PurposeThe Lifelines COVID-19 cohort was set up to assess the psychological and societal impacts of the COVID-19 pandemic and investigate potential risk factors for COVID-19 within the Lifelines prospective population cohort.ParticipantsParticipants were recruited from the 140 000 eligible participants of Lifelines and the Lifelines NEXT birth cohort, who are all residents of the three northern provinces of the Netherlands. Participants filled out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March 2020, and the cohort consists of everyone who filled in at least one questionnaire in the first 8 weeks of the project.Findings to date>71 000 unique participants responded to the questionnaires at least once during the first 8 weeks, with >22 000 participants responding to seven questionnaires. Compiled questionnaire results are continuously updated and shared with the public through the Corona Barometer website. Early results included a clear signal that younger people living alone were experiencing greater levels of loneliness due to lockdown, and subsequent results showed the easing of anxiety as lockdown was eased in June 2020.Future plansQuestionnaires were sent on a (bi)weekly basis starting in March 2020 and on a monthly basis starting July 2020, with plans for new questionnaire rounds to continue through 2020 and early 2021. Questionnaire frequency can be increased again for subsequent waves of infections. Cohort data will be used to address how the COVID-19 pandemic developed in the northern provinces of the Netherlands, which environmental and genetic risk factors predict disease susceptibility and severity and the psychological and societal impacts of the crisis. Cohort data are linked to the extensive health, lifestyle and sociodemographic data held for these participants by Lifelines, a 30-year project that started in 2006, and to data about participants held in national databases.

Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesterol from highdensity lipoprotein (HDL) particles by the liver and influences biliary cholesterol secretion. However, it is not clear, if this effect is direct or indirect. The aim of this study was to determine the impact of SR-BI on biliary cholesterol secretion, especially in a functional context with ATP-binding cassette transporter g5 (Abcg5)/Abcg8 and Abcb4. SR-BI was overexpressed by means of adenovirus (AdSR-BI) in livers of wild-type, liver X receptor-null (Lxr ؊/؊ ), Abcg5 ؊/؊ , and Abcb4 ؊/؊ mice. Consistent with previous reports, AdSR-BI decreased plasma HDL cholesterol levels in all models (P < 0.001). Hepatic cholesterol content increased (at least P < 0.05), whereas expression of sterol regulatory element binding protein 2 target genes was decreased (at least P < 0.05,) and established Lxr target genes were unaltered. Biliary cholesterol secretion was increased by AdSR-BI in wild-type as well as in Lxr ؊/؊ and Abcg5 ؊/؊ mice, and considerably less in Abcb4 ؊/؊ mice (each P < 0.001), independent of bile acid and phospholipid secretion. T he scavenger receptor class B type I (SR-BI) has been characterized as a receptor that mediates cholesterol transport across membranes. 1,2 In nonpolarized cells, namely macrophages and the hepatoma cell line Fu5AH, SR-BI expression either results in selective uptake of cholesterol, mainly from high-density lipoprotein (HDL), or in cholesterol efflux toward suitable acceptors. [3][4][5][6] In hepatocytes, which is a highly polarized cell type, SR-BI is the main receptor responsible for selective uptake of cholesterol from plasma HDL. 7 Consequently, hepatic overexpression of SR-BI results in decreased plasma HDL cholesterol levels, 8-10 whereas SR-BI knockout mice have increased plasma HDL cholesterol. 11,12 Interestingly, hepatocyte SR-BI appears to accelerate reverse cholesterol transport in vivo in the face of decreased plasma HDL cholesterol levels, 13 which is in line with studies demonstrating that hepatic SR-BI expression protects against atherosclerosis development in mouse models. 14,15 Hepatic SR-BI expression is also linked to biliary cholesterol

Endothelial lipase (EL) is a negative regulator of high density lipoprotein (HDL) cholesterol plasma levels, and scavenger receptor BI (SR-BI) is involved in remodeling of HDL. The present study investigates the requirement of SR-BI for the effects of EL-mediated phospholipid hydrolysis on HDL metabolism in vivo. In vitro, selective uptake from EL-modified HDL was 129% higher than selective uptake from control HDL in SR-BI-overexpressing cells (p ‫؍‬ 0.01). In vivo overexpression of human EL by means of recombinant adenovirus decreased HDL plasma levels significantly (p < 0.01). Fast protein liquid chromatography analysis and agarose gel electrophoresis revealed that EL expression resulted in the generation of small pre-␤ HDL particles in wild-type mice, whereas in SR-BI ؊/؊ mice small HDL were preferentially removed. In kinetic experiments the fractional catabolic rate (FCR) of HDL cholesteryl ester increased by 110% (p < 0.001), and the FCR of HDL apolipoproteins increased by 64% (p < 0.001) in response to EL overexpression in wild-type mice. In SR-BI ؊/؊ mice a similar increase in the HDL apolipoprotein FCR occurred (p < 0.001); however, there was no further increase in HDL cholesteryl ester catabolism. The apparent whole body selective uptake was increased 3-fold by EL in wild-type mice (p < 0.001), whereas there was no selective uptake in SR-BI knock-out mice. EL overexpression increased hepatic selective uptake as well as holoparticle uptake (each p < 0.01) in wild-type mice, whereas in SR-BI knock-out mice only holoparticle uptake increased (p < 0.01). Our results indicate that SR-BI-mediated selective uptake of HDL cholesteryl ester is essential for the remodeling of large ␣-migrating HDL particles by EL. Plasma levels of high density lipoprotein (HDL)3 cholesterol and its major apolipoprotein apoA-I are inversely correlated with the risk of atherosclerotic cardiovascular disease, a major cause of mortality in developed countries (1, 2). The factors responsible for the considerable variation in HDL cholesterol plasma levels are still incompletely understood. However, metabolic studies of HDL and apoA-I in humans have established that the substantial variation in their levels is primarily due to variation in the rate of apoA-I catabolism (3).Among the factors impacting on the remodeling and catabolism of HDL particles within the plasma compartment, the recently discovered endothelial lipase (EL) is of prime importance (4). EL is expressed in endothelial cells and macrophages, as well as in hepatocytes (5). EL has merely phospholipase and very little apparent triglyceridase activity (6), and HDL phospholipids represent a preferred substrate for the enzyme in in vitro assays (6, 7). The physiological relevance of EL-mediated hydrolysis of HDL particles for determining the plasma levels of HDL cholesterol has been established in experimental animals using both overexpression (5, 8) as well as loss-of-function models (9 -11). Overexpression of EL resulted in significantly decreased HDL cholesterol plasma leve...