Long Covid, Covid-19, & ME/CFS "Brain Fog"
Is the SARS CoV-2 virus the culprit—or is HHV-6?
One of the most disabling symptoms experienced by both ME/CFS and Long Covid patients is “brain fog.” This seemingly innocuous term is used to describe many levels of cognitive dysfunction, from memory loss to serious disorientation and the inability to function in a job, a relationship, and managing tasks of daily living. Yet Covid-19 and Long Covid are classified as respiratory diseases, and ME/CFS has become mired in a pervasive fatigue that prevents its most severe symptoms from being taken seriously.
So, what’s happening in the brains of these patients? Are their neurological symptoms caused by a virus—by the same virus, different viruses, numerous viruses—or are these patients’ cognitive difficulties simply collateral damage?
A study from the University of Oxford (Oxford, UK) published online August 17, 2022, examined medical records of Covid-19 patients from around the world. Starting with data from the health care records of “approximately 89 million patients” collected from “hospital, primary care, and specialist providers (mostly from the USA, but also from Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan),” more than one million Covid-19 patients of all ages were paired with patients who’d been diagnosed with “other respiratory diseases.” The Covid-19 patients had been diagnosed between Jan 20, 2020, and April 13, 2022. (1)
Fourteen different cognitive disorders were examined in this retrospective study. It found that patients with both Covid-19 and “other” respiratory infections had approximately the same increases in anxiety and mood disorders, which did not last more than a couple of months.
“In contrast,” these British researchers point out, “the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes.” In other words: The cause of anxiety and depression in Covid-19 patients could be completely different from the cause of the long term, severe brain dysfunction they suffer, turning Covid-19 patients into those with Long Covid.
After all the number crunching, the Oxford team concluded, “In summary, post-Covid neurological and psychiatric outcomes followed different risk trajectories: The risk of cognitive deficit, dementia, psychotic disorder, and epilepsy or seizures remained increased at 2 years after a Covid-19 diagnosis,” while the risks of mood and anxiety disorders “subsided early” in all groups. Although they had not identified the mechanisms underlying these brain conditions, this research team emphasized the necessity of such research, not only for patient management but also for “anticipating the burden of the pandemic.”
And what has become a major burden of the Covid-19 pandemic? Patients who develop Long Covid and cannot return to their lives because of cognitive deficit, dementia, psychotic disorder and/or seizures.
Attempting to answer the question of what causes the neurologic disorders in Covid-19 and Long Covid, a research team from Brazil looked for co-infection with any of the nine human herpesviruses in patients with “severe” Covid-19. In a June 2022 paper, they reported that the neurological conditions associated with herpesviruses in some severe Covid-19 patients include stroke, headache, dizziness, mental confusion, loss of smell and taste, nerve inflammation and pain (myelitis), and brain inflammation (encephalitis). (2)
The Brazilian team found that 47.2% of these Covid-19 patients were coinfected with HHV-6. They reported that, “even though SARS‐CoV‐2 and [human herpesvirus] coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV‐6 detection.”
Do these results from Brazil explain why the neurological symptoms seen in patients with Covid-19 and Long Covid are so similar to those seen in ME/CFS patients?
Not surprisingly, the description of patients’ cognitive dysfunction in the US government’s most recent ME/CFS definition—the 2015 Institute of Medicine (IOM) case definition—is minimal: It says only, “Cognitive impairment (problems with thinking exacerbated by exertion, effort, or stress or time pressure).” (3)
Like nearly all US government-funded ME/CFS research, IOM has made no effort to determine what might be causing this cognitive impairment, or the illness itself.
Just as HHV-6 has been identified in Covid-19 patients with neurological disease, it’s also been found in brain tissue from people diagnosed with mental illness. Bhupesh Prusty and colleagues in Germany (Julius Maximilian University, Wuerzburg) examined brain tissues from patients with bipolar disorder, schizophrenia, and major depressive disorder, and compared them to brain tissues from mentally healthy individuals. Prusty and colleagues found “significantly high levels of HHV-6A protein and DNA” in brain tissues from people with bipolar and major depressive disorders. Both HHV-6A and HHV-6B (usually found in infants) were found in brain tissues from all three groups of psychiatric patients. (4)
A 2021 investigation examined whether HHV-6 might be present in another form of mental illness: catatonia. While uncommon, catatonia causes a seemingly semi-conscious state in which patients can be agitated, demonstrate ecolalia (repeating a phrase over and over) or mutism (not responding to verbal cues), and other cognitive symptoms. Based in part on Prusty’s study of HHV-6 in mental illnesses, this investigation suggested HHV-6 could be involved in other mental disorders, including catatonia and various encephalopathies. (5)
Just as we now know there’s an association between Covid-19 and HHV-6 infection, there’s also an association between ME/CFS and HHV-6. A statistical review of 17 published studies by researchers in Iran notes that some ME/CFS patients improve when treated with antiviral medications (Alborz University of Medical Sciences in Karaj, Iran). In one study, 74.5% of ME/CFS patients returned to “near-normal or normal” life after treatment with anti-herpesvirus medications like valacyclovir. “The pooled odds ratio also suggests the possible association between HHV-6 infection and CFS incidence,” the authors conclude. (6)
If HHV-6 is found in the brains of people with mental illness, as well as in ME/CFS patients, Covid-19 and Long Covid patients who share numerous types of cognitive impairment, isn’t it logical that HHV-6 is involved in causing some of the most serious neurological symptoms in all of these conditions?
BIBLIOGRAPHY
(1) Taquet, Maxime et al.; “Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients”; Lancet Psychiatry; Published Online August 17, 2022. https://doi.org/10.1016/S2215-0366(22)00260-7
(2) Carneiro et al.; “Herpesvirus and Neurological Manifestations in Patients with Severe Coronavirus Disease”; Published Online 6-8-22; Virology Journal (2022) 19:101 https://doi.org/10.1186/s12985-022-01828-9
(3) Institute of Medicine (US). Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. National Academies Press, 2015. https://doi.org/10.17226/19012
(4) Prusty, B.K.; Gulver, N.; Govind, S.; Krueger, G.R.F.; Feichtinger, J.; Larcombe, L.; Aspinall, R., Ablashi, D.V. and Toro, C.T. “Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders”; Front. Microbiol. 2018; 9: 1955. doi: 10.3389/ fmicb.2018.01955
(5) Das, S. (2021) “An Investigation into the Significance of HHV-6 in Catatonia and Mental Health Disorders”; Sushruta J Health Pol & Opin. Vol 14; Issue 2: Art 6ePub 12.6.21. https://doi.org/10.38192/14.2
(6) Mozhgani, S-H, Rajabi F, Qurbani M, Erfani Y, Yaslianifard S, Moosavi A, Pourrostami K, Baradaran Bagheri A, Soleimani A, Behzadian F, Safavi M, Rezaei F. “Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-analysis”; Intervirology, June 22, 2021. doi: 10.1159/000517930