Long COVID (LC), characterized by persistent somatic symptoms following SARS-CoV-2 infection, has become a major concern, affecting approximately 1 in 8 individuals in the general population. LC encompasses a range of symptoms, including fatigue, cognitive disturbances, neurogenic and musculoskeletal pain, and dysautonomia. These symptoms mirror those commonly observed in hypermobility spectrum disorders (HSD), particularly affecting females. Given the overlap in clinical presentation, this study was conducted to investigate whether intractable LC cases might be indicative of underlying, undiagnosed hypermobility disorders.

This report describes the cases of five female patients aged 33 to 51 years, with no prior hypermobility disorder, but reported persistent and debilitating symptoms such as fatigue, cognitive dysfunction, dysautonomia, and joint pain following acute SARS-CoV-2 infection. These patients were evaluated in an Ehlers-Danlos Syndrome (hEDS)/HSD Clinic.

We conclude that hEDS/HSD should be considered when patients with intractable LC symptoms, particularly in female patients presenting with multisystem neurogenic/ musculoskeletal pain. Mast cell activation and molecular mimicry may contribute to the new onset or exacerbation of hEDS/HSD symptoms in LC. Further research should determine the relationship between hEDS/HSD and LC pathophysiology and leverage that relationship for safe and effective management options.