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Long COVID and Immunodeficiency

Patients who have primary immunodeficiencies could be more at risk of long COVID, a researcher recently told the Immune Deficiency Foundation.

Long COVID against a pale background of COVID virus

Researchers are starting to unravel the mysteries of “long COVID” – symptoms like fatigue, respiratory problems and brain fog that follow a SARS-CoV-2 infection. But even as scientists zero in on risk factors, they’re not sure how it affects primary immunodeficiency (PI) patients.

One study of 100 patients in the United Kingdom found PI patients were more at risk of severe symptoms and death. But with 200+ different PIs, the kind of immunodeficiency a person has will affect the outcome, James Heath, a professor of molecular and medical pharmacology at UCLA and the president of the Institute of Systems Biology, told patients during a webinar hosted by the Immune Deficiency Foundation. For example, if a person is able to make T cells, they will be able to mount a partial defense, Heath said.

“The best way is, if you are immunodeficient and you have COVID-19, to isolate until you are recovered,” Heath says.

It’s unclear how “long COVID” will affect PI patients, he said, but immunodeficient patients are likely to be at a higher risk because they will have higher amounts of the virus in their bodies during an infection. He encouraged PI patients to participate in the U.S. National Institutes of Health RECOVER Initiative, a large, long-term study about long COVID. People with immunodeficiencies will add diversity to the study and function as important controls, Heath said.

Heath is one of the authors of a recent paper in Cell that followed 209 COVID patients for several months after their initial diagnosis to if they could pin down any of the risk factors that might lead to long COVID. They identified these risk factors:

  • type 2 diabetes
  • the presence of the Epstein-Barr virus (EBV), which is responsible for mononucleosis
  • high levels of SARS-CoV-2 RNA in blood serum
  • specific autoantibodies, which play a role in autoimmune diseases like lupus and multiple sclerosis

The presence of autoantibodies was the single biggest factor predicting whether someone would get long COVID, Heath said. What’s the difference between antibodies, which fight off infections, and autoantibodies? Antibodies, also called immunoglobulins, are molecules made by our immune systems that find and attach to specific pathogens, preventing them from getting inside cells and helping other immune cells find and kill them.

“Autoantibodies are basically when your body is making exactly those same kind of molecules, but against proteins that your body naturally makes,” Heath said.

In that regard, long COVID may actually look similar to other autoimmune conditions.

“Long COVID, and the causes associated with it, may not be that crazy different from some other chronic conditions such as post-acute Lyme, chemo brain, other auto immune conditions,” Heath said.

Long COVID symptoms vary, but often include fatigue and shortness of breath. Some people experience memory loss, gastrointestinal distress and loss of taste or smell. Fortunately, long COVID symptoms do seem to clear up for most people over time, though it can take months.

“Most patients that are feeling miserable two or three months after infection will actually be OK after six months,” Heath said. “But there is a non-trivial number … that are still going to be feeling something six months out.”