symptoms naturally.”

This fits with the plateauing of symptoms seen in the study in The Lancet at the same time point.

However, Koziel said some patients in their trial have had their symptoms for much longer, including some who got sick when the pandemic first hit in the United Kingdom and still have fatigue.

As for prevalence, Koziel said more than 26 million Americans likely have long COVID, based on recent estimates from the American Academy of Physical Medicine and Rehabilitation.

Not all of those people will have severe symptoms, but Koziel thinks enough have severe fatigue from long COVID that it is negatively impacting society.

“Some people either can’t go back to work, or when they do go back to work, they’re less productive because they have to modify their schedule in order to not feel worse,” she said.