ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Abstract

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars. In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.

Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Patients with ME/CFS may also present with fluctuations in severity of the disease akin to MS where symptoms rise and fall through cycles of relapse and remission . Onset or exacerbation of ME/CFS symptoms may be triggered as well by factors including (1) infection (viral and bacterial), (2) diet, (3) hormonal changes, (4) age, (5) environment, and (6) drug induction. , Molecular mimicry has also been proposed to induce autoimmunity in ME/CFS where viruses present infectious material such as peptides that have similar residue sequences as the host antigen(s); these foreign agents, which may cause an autoimmune response, include, for example, herpes 6, Epstein-Bar, and corona virus 229E. − …”

“…Demyelination may also be a common denominator with ME/CFS where some patients experience symptoms of muscle pain and weakness as a results of diminished nerve function . To strengthen this idea, there are several reports of abnormal brain magnetic resonance imagining (MRI) studies in patients with ME/CFS. − Based on images with white/gray matter hyperintensities and cerebral atrophy, Cook et al found that ME/CFS patients had a higher level of physical impairment (motor and cognitive functions) compared to patients with normal MRI scans. , Furthermore, there is a growing body of literature on COVID-related research postpandemic (e.g., Long-COVID) that makes a strong connection to ME/CFS; this suggests that COVID-19 infection may act as a precursor/trigger for ME/CFS. Demyelination in particular, which has been reported numerous times in cases of COVID-19, − may play a larger role in neurological-related symptoms in patients recently diagnosed with ME/CFS.…”

A global need for more awareness of dysautonomia in postviral syndromes

“…It is recognized that viral illnesses can be a trigger for the onset of dysautonomia symptoms and this can lead to the development of long-term debilitating health problems such as long COVID and ME/CFS. 7,8 Identifying dysautonomia is primarily based on detailed history taking which can be done in any healthcare setting, looking for evidence of orthostatic intolerance, palpitations, temperature dysregulation, sweating problems, gastrointestinal symptoms, or sexual dysfunction. There are simple bedside/clinic tests that can be performed to look for evidence of pulse and BP changes in response to physiological demands such as standing and eating.…”

Complement dysregulation is a predictive and therapeutically amenable feature of long COVID

“…Common symptoms include cognitive blunting, also called "brain fog", chest pain, dyspnoea, fatigue, and sensory dysregulation, which often have a substantial impact on daily activities and quality of life, akin to myalgic encephalomyelitis/chronic fatigue syndrome. 4 A recent systematic review concluded that 45% of individuals experience diverse and unresolved symptoms 4 months after infection with SARS-CoV-2, irrespective of initial disease severity. 5 Chronic disease is also common.…”