After recovering from COVID-19, many experience long-term symptoms, including brain fog, fatigue, and skin rashes. This syndrome is known as long COVID, and researchers are in the early stages of understanding its risk factors.

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What do we know so far about the risk factors for long COVID? Louise Delmontte/Bloomberg via Getty Images.

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According to the Centers for Disease Control and Prevention (CDC), long COVID is a condition in which COVID-19-related health issues last 4 weeks or more after contracting the virus that causes the disease.

Even those who did not have COVID-19 symptoms immediately after contracting SARS-CoV-2 can develop long COVID. Symptoms may last for several weeks or months.

Research suggests that at least 54% of those who develop COVID-19 experience long COVID. According to a 2021 meta-analysis, the most common outcomes and symptoms among those with long COVID include:

  • chest imaging abnormalities for 62.2% of people
  • general functional impairments for 44%
  • fatigue or muscle weakness for 37.5%
  • general pain for 32.4%
  • generalized anxiety disorder for 29.6%
  • sleep disorders for 27%
  • difficulty concentrating for 23.8%

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Other symptoms include:

Research is emerging on risk factors for long COVID. To help parse through these studies, MNT has summarized some of the main findings so far. We also spoke with three experts on the best ways to mitigate the risk factors for long COVID.

One study that followed 309 participants for 2–3 months after contracting SARS-CoV-2 identified four factors that increase a person’s risk of long COVID:

However, the study authors noted that their research might not be conclusive as they could not confirm causation, and their sample size makes it difficult to establish any specific predictors.

Nevertheless, other studies support their findings. One study found that SARS-CoV-2 may reactivate EBV and, in turn, lead to long COVID symptoms. Around 95% of the world’s population carries this virus, although EBV largely lays dormant and is asymptomatic.

Another study found that older age, being female, and having preexisting health conditions were also linked to long COVID.

“Clinical risk factors are largely related to the severity of illness, duration of hospitalization, age at the time of infection, and preexisting comorbidities, such as lung disease, asthma, diabetes, etc.,” Prof. Elizabeta Mukaetova-Ladinska, a professor of psychiatry of old age at the University of Leicester in the United Kingdom, told Medical News Today.

“Thus, the severity of the SARS-CoV-2 infection can increase the risk for long COVID by nearly fourfold, preexisting lung disease and asthma increase the likelihood [by] six- [and] nearly 10-fold, respectively, whereas age increases the risk by 67%,” she added.

“In addition, female sex and age under 50 years are now also acknowledged as risk factors for long COVID. The latter is of importance, since [there] appears to be some overlap of symptoms of long COVID with those of perimenopause and menopause,” she explained.

Prof. Mukaetova-Ladinska further explained that lower levels of immunoglobulin (Ig) antibodies IgM and IgG3, when combined with clinical risk factors, may also increase a person’s risk of developing long COVID.

She also said that research suggests a link between alterations to the gut microbiome and long COVID: “Namely, COVID-19 patients with healthy gut bacteria and a microbiome similar to [that of a healthy person] appear to be less likely to develop long COVID, whereas those COVID patients who develop long COVID have a less diverse and abundant microbiome.”

When asked about likely risk factors for long COVID, Dr. Donald J. Alcendor, an adjunct associate professor of pathology, microbiology, and immunology at Vanderbilt University School of Medicine, told MNT that “[t]he most important risk factor for long COVID is being unvaccinated, getting a primary COVID-19 infection, and having [one or more] underlying health [conditions].”

“Studies show that getting the vaccine will greatly reduce your risk of developing long COVID. It was also shown that being vaccinated with only one dose of the COVID-19 vaccine even after being diagnosed could reduce your risk of developing long COVID.”

– Dr. Donald J. Alcendor

“Finally, people who received at least one dose of any of the three COVID-19 vaccines — Pfizer-BioNTech, Moderna, and Johnson & Johnson — before diagnosis were 7–10 times less likely to have two or more long COVID symptoms compared to unvaccinated people,” he added.

While the study Dr. Alcendor cited has not yet undergone peer review, other research published in peer-reviewed journals supports these claims.

For example, one study published in The Lancet: Infectious Diseases in January 2022 found that two-dose vaccination approximately halved the odds of experiencing COVID-19 symptoms for 28 days or more after the initial illness.

Dr. Alcendor also warned about the risk to children: “We must remember that children — although [this is] rare — can develop long COVID, and individuals who have breakthrough [or] post-immune infections or asymptomatic COVID infections can also develop long COVID. Some individuals who developed long COVID have recovered after being vaccinated.”

A press release from the U.K. Health Security Agency supports his comments. The release highlights a recent review of 15 studies, suggesting that those who have received vaccinations are less likely to experience long COVID than unvaccinated individuals.

When asked about ways that people can mitigate their chances of developing long COVID, Dr. Janis Orlowski, chief healthcare officer at the Association of American Medical Colleges, told MNT: “Taking good care of yourself and, if you’re [someone who has diabetes], trying to maintain normal blood sugar, exercise, and overall health are always helpful. We will continue to study and learn more in the future.”

To the same question, Dr. Alcendor, once again, stressed the importance of getting vaccinated: “The most important mitigation strategy against long COVID is to get vaccinated and boosted. If the vaccine is contraindicated for [a person], then they should practice CDC mitigation protocols of social distancing, masking, and hand washing.”

“This is especially important when indoors or in crowded, poorly ventilated spaces. Other members of their household should be vaccinated if eligible or proceed with the mitigation protocol if they are ineligible or remain unvaccinated,” he added.

Prof. Mukaetova-Ladinska said that as we are still in the early stages of understanding long COVID, potential treatments and mitigation strategies are largely based on those for chronic illnesses or other post-viral syndromes.

As long COVID presents in a variety of symptoms, she highlighted the importance of multidisciplinary action, including occupational therapy, physiotherapy, mental health support, and medical intervention.

She also noted some novel ways currently under investigation to both mitigate and manage long COVID symptoms:

“A novel therapeutic intervention consisting of changing the gut microbiome may help alleviate and even normalize long COVID symptoms. Based on previous studies, this may be achieved via high dietary fiber intake, plant foods low in choline, fruits and vegetables, prebiotic-containing foods, anti-inflammatory omega-3, regular intestinal motility, intermittent fasting, etc.”

Lastly, Prof. Mukaetova-Ladinska cautioned against taking drugs for long COVID without consulting a medical professional.

“Many people suffering from long COVID have looked for information and sought help outside […] medical circles. This is largely due to the lack of information and understanding of long COVID, and, in some instances, limited access to the overwhelmed health services,” she said.

“It is not surprising that over-the-counter medicine and social media platforms have been widely used, with people subjected to costly and sometimes harmful drugs and drug interactions, [alongside] conflicting information. There is an overwhelming need to understand current self-management practices regarding long COVID, [including] their benefits and harms, and [to] subject them to evidence-based rigor,” she concluded.

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