A Systematic Scoping Review and Conceptual Analysis of New-Onset Fibromyalgia Manifestations After Non-Hospitalized COVID-19: Empirics, Definitions, Methodologies, Pathophysiology, Mapping of Literature, and Knowledge Gaps

The global coronavirus pandemic has led to a quiet wave of a chronic illness referred to as Long/Post Covid-19 syndrome (LC) which bears a notable resemblance to functional somatic or fibromyalgia-type syndromes, and whose pathophysiology is undetermined. The lack of effective therapies for LC is straining healthcare systems worldwide and causing widespread public health and socioeconomic concerns. "Fibromyalgia" is a controversial chronic pain condition of unknown etiology largely attributed to generalized sensory hypersensitivity due to dysregulated central pain processing pathways (i.e., central sensitization). Despite intense research and growing attention in the scientific community, the clinical overlap of fibromyalgia, somatic symptom disorder, and post-viral chronic fatigue, is a medical puzzle yet to be solved, especially when occurring in non-severe infections and previously healthy individuals. This systematic scoping review covers the empirical findings on new-onset fibromyalgia manifestations after non-hospitalized covid-19. MEDLINE, Web of Science, and APA PsycINFO were searched in a systematic scoping approach for empirical studies on new-onset fibromyalgia after non-severe non-hospitalized covid-19, charting study characteristics and outcome data. A total of 228 records were included. Various types of methods, tools, and study designs are being used for LC research, with inconsistency in key concepts and definitions. This leads to a fragmented understanding of the relationship between SARS-CoV-2 infection and LC. Prevalence studies of post-Covid fibromyalgia are ongoing and susceptible to bias. The empirical evidence supports an overlap between LC, chronic fatigue syndrome, and fibromyalgia but the molecular mechanisms still remain unclear. There are conflicting findings regarding presence of viral particles, central sensitization, autoantibodies, and more. This review highlights the need for standardized definitions and rigorous methodologies in research on LC. Future research should focus on epidemiological population-based studies with representative sampling and improving methodology, refining evolving definitions, harmonization of research, elucidating neurological mechanisms in hypothesis driven studies, and developing effective therapeutic strategies. The discussion synthesizes findings and offers an integrative mechanism for the pathophysiology of fibromyalgia and multisystem medically unexplained manifestations of LC as a non-autoimmune connective tissue disease and is used to make testable theory-based predictions for future investigations.