Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.     

Systemic lupus erythematosus after thymectomy for myasthenia gravis: a case report and review of the literature

Here, we report a case of systemic lupus erythematosus in a 13-year-old girl who developed the disease 3 years after thymectomy performed for the treatment of myasthenia gravis. The presenting symptoms were fever, generalized fatigability, bilateral loin pain, weight loss, arthralgia, hair loss, and recurrent painless mouth ulcers. Laboratory findings revealed proteinuria, hematuria, anemia, leucopenia, a high titer of antinuclear antibodies (ANA), anti-dsDNA, and decreased complement (C3 and C4) levels. There was minimal ascitis and pericardial effusion. Renal biopsy showed lupus nephritis class IV. The diagnosis of systemic lupus erythematosus was established based on the clinical and laboratory findings. The activity of systemic lupus erythematosus was controlled by pulsed treatment with methyl prednisolone followed by long-term oral glucocorticoid and immunosuppressive therapy. This study highlights the immune system derangement following thymectomy. It also examines the relevant literature.     

Identification of human and rabbit cytochromes P450 1A2 as major isoforms involved in thiabendazole 5-hydroxylation

Summary— This report characterized one of the major cytochrome P450 isozyme involved in thiabendazole metabolism. This study was undertaken by using both cultured rabbit hepatocytes treated or not with drugs known to specifically induce various cytochromes P450 isoenzymes (ie, P450 1A1/2 by β-naphthoflavone, P450 2B4 by phenobarbital, P450 3A6 by rifampicine and P450 4A by clofibrate) and human liver (THLE-5) and bronchial (BEAS-2B) epithelial cells expressing or not the major constitutive human cytochromes P450 (ie, CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1 or 3A4). Only hepatocytes exposed to β-naphthoflavone and clofibrate significantly metabolized thiabendazole to 5-hydroxythiabendazole. Extensive biotransformation of this anthelmintic only occurred in human cells expressing CYP1A2. Moreover, experiments performed on rabbit preparations showed good correlations between thiabendazole 5-hydroxylase activity and both ethoxyresorufin and methoxyresorufin O -dealkylase activities. Thus, CYP1A2 is a major isoenzyme involved in thiabendazole 5-hydroxylation.     

Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption

The aims of the study were to evaluate the use of bone-specific biochemical markers of turnover in type I osteoporosis, to test for evidence of heterogeneity of bone turnover in this condition, and to attempt to devise an uncoupling index by using the relationship between bone-specific biochemical markers of bone formation and bone resorption. In women with type I osteoporosis (mean age 64 years, SD 5;n=63) the mean level of serum osteocalcin, a specific biochemical marker of bone formation, was 9.9 ng/ml (SD 2.0), which was higher than the level in normal postmenopausal women (mean age 65 years, SD 6;n=8.9 ng/ml (SD 2.0;p<0.01). The variance of serum osteocalcin levels in the two groups was similar. Compared with this 11% increase in the biochemical marker for bone formation, the markers of bone resorption, total urinary deoxypyridinoline (bone-specific), pyridinoline and hydroxyproline were increased by 40% (p<0.0001), 61% (p<0.0001) and 25% (p<0.01), respectively. Furthermore, these biochemical markers of bone resorption had greater variance in women in type I osteoporosis than in the normal postmenopausal women (p<0.001). The urinary excretion of the free crosslinks deoxypyridinoline, pyridinoline and glycosylated pyridinoline were increased by 26% (p<0.001), 17% (p<0.01) and 13% (NS) respectively. An uncoupling index was calculated for the difference between urinary deoxypyridinoline and serum osteocalcin using the results from the normal women and expressed asz-scores. We conclude that the pyridinium crosslinks of collagen enable better discrimination between normal and osteoporotic women than does hydroxyproline. In osteoporosis there appears to be heterogeneity of bone resorption. Finally, an uncoupling index indicated that in osteoporosis bone resorption was increased to a greater extent than bone formation as compared with normal postmenopausal women.     

Demographics,comorbidities, and outcomes among young and middle-aged COVID-19 patients in Saudi Arabia

The impact of different sociodemographic and clinical characteristics on the COVID-19-related morbidity and mortality rates have been studied extensively around the world; however, there is a dearth of data on the impact of different clinical and sociodemographic variables on the COVID-19-related outcomes in Saudi Arabia. This study aimed to identify those at high risk of worse clinical outcomes, such as hospitalization and longer length of stay (LOS) among young and middle-aged adults (18 to 55 years). In this questionnaire-based cross-sectional study, 706 patients with real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 infection were interviewed. Patients’ demographic characteristics, dietary habits, medical history, and lifestyle choices were collected through phone interviews. Patients with chronic health conditions, such as diabetes and hypertension, reported a higher rate of hospitalization, ICU admission, oxygen-support needs, and a longer period of recovery and LOS. Multiple logistic regression showed that diabetes, hypertension, and pulmonary disease (e.g., asthma and chronic obstructive pulmonary disease (COPD)) were associated with a higher risk of hospitalization and longer LOS. Multiple logistic regression showed that symptoms of breathlessness, loss of smell and/or taste, diarrhea, and cough were associated with a longer recovery period. Similarly, breathlessness, vomiting, and diarrhea were associated with higher rates of hospitalization. The findings of this study confirm the similarity of the factors associated with worse clinical outcomes across the world. Future studies should use more robust designs to investigate the impact of different therapies on the COVID-19-related morbidity and mortality in Saudi Arabia.