A tissue specific-infection mouse model of SARS-CoV-2.

Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.

Using allocative efficiency analysis to inform health benefits package design for progressing towards Universal Health Coverage: Proof-of-concept studies in countries seeking decision support.

BACKGROUND: Countries are increasingly defining health benefits packages (HBPs) as a way of progressing towards Universal Health Coverage (UHC). Resources for health are commonly constrained, so it is imperative to allocate funds as efficiently as possible. We conducted allocative efficiency analyses using the Health Interventions Prioritization tool (HIPtool) to estimate the cost and impact of potential HBPs in three countries. These analyses explore the usefulness of allocative efficiency analysis and HIPtool in particular, in contributing to priority setting discussions. METHODS AND FINDINGS: HIPtool is an open-access and open-source allocative efficiency modelling tool. It is preloaded with publicly available data, including data on the 218 cost-effective interventions comprising the Essential UHC package identified in the 3rd Edition of Disease Control Priorities, and global burden of disease data from the Institute for Health Metrics and Evaluation. For these analyses, the data were adapted to the health systems of Armenia, Côte d'Ivoire and Zimbabwe. Local data replaced global data where possible. Optimized resource allocations were then estimated using the optimization algorithm. In Armenia, optimized spending on UHC interventions could avert 26% more disability-adjusted life years (DALYs), but even highly cost-effective interventions are not funded without an increase in the current health budget. In Côte d'Ivoire, surgical interventions, maternal and child health and health promotion interventions are scaled up under optimized spending with an estimated 22% increase in DALYs averted-mostly at the primary care level. In Zimbabwe, the estimated gain was even higher at 49% of additional DALYs averted through optimized spending. CONCLUSIONS: HIPtool applications can assist discussions around spending prioritization, HBP design and primary health care transformation. The analyses provided actionable policy recommendations regarding spending allocations across specific delivery platforms, disease programs and interventions. Resource constraints exacerbated by the COVID-19 pandemic increase the need for formal planning of resource allocation to maximize health benefits.

Relationship of Physical Activity With Anxiety and Depression Symptoms in Chinese College Students During the COVID-19 Outbreak.

INTRODUCTION: During the COVID-19 outbreak, many citizens were asked to stay at home in self-quarantine, which can pose a significant challenge with respect to remaining physically active and maintaining mental health. This study aimed to evaluate the prevalence of inadequate physical activity, anxiety, and depression and to explore the relationship of physical activity with anxiety and depression symptoms among Chinese college students during quarantine. METHOD: Using a web-based cross-sectional survey, we collected data from 1,396 Chinese college students. Anxiety and depression were assessed with the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS), respectively. The data on physical activity were collected by types of physical activity and the International Physical Activity Questionnaire (IPAQ-SF). RESULTS: During the COVID-19 outbreak, about 52.3% of Chinese college students had inadequate physical activity. The rates of anxiety and depression symptoms were 31.0 and 41.8%, respectively. A high level of physical activity (ß = -0.121, P < 0.001) was significantly closely associated with low anxiety, while a moderate (ß = -0.095, P = 0.001), or high (ß = -0.179, P < 0.001) level of physical activity was significantly closely associated with reduced depression after adjusting confounding demographic factors. Moreover, specific types of physical activity, such as stretching and resistance training, were negatively correlated with both anxiety and depression; doing household chores was negatively correlated with depression. CONCLUSION: Our findings highlight specific levels and types of home-based physical activities that need to be taken into consideration to protect the mental health of college students during the COVID-19 epidemic.