The False Equivalence of Long Covid and ME/CFS

How can unremitting symptoms of Covid-19 produce ME/CFS when the two syndromes have different viruses in bodily tissues, including their brains?

There are many ways in which medical research changed over the last century, and one of the most important is the drop in frequency of autopsies. In the 1950s, hospital autopsies were performed in about 50% of deaths. “Today, pathologists estimate the rate to be as low as 5%,” Eva Cornman reported on the Yale Medicine website in September 2024. (1)

Why is that important?

Among the physicians interviewed by Cornman was Harry Sanchez, MD, assistant professor and director of Autopsy Services in the Department of Pathology at Yale School of Medicine. According to Sanchez, he finds undiagnosed conditions in 15-20% of autopsies he performs. Among them are tumors, Covid-19, lung masses that turned out to be fungal infections, microscopic tumors, and rare inflammatory diseases. (1)

Why does this matter?

“There is a wealth of information that we glean through an autopsy process that can help inform future care,” according to Yale MICU physician Shyoko Honiden. (1)

One way of differentiating Long Covid from ME/CFS is by microscopic examination of tissues, as is done at autopsy. The two illnesses have been lumped together by many clinicians and researchers since Long Covid was recognized; some have gone so far as to state that people with lingering Covid-19 symptoms actually develop ME/CFS. A veteran ME/CFS researcher, Dr. Anthony Komaroff, is one.

“It is therefore entirely plausible that some cases of ME/CFS will develop in people who get COVID-19,” Komaroff wrote in an online article for Columbia University’s Mailman School of Public Health. “It is important to conduct studies that follow people with COVID-19 for several years, even after they recover, to see whether ME/CFS or other long-term complications will develop.” (2)

As I’ve noted before, this argument is an attempt to throw ME/CFS into a wastebasket with every other “post-infectious syndrome” found in patients who recover slowly from other viral infections—including Ebola, dengue, SARS, West Nile Virus, and, of course, SARS-CoV-2—and then kick that wastebasket under someone unimportant’s desk. (2)

It does an inexcusable disservice to all of these patient cohorts.

How can medicine argue that a person who became ill four to five years ago during a pandemic of SARS-CoV-2 virus, i.e. Covid-19, has the same illness as a person who became ill 20+ years ago with ME/CFS, cause unknown (and mostly unsought)?

In one case, medicine has assigned a cause to the “post-infectious” syndrome: SARS-CoV-2 virus. In the other case, science has twisted itself into a pretzel trying to prove that there’s NO cause, or that there are numerous causes—a theory that means there is no accepted cause of ME/CFS now and probably never will be, if the “post-viral syndrome” paradigm continues into the future.

Let’s examine one symptom suffered by both groups of patients, brain fog. What causes it?  Nobody knows.

But if one looks at brain tissues from Long Covid and ME/CFS patients, it’s clear that their brains are affected by completely different pathogens.

In 2022, Daniel S. Chernov (Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health) and colleagues from NIH and NIAID published a paper in Nature magazine describing their findings from autopsies of patients who died from “severe” Covid-19.  One conclusion they reached was that “in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.” They were describing a condition now called Long Covid. (3)

Chernov and colleagues examined the bodies of 44 deceased SARS-CoV-2 patients.

“We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection,” they reported. “Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. ... Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.” (3)

They concluded that “sequencing in the CNS [central nervous system] prove definitively that SARS-CoV-2 is capable of infecting and replicating within the human brain.” (3)

Although their study was not designed to answer questions related to Long Covid, they pointed out that “...our findings fundamentally improve the understanding of SARS-CoV-2 cellular distribution and persistence in the human body and brain and provide a strong rationale for pursuing future similar studies to define mechanisms of SARS-CoV-2 persistence and contribution to post-acute sequelae of SARS-CoV-2.” (3)

“Post-acute sequelae of Covid-19,” or PASC, was a term used early in the identification of Long Covid as a discrete syndrome.

Also in 2022, Bhupesh K. Prusty (Julius-Maximilians-University of Würzburg, Germany) and an international group of colleagues examined biopsied brain tissues from ME/CFS patients. (4)

While the number of brain biopsies performed was acknowledged as a drawback in study design—three ME/CFS patients, compared to three control subjects—Prusty and colleagues referenced previous studies that had found herpesviruses in the brains of ME/CFS patients, but not in the control subjects. (4)

“Symptomatic HHV-6 is associated with neuroinflammation when identified in the brain,” Prusty et al. reported. “In addition to ME/CFS, active HHV-6 in the brain has been linked to mesial temporal lobe epilepsy (MTLE), multiple sclerosis (MS), and Alzheimer’s disease (AD).”

Prusty and colleagues found “abundant viral miRNA [micro RNA]” of HHV-6A, HHV-6B, and HHV-7 in not only the brains of ME/CFS patients but also in spinal cord tissues. While noting that HHV-6 in the cerebellum has been associated with mood disorders, including depression, they reported that their results “suggest that HHV-6 infection within the cerebellum is not associated with any depressive physiology in ME/CFS patients.” (4)

If a patient is infected with Ebola virus, is that the same as being infected with influenza virus?  Do they share some symptoms, like fever, fatigue, pain?  Sure. Do they have the same disease?

What might medicine discover if it returned to the 1950s level of doing autopsies on 50% of patients who died in hospitals?  Why can’t that be done?  And to those who say it will cost too much, compare that to lost wages in the US from both ME/CFS ($9.1 billion) and Long Covid ($168 billion). 

BIBLIOGRAPHY
1.        Eva Cornman. “What Gets Lost When Autopsies Aren’t Done? Not Just Cause of Death. Fewer autopsies mean less information for scientists, doctors, and doctors-to-be.” Yale School of Medicine. September 20, 2024. https://medicine.yale.edu/news-article/what-gets-lost-when-autopsies-arent-done-not-just-cause-of-death/
2.        Anthony L. Komaroff. “Will There Be a Post-COVID-19 Form of ME/CFS?” Columbia University Mailman School of Public Health website, 2024. https://www.publichealth.columbia.edu/will-there-be-post-covid-19-form-me-cfs
3.        Daniel S. Chernov et al. “SARS-CoV-2 infection and persistence in the human body and brain at autopsy.” Nature. December 22/29, 2022. https://doi.org/10.1038/s41586-022-05542-y
4.        Francesca Kasimir, Danny Toomey, Zheng Liu, Agnes C. Kaiping, Maria Eugenia Ariza, and Bhupesh K. Prusty. “Tissue specific signature of HHV-6 infection in ME/CFS.” Frontiers, Vol. 9, December 13, 2022. https://doi.org/10.3389/fmolb.2022.1044964
5.        Leonard A Jason, Mary C Benton, Lisa Valentine, Abra Johnson, Susan Torres-Harding. “The Economic impact of ME/CFS: Individual and societal costs.” Dyn. Med., April 2008. doi: 10.1186/1476-5918-7-6
6.        Katie Bach. “New Data Shows that Long Covid is keeping as many as four million people out of work.” Brookings Institute Metro, August 24, 2022. https://www.brookings.edu/articles/new-data-shows-long-covid-is-keeping-as-many-as-4-million-people-out-of-work/#:~:text=Using%20the%20average%20U.S.%20wage,is%20a%20%24230%20billion%20cost.