Risk Factors for Long Covid

Long Covid was mocked when first reported in 2020. I confess to posting a critical article about a year ago (Fake Science Behind Long Covid Symptoms) that reported on the work of Dr. Jeremy Devine, a psychiatry resident at McMaster University in Hamilton, Ontario. He believed there was no scientific basis for the condition. However, he did say it deserves serious study.

The National Institutes of Health devoted $1.15 billion to research the “prolonged health consequences” of Covid-19 infection. That research may be proving a good investment as new studies are helping advance our understanding of the biology behind long Covid, and providing clues to potential treatment.

Long Covid is characterized by a range of symptoms including fatigue, brain fog, and racing heart rates that persist months after an initial Covid-19 infection. Sumathi Reddy, writing in The Wall Street Journal, says scientists have identified four risk factors for which they tested upon a patient’s initial diagnosis.

  • Autoantibodies
  • Epstein-Barr virus
  • Type 2 diabetes
  • Genetic material of Covid-19 in the blood


The first of these risk factors was the presence of certain autoantibodies, which are antibodies that mistakenly attack the body in autoimmune conditions such as lupus. Researchers found the autoantibodies in about 60% of the patients who developed long Covid. Most patients didn’t have a diagnosed autoimmune disease, but rather had very low levels of autoantibodies associated with various autoimmune diseases.

A second risk factor was reactivated Epstein-Barr virus (EBV). EBV is associated with mononucleosis and infects about 90% of people, usually in their teens. Normally, the virus remains dormant afterward, but may become reactivated in some people for various reasons, including those who later developed long Covid.

Dr. Jim Heath, senior author of the study and president and professor of the Institute for Systems Biology in Seattle, says, “Your immune system is probably doing a reasonable job of keeping EBV in check and with a SARS-CoV-2 (Covid-19) infection you lose that brake. It seems to happen very early in an infection.”

Two other risk factors were Type 2 diabetes (adult onset) and the detection of genetic material from SARS-CoV-2 in the blood, which means the virus escaped the lungs and is spreading to other parts of the body. The researchers collected and analyzed blood and swab samples from more than 200 Covid-19 patients up to two to three months post-infection. The majority of patients were hospitalized for Covid, but the tests were replicated on a separate group of roughly 100 patients with mostly mild Covid-19 infections. The tests were also conducted on about 460 healthy people in a control group.

In a separate new study in Nature Communications, researchers in Switzerland found five different factors that they concluded will help predict who will develop long Covid. Those five factors include:

  • Lower levels of two immunoglobulins – IgM and IgG3 (antibodies)
  • Older age
  • History of asthma
  • Symptoms of fever, fatigue, cough, difficulty breathing and G.I. issues during an acute Covid-19 infection (people with long Covid had at least 3 of these)


What treatment is available for long Covid?

Identifying treatments for long Covid is the goal of this research. One possibility is treating those with the virus in the blood with one of the new Covid antiviral drugs. Researchers also found that some long Covid patients have very depleted levels of cortisol, resulting in Addison’s disease, which has symptoms such as fatigue and muscle aches. Addison’s patients are often treated with cortisol replacement therapy.

More research is needed to accurately predict and effectively treat those who develop long Covid.

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