Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2, 2024, Bartlett et al.

SNT Gatchaman · Mar 30, 2024

Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2
Bartlett, Maggie L.; Sova, Daniel; Jain, Mahim

We completed a retrospective review of data collected by the JH-CROWN consortium based on ICD10 codes for a hospitalized cohort. The severity and prevalence of COVID-19 and development of PASC within heritable connective tissue diseases were unknown; however, clinical observation suggested a thorough examination was necessary.

We compared rates of disease severity, death, and PASC in connective tissue diseases versus the entire cohort as well as in diabetes and hypertension to determine if connective tissue disease was a risk factor. Of the 15,676 patients in the database, 63 (0.40%) had a connective tissue disease, which is elevated relative to the distribution in the population, suggesting a higher risk of severe disease. Within these 63 patients, 9.52% developed PASC compared to 2.54% in the entire cohort (p < 0.005).

Elucidation of populations at high risk for severe disease and development of PASC is integral to improving treatment approaches. Further, no other study to date has examined the risk in those with connective tissue diseases and these data support a need for enhanced awareness among physicians, patients, and the community.

Link | PDF (Viruses) [Open Access]

Hutan · Mar 30, 2024

Hereditary connective tissue diseases (hCTDs) or genetic collagen disorders include a broad grouping of syndromes that range from mild to debilitating. In this study, we focus on specific collagen disorders such as Ehlers–Danlos syndrome (EDS; types 3 and 5 collagen), Stickler Syndrome (STL; types 2, 9, and 11 collagen), and Osteogenic imperfecta (OI; type 1 collagen). Approximately 0.3% of people suffer from an hCTD, which is likely an underestimation due to lack of diagnostic criteria and awareness in the clinical setting outside of specialized clinics. The conditions involve multiple body systems, with common clinical features amongst these conditions including joint hypermobility, vascular abnormalities, risk of injuries/fractures, and risk of chronic pain and fatigue [10]. This population was hypothesized to have an increased propensity for development of post-viral diseases including PASC.
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To discern the prevalence of COVID-19 severity and PASC among patients with hCTDs, we utilized the COVID-19 Precision Medicine Analytics Platform Registry (JH-CROWN) to conduct a retrospective analysis [11]. We found that individuals with hCTDs had higher rates of COVID-19 as well as PASC compared to in the general population as well as in well-known comorbidities that increase risk such as hypertension (HT) and diabetes (DB).
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This represents a retrospective cohort analysis of patients who were tested and treated for SARS-CoV-2 between 11 March 2020 and 31 August 2022 at the Johns Hopkins Medicine healthcare system locations in Maryland.
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This cohort of PASC patients represents 0.40% of the subjects in the CROWN database from which these data were collated and is likely an under-representation. A major hurdle of retrospective analyses like these is that they rely on the database to be capable of distinguishing phenotypes of a yet-to-be-well-defined syndrome. Given the complexities of these phenotypes, we preferred to focus only on the patients in which the ICD10 code for PASC were utilized. Of the 15,676 patients in the JH-CROWN database, those with diabetes (n = 4819), hypertension (n = 9402), hCTD (n = 63), and PASC (n = 398) were extracted by ICD10 code. For PASC, the database contained hCTD (n = 6), HT (n = 291), and DB (n = 163).
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During the SARS-CoV-2 pandemic, the JH-CROWN database was developed to catalog and document patient outcomes [11]. Clinical observation suggested that individuals with hCTDs were more likely to develop PASC; however, no retrospective analyses have been performed.
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Out of 15,676 individuals, 396 had the ICD10 code for PASC or one of the following reported diagnoses: long COVID-19 or post-acute COVID. Within this cohort, the percent of PASC was 2.54% vs. 9.52% within hCTDs (p < 0.005).
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Hutan · Mar 30, 2024

I note that Peter Rowe is based at the John Hopkins University School of Medicine and this is a John Hopkins database study

Dr. Peter Rowe is a Professor of Pediatrics at the Johns Hopkins University School of Medicine. He is the inaugural Sunshine Natural Wellbeing Foundation Professor of Chronic Fatigue and Related Disorders and serves as the Director of the Chronic Fatigue Clinic at Johns Hopkins Children’s Center.

His areas of clinical expertise include chronic fatigue syndrome and other disorders characterized by fatigue and orthostatic intolerance. Dr. Rowe and his colleagues were the first to describe the relationship between chronic fatigue syndrome (CFS) and treatable orthostatic intolerance syndromes, as well as the association between Ehlers-Danlos syndrome and CFS.
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Hutan · Mar 30, 2024

So, 15,676 people who were diagnosed and treated for Covid-19 at a John Hopkins healthcare system location.
Of these, 398 were coded as having PASC or long Covid or post acute-Covid (0.4%).
Of the 398 diagnosed with PASC etc, there were 6 people who had a prior diagnosis of a genetic collagen disorder. That clearly is a small number, so any result is going to be statistically imprecise.

Then throw in the facts that Peter Rowe works in the John Hopkins health care system, and he is the epicentre of the ME/CFS - EDS link, and this study reports that clinicians had a suspicion that individuals with a genetic collagen disorder were more likely to develop PASC. Then consider that PASC is a vague diagnosis with symptoms that substantially overlap with those of genetic collagen disorders - fatigue and pain.

I don't think we can rule out clinicians having a higher level of suspicion around PASC in people with genetic collagen disorders and then finding exactly what they expected (whether that was because they were over diagnosing PASC in this group and/or under diagnosing it in the rest of the people without genetic collagen disorders).

There's also the confounder that the people with genetic collagen diseases were more likely to have a severe Covid-19 infection, and so would be more likely to have lingering symptoms that are a consequence of the severe infection or the treatment.

Dolphin · Apr 3, 2024

"Patients with a diagnosis of POTS made up 2.65% of patients, which is significantly greater than the estimated ~1% prevalence worldwide. None of the patients with hCTD and PASC were diagnosed with POTS, MCAS, or CE/MFS at admittance to the hospital."

For anyone who missed it (e.g. in the weekly update), CE/MFS is a typo and should be ME/CFS.

SNT Gatchaman · Apr 4, 2024

Yes, I should have corrected that in the weekly news.

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Hereditary Connective Tissue Diseases and Risk of Post-Acute SARS-CoV-2, 2024, Bartlett et al.

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