This study aims to explore the relationship between hypermobility and long COVID by analyzing clinical and genetic findings in affected patients.

Post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID, causes symptoms such as fatigue, brain fog, and musculoskeletal pain. Emerging evidence suggests a potential link between long COVID and connective tissue disorders, including hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD).

A retrospective cohort study was conducted with 20 adult patients (aged 22-67) who were seen at the Post-COVID Care and Ehlers-Danlos/Hypermobility Spectrum Disorders Clinics. All 20 patients had Beighton scores ≥ 5 and were diagnosed with long COVID. Data collected included patient characteristics, Beighton score, COVID-19 infection history, vaccination status, degree of symptoms, methylenetetrahydrofolate reductase (MTHFR) variants, and other relevant laboratory results. 

Patients < 40 were more likely to have Beighton scores ≥ 7 (OR = 0.047, p = 0.0098; χ² = 5.31, p = 0.0212). The mean symptom count per patient was 11.8 ± 8.95, with fatigue (100%), brain fog (80%), and post-exertional malaise (80%) being the most common. No significant associations were observed between COVID-19 infection count and Beighton score or the number of symptoms reported (p-value = 1; p-value = 0.69). No significant association was found between vaccination status and hypermobility or the number of symptoms reported (p-value = 1; p-value = 0.65). MTHFR variants were present in 70% of the patient cohort.

Our findings suggest a possible association between long COVID and hEDS/HSD, particularly in younger adults. The high rate of MTHFR variants in this cohort may point to a connection between one-carbon metabolism, connective tissue integrity, and long COVID symptoms in hypermobile patients. Larger studies are needed to better understand the role of hypermobility in PASC pathogenesis and to inform targeted diagnostic and therapeutic strategies.