Background Population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) is urgently needed to inform targeted protection strategies in the general population. Methods We examined characteristics and predictors of hospitalization and death in a nationwide cohort of all Danish individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 27 February 2020 until 19 May 2020. Results We identified 11 122 SARS-CoV-2 polymerase chain reaction-positive cases of whom 80% were community-managed and 20% were hospitalized. Thirty-day all-cause mortality was 5.2%. Age was strongly associated with fatal disease {odds ratio [OR] 15 [95% confidence interval (CI): 9–26] for 70–79 years, increasing to OR 90 (95% CI: 50–162) for ≥90 years, when compared with cases aged 50–59 years and adjusted for sex and number of co-morbidities}. Similarly, the number of co-morbidities was associated with fatal disease [OR 5.2 (95% CI: 3.4–8.0), for cases with at least four co-morbidities vs no co-morbidities] and 79% of fatal cases had at least two co-morbidities. Most major chronic diseases were associated with hospitalization, with ORs ranging from 1.3–1.4 (e.g. stroke, ischaemic heart disease) to 2.6–3.4 (e.g. heart failure, hospital-diagnosed kidney disease, organ transplantation) and with mortality with ORs ranging from 1.1–1.3 (e.g. ischaemic heart disease, hypertension) to 2.5–3.2 (e.g. major psychiatric disorder, organ transplantation). In the absence of co-morbidities, mortality was <5% in persons aged ≤80 years. Conclusions In this nationwide population-based COVID-19 study, increasing age and multimorbidity were strongly associated with hospitalization and death. In the absence of co-morbidities, the mortality was, however, <5% until the age of 80 years.

No abstract

The Danish Microbiology Database (MiBa) is a national database that receives copies of reports from all Danish departments of clinical microbiology. The database was launched in order to provide healthcare personnel with nationwide access to microbiology reports and to enable real-time surveillance of communicable diseases and microorganisms. The establishment and management of MiBa has been a collaborative process among stakeholders, and the present paper summarises lessons learned from this nationwide endeavour which may be relevant to similar projects in the rapidly changing landscape of health informatics.

Objective-This study assessed the role of cholesterol-rich membrane regions, including caveolae, in the regulation of arterial contractility. Methods and Results-Rat tail artery devoid of endothelium was treated with the cholesterol acceptor methyl-␤-cyclodextrin, and the effects on force and Ca 2ϩ handling were evaluated. In cholesterol-depleted preparations, the force responses to ␣ 1 -adrenergic receptors, membrane depolarization, inhibition of myosin light chain phosphatase, and activation of G proteins with a mixture of 20 mmol/L NaF and 60 mol/L AlCl 3 were unaffected. In contrast, responses to 5-hydroxytryptamine (5-HT), vasopressin, and endothelin were reduced by Ͼ50%. The rise in global intracellular free Ca 2ϩ concentration in response to 5-HT was attenuated, as was the generation of Ca 2ϩ waves at the cellular level. By electron microscopy, cholesterol depletion was found to disrupt caveolae. The 5-HT response could be restored by exogenous cholesterol, which also restored caveolae. Western blots showed that the levels of 5-HT 2A receptor and of caveolin-1 were unaffected by cholesterol extraction. Sucrose gradient centrifugation showed enrichment of 5-HT 2A receptors, but not ␣ 1 -adrenergic receptors, in the caveolin-1-containing fractions, suggesting localization of the former to caveolae. Conclusions-These results show that a subset of signaling pathways that regulate smooth muscle contraction depends specifically on cholesterol. Furthermore, the cholesterol-dependent step in serotonergic signaling occurs early in the pathway and depends on the integrity of caveolae. Key Words: smooth muscle Ⅲ caveolae Ⅲ 5-hydroxytryptamine Ⅲ endothelin Ⅲ intracellular calcium C ellular cholesterol, of which most (up to 90%) 1 resides in the plasma membrane, is crucial for normal membrane permeability and fluidity and also plays a role in cellular signaling, via several proposed mechanisms that fall into at least 4 categories. First, cellular cholesterol may influence gene transcription in the nucleus through sterol regulatory element binding proteins. 2 Second, the activity of membrane receptors, ion channels, and transporters may depend on the membrane fluidity, per se. 3 Third, membrane protein function may be regulated through specific cholesterol-protein interactions. 3,4 Fourth, cholesterol stabilizes the structure of caveolae and lipid rafts.Caveolae, which are 50-to 100-nm membrane invaginations that are abundant in vascular endothelium and smooth muscle cells, are defined by their characteristic morphology and contents of caveolin and cav-p60. 5,6 No definitive definition of rafts has appeared because they do not exhibit a characteristic structure, but the term is used for planar aggregations of specific lipids and proteins. Caveolae and lipid rafts are envisaged to serve as platforms for a dynamic association of signaling proteins and for the initiation or modulation of signaling. 5,7,8 Some agonists causing contraction of vascular smooth muscle act on receptors that are believed to be located in caveo...