A small but intensive study of COVID long-haulers has revealed several abnormalities in their blood, Science Insider journal reports. Not only do the new findings add to the mounting evidence that Long COVID shares similarities with other post-viral conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but they also open the door to testing possible treatments for Long COVID sufferers.* 

What the researchers did

The study, led by Yale University immunologist Akiko Iwasaki and David Putrino, a neurophysiologist at the Icahn School of Medicine at Mount Sinai, began in late 2020. Iwasaki, a laboratory scientist, and Putrino, who was caring for affected patients, wanted to compare current patients with patients who had recovered, and also with people who had never been infected. For this study, they examined 99 patients with brain fog, severe fatigue, and other common Long COVID symptoms.

What they found

Putrino and Iwasaki found that the current patients’ blood contained two important features:

• Low levels of cortisol (approximately half the normal level), and
• High levels of “exhausted” T cells.

Low cortisol levels

Cortisol, also known as a ‘stress hormone,’ has a range of functions that include, among others:

• Helping the body control inflammation,
• Regulating glucose, and
• Regulating sleep cycles.

The cortisol findings were not that surprising, and supported similar results from a paper published in the January 2022 issue of Cell that reported low cortisol in patients with lingering respiratory symptoms, and virus reactivations in patients with neurological symptoms.

Low cortisol is associated with muscle weakness and fatigue, so would explain some of the symptoms. The reason for the low cortisol levels is still unclear, however, as the hormone (ACTH) in the pituitary gland that controls cortisol production was at a normal level. 

“Exhausted” T cells

About 20-30% of the Long COVID patients had elevated levels of exhausted T cells. Exhausted, or dysfunctional, T cells are often seen in people with chronic infections or tumors, where the immune system is constantly cranking out soldier cells to fight off the toxic intruders.

The presence of the cells, combined with certain biomarkers, indicated that the patients’ immune systems were still battling some sort of virus, whether SARS-CoV-2 fragments or a reactivated virus. Such ongoing confrontations cause chronic inflammation, which is at least partly responsible for many Long COVID symptoms.

The researchers also found reactivation of Epstein-Barr and other herpesviruses that can lie dormant for long periods of time. They also found that T cell exhaustion seemed to track with Epstein-Barr virus reactivation, specifically.

Interestingly, low cortisol, Epstein-Barr reactivation, and T cell exhaustion have all been discovered in certain ME/CFS patients, as well.

What it means

The study makes it clear that while Long COVID has notable similarities with other post-viral syndromes, there is still much to learn about its uniqueness. Fortunately, the new findings suggest possible treatments that already exist, and Iwasaki’s experimental therapy “wish list” includes:

• Cortisol supplementation, 
• Epstein-Barr virus–targeting therapy, 
• Paxlovid, the antiviral drug used for acute COVID-19 infection, and 
• Therapies that deplete B cells, used to treat autoimmune disease and quiet the immune system.

She and Putrino are eager to start the testing process. “We should be trying these right now,” Iwasaki says. As a scientist, she adds, she would prefer to have “all the pieces of the puzzle” in place before starting any trials, “but the patients, they can’t wait.”

*Couzin-Frankel, J. (2022, August 16). Blood abnormalities found in people with Long COVID. ScienceInsider. https://www.science.org/content/article/blood-abnormalities-found-people-long-covid