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Background Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. Methods/Design This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. Discussion Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.

Replication of SARS-CoV-2, the coronavirus causing COVID-19, requires a main protease (Mpro) to cleave viral proteins. Consequently, Mpro is a target for antiviral agents. We and others previously demonstrated that GC376, a bisulfite prodrug with efficacy as an anti-coronaviral agent in animals, is an effective inhibitor of Mpro in SARS-CoV-2. Here, we report structure-activity studies of improved GC376 derivatives with nanomolar affinities and therapeutic indices >200. Crystallographic structures of inhibitor-Mpro complexes reveal that an alternative binding pocket in Mpro, S4, accommodates the P3 position. Alternative binding is induced by polar P3 groups or a nearby methyl. NMR and solubility studies with GC376 show that it exists as a mixture of stereoisomers and forms colloids in aqueous media at higher concentrations, a property not previously reported. Replacement of its Na+ counter ion with choline greatly increases solubility. The physical, biochemical, crystallographic, and cellular data reveal new avenues for Mpro inhibitor design. Graphical abstract Image 1

Abstract Background The COVID-19 pandemic and pandemic response created novel challenges for abortion services. Canada was uniquely positioned to transition to telemedicine because internationally common restrictions on abortion medication were removed before the pandemic. Objective We sought to characterize the experiences of abortion health care professionals in Canada during the COVID-19 pandemic and the impact of the pandemic response on abortion services. Methods We conducted a sequential mixed methods study between July 2020 and January 2021. We invited physicians, nurse practitioners and administrators to participate in a cross-sectional survey containing an open-ended question about the impact of the pandemic response on abortion care. We employed an inductive codebook thematic analysis, which informed the development of a second, primarily quantitative survey. Results Our initial survey had 307 respondents and our second had 78. Fifty-three percent were family physicians. Our first survey found respondents considered abortion access essential. We identified three key topicss: access to abortion care was often maintained despite pandemic-related challenges (e.g. difficulty obtaining tests, additional costs); change of practice to low-touch medication abortion care and provider perceptions of patient experience, including shifting demand, telemedicine acceptability and increased rural access. The second survey indicated uptake of telemedicine medication abortion among 89% of participants except in Quebec, where regulations meant procedures were nearly exclusively surgical. Restrictions did not delay care according to 76% of participants. Conclusions Canadian health care professionals report their facilities deemed abortion an essential service. Provinces and territories, except Quebec, described a robust pandemic transition to telemedicine to ensure access to services. Podcast An accompanying podcast is available in the Supplementary Data, in which the authors Dr Madeleine Ennis and Kate Wahl discuss their research on how family planning care and access to abortion services have changed during the COVID-19 pandemic. Lay Summary Access to abortion care was challenged by the response to COVID-19. Canada had fewer restrictions on medical abortion than many other countries when the pandemic began. The goal of this study was to describe the experiences of health care practitioners providing abortion in Canada and the impact of the pandemic and the pandemic response measures on abortion services. We conducted two surveys of physicians, nurse practitioners and administrators between July 2020 and January 2021. Most of the health care practitioners who participated reported that medical and surgical abortion care were essential and that, except in the province of Quebec, there was a rapid transition to virtual telemedicine care for first trimester abortions. Several practitioners said that virtual care made abortion more accessible. Other practitioners reported that it was challenging to order certain tests, access operating room facilities or make referrals for late second trimester cases. Practitioners felt that patients had strong fears about COVID-19 exposure and reported that limited contraception access was increasingly a reason for seeking abortion care. The results of the study suggested that abortion was considered essential and that the pandemic instigated a transition to virtual care in all provinces and territories except Quebec.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.

The Vero cell line is considered the most used continuous cell line for the production of viral vectors and vaccines. Historically, it is the first cell line that was approved by the WHO for the production of human vaccines. Comprehensive experimental data on the production of many viruses using the Vero cell line can be found in the literature. However, the vast majority of these processes is relying on the microcarrier technology. While this system is established for the large-scale manufacturing of viral vaccine, it is still quite complex and labor intensive. Moreover, scale-up remains difficult and is limited by the surface area given by the carriers. To overcome these and other drawbacks and to establish more efficient manufacturing processes, it is a priority to further develop the Vero cell platform by applying novel bioprocess technologies. Especially in times like the current COVID-19 pandemic, advanced and scalable platform technologies could provide more efficient and cost-effective solutions to meet the global vaccine demand. Herein, we review the prevailing literature on Vero cell bioprocess development for the production of viral vectors and vaccines with the aim to assess the recent advances in bioprocess development. We critically underline the need for further research activities and describe bottlenecks to improve the Vero cell platform by taking advantage of recent developments in the cell culture engineering field.

Students have been multiply impacted by the COVID-19 pandemic: threats to their own and their family’s health, the closure of schools, and pivoting to online learning in March 2020, a long summer of physical distancing, and then the challenge of returning to school in fall 2020. As damaging as the physical health effects of a global pandemic are, much has been speculated about the “second wave” of mental health crises, particularly for school-aged children and adolescents. Yet, few studies have asked students about their experiences during the pandemic. The present study engaged with over two thousand ( N = 2,310; 1,288 female; Mage = 14.5) 12- to 18-year-old Alberta students during their first few weeks of return-to-school in fall 2020. Students completed an online survey that asked about their perceptions of COVID-19, their fall return-to-school experiences (84.9% returned in-person), their self-reported pandemic-related stress, and their behavior, affect, and cognitive functioning in the first few weeks of September. The majority of students (84.9%) returned to school in person. Students reported moderate and equal concern for their health, family confinement, and maintaining social contact. Student stress levels were also above critical thresholds for 25% of the sample, and females and older adolescents (age 15–18 years) generally reported higher stress indicators as compared to males and younger (age 12–14 years) adolescents. Multivariate analysis showed that stress indicators were positively and significantly correlated with self-reported behavioral concerns (i.e., conduct problems, negative affect, and cognitive/inattention), and that stress arousal (e.g., sleep problems, hypervigilance) accounted for significant variance in behavioral concerns. Results are discussed in the context of how schools can provide both universal responses to students during COVID-19 knowing that most students are coping well, while some may require more targeted strategies to address stress arousal and heightened negative affect.

Additional file 1. It contains further information on methodology as well as 4 tables and 2 figures.