By Todd E. Davenport, Svetlana Blitshteyn, Nicola Clague-Baker, David Davies-Payne, Glenn J. Treisman and Sarah F. Tyson.
Abstract
Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions.
However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID.
The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID.
We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.
Discussion
Extracts
1. Introduction
Severe fatigue that impairs usual function long has been described throughout recorded human history. The neurologists Beard and Charcot were among the first to characterize the health condition ‘neurasthenia’ in the latter half of the 19th century. Based on this common historical root in neurasthenia, two divergent scholarly and clinical paths have taken shape over time.
The first path involves a pathogenic disease model rooted in the scientific process, resulting in a rich literature describing pathobiology and various attempts at creating specific case definition criteria. This path has resulted in the label of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
The second path is a psychosomatic/sociogenic illness construction that has incorporated ideas from contemporary neuroscience into an unbroken conceptual chain linking back to neurasthenia. This path has resulted in the label of functional neurologic disorders (FND)…
The intensity and disablement of fatigue associated with long COVID is similar to other post-viral conditions, including post-treatment Lyme disease, chronic Epstein–Barr infection, and post-mononucleosis syndrome. The condition may range from mild impairment of function to severely disabling exhaustion.
Patient complaints include severe waxing and waning fatigue, worsening fatigue the day after exertion, and dramatic exacerbation by efforts to exercise. Associated symptoms, including cognitive impairment (often referred to by patients as brain fog, diffuse chronic pain, sleep disruption, and autonomic dysfunction, including POTS, migraine, gastrointestinal dysmotility, and temperature intolerance are common concomitants. The onset of symptoms may be continuous from the time of infection or delayed in onset by weeks or months following an apparent full recovery from the acute phase of infection.
Long COVID disablement can range from mild to severe, and it can resolve in a period of months, or it can persist and worsen over time. Disablement related to long COVID may result in profound functional impairments in self-care, as well as family, social, school, and occupational roles. Post-exertional malaise/post-exertional neuroimmune exhaustion (PEM/PENE) is common among people with long COVID, which accounts for the persistent, severe, and often progressive pattern of disablement in long COVID.
PEM/PENE is a clinical hallmark of ME/CFS, suggesting an ME-like subtype of long COVID is prevalent. Therefore, it is perhaps unsurprising that many of the same themes historically characterizing the narrative about ME/CFS are still influencing the discourse surrounding long COVID…
2. Pathobiological Disease Characterization: From Neurasthenia to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
ME was first discussed as being different from other neurological disease processes in a 1956 paper that first used the term “benign myalgic encephalitis” to distinguish it from other infectious encephalitic infections and, perhaps most importantly, hysteria.
It was first assigned an International Classification of Diseases (ICD) code in the ICD-8 1969 (code 332). ME and CFS are included in ICD-11 as post-viral syndromes (8E49).
Inclusion of ME is evidence of improving legitimacy within the biomedical community, as the clinical characteristics and courses of these conditions have become better understood over time.
Notably, ME and CFS are not included in the ICD as mental or behavioral disorders. Key points in the development of a pathobiological disease construction resulting in the collective understanding of ME/CFS are summarized below:
5. Conclusions
Long COVID continues to be a major public health issue. While several phenotypes of long COVID clinical presentation have emerged based on observational studies and collective clinical experience over the past four years, it is important to emphasize that the vast majority of patients with long COVID do not have FND.
As this perspective indicates, long COVID is not based in ‘functional’ etiology, as demonstrated by numerous studies identifying a complex pathophysiology as well as common findings from the clinical examination and a summary of extant structural neuroimaging studies. Further research is needed to delineate precise pathophysiological pathways and effective therapies for long COVID and numerous post-COVID-19 neurologic manifestations.
Additionally, studies applying accepted case definition criteria are also needed to determine the true prevalence of FND as the sole or major contributor to symptoms and disability among individuals with persistent symptoms following SARS-CoV-2 infection.
These studies will help establish clinical practices that best differentiate this small subset of patients with FND-related specialized needs from the vast majority of people who experience long COVID in the forms of ME/CFS, dysautonomia, immune dysfunction, small fiber neuropathy and other post-COVID-19 neurologic syndromes.