In a recent study published in BMJ Public Health, researchers investigated whether generalized joint hypermobility (GJH), which indicates varying connective tissue, was associated with self-reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection recovery failure.

Study:  Is joint hypermobility linked to self-reported non-recovery from COVID-19? Case-control evidence from the British COVID Symptom Study Biobank. Image Credit: BigBlueStudio / Shutterstock.com

Background

Long coronavirus disease 2019 (COVID-19) presents a severe therapeutic issue and public health burden, with symptoms ranging from fatigue and trouble focusing to muscular pains and shortness of breath. To date, over 200 symptoms have been associated with delayed recovery after acute SARS-CoV-2 infection. The potentially deleterious effects associated with long COVID-19, combined with the prevalence of SARS-CoV-2 infection history among the general population, emphasize the importance of identifying factors predisposing an individual to long COVID.

Demographic variables such as age and female sex, as well as pre-existing activity-limiting health disorders or impairments like fibromyalgia, irritable bowel syndrome, migraines, allergies, anxiety, depression, and back pain, increase the likelihood of prolonged COVID-19.

Recent research has identified that joint hypermobility contributes to incomplete recovery after SARS-CoV-2 infection. However, further research is needed to elucidate the etiology of long COVID and identify cost-effective and timely therapeutics for patients.

About the study

In the present prospective-type observational study, researchers investigate whether widespread joint hypermobility is related to an increased risk of not fully recovering from SARS-CoV-2 infection.

To this end, the researchers examined the United Kingdom COVID-19 Symptom Study Biobank (CSSB) data, linked with demographic information, COVID-19 reports, and symptom ratings from ZOE Global’s COVID-19 Symptom Study digital application. Researchers from Massachusetts Hospital, Uppsala and Lund Universities, and King’s College London created the mobile application.

During August 2022, 81% of respondents experienced a minimum of one COVID-19-related illness and self-reported their recovery status. All study participants completed a five-component Hakim and Grahame questionnaire (5PQ) to determine widespread joint hypermobility.

The primary research outcome was a lack of self-documented recovery from SARS-CoV-2 infection. Secondary outcomes included 5PQ scores and self-documented fatigue levels.

Binary logistic regression analysis was performed to determine whether widespread joint hypermobility predicted non-recovery after SARS-CoV-2 infection. Age, gender, ethnicity, socioeconomic situation, educational attainment, and received COVID-19 vaccinations were considered as potential variables in the sequential models.

Linear regression was used to investigate the relationship between generalized joint hypermobility and fatigue. Furthermore, mediation studies using Hayes’ technique allowed the researchers to explore potential mediation of the association between widespread joint hypermobility and COVID-19 non-recovery by fatigue levels.

Study findings

Among 3,064 individuals who reported a minimum of one SARS-CoV-2-related infection, data on self-documented COVID-19 recovery were accessible for 2,854 participants, 82% of whom were female and 97% identified as white, with an average age of 58 years.

Among 32% of the study cohort who reported incomplete recovery from acute COVID-19, 269 individuals exhibited widespread joint hypermobility, 29% of whom were female. Among recovered individuals, 439 of 1,940 patients experienced widespread joint hypermobility.

Generalized joint hypermobility was not significantly associated with the reported SARS-CoV-2 infection risk. Nevertheless, joint hypermobility was strongly associated with incomplete recovery from acute COVID-19, with an odds ratio (OR) of 1.4. This association persisted in sequential modeling studies controlling for age, gender, ethnicity, educational attainment, multiple deprivation index, and COVID-19 vaccination doses received with an OR of 1.3.

Hypermobility also strongly predicted greater fatigue levels in models that controlled for all factors. Fatigue levels influenced the relationship between widespread joint hypermobility and COVID-19 non-recovery.

Conclusions

The study findings indicate that individuals with widespread joint hypermobility are 30% more likely to not recover from acute COVID-19. These observations provide critical information needed to identify long COVID phenotypes for screening, appropriate patient classification, and personalized treatment implementation.

Taken together, the current study emphasizes the importance of stratified individualized healthcare for individuals, which influences policy and interdisciplinary services for individuals with long-term COVID and related illnesses. These findings also have implications for clinical practice, future research, and population healthcare, including precision techniques.

There remains an urgent need to investigate predisposing variables and comorbidities associated with joint hypermobility. Future research is also needed to explore the role of pre-existing illnesses as possible risk factors, particularly those linked with numerous physical symptoms, including larger sample sizes, more diverse populations, and a stringent long COVID definition to improve the generalizability and validity of the study findings.