More common than we thought: Hypermobile Ehlers-Danlos Syndrome, comorbidity burden, and long COVID risk in a national cohort
- 1Department of Dermatology, Gates Institute, University of Colorado Anschutz, Aurora, Colorado, United States of America
- 2Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
- 3Department of Pediatrics and Genetics, Children’s Hospital Colorado, Aurora, Colorado, United States of America
Abstract
Hypermobile Ehlers-Danlos Syndrome (hEDS) is a complex, underdiagnosed connective tissue disorder characterized by widespread symptoms affecting multiple organ systems. Recent clinical observations suggest that individuals with hEDS may be at increased risk for persistent symptoms following COVID-19, commonly referred to as Long COVID. Using data from over 19 million patients across the United States, we examined associations between hEDS, COVID-19 infection, Long COVID, and related chronic conditions. We identified just over 25,000 individuals with hEDS and estimated a prevalence of approximately 1 in 800, which is higher than previously recognized. Despite similar rates of COVID-19 infection between patients with hEDS and matched controls, patients with hEDS were nearly three times more likely to develop Long COVID. This risk was concentrated among patients with hEDS who also had overlapping conditions commonly seen in post-viral syndromes, including autonomic dysfunction (POTS), immune dysregulation (MCAS), and chronic fatigue (ME/CFS). Patients with hEDS also exhibited higher odds of having additional risk factors for severe or prolonged illness, including chronic lung and autoimmune conditions, depression, and cerebrovascular disease. A subgroup of patients received their hEDS diagnosis only after a COVID-19 or Long COVID diagnosis, and this subgroup was highly enriched for multimorbidity, particularly POTS and MCAS. These findings establish hEDS as more prevalent than previously recognized and identify a substantially elevated, comorbidity-driven risk of Long COVID in this population. Improved screening, earlier diagnosis, and integrated care pathways are urgently needed to support this complex and underserved patient group. Author summary: We studied patients with hypermobile Ehlers-Danlos Syndrome (hEDS), a connective tissue condition affecting joints, skin, and many body systems that is often overlooked and undiagnosed. During the COVID-19 pandemic, people with hEDS appeared more likely to develop long-term symptoms after infection, known as Long COVID. We analyzed health records from millions of U.S. patients to better understand these outcomes. Patients with hEDS were more likely to be diagnosed with Long COVID than similar patients without hEDS, despite similar infection rates. This risk was highest among those who also had chronic fatigue, immune conditions, or heart rate and blood pressure problems. People with hEDS also had higher rates of other conditions linked to worse outcomes after infection, including autoimmune disease, lung disease, and depression. A subgroup of patients was diagnosed with hEDS for the first time only after having COVID-19 or Long COVID, with high rates of POTS and MCAS. Our findings show that hEDS may be more common than previously thought and that people with hEDS face a substantially higher risk of Long COVID, especially when other conditions are also present. Greater awareness and earlier recognition of hEDS could improve care for many patients with complex, long-lasting symptoms.
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BibTeX
@article{pearson2026more,
title = {{More common than we thought: Hypermobile Ehlers-Danlos Syndrome, comorbidity burden, and long COVID risk in a national cohort}},
author = {Megan L. Pearson and Bryan J. Laraway and Ellen R. Elias and Ganna Bilousova and Melissa A. Haendel},
journal = {PLOS Digital Health},
year = {2026},
month = nov,
doi = {10.1371/journal.pdig.0001707},
url = {https://journals.plos.org/digitalhealth/article?id=10.1371/journal.pdig.0001707},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - More common than we thought: Hypermobile Ehlers-Danlos Syndrome, comorbidity burden, and long COVID risk in a national cohort
AU - Megan L. Pearson
AU - Bryan J. Laraway
AU - Ellen R. Elias
AU - Ganna Bilousova
AU - Melissa A. Haendel
PY - 2026
DA - 2026/11/05
JO - PLOS Digital Health
DO - 10.1371/journal.pdig.0001707
UR - https://journals.plos.org/digitalhealth/article?id=10.1371/journal.pdig.0001707
AB - Hypermobile Ehlers-Danlos Syndrome (hEDS) is a complex, underdiagnosed connective tissue disorder characterized by widespread symptoms affecting multiple organ systems. Recent clinical observations suggest that individuals with hEDS may be at increased risk for persistent symptoms following COVID-19, commonly referred to as Long COVID. Using data from over 19 million patients across the United States, we examined associations between hEDS, COVID-19 infection, Long COVID, and related chronic conditions. We identified just over 25,000 individuals with hEDS and estimated a prevalence of approximately 1 in 800, which is higher than previously recognized. Despite similar rates of COVID-19 infection between patients with hEDS and matched controls, patients with hEDS were nearly three times more likely to develop Long COVID. This risk was concentrated among patients with hEDS who also had overlapping conditions commonly seen in post-viral syndromes, including autonomic dysfunction (POTS), immune dysregulation (MCAS), and chronic fatigue (ME/CFS). Patients with hEDS also exhibited higher odds of having additional risk factors for severe or prolonged illness, including chronic lung and autoimmune conditions, depression, and cerebrovascular disease. A subgroup of patients received their hEDS diagnosis only after a COVID-19 or Long COVID diagnosis, and this subgroup was highly enriched for multimorbidity, particularly POTS and MCAS. These findings establish hEDS as more prevalent than previously recognized and identify a substantially elevated, comorbidity-driven risk of Long COVID in this population. Improved screening, earlier diagnosis, and integrated care pathways are urgently needed to support this complex and underserved patient group. Author summary: We studied patients with hypermobile Ehlers-Danlos Syndrome (hEDS), a connective tissue condition affecting joints, skin, and many body systems that is often overlooked and undiagnosed. During the COVID-19 pandemic, people with hEDS appeared more likely to develop long-term symptoms after infection, known as Long COVID. We analyzed health records from millions of U.S. patients to better understand these outcomes. Patients with hEDS were more likely to be diagnosed with Long COVID than similar patients without hEDS, despite similar infection rates. This risk was highest among those who also had chronic fatigue, immune conditions, or heart rate and blood pressure problems. People with hEDS also had higher rates of other conditions linked to worse outcomes after infection, including autoimmune disease, lung disease, and depression. A subgroup of patients was diagnosed with hEDS for the first time only after having COVID-19 or Long COVID, with high rates of POTS and MCAS. Our findings show that hEDS may be more common than previously thought and that people with hEDS face a substantially higher risk of Long COVID, especially when other conditions are also present. Greater awareness and earlier recognition of hEDS could improve care for many patients with complex, long-lasting symptoms.
SN - 2767-3170
ER -