Study: Long COVID Patients Have Immune System Differences

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Using immune profiling, a small but intense study found that people with long COVID have increased antibody responses to other non-COVID viruses, like Epstein-Barr Virus (EBV), as well as significantly lowered cortisol levels compared with people without long COVID.

The study — which is still a preprint, meaning it has yet to be peer-reviewed — looked at 215 people from Mount Sinai Hospital in New York City and Yale New Haven Hospital in Connecticut.

The 215 study participants were placed into four groups:

  • healthy individuals who haven’t been previously infected with COVID-19

  • healthy, unvaccinated people who have had COVID

  • healthy, vaccinated people who have had COVID with no lingering symptoms

  • individuals who have had persistent symptoms following acute COVID infection

According to Yale immunology professor Akiko Iwasaki, PhD, and co-authors, an unexpected development in the group’s research revealed that subsets of long COVID patients had antibody reactivity against non-COVID viruses, particularly Epstein-Barr Virus (EBV), a member of the herpes virus family.

The presence of EBV has been previously reported during severe COVID-19 infection in hospitalized patients. But the elevated immune responses to EBV found among patients in this study indicate a recent reactivation of this particular virus may be a common feature of long COVID.

The profiling conducted in the study found that the reactivation of EBV is not just incidental following a COVID-19 infection. In fact, the researchers write that these kinds of non-COVID viral pathogens “may alternatively mediate, aggravate, or exploit the persistent changes” in people with long COVID.

It’s unclear, however, whether EBV reactivation may predispose those with long COVID to the development or worsening of autoimmune diseases, which has been reported among people with multiple sclerosis.

Additionally, one of the most striking findings was that participants with long COVID had significant decreases in levels of cortisol, the body’s main stress hormone.

“Prior reports have associated low cortisol levels during the early phase of COVID-19 in patients that develop respiratory long COVID symptoms,” Iwasaki and colleagues write in the study. “Thus, our current finding of persistently decreased cortisol production in participants with long COVID more than a year following acute infection warrants expanded investigation.”

The authors note several important limitations to this study, primarily its small participant pool of 215 persons. While the individuals who participated were extensively immune profiled, the limited number hinders the study’s ability to be broadly applicable to the general population.

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