Outcome of COVID19 in Patients With Osteogenesis Imperfecta: A Retrospective Multicenter Study in Saudi Arabia

BackgroundAlthough genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI.MethodologyA retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients.ResultsTwelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination.ConclusionPatients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.

Vitamin D deficiency, impaired lung function and total and respiratory mortality in a cohort of older men: cross-sectional and prospective findings from The British Regional Heart Study

ObjectivesVitamin D deficiency is associated with chronic obstructive pulmonary disease (COPD). We examined the cross-sectional association between 25-hydroxyvitamin D (25(OH)D) and lung function impairment and assessed whether vitamin D deficiency is related to long-term mortality in those with impaired lung function.DesignProspective studySettingGeneral practices in the UK.Participants3575 men aged 60–79 years with no prevalent heart failure.Outcome measuresAirway obstruction and mortality. The Global Initiative on Obstructive Lung diseases (GOLD) spirometry criteria was used to define airway obstruction.ResultsDuring the follow-up period of 20 years, there were 2327 deaths (114 COPD deaths). Vitamin D deficiency was defined as serum 25(OH)D levels<10 ng/mL; insufficiency as 25(OH)D 10–19 ng/mL; sufficient as 25(OH)D>20 ng/mL. In cross-sectional analysis, vitamin D deficiency was more prevalent in those with moderate COPD (FEV/FVC <70% and FEV1 50 to <80%; FEV1, forced expiratory volume in 1 s and FVC, forced vital capacity) and severe COPD (FEV/FVC <70% and FEV1 <50%) but not in those with mild COPD (FEV/FVC <70% and FEV1>80%) or restrictive lung disease (FEV1/FVC >70% and FVC <80%) compared with men with normal lung function . Vitamin D deficiency was associated with increased risk of total and respiratory mortality in both men with COPD and men with restrictive lung disease after adjustment for confounders and inflammation. The adjusted HRs (95% CI) for total mortality comparing levels of 25(OH)D<10 ng/mL to 25(OH)D>=20 ng/mL were 1.39 (1.10 to 1.75), 1.52 (1.17 to 1.98), 1.58 (1.17 to 2.14) and 1.39 (0.83 to 2.33) for those with no lung impairment, restrictive lung function, mild/moderate COPD and severe COPD, respectively.ConclusionMen with COPD were more likely to be vitamin D deficient than those with normal lung function. Vitamin D deficiency is associated with increased all-cause mortality in older men with no lung impairment as well as in those with restrictive or obstructive lung impairment.

A Case of Restrictive Lung Disease Masquerading as Sars-Cov-2 Pneumonia: The Complexity of Integrating Lung Ultrasound in Clinical Management

This report aims to highlight the importance of integrating the lung ultrasound findings in the clinical judgement, and to integrate its findings, exemplified in this patient, thought to have COVID-19 bilateral pneumonia, and turn out to have an infectious spondylodiscitis and secondary, a restrictive lung disease.As ultrasound devices become increasingly portable and affordable, the future potential of lung ultrasound relies on a not lesser degree of clinical skills acquisition.

Restrictive lung disease in β-thalassemia major is associated with myocardial iron overload

Background: Pulmonary dysfunction has been reported in patients with β-thalassaemia major but data are conflicting and the association with iron overload remains unclear. Objectives: To determine the pattern of pulmonary dysfunction in patients with β-thalassaemia major and their associations with iron overload. Methods: Subjects with β-thalassaemia major were recruited for lung function assessment. Serum ferritin and magnetic resonance imaging (MRI) measurements of iron status of the myocardium and the liver were used as surrogate indexes of body iron content. A subgroup of this cohort provided data on the longitudinal progress of their lung function. Results: One hundred and one patients were recruited with a mean age of 25.1 years (SD 7.9 years). Thirty-eight (38%) and five (5%) had restrictive and obstructive lung function deficits, respectively. There was a significant correlation between MRI myocardial T2* relaxation time and forced vital capacity (r=0.291, p=0.048). Higher MRI cardiac T2* relaxation time was associated with lower risk of having restrictive lung function deficit (Odds ratio (OR): 0.94; 95% CI: 0.89-0.99; p=0.023) after adjusting for age, gender and BMI. Twenty-three subjects underwent lung function reassessment with a mean follow-up duration of 13 years. Overall, they did not demonstrate significant changes in pulmonary function over time, 3 patients who had normal lung function at baseline developed restrictive abnormality at follow-up. Conclusions: Restrictive lung disease is prevalent in patients with β-thalassaemia major, and the severity correlates with myocardial iron overload. Monitoring of lung function in this group of patients is important, particularly for those with iron overload.

A.4 A Novel Recessive TNNT1 Congenital Core-Rod Myopathy in French Canadians

Background: Mutations in the slow skeletal muscle troponin T (TNNT1) gene cause a congenital nemaline myopathy resulting in death from respiratory insufficiency in early infancy. We report on four French Canadians with a novel congenital TNNT1 myopathy. Methods: Patients underwent lower extremity and paraspinal MRI, quadriceps biopsy and genetic testing. TNNT1 expression in muscle was assessed by quantitative PCR and immunoblotting. Wild type or mutated TNNT1 mRNAs were co-injected with morpholinos in a zebrafish knockdown model to assess for rescue of the morphant phenotype. Results: Four patients shared a novel missense homozygous mutation in TNNT1. They developed from childhood slowly progressive limb-girdle weakness with spinal rigidity and contractures. They suffered from restrictive lung disease and recurrent episodes of rhabdomyolysis. Older patients remained ambulatory into their sixties. Lower extremity MRI showed symmetrical myopathic changes. Paraspinal MRI showed diffuse fibro-fatty involution. Biopsies showed multi-minicores. Nemaline rods were seen in half the patients. TNNT1 mRNA expression was similar in controls and patients, while levels of TNNT1 protein were reduced in patients. Wild type TNNT1 mRNA rescued the zebrafish morphants but mutant transcripts failed to do so. Conclusions: This study expands the spectrum of TNNT1-related myopathy to include a milder clinical phenotype caused by a functionally-confirmed novel mutation.

Post-COVID-19 Pulmonary Fibrosis: Report of Two Cases

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 has led to a pandemic situation worldwide. However, remarkable progress has been made in evolving policies, strengthening healthcare efforts, and pharmacotherapy. As more patients are recovering from COVID-19, clearer concepts about possible short- and long-term complications are emerging. Respiratory failure is the most common morbidity in hospitalised patients, and post-COVID-19 pulmonary fibrosis is the most common respiratory complication after recovery. The authors report two cases of COVID-19 pneumonia with respiratory failure who were cured but developed pulmonary fibrosis with restrictive lung disease in the follow-up period.