Review Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature, 2024, Cáceres

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https://www.tandfonline.com/doi/full/10.1080/14737175.2024.2440543

Review
Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature

Eder Cáceres a,b,c, Afshin A. Divanid, Andre Emilio Viñan-Garcesc, Juan Olivella-Gomezc, Alejandro Quintero-Altarec,Sebastián Pérezc, Luis F. Reyesa,e, Nicholas Sassof and Jose Billerf

aUnisabana Center for Translational Science, School of Medicine, Universidad de La Sabana, Chía, Colombia; bSchool of Engineering, Universidad deLa Sabana, Chía, Colombia; cDepartment of Critical Care, Clínica Universidad de La Sabana, Chía, Colombia; dDepartment of Neurology, TheUniversity of New Mexico, Albuquerque, NM, USA; ePandemic Sciences Institute, University of Oxford, Oxford, UK; fDepartment of Neurology,Loyola University Stritch School of Medicine, Loyola University Health System, Maywood, IL, USA

Received 30 Apr 2024, Accepted 06 Dec 2024, Published online: 23 Dec 2024

ABSTRACT

Introduction:

The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered. Researchers started to recognize those persisting symptoms as a new entity termed ‘Long COVID,’ where neurological symptoms are evident and have a major impact on quality of life.

Areas covered:

The main purpose of this narrative review is to analyze and synthesize the current literature regarding Long COVID, its relation to the nervous system, and to explore the evidence on treatments for persistent neurological symptoms. The most common reported and observed neurologic manifestations include fatigue, cognitive impairment, pain, polyneuropathy, and neuropsychiatric dis-orders. A variety of pharmacologic and non-pharmacologic therapies have been evaluated and yielded mixed results. Many of them focused on immunomodulation and none currently have U.S. FDA approval.

Expert opinion:

Challenges remain in terms of clinical characterization and prognosis of Long COVID, besides understanding its pathophysiology. Standardization of biomarkers and diagnostic criteria will allow the use of common nomenclature and data elements in the design of future clinical studies.

 

5.3. Myalgic encephalomyelitis/chronic fatigue syndrome and long COVID

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, multi-organ system disease characterized by debilitating fatigue, post-exertional malaise (PEM), unrefreshing sleep, cognitive impairment, and orthostatic intolerance that typically follows an acute infection [71,72]. The CDC estimates that 1.3% of all U.S. adults had ME/CFS during 2021–2022, with women (1.7%) more affected than men (0.9%) [73]. The hallmarks of the disease are persistent fatigue that has impaired personal, social, and occupational activity; worsening of symptoms after cognitive, physical, sensory, emotional, or orthostatic exertion (PEM); sleep that fails to be restorative or alleviative symptoms; cognitive impairment affecting memory, attention, and processing speed; and worsening of symptoms when in the upright position (orthostatic intolerance) [71,72]. The onset of ME/CFS is highly associated with antecedent Epstein–Barr virus infection, though several other viral, bacterial, and parasitic etiologies have been documented [25,71,74]. Notably, fatigue and ME/CFS are known to have followed both Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) [75]. It is recognized that infection with SARS-CoV-2 can precede the onset of severe fatigue or comorbid ME/CFS [25,76].

There is considerable overlap in the semiology and hypothesized mechanisms of ME/CFS and Long COVID [25,76–78]. A systematic review and comparison of ME/CFS and Long COVID symptomology showed numerous overlapping features with fatigue, post-exertional malaise, and reduced levels of activity being among the most salient [79]. Both ME/CFS and Long COVID are hypothesized to involve persistent infection or reactivation, immune dysfunction, dysbiosis of gut microbiota, autoimmunity, tissue damage, dysautonomia, and dysfunctional signaling between the brain and other systems [25,74,76]. Dysfunction of mitochondrial energetics and subsequent impairment of adenosine triphosphate (ATP) production are further documented to play a role in the pathogenesis of both disorders [25,72,78]. Given these similarities, research into the pathogenesis, diagnosis, and prognosis of Long COVID might well benefit from the decades of research already conducted in the study of ME/ CFS [25,72,76].

Although there are no US Food and Drug Administration (FDA)-approved treatments for ME/CFS, there is a wealth of guidance in the literature on management approaches and pharmaco-therapeutics aimed at symptom management and treatment of comorbidities [72]. The clinical and mechanistic overlap between ME/CFS and Long COVID allows for the consideration of such approaches to be applied in the latter. Validation of the patient’s experience with their disease process, proper assessment of their needs, providing access to resources, teaching pacing techniques for the management of PEM, treating the symptoms of orthostatic intolerance, and treatment of comorbidities are all aspects of ME/CFS management that can translate into the care of Long COVID patients [72]. Interventions such as intravenous immunoglobulin, coenzyme Q10, D-ribose, low-dose naltrexone, low-dose aripiprazole, apheresis, and antivirals have also been explored in the ME/CFS literature and could potentially be utilized in Long COVID although they are not recommended outside of the setting of a clinical trial [25,80]. Future research into the pathogenesis of Long COVID and the elucidation of interventions stands to benefit from the decades of insight into understanding ME/CFS.