Symptomatic hypermobility as a risk factor for Long COVID with high post-exertional symptom exacerbation: further analysis of data from a retrospective online survey of adults in the United States and United Kingdom

Background In a retrospective online survey, we assessed the extent to which people with symptomatic hypermobility are at risk of Long COVID with a high degree of post-exertional symptom exacerbation, a form of Long COVID similar to myalgic encephalomyelitis. Methods Participants were 1,816 adults with prior COVID-19 infection; 19.4% reported Long COVID, defined as symptoms persisting [≥]3 months. Survey measures identified Long COVID with high post-exertional symptom exacerbation, generalized joint hypermobility (GJH), extreme hypermobility, and a pre-COVID orthostatic/neurocognitive symptom burden (ONS profile). Logistic regression assessed whether ONS profile and hypermobility, together defined as symptomatic hypermobility, were associated with increased risk of Long COVID with post-exertional symptom exacerbation. Results In the full sample, both extreme hypermobility (OR 3.15, 95 % CI 2.00-4.95) and an ONS profile pre-COVID (OR 3.29, 95% CI 2.34-4.61) were strongly predictive of Long COVID with high post-exertional symptom exacerbation. These effects were cumulative, leading to an OR of 9.46 (95% CI 4.93-18.17) for people with both conditions. People who both had an ONS profile pre-COVID and had generalized joint hypermobility also had a higher risk of Long COVID with high post-exertional symptom exacerbation (OR 5.54, 95% CI 3.51-8.75). Conclusions In this dataset, people with symptomatic hypermobility were at high risk of Long COVID with high levels of post-exertional symptom exacerbation. Further research is needed to understand the biological mechanisms of viral-onset illness to promote more effective and targeted treatments tailored to the disease pathways shared by groups of individuals with common vulnerabilities.