ROCHESTER, Minn. Those who say the days of mystery for medicine are over have not seen long COVID.

The lack of even a scientific vocabulary for describing the debilitating bodily hangover that is long COVID is a source of medical humility about illness, one not seen since the years before germ theory.

"We are keeping an open mind for everything at this point," says occupational medicine specialist Dr. Greg Vanichkachorn, medical director of the COVID-19 Rehabilitation Activity Program at Mayo Clinic.

Long COVID is known to cause fatigue and shortness of breath, an exhaustion leading to difficulty with basic tasks of living.

But it also comes with an unusual set of highly distressing cognitive symptoms. Almost half of all patients develop "brain fog": difficulty finding words, short term memory lapses and troubles with multi-tasking.

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In a media call on Thursday, Oct. 7, Vanichkachorn described a plethora of basic questions still attached to long COVID, ranging from what bodily system it inhabits, to who gets it, to how it manifests symptomatically — and why.

At a year and 400 patients into two programs for the care of long COVID, there are still no wrong symptoms.

"If a patient is complaining of something that looks like it doesn't quite fit," Vanichkachorn says, "well even that deserves an investigation."

One emerging area of interest seems to be the role of the body's essential hardware that is the autonomic nervous system, including its ability to go haywire for patients with comparable mystery syndromes such as myalgic encephalomyelitis, POTS and central sensitization.

"It seems to be a much more of a neurological condition than we anticipated," says Vanichkachorn.

"One of the things we are worried about is central sensitization," he adds. "Which is where the body becomes more sensitive to stimuli, and some of those stimuli become more painful than they should be. That may sound like a fancy way to say it's all in a person's head, but what we are talking about is an actual rewiring of how the brain is interpreting impulses from the skin and the limbs."

Vanichkachorn believes the long hospitalization of COVID-19 may play a role in the neuropathology of long COVID.

"Many of these individuals who come out of the ICU are very debilitated .... On top of that, the body's experiencing some form of ongoing immune dysregulation or inflammation. That results in shortness of breath, tingling in hands or feet, and dizziness, all making it difficult to get their strength back."

Other research is considering the role of a speculative autoimmune house of cards at work in long COVID, one in which antibodies can strike at an enzyme that helps the body to lessen inflammation, causing pain. "If there are antibodies that we're making against this enzyme," he says, "that can lead to a wide variety of symptoms like we see in long haul COVID."

"I think there is an autonomic neuropathy issue underlying many of these patient symptoms ... It does seem very similar to conditions like chronic fatigue syndrome and fibromyalgia, but I think it's too early to put all these things together in one combined diagnosis."

Vanichkachorn says treatment goals are to "try to minimize symptoms so they can get back to activities and lives, and that is what leads to improvement over time."

The best way to prevent long COVID, he says, is to not get COVID-19.

"And the best way to not get COVID-19 is to first get vaccinated, and to also take precautions like social distancing and masking in appropriate settings."

"I don't want patients to lose hope, because I feel like we are in a waiting pattern right now but there is a possibility we are going to find some very effective treatments ... I feel confident that things could get a whole lot better in the future."