Yale research hints at possible long-term COVID causes and relief
New findings published by researchers at Yale are shedding new light on how long COVID affects the body, hinting at possible treatments. Those findings are also raising questions questions about COVID’s possible effects on the human body in the decades after infection. Akiko Iwasaki recently co-authored a paper studying a small, but diverse cohort of COVID patients. She is a professor of immunobiology and molecular, cellular and developmental biology at Yale University.
In addition to a control group, Iwasaki and her colleagues studied COVID patients who had fully recovered and those who were suffering symptoms associated with COVID months and years after infection.
Their primary findings were three-fold. First, T cells, key aspects of a body’s immune system, were found to be “exhausted” in long COVID patients, meaning those cells had been consistently fighting the same infection.
“These cells are very well known in chronic infections and cancer, and T cells get ‘exhausted’ when they see the same antigen over and over,” Iwasaki said. “This implies that there is something that’s triggering these T cells for extended time periods in the long COVID patients. We don’t know what they’re seeing, but it could be the SARS-cov-2 antigen.”
The researchers also found that Epstein-Barr viral cells already present in patients’ bodies had been reactivated. One of the most common viruses in the world, EBV is best known as the cause of mononucleosis.
Epstein-Barr infection has been associated with a multiple sclerosis diagnosis decades after infection, and Iwasaki said her findings suggest the possibility that the same may be true for long COVID, though that won’t be confirmed for a long time.
“It takes years or decades for MS and other autoimmune diseases to manifest after an infection,” she said. “I wouldn’t want to say that there is going to be an increased risk, but it’s possible that some of these patients might develop autoimmune diseases later in life. But this is completely speculation at this point.”
However, some of the symptoms of long COVID may in fact be a result of the EBV, and might therefore be treated with EBV-specific therapies.
“If they are indeed reactivating these viruses, the EBV itself can cause a lot of symptoms on its own,” Iwasaki said. “So, maybe some of the symptoms that they’re experiencing may be coming from EBV rather than the SARS-cov-2.”
Long COVID patients were also found to have particularly low levels of cortisol, which Iwasaki said is “an essential hormone that regulates many aspects of physiology, including nutrient handling, as well as glucose level, blood pressure, inflammation reduction, so on.”
That might also suggest that long COVID symptoms could be the result of low cortisol levels.
“That could mean that, again, a lot of the symptoms associated with low levels of cortisol are overlapping with symptoms that are seen in long COVID,” she said. “So this could also be one of the sort of drivers of symptoms, in addition to having this viral infection.”
The study examined 215 patients at Yale and Mount Sinai’s Center for Post-COVID Care, and Iwasaki said the next step is to widen the participant base to see if the findings hold true for patients around the world.
If so, treating the symptoms of EBV and low cortisol levels might provide some relief for long COVID sufferers.
“If people are indeed suffering from low-level cortisol, can we give them low-dose hydrocortisone and relieve some of the symptoms?” she asked. “And then, for EBV, should we be treating these people with ganciclovir or other antivirals against EBV? Is that going to be helpful? These are just some of the, like, hypotheses that are being driven by the by the study.”