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What If You Never Get Better From Covid-19?

Anecdotally, at least, some long-haulers are experiencing the type of viral reactivation Klimas describes. In late October, seven months after contracting the coronavirus, Lauren Nichols developed shingles — a reactivation of the virus that causes chickenpox. The episode, which featured burning, “out of this world” nerve pain, sent her to the emergency room. A lesion developed on the cornea of her left eye, threatening her vision. Antiviral medication helped bring the shingles under control. Nichols, an administrator of a long-Covid support group, told me that reactivation of Epstein-Barr, cytomegalovirus and other herpesviruses occurs in a small but significant percentage of long-haulers on the site.

A similar argument over what drives chronic symptoms — persistent infection versus lingering inflammation from a past infection — appears prominently in the study of Lyme disease. Some people infected with Borrelia burgdorferi, the tick-borne bacterium that causes Lyme, fail to recover even after antibiotic treatment. Patients may refer to this illness as “chronic Lyme disease,” but doctors prefer to call it “post-treatment Lyme disease syndrome,” because they’re not sure an infection is still really there. As in ME/CFS research, the debate over the root cause of this post-Lyme illness has for years polarized the field.

There are other similarities as well. The Lyme problem is underrecognized but immense. Every year, an estimated 329,000 people are infected by B. burgdorferi. About 10 percent of those treated with antibiotics develop lasting symptoms, including fatigue, pain and occasionally nervous-system conditions like dysautonomia — heart rate, blood pressure and other basic bodily functions in disarray. It appears to strike women more than men, it has long been dismissed as psychological and the long-term illness is often judged worse than the acute infection.

Like ME/CFS, post-Lyme syndrome has no biological marker that allows for concrete diagnosis. The three nonmutually exclusive ideas about what causes long-term symptoms roughly correspond with those for ME/CFS: a persistent infection (or perhaps merely debris from the Lyme spirochetes); an autoimmune or inflammatory dysfunction triggered by the infection that continues after the bacteria are gone; or changes in the nervous system that mirror Jarred Younger’s “angry microglia” idea, but that are described by Lyme researchers as “central nervous system sensitization.” Perhaps the infection changes how the brain works in such a way that once-easily bearable stimuli — pain, light, sound — become unbearable.

The parallels between ME/CFS and Lyme reinforce the notion that many different infections — including the Lyme spirochete — can trigger debilitating long-term syndromes. It’s a lesson that we as a society have perhaps forgotten, Allen Steere, a Lyme expert and rheumatologist at Harvard Medical School, told me. “Now we have millions infected, and it becomes apparent to people that this type of problem can follow.”

It’s a maddening prospect, but long Covid may not be a single syndrome at all. It could, as seems to be the case with ME/CFS, be an array of problems connected in various ways with an initial trigger — in Covid’s case, the invasion of the human body by a virus thought to be originally native to bats. ME/CFS doctors and researchers have faced this sort of frustrating complexity for years. It’s an unavoidable challenge in managing a condition, be it ME/CFS or long Covid, whose diagnosis is based almost entirely on the subjective reporting of symptoms. There are, after all, many ways to produce symptoms like fatigue, brain fog and even dysautonomia. As Peter Rowe puts it, treating ME/CFS is like peeling an artichoke. “You’re trying to remove treatable layers of problems and see what the essence is,” he told me.

In the case of ME/CFS, scientists have identified a few more leaves of the proverbial artichoke — a grab bag of treatable, somewhat obscure conditions that seem to be associated with it. One is mast cell activation syndrome, which can produce fatigue, pain and problems with thinking and memory; infection can sometimes initiate it. Another is small-fiber neuropathy, a condition in which the body’s nerves begin to misfire and can die off, causing pain, fatigue and disruption to basic bodily functions like breathing. Infections can sometimes trigger it, and given the current description of long-Covid symptoms, Anne Louise Oaklander, a pioneer in understanding this neuropathy, suspects it will be found to occur among long-haulers as well. “Small-fiber neuropathy is usually treatable,” Oaklander told me, “and in some cases curable.”

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