Neonatal abstinence syndrome hospitalizations in Canada: a descriptive study.

OBJECTIVE: The objective of this paper is to describe the trend of newborn hospitalizations with neonatal abstinence syndrome (NAS) in Canada, between 2010 and 2020, and to examine severity indicators for these hospitalizations. METHODS: National hospitalization data (excluding Quebec) from the Canadian Institute for Health Information's Discharge Abstract Database, from January 2010 to March 2021, and Statistics Canada's Vital Statistics Birth Database were used. Analyses were performed to examine NAS hospitalizations by year and quarter, and by severity indicators of length of stay, Special Care Unit admission and status upon discharge. Severity indicators were further stratified by gestational age at birth. RESULTS: An increasing number and rate of NAS hospitalizations in Canada between 2010 (n = 1013, 3.5 per 1000 live births) and 2020 (n = 1755, 6.3 per 1000 live births) were identified. A seasonal pattern was observed, where rates of NAS were lowest from April to June and highest from October to March. Mean length of stay in acute inpatient care was approximately 15 days and 71% of NAS hospitalizations were admitted to the Special Care Unit. Hospitalizations for pre-term births with NAS had longer durations and greater rates of Special Care Unit admissions compared to term births with NAS. CONCLUSION: The number and rate of NAS hospitalizations in Canada increased during the study, and some infants required a significant amount of specialized healthcare. Additional research is required to determine what supports and education for pregnant people can reduce the incidence of NAS hospitalizations.

RéSUMé: OBJECTIF: Le présent article a pour but de décrire la tendance des hospitalisations de nouveau-nés atteints du syndrome d'abstinence néonatale (SAN) au Canada, entre 2010 et 2020, et d'examiner les indicateurs de gravité de ces hospitalisations. MéTHODE: Les données nationales sur les hospitalisations (à l'exclusion du Québec) provenant de la base de données sur les congés des patients de l'Institut canadien d'information sur la santé, de janvier 2010 à mars 2021, ainsi que la base de données sur les naissances des statistiques de l'état civil de Statistique Canada ont été utilisées. Des analyses ont été réalisées pour examiner les hospitalisations liées au SAN par année et par trimestre, et par indicateurs de gravité de la durée du séjour, de l'admission dans une unité de soins spéciaux et de l'état à la sortie de l'hôpital. Les indicateurs de gravité ont en outre été stratifiés en fonction de l'âge gestationnel à la naissance. RéSULTATS: Un nombre et un taux croissants d'hospitalisations liées au SAN au Canada entre 2010 (n=1 013, 3,5 pour 1 000 naissances vivantes) et 2020 (n=1 755, 6,3 pour 1 000 naissances vivantes) ont été identifiés. Une tendance saisonnière a été observée, où les taux de SAN étaient les plus bas d'avril à juin et les plus élevés d'octobre à mars. La durée moyenne du séjour en soins de courte durée était d'environ 15 jours et 71 % des hospitalisations liées au SAN ont été admises à l'unité de soins spéciaux. Les hospitalisations pour les accouchements prématurés de nouveau-nés atteints du SAN avaient des durées plus longues et des taux plus élevés d'admissions dans des unités de soins spéciaux par rapport aux naissances à terme de nouveau-nés atteints du SAN. CONCLUSION: Le nombre et le taux d'hospitalisations liées au SAN au Canada ont augmenté au cours de l'étude, et certains nourrissons nécessitent une quantité importante de soins spécialisés. Des recherches supplémentaires sont nécessaires pour déterminer quels soutiens et quelle éducation pour les personnes enceintes peuvent réduire l'incidence des hospitalisations liées au SAN.

SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication.

Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn't. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Enhanced Two-Step Virtual Catchment Area (E2SVCA) model to measure telehealth accessibility.

The use of telehealth has increased significantly over the last decade and has become even more popular and essential during the COVID-19 pandemic due to social distancing requirements. Telehealth has many advantages including potentially improving access to healthcare in rural areas and achieving healthcare equality. However, there is still limited research in the literature on how to accurately evaluate telehealth accessibility. Here we present the Enhanced Two-Step Virtual Catchment Area (E2SVCA) model, which replaces the binary broadband strength joint function of the previous Two-Step Virtual Catchment Area (2SVCA) with a step-wise function that more accurately reflects the requirements of telehealth video conferencing. We also examined different metrics for representing broadband speed at the Census Block level and compared the results of 2SVCA and E2VCA. Our study suggests that using the minimum available Internet speed in a Census Block can reveal the worst-case scenario of telehealth care accessibility. On the other hand, using the maximum of the most frequent available speeds reveals optimal accessibility, while the minimum of the most frequent reflects a more common case. All three indicators showed that the 2SVCA model generally overestimates accessibility results. The E2SVCA model addresses this limitation of the 2SVCA model, more accurately reflects reality, and more appropriately reveals low accessibility regions. This new method can help policymakers in making better decisions about healthcare resource allocations aiming to improve healthcare equality and patient outcomes.

Cross-regional analysis of the association between human mobility and COVID-19 infection in Southeast Asia during the transitional period of "living with COVID-19”

Background In response to COVID-19, Southeast Asian (SEA) countries had imposed stringent lockdowns and restrictions to mitigate the pandemic ever since 2019. Because of a gradually boosting vaccination rate along with a strong demand for economic recovery, many governments have shifted the intervention strategy from restrictions to "Living with COVID-19” where people gradually resumed their normal activities since the second half of the year 2021. Noticeably, timelines for enacting the loosened strategy varied across Southeast Asian countries, which resulted in different patterns of human mobility across space and time. This thus presents an opportunity to study the relationship between mobility and the number of infection cases across regions, which could provide support for ongoing interventions in terms of effectiveness. Objective This study aimed to investigate the association between human mobility and COVID-19 infections across space and time during the transition period of shifting strategies from restrictions to normal living in Southeast Asia. Our research results have significant implications for evidence-based policymaking at the present of the COVID-19 pandemic and other public health issues. Methods We aggregated weekly average human mobility data derived from the Facebook origin and destination Movement dataset. and weekly average new cases of COVID-19 at the district level from 01-Jun-2021 to 26-Dec-2021 (a total of 30 weeks). We mapped the spatiotemporal dynamics of human mobility and COVID-19 cases across countries in SEA. We further adopted the Geographically and Temporally Weighted Regression model to identify the spatiotemporal variations of the association between human mobility and COVID-19 infections over 30 weeks. Our model also controls for socioeconomic status, vaccination, and stringency of intervention to better identify the impact of human mobility on COVID-19 spread. Results The percentage of districts that presented a statistically significant association between human mobility and COVID-19 infections generally decreased from 96.15% in week 1 to 90.38% in week 30, indicating a gradual disconnection between human mobility and COVID-19 spread. Over the study period, the average coefficients in 7 SEA countries increased, decreased, and finally kept stable. The association between human mobility and COVID-19 spread also presents spatial heterogeneity where higher coefficients were mainly concentrated in districts of Indonesia from week 1 to week 10 (ranging from 0.336 to 0.826), while lower coefficients were mainly located in districts of Vietnam (ranging from 0.044 to 0.130). From week 10 to week 25, higher coefficients were mainly observed in Singapore, Malaysia, Brunei, north Indonesia, and several districts of the Philippines. Despite the association showing a general weakening trend over time, significant positive coefficients were observed in Singapore, Malaysia, western Indonesia, and the Philippines, with the relatively highest coefficients observed in the Philippines in week 30 (ranging from 0.101 to 0.139). Conclusions The loosening interventions in response to COVID-19 in SEA countries during the second half of 2021 led to diverse changes in human mobility over time, which may result in the COVID-19 infection dynamics. This study investigated the association between mobility and infections at the regional level during the special transitional period. Our study has important implications for public policy interventions, especially at the later stage of a public health crisis.

Spatio-temporal heterogeneity in the international trade resilience during COVID-19

The COVID-19 pandemic and subsequent lockdowns have created immeasurable health and economic crises, leading to unprecedented disruptions to world trade. The COVID-19 pandemic shows diverse impacts on different economies that suffer and recover at different rates and degrees. This research aims to evaluate the spatio-temporal heterogeneity of international trade network vulnerabilities in the current crisis to understand the global production resilience and prepare for the future crisis. We applied a series of complex network analysis approaches to the monthly international trade networks at the world, regional, and country scales for the pre- and post- COVID-19 outbreak period. The spatio-temporal patterns indicate that countries and regions with an effective COVID-19 containment such as East Asia show the strongest resilience, especially Mainland China, followed by high-income countries with fast vaccine roll-out (e.g., U.S.), whereas low-income countries (e.g., Africa) show high vulnerability. Our results encourage a comprehensive strategy to enhance international trade resilience when facing future pandemic threats including effective non-pharmaceutical measures, timely development and rollout of vaccines, strong governance capacity, robust healthcare systems, and equality via international cooperation. The overall findings elicit the hidden global trading disruption, recovery, and growth due to the adverse impact of the COVID-19 pandemic.

Cross-regional analysis of the association between human mobility and COVID-19 infection in Southeast Asia during the transitional period of "living with COVID-19".

BACKGROUND: In response to COVID-19, Southeast Asian (SEA) countries had imposed stringent lockdowns and restrictions to mitigate the pandemic ever since 2019. Because of a gradually boosting vaccination rate along with a strong demand for economic recovery, many governments have shifted the intervention strategy from restrictions to "Living with COVID-19" where people gradually resumed their normal activities since the second half of the year 2021. Noticeably, timelines for enacting the loosened strategy varied across Southeast Asian countries, which resulted in different patterns of human mobility across space and time. This thus presents an opportunity to study the relationship between mobility and the number of infection cases across regions, which could provide support for ongoing interventions in terms of effectiveness. OBJECTIVE: This study aimed to investigate the association between human mobility and COVID-19 infections across space and time during the transition period of shifting strategies from restrictions to normal living in Southeast Asia. Our research results have significant implications for evidence-based policymaking at the present of the COVID-19 pandemic and other public health issues. METHODS: We aggregated weekly average human mobility data derived from the Facebook origin and destination Movement dataset. and weekly average new cases of COVID-19 at the district level from 01-Jun-2021 to 26-Dec-2021 (a total of 30 weeks). We mapped the spatiotemporal dynamics of human mobility and COVID-19 cases across countries in SEA. We further adopted the Geographically and Temporally Weighted Regression model to identify the spatiotemporal variations of the association between human mobility and COVID-19 infections over 30 weeks. Our model also controls for socioeconomic status, vaccination, and stringency of intervention to better identify the impact of human mobility on COVID-19 spread. RESULTS: The percentage of districts that presented a statistically significant association between human mobility and COVID-19 infections generally decreased from 96.15% in week 1 to 90.38% in week 30, indicating a gradual disconnection between human mobility and COVID-19 spread. Over the study period, the average coefficients in 7 SEA countries increased, decreased, and finally kept stable. The association between human mobility and COVID-19 spread also presents spatial heterogeneity where higher coefficients were mainly concentrated in districts of Indonesia from week 1 to week 10 (ranging from 0.336 to 0.826), while lower coefficients were mainly located in districts of Vietnam (ranging from 0.044 to 0.130). From week 10 to week 25, higher coefficients were mainly observed in Singapore, Malaysia, Brunei, north Indonesia, and several districts of the Philippines. Despite the association showing a general weakening trend over time, significant positive coefficients were observed in Singapore, Malaysia, western Indonesia, and the Philippines, with the relatively highest coefficients observed in the Philippines in week 30 (ranging from 0.101 to 0.139). CONCLUSIONS: The loosening interventions in response to COVID-19 in SEA countries during the second half of 2021 led to diverse changes in human mobility over time, which may result in the COVID-19 infection dynamics. This study investigated the association between mobility and infections at the regional level during the special transitional period. Our study has important implications for public policy interventions, especially at the later stage of a public health crisis.

Spatio-temporal heterogeneity in the international trade resilience during COVID-19.

The COVID-19 pandemic and subsequent lockdowns have created immeasurable health and economic crises, leading to unprecedented disruptions to world trade. The COVID-19 pandemic shows diverse impacts on different economies that suffer and recover at different rates and degrees. This research aims to evaluate the spatio-temporal heterogeneity of international trade network vulnerabilities in the current crisis to understand the global production resilience and prepare for the future crisis. We applied a series of complex network analysis approaches to the monthly international trade networks at the world, regional, and country scales for the pre- and post- COVID-19 outbreak period. The spatio-temporal patterns indicate that countries and regions with an effective COVID-19 containment such as East Asia show the strongest resilience, especially Mainland China, followed by high-income countries with fast vaccine roll-out (e.g., U.S.), whereas low-income countries (e.g., Africa) show high vulnerability. Our results encourage a comprehensive strategy to enhance international trade resilience when facing future pandemic threats including effective non-pharmaceutical measures, timely development and rollout of vaccines, strong governance capacity, robust healthcare systems, and equality via international cooperation. The overall findings elicit the hidden global trading disruption, recovery, and growth due to the adverse impact of the COVID-19 pandemic.

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2.

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

Investigating Linkages Between Spatiotemporal Patterns of the COVID-19 Delta Variant and Public Health Interventions in Southeast Asia: Prospective Space-Time Scan Statistical Analysis Method.

BACKGROUND: The COVID-19 Delta variant has presented an unprecedented challenge to countries in Southeast Asia (SEA). Its transmission has shown spatial heterogeneity in SEA after countries have adopted different public health interventions during the process. Hence, it is crucial for public health authorities to discover potential linkages between epidemic progression and corresponding interventions such that collective and coordinated control measurements can be designed to increase their effectiveness at reducing transmission in SEA. OBJECTIVE: The purpose of this study is to explore potential linkages between the spatiotemporal progression of the COVID-19 Delta variant and nonpharmaceutical intervention (NPI) measures in SEA. We detected the space-time clusters of outbreaks of COVID-19 and analyzed how the NPI measures relate to the propagation of COVID-19. METHODS: We collected district-level daily new cases of COVID-19 from June 1 to October 31, 2021, and district-level population data in SEA. We adopted prospective space-time scan statistics to identify the space-time clusters. Using cumulative prospective space-time scan statistics, we further identified variations of relative risk (RR) across each district at a half-month interval and their potential public health intervention linkages. RESULTS: We found 7 high-risk clusters (clusters 1-7) of COVID-19 transmission in Malaysia, the Philippines, Thailand, Vietnam, and Indonesia between June and August, 2021, with an RR of 5.45 (P<.001), 3.50 (P<.001), 2.30 (P<.001), 1.36 (P<.001), 5.62 (P<.001), 2.38 (P<.001), 3.45 (P<.001), respectively. There were 34 provinces in Indonesia that have successfully mitigated the risk of COVID-19, with a decreasing range between -0.05 and -1.46 due to the assistance of continuous restrictions. However, 58.6% of districts in Malaysia, Singapore, Thailand, and the Philippines saw an increase in the infection risk, which is aligned with their loosened restrictions. Continuous strict interventions were effective in mitigating COVID-19, while relaxing restrictions may exacerbate the propagation risk of this epidemic. CONCLUSIONS: The analyses of space-time clusters and RRs of districts benefit public health authorities with continuous surveillance of COVID-19 dynamics using real-time data. International coordination with more synchronized interventions amidst all SEA countries may play a key role in mitigating the progression of COVID-19.

Editorial: Infectious Disease Epidemiology and Transmission Dynamics.

Infectious diseases, such as COVID-19 [...].

Long-read assembly of major histocompatibility complex and killer cell immunoglobulin-like receptor genome regions in cynomolgus macaque.

BACKGROUND: The major histocompatibility complex (MHC) and the killer cell immunoglobulin-like receptors (KIR) are key regulators of immune responses. The cynomolgus macaque, an Old World monkey species, can be applied as an important preclinical model for studying human diseases, including coronavirus disease 2019 (COVID-19). Several MHC-KIR combinations have been associated with either a poor or good prognosis. Therefore, macaques with a well-characterized immunogenetic profile may improve drug evaluation and speed up vaccine development. At present, a complete overview of the MHC and KIR haplotype organizations in cynomolgus macaques is lacking, and characterization by conventional techniques is hampered by the extensive expansion of the macaque MHC-B region that complicates the discrimination between genes and alleles. METHODS: We assembled complete MHC and KIR genomic regions of cynomolgus macaque using third-generation long-read sequencing approach. We identified functional Mafa-B loci at the transcriptome level using locus-specific amplification in a cohort of 33 Vietnamese cynomolgus macaques. RESULTS: This is the first physical mapping of complete MHC and KIR gene regions in a Vietnamese cynomolgus macaque. Furthermore, we identified four functional Mafa-B loci (B2, B3, B5, and B6) and showed that alleles of the Mafa-I*01, -B*056, -B*034, and -B*001 functional lineages, respectively, are highly frequent in the Vietnamese cynomolgus macaque population. CONCLUSION: The insights into the MHC and KIR haplotype organizations and the level of diversity may refine the selection of animals with specific genetic markers for future medical research.

[Degradation of Chloroquine Phosphate by UV-activated Persulfate].

The degradation of chloroquine phosphate (CQP), an anti-COVID-19 drug, was investigated in a UV-activated persulfate system (UV/PS). The second-order rate constants of CQP with hydroxyl radicals (HO·) and sulfate radicals (SO4-·) were determined using a competition kinetics experiment, and the effects of persulfate concentration, pH, and inorganic anions on the degradation of CQP were also systematically studied. Furthermore, a kinetic model was established to predict the concentration of CQP and major free radicals to explore its mechanism of influence. The results showed that the degradation efficiency of CQP could reach 91.3% after 10 min under UV/PS, which was significantly higher than that under UV, sunlight, or PS alone. At pH=6.9, the second-order rate reaction constants of CQP with HO· and SO4-· were 8.9×109 L·(mol·s)-1and 1.4×1010 L·(mol·s)-1, respectively, and the main active species was SO4-·. The degradation rate of CQP increased with increasing concentrations of PS and decreased with the addition of HCO3- and Cl-. The removal efficiency of CQP was inhibited under stronger alkaline conditions. N-de-ethylation, cleavage of the C-N bond, and hydrogen abstraction were proposed as the principal pathways of CQP degradation based on LC-MS analysis. The mineralization rate of CQP could be improved by increasing PS concentration and pH values. This study could be helpful for the treatment of anti-COVID-19 pharmaceutical wastewater.

The impact of COVID-19 on NO2 and PM2.5 levels and their associations with human mobility patterns in Singapore

The decline in NO2 and PM2.5 pollutant levels were observed during COVID-19 around the world, especially during lockdowns. Previous studies explained such observed decline with the decrease in human mobility, overlooking the meteorological changes that could simultaneously mediate air pollution levels. This pitfall could potentially lead to over- or under-estimation of the effect of COVID-19 on air pollution. This study, thus, aims to re-evaluate the impact of COVID-19 on NO2 and PM2.5 pollutant levels in Singapore, by incorporating the effect of meteorological parameters in predicting NO2 and PM2.5 baseline in 2020 using machine learning methods. The results show that the mean NO2 and PM2.5 declined by 12% and 19%, which were less than the observed drops (i.e. 54% and 29%, respectively) without considering the effect of meteorological parameters. As two proxies for change in human mobility, taxi availability and carpark availability were found to increase and decrease by a maximum of 12.6% and 9.8%, respectively, in 2020 from 2019. Two correlation analyses were conducted to investigate how human mobility influenced air pollutant levels: one between daily PM2.5 and mobility changes at a regional scale and the other between weekly NO2 and mobility changes at a spatial resolution of 0.01°. The NO2 variation was found to be more associated with the change in human mobility and a cluster of stronger correlations was found in the South and East Coast of Singapore. Contrarily, PM2.5 and mobility had a weak correlation, which could be due to the limit of a coarse spatial resolution. [ FROM AUTHOR] Copyright of Annals of GIS is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Perceived Benefits and Barriers to Chinese COVID-19 Vaccine Uptake Among Young Adults in China.

Survey-based research has provided us with breadth regarding perceived benefits and barriers to COVID-19 vaccination among Chinese people. Most such research has been conducted within hypothetical COVID-19 vaccine contexts, and few studies are specific to young adults aged 18-40, a pivotal target population for COVID-19 vaccination. Now that the Sinopharm and Sinovac COVID-19 vaccines have been conditionally approved in China, qualitative investigation of young adults' perceptions of benefits and barriers to taking them is warranted. Such research may suggest potential candidate themes in the COVID-19 vaccination promotional messages targeting this population. Through in-depth interviews with 55 Chinese young adults and thematic analysis guided by the health belief model, social benefits and worry reduction emerged as significant positive factors in young adults' intention to vaccinate. Several novel barriers emerged as well, including perceptions that the vaccines' advantages are weak relative to non-medical preventions and beliefs regarding Ti Zhi (the individual human constitution), which confused some participants about their suitability for vaccination. The study also identified two modifying factors, trust in the government and perceived vaccine information insufficiency, both of which appeared to be indirectly associated with vaccination intention by augmenting the perceived barriers. The results suggest that more attention could be paid to young adults' cultural background when developing relevant health communications.

Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice.

Adjuvants enhance the magnitude and the durability of the immune response to vaccines. However, there is a paucity of comparative studies on the nature of the immune responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice-alum, AS03 (a squalene-based adjuvant supplemented with α-tocopherol), AS37 (a TLR7 ligand emulsified in alum), CpG1018 (a TLR9 ligand emulsified in alum), O/W 1849101 (a squalene-based adjuvant)-for their capacity to stimulate immune responses when combined with a subunit vaccine under clinical development. We found that all four of the adjuvant candidates surpassed alum with respect to their capacity to induce enhanced and durable antigen-specific antibody responses. The TLR-agonist-based adjuvants CpG1018 (TLR9) and AS37 (TLR7) induced Th1-skewed CD4+ T cell responses, while alum, O/W, and AS03 induced a balanced Th1/Th2 response. Consistent with this, adjuvants induced distinct patterns of early innate responses. Finally, vaccines adjuvanted with AS03, AS37, and CpG1018/alum-induced durable neutralizing-antibody responses and significant protection against the B.1.351 variant 7 months following immunization. These results, together with our recent results from an identical study in non-human primates (NHPs), provide a comparative benchmarking of five clinically relevant vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV-2 subunit vaccines to provide durable protection against the B.1.351 variant. Furthermore, these results reveal differences between the widely-used C57BL/6 mouse strain and NHP animal models, highlighting the importance of species selection for future vaccine and adjuvant studies.

The Structural Evolution of Semipolar (11-22) Plane AlN Tem-Plate on m-Plane Sapphire Prepared by Sputtering and High Temperature Annealing.

In this work, the epitaxial semipolar (11-22) AlN was prepared on nonpolar m-sapphire substrate by combining sputtering and high-temperature annealing. According to our systematic measurements and analysis from XRD, Raman spectra, and AFM, the evolution of crystalline structure and morphology was investigated upon increasing AlN thickness and annealing duration. The annealing operation intensively resets the lattice and improves the crystalline quality. By varying the film thickness, the contribution from the AlN-sapphire interface on crystalline quality and lattice parameters during the annealing process was investigated, and its contribution was found to be not so obvious when the thickness increased from 300 nm to 1000 nm. When the annealing was performed under durations from 1 to 5 h, the crystalline quality was found unchanged; meanwhile, the evolution of morphology was pronounced, and it means the crystalline reorganization happens prior to morphology reset. Finally, the annealing treatment enabled a zig-zag morphology on the AlN template along the sapphire [0001] direction in the plane, which potentially affects the subsequent device epitaxy process. Therefore, our results act as important experience for the semipolar nitride semiconductor laser device preparation, particularly for the epitaxy of microcavity structure through providing the crystalline evolution.

Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine.

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8+ T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8+ T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.

Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice.

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.

Spatiotemporal patterns and progression of the Delta variant of COVID-19 and their health intervention linkages in Southeast Asia (preprint)

The global pandemic of COVID-19 presented an unprecedented challenge to all countries in the world, among which Southeast Asia (SEA) countries managed to maintain and mitigate the first wave of COVID-19 in 2020. However, these countries were caught in the crisis after the Delta variant was introduced to SEA, though many countries had immediately implemented non-pharmaceutical intervention (NPI) measures along with vaccination in order to contain the disease spread. To investigate the potential linkages between epidemic dynamics and public health interventions, we adopted a prospective space-time scan method to conduct spatiotemporal analysis at the district level in the seven selected countries in SEA from June 2021 to October 2021. Results reveal the spatial and temporal propagation and progression of COVID-19 risks relative to public health measures implemented by different countries. Our research benefits continuous improvements of public health strategies in preventing and containing this pandemic.