Middle East Respiratory Syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). More than 80% of reported cases have occurred in Saudi Arabia, with a mortality exceeding 50%. Health-care workers (HCWs) are at risk of acquiring and transmitting this virus, so the concerns of HCWs in Saudi Arabia regarding MERS were evaluated. An anonymous, self-administered, previously validated questionnaire was given to 1031 HCWs at three tertiary hospitals in Saudi Arabia from October to December, 2014. Concerns regarding the disease, its severity and governmental efforts to contain it, as well as disease outcomes were assessed using 31 concern statements in five distinct domains. A total concern score was calculated for each HCW. Multiple regression analyses were used to identify predictors of high concern scores. The average age of participants was 37.1 ± 9.0 years, 65.8% were married and 59.1% were nurses. The majority of respondents (70.4%) felt at risk of contracting a MERS-CoV infection at work, 69.1% felt threatened if a colleague contracted MERS-CoV, 60.9% felt obliged to care for patients infected with MERS-CoV and 87.8% did not feel safe at work using standard precautions. In addition, 87.7% believed that the government should isolate patients with MERS in specialized hospitals, 73.7% agreed with travel restriction to and from areas affected by MERS and 65.3% agreed with avoiding inviting expatriates from such areas. After adjustment for covariates, high concern scores were significantly associated with being a Saudi national (p < 0.001), a non-physician (p < 0.001) and working in the central region (p < 0.001). The majority of respondents reported concern regarding MERS-CoV infection from exposure at work. The overall level of concern may be influenced by previous experience of MERS outbreaks and related cultural issues. The concerns of HCWs may affect their overall effectiveness in an outbreak and should be addressed by incorporating management strategies in outbreak planning.

Lipid rafts in cell plasma membranes play a critical role in the life cycle of many viruses. However, the involvement of membrane cholesterol-rich lipid rafts in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether the presence of cholesterol-rich microdomains is required for the entry of SARS-CoV-2 into host cells. Our results show that depletion of cholesterol in the rafts by methyl-beta-cyclodextrin (MβCD) treatment impaired the expression of the cell surface receptor angiotensin-converting enzyme 2 (ACE2), resulting in a significant increase in SARS-CoV-2 entry into cells. The effects exerted by MβCD could be substantially reversed by exogenous cholesterol replenishment. In contrast, disturbance of intracellular cholesterol homeostasis by statins or siRNA knockdown of key genes involved in the cholesterol biosynthesis and transport pathways reduced SARS-CoV-2 entry into cells. Our study also reveals that SREBP2-mediated cholesterol biosynthesis is involved in the process of SARS-CoV-2 entry in target cells. These results suggest that the host membrane cholesterol-enriched lipid rafts and cellular cholesterol homeostasis are essential for SARS-CoV-2 entry into cells. Pharmacological manipulation of intracellular cholesterol might provide new therapeutic strategies to alleviate SARS-CoV-2 entry into cells.

This cross-sectional study aimed to estimate the prevalence of obesity and its association with diabetes and hypertension among beneficiaries in the National Guard Health Affairs system of Saudi Arabia. We included individuals aged 17 years and older, and patients were classified as diabetic or hypertensive if they had any visit during the 4 years where the primary diagnosis was one of those conditions or they were taking diabetes or hypertension medications. The association between obesity (body mass index ≥30) and diabetes and hypertension were evaluated using a multiple logistic regression model, adjusting for age, gender, nationality, and region. A total of 616,092 individuals were included. The majority were Saudi nationals (93.1%). Approximately 68% of the population were either obese (38.9%) or overweight (29.30%). Obesity was more prevalent among Saudi nationals (39.8% vs. 26.7%, p < 0.01) and females (45.3% vs. 31.2%, p < 0.01). Obesity was independently associated with diabetes mellitus (OR = 2.24, p < 0.01) and hypertension (OR = 2.15, p < 0.01). The prevalence of obesity in the study population was alarming and more pronounced among women. Our findings call for efforts to intensify preventive measures to reduce obesity and associated conditions. Using electronic records to examine the impact of interventions to reduce obesity and chronic conditions may help monitor and improve population health.

Childhood obesity is a significant global public health problem. Worldwide data showed an increasing trend over the years. We aimed to explore the prevalence of obesity, and its association with vitamin D status. This cross-sectional study was conducted during the period from 2016 to 2017. The study included 3613 schoolchildren aged 6-19 years in the western, central, and eastern regions in Saudi Arabia. Anthropometric data including age, sex and body mass index (BMI) was collected and the serum 25OH- vitamin D (25OHD) was measured. Age-sex standardized BMI Z-scores using the 2007 World Health Organization growth standards were applied. Data from 3613 school-aged children (females = 51.8%), with equal percentage of participants from each region were analyzed. Prevalence of obesity and overweight was estimated at 7.1% and 14.4% respectively. An increasing trend was detected with age (p: 0.006). Obesity started to increase at the age of 10 years and continued to increase until 19 years. Most of the obese children (64.2%) had deficient vitamin D levels, compared to 33.7% of them with suboptimal levels and only 2.0% with optimal levels (p: <0.001). This large cohort study revealed a high prevalence (21.5%) of obesity and overweight in school children aged between 6-19 years with increasing trend with age. Children with high BMI showed extremely high prevalence of VDD and VDI. These findings are alarming and point to the need for effective national interventions that include improving and encouraging access to physical activity and exposure to sunlight, educational activities for students, parents, and schoolteachers and possible enrichment of staple food with vitamin D.

Background: SARS-Co-V2 infection can induce ER stress-associated activation of unfolded protein response (UPR) in host cells, which may contribute to the pathogenesis of COVID-19. To understand the complex interplay between SARS-Co-V2 infection and UPR signaling, we examined the effects of acute pre-existing ER stress on SARS-Co-V2 infectivity. Methods: Huh-7 cells were treated with Tunicamycin (TUN) and Thapsigargin (THA) prior to SARS-CoV-2pp transduction (48 h p.i.) to induce ER stress. Pseudo-typed particles (SARS-CoV-2pp) entry into host cells was measured by Bright Glo^TM luciferase assay. Cell viability was assessed by cell titer Glo^® luminescent assay. The mRNA and protein expression was evaluated by RT-qPCR and Western Blot. Results: TUN (5 µg/mL) and THA (1 µM) efficiently inhibited the entry of SARS-CoV-2pp into host cells without any cytotoxic effect. TUN and THA’s attenuation of virus entry was associated with differential modulation of ACE2 expression. Both TUN and THA significantly reduced the expression of stress-inducible ER chaperone GRP78/BiP in transduced cells. In contrast, the IRE1-XBP1s and PERK-eIF2α-ATF4-CHOP signaling pathways were downregulated with THA treatment, but not TUN in transduced cells. Insulin-mediated glucose uptake and phosphorylation of Ser³⁰⁷ IRS-1 and downstream p-AKT were enhanced with THA in transduced cells. Furthermore, TUN and THA differentially affected lipid metabolism and apoptotic signaling pathways. Conclusions: These findings suggest that short-term pre-existing ER stress prior to virus infection induces a specific UPR response in host cells capable of counteracting stress-inducible elements signaling, thereby depriving SARS-Co-V2 of essential components for entry and replication. Pharmacological manipulation of ER stress in host cells might provide new therapeutic strategies to alleviate SARS-CoV-2 infection.

Background: To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality. Methods: The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of “possible sepsis alert” to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days. Discussion: The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021. Trial registration: ClinicalTrials.gov NCT04078594. Registered on September 6, 2019