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By Mary Carpenter
“MY OXYGEN level is 93 [compared to] 98 and 99 before Covid . . . my doctor says my inflammation is rampant and my antibodies for Covid are enough for an elephant,” said Florida watersports enthusiast C.T., in his early 70s, who remains too fatigued to enjoy his daily pre-Covid kite-sailing, paddleboarding and windsurfing. “The thing that jumped out at me was the Epstein-Barr being triggered . . . went from 18 to 600 and 800 over the last year that I’ve had Long Covid.”
Alarming numbers aside, what’s most debilitating for C.T. is post-exertion malaise (PEM), the so-called “energy crash” that can follow physical exertion, often worsens over time and creates a life-changing burden for hundreds of thousands of Long Covid sufferers. According to Nature, PEM “fatigue is a subjectively perceived exhaustion that follows disproportionately after exertion and does not improve adequately after sleep or rest” — and is the most frequently reported symptom among post-Covid syndrome (PCS) patients.
Many physicians who struggle to help PEM sufferers are now voicing their excitement about possible treatments emerging from extensive research on Long Covid. In addition, the treatments might help an enormous number of people suffering from a variety of other conditions—notably myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), believed also to be a post-viral condition, which shares PEM symptoms with Long Covid.
For the first time, PEM has a single cause—the Covid virus—which provides an enormous boon for researchers. In contrast, for previous research on ME/CFS, assessing symptoms proved challenging, and diagnosis often came years after extensive damage to the body had already occurred.
“The contribution of Long Covid is an N [number of patients] so big—all having the same, well-documented original infection,” said one local D.C. internist. An estimated 23 million people, about 10% of those infected by the Covid virus, report symptoms lasting seven months or longer, according to initial findings from the Research Covid to Enhance Recovery (RECOVER) trial. Of 12 symptoms highlighted by RECOVER, number one is PEM—reported by around 70%—with dyspnea (difficulty breathing), by around 55%.
The RECOVER trial, begun in October 2021, has to date enrolled more than 8,500 adults—from an original database of more than 7 million people who had been sick with Covid and reported symptoms lasting more than three months. Trial participants continue receiving whatever treatment they or their doctor has chosen and undergo different tests or measurements depending on their personal health.
Recently, however, research on PEM has led patients and patient advocates to protest against RECOVER testing that involves increasingly intense physical challenges—concerned that participants will not be well informed about potential risks, and that researchers will not sufficiently monitor people for harm after the exercise regimen or after the trial concludes. ME/CSF patients with PEM have reported that “continuously pushing past their limits has caused [their symptoms] to permanently worsen.”
“I now think of Covid as a neurological disease as much . . . as a pulmonary disease,” said UCLA physician William Pittman. “And that’s definitely true in Long Covid.” Cognitive difficulties for Long Covid patients include difficulty with memory, attention, sleep and mood; and PEM also involves nerve dysfunction, often in the autonomic nervous system — called dysautonomia.
“Persistent viral loads or remnants hidden away in the tissues and causing chronic inflammation” may explain Long Covid symptoms, according to Yale researchers. Other theories point to inflammation in the brain due to increased auto-immune activity—which lasts beyond the acute Covid infection, or which is stimulated by the reactivation of dormant viruses such as Epstein-Barr.
PET scans have detected evidence of brain inflammation in patients with Long Covid, according to Canadian research published in late May from the Campbell Family Mental Health Research Institute. Said Neuroimaging Program Head Jeffrey Meyer, “We already knew that there is brain inflammation in people who died in the midst of a severe, active COVID-19 infection. What’s new about this study is that it shows that inflammation is hanging around for a long time in the brains of people with long COVID even after only mild to moderate symptoms of active COVID-19.”
The possibility that Long Covid symptoms are caused by lingering viral remnants offers hope that it might be necessary to extend treatment with antiviral drugs such as Paxlovid beyond the current regimen of five days to completely clear the Covid virus from the body. And if one cause of Long Covid is a chronic autoimmune response, anti-inflammatory drugs, such as metformin, could help treat the symptoms. In a multi-center study, 564 overweight or obese adults who started a two-week course of metformin while suffering from acute Covid had a 42% lower chance of being diagnosed with Long Covid compared to those who took a placebo when they first got sick.
Yale Medicine is now recruiting participants for a new study, Listen to Immune, Symptom and Treatments Experiences Now (LISTEN) that will investigate Long Covid along with other pathogens causing chronic illness in a “subset of people, called post-acute infection syndrome (PAIS), which includes ME/CFS” — another example of how the research spurred by huge numbers of Long Covid patients could help sufferers of other PAIS, such as that following Lyme disease.
For my symptoms that lingered following acute Lyme infection, notably peripheral neuropathy, my internist prescribed several additional weeks of doxycycline treatment – under the same theory as that for Long Covid, that ongoing issues might be occurring as the result of infectious remnants, in my case of the bacteria causing Lyme disease. While the effort did not help me — and the final verdict is not in on adding more days of Paxlovid — my only issue is wobbly walking, nothing like the disabling fatigue suffered by C.T. with PEM.
—Mary Carpenter regularly reports on topical issues in health and medicine.
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This is fascinating. The research showing that subjects with metformin were much less likely to develop long covid is very interesting. I wonder if it is getting followup… also, I wonder how many different viruses actually linger and cause perhaps less dramatic symptoms after getting sick.