Early prediction of COVID-19 severity using extracellular vesicle COPB2.

The clinical manifestations of COVID-19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID-19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID-19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID-19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID-19 severity. Strikingly, we identified three distinct groups of markers (antiviral response-related EV proteins, coagulation-related markers, and liver damage-related exRNAs) with the potential to serve as early predictive biomarkers for COVID-19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID-19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00-1.00)). The validation set included 40 COVID-19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73-0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID-19 therapy.

Circulating Anti-Coatomer Protein Complex Subunit Epsilon (COPE) Autoantibodies as a Potential Biomarker for Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

STUDY OBJECTIVES: Although moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for severe arteriosclerotic diseases such as cardiovascular disease (CVD) and stroke, the development of atherosclerosis-related diseases cannot yet be predicted in patients with OSA. In a pilot study, we identified autoantibodies against the coatomer protein complex, subunit epsilon [circulating anti-coatomer protein complex subunit epsilon autoantibody (COPE-Ab)], a cytosolic complex that mediates protein transport in the Golgi compartment, as a potential novel biomarker of atherosclerosis. This study aimed to evaluate whether COPE-Ab levels had an association with cardiovascular and cerebrovascular events in patients with OSA. METHODS: Eighty-two adult patients with a diagnosis of OSA via polysomnography and 64 healthy donors were studied. Serum COPE-Ab levels were measured using an amplified luminescence proximity homogeneous assay. Then, clinical factors related to atherosclerosis were evaluated with respect to COPE-Ab levels. RESULTS: Significant differences in COPE-Ab levels were observed in terms of OSA severity. COPE-Ab levels were significantly higher in patients with OSA and also CVD and/or stroke, hypertension, and a high body mass index. Univariate and multivariate logistic regression analyses of patients with OSA identified elevated COPE-Ab level as a significant predictor of CVD and/or stroke. CONCLUSIONS: An elevated COPE-Ab level may be a potential predictor of the risks of cardiovascular and cerebrovascular events in patients with OSA. Therefore, patients with higher COPE-Ab levels may require more careful and intensive treatment. COMMENTARY: A commentary on this article appears in this issue on page 361.

Association between omentin-1, bone metabolism markers, and cytokines of the RANKL/RANK/OPG system in girls with anorexia nervosa.

INTRODUCTION: Omentin-1, secreted by visceral adipose tissue, has been indicated in the regulation of bone metabolism in girls with anorexia nervosa (AN). The aim of the study was to evaluate the relationship between omentin-1 and bone metabolism in girls with AN as well as the potential involvement of OPG and RANKL in this relationship. MATERIAL AND METHODS: Serum omentin-1, OC, CTx, OPG, and sRANKL were determined by ELISA in 49 girls with AN and in 30 healthy controls, aged 13 to 17 years. RESULTS: Girls with AN exhibited significant reduction in body weight, BMI, and Cole index as well as a significant increase in serum omentin-1 levels, compared to healthy participants. These changes were associated with a significant decrease in serum OC and CTx levels and a significant increase in OPG and sRANKL while the OC/CTx and OPG/sRANKL ratios were significantly decreased. BMI and the Cole index correlated negatively and significantly with omentin-1 levels, positively with CTx levels and the OC/CTx ratio in the control group (C), girls with AN, and all study participants (C + AN). Girls with AN showed a significant negative correlation between BMI, the Cole index, and OPG levels. The combined group (C + AN) showed a significant positive correlation between BMI, the Cole index, and the OPG/sRANKL ratio. Omentin-1 levels correlated negatively and significantly with OC and CTx levels as well as with the OC/CTx and OPG/sRANKL ratios in the C, AN, and C + AN groups. CONCLUSIONS: The relationship between omentin-1, bone markers, and the OC/CTx and OPG/sRANKL ratios observed in girls with AN indicates the involvement of this adipokine in the regulation of dynamic balance between bone formation and resorption processes. Omentin-1 might exert a negative effect on bone remodelling in girls with AN by inhibiting both bone formation and resorption. The OPG/sRANKL system plays an important role in the latter.