Clinical translation of gold nanoparticles.

Gold nanoparticles display unique physicochemical features, which can be useful for therapeutic purposes. After two decades of preclinical progress, gold nanoconstructs are slowly but steadily transitioning into clinical trials. Although initially thought to be "magic golden bullets" that could be used to treat a wide range of diseases, current consensus has moved toward a more realistic approach, where gold nanoformulations are being investigated to treat specific disorders. These therapeutic applications are dictated by the pharmacokinetics and biodistribution profiles of gold nanoparticles. Here, we analyze the current clinical landscape of therapeutic gold nanoconstructs, discuss the shared characteristics that allowed for their transition from bench to bedside, and examine existing hurdles that need to be overcome before they can be approved for clinical use.

Interpreting global variations in the toll of COVID-19: The case for context and nuance in hypothesis generation and testing

Key points As of January 2022, the COVID-19 pandemic was on-going, affecting populations worldwide. The potential risks of the Omicron variant (and future variants) still remain an area of active investigation. Thus, the ultimate human toll of SARS-CoV-2, and, by extension, the variations in that toll among diverse populations, remain unresolved. Nonetheless, an extensive literature on causal factors in the observed patterns of COVID-19 morbidity and cause-specific mortality has emerged—particularly at the aggregate level of analysis. This article explores potential pitfalls in the attribution of COVID outcomes to specific factors in isolation by examining a diverse set of potential factors and their interactions. Methods We sourced published data to establish a global database of COVID-19 outcomes for 68 countries and augmented these with an array of potential explanatory covariates from a diverse set of sources. We sought population-level aggregate factors from both health- and (traditionally) non-health domains, including: (a) Population biomarkers (b) Demographics and infrastructure (c) Socioeconomics (d) Policy responses at the country-level. We analyzed these data using (OLS) regression and more flexible non-parametric methods such as recursive partitioning, that are useful in examining both potential joint factor contributions to variations in pandemic outcomes, and the identification of possible interactions among covariates across these domains. Results Using the national obesity rates of 68 countries as an illustrative predictor covariate of COVID-19 outcomes, we observed marked inconsistencies in apparent outcomes by population. Importantly, we also documented important variations in outcomes, based on interactions of health factors with covariates in other domains that are traditionally not related to biomarkers. Finally, our results suggest that single-factor explanations of population-level COVID-19 outcomes (e.g., obesity vs. cause-specific mortality) appear to be confounded substantially by other factors. Conclusions/implications Our methods and findings suggest that a full understanding of the toll of the COVID-19 pandemic, as would be central to preparing for similar future events, requires analysis within and among diverse variable domains, and within and among diverse populations. While this may seem apparent, the bulk of the recent literature on the pandemic has focused on one or a few of these drivers in isolation. Hypothesis generation and testing related to pandemic outcomes will benefit from accommodating the nuance of covariate interactions, in an epidemiologic context. Finally, our results add to the literature on the ecological fallacy: the attempt to infer individual drivers and outcomes from the study of population-level aggregates.

A retrospective assessment of COVID-19 model performance in the USA.

Coronavirus disease 2019 (COVID-19) forecasts from over 100 models are readily available. However, little published information exists regarding the performance of their uncertainty estimates (i.e. probabilistic performance). To evaluate their probabilistic performance, we employ the classical model (CM), an established method typically used to validate expert opinion. In this analysis, we assess both the predictive and probabilistic performance of COVID-19 forecasting models during 2021. We also compare the performance of aggregated forecasts (i.e. ensembles) based on equal and CM performance-based weights to an established ensemble from the Centers for Disease Control and Prevention (CDC). Our analysis of forecasts of COVID-19 mortality from 22 individual models and three ensembles across 49 states indicates that-(i) good predictive performance does not imply good probabilistic performance, and vice versa; (ii) models often provide tight but inaccurate uncertainty estimates; (iii) most models perform worse than a naive baseline model; (iv) both the CDC and CM performance-weighted ensembles perform well; but (v) while the CDC ensemble was more informative, the CM ensemble was more statistically accurate across states. This study presents a worthwhile method for appropriately assessing the performance of probabilistic forecasts and can potentially improve both public health decision-making and COVID-19 modelling.

PHYLOGENETIC TRACKING of HIV EPIDEMIC GROWTH in QUEBEC from 2014 to 2020

Background: Ending the HIV Epidemic by 2030 initiative includes phylogenetics as a molecular framework to track patterns of HIV spread. In this study, phylogenetics was combined with available epidemiological data to elucidate track evolving trends in HIV-1 spread among Men having Sex with Men (MSM) and Heterosexual (HET) populations in Quebec. Methods: Phylogenetic linkage analysis was performed using MEGA-10 and HIV-TRACE/Microbe-TRACE methodologies. New infections genotyped between 2014-2020 were stratified into groups: i) Subtype B MSM (subtype B male singletons/male-male clusters, n=1812);ii) Subtype B Heterosexual (female singletons/female-male clusters, n=432), including migrants from the Caribbean and Americas;and iii) Non-B subtype (n=737) epidemics. Test requisition data and clinical data from Clinique Actuel (n=141 and 50, 2016-2018) monitored epidemiological features in a subset of newly diagnosed persons. Results: Among MSM, annual new infections declined by 20% and 40% over the 2015-2017 and 2018-2020 periods, respectively. Overall, 45% of new infections in MSM were associated with 20 active large clusters, adding 8-96 infections/clusters from 2014-2020. Clinical data showed 37% newly diagnosed MSM were born outside Canada, 28% of whom were linked to large cluster outbreaks. Among heterosexuals with subtype B infections, there was a 31% increase from 2015-2017 followed by a 36% decline from 2018-2020 post-COVID. Of note, large cluster HET outbreaks occurred in Quebec City, Richelieu, and Northern Quebec Overall, non-B subtype infections remained steady (median 100 annually) over the 2014 to 2020 period. Several non-B subtype clusters reflect the domestic introduction and spread of subtype CRF02- AG variants. Cluster membership and cluster size was associated with recent stage infection, viral sequence recency (based on % mixed base calls) and younger age of members within individual clusters. Conclusion: Annual numbers of new HIV-1 infections have steadily declined among MSM post-2008, concomitant to improved HIV prevention paradigms. Epidemic control among MSM and HET groups has been thwarted by large cluster outbreaks. Recent arrivals to Quebec accounted for a growing number of subtype B and non-B subtype infections. HIV prevention efforts must continue in the post-COVID era, tailored to avert transmission cascades in younger persons and recent migrant populations.

A Whole Genome Sequencing Analysis of a Multi-unit Long-term Care Facility COVID-19 Outbreak

Background. The coronavirus disease (COVID-19) pandemic has affected residents in long-term care facilities (LTCF) significantly. Understanding transmission dynamics in this setting is crucial to control the spread of COVID-19 in this population. Using whole genome sequencing (WGS) of SARS-CoV-2, we aimed to delineate the points of introduction and transmission pathways in a large LTCF in Quebec, Canada. Methods. Between 2020-10-28 and 2021-01-09, COVID-19 cases occurred in 102 residents and 111 HCW at a 387-bed LTCF;cases were distributed in 11 units on 6 floors. As part of outbreak analysis, SARS-CoV-2 isolates underwent WGS using the Oxford Nanopore Minion and the Artic V3 protocol. Lineage attribution and sequence types (ST, within 3 mutations) were assigned based on Pangolin classification and variant analysis. Epidemiologic data including date of positive PCR test, resident room number and HCW work location were collected. Self-reported high-risk exposures were collected by HCW questionnaire via phone interview after consent. Cases and their ST, geo-temporal relations and HCW-reported exposures were examined via network plots and geography-based epidemic curves to infer points of introduction and paths of transmission. Results. Of 170 isolates available from 100/102 residents and 70/111 HCW, 130 (76.4%) were successfully sequenced. Phylogenetic analysis revealed 7 separate introductions to the LTCF. Grouping of ST by units was observed, with temporal appearance of ST supporting HCW introduction in 7/11 units. Proportion of phone interview completion was low at 35% (26/70). Few HCW recalled specific high-risk exposures. Recalled exposures supported by genetic linkage revealed potential between-unit introductions from HCW-to-HCW transmission at work and outside the workplace (e.g. carpooling). On one unit, a wandering resident was identified as a likely source of transmission to other residents (Figure 1). Network plot of cases clustered by geographic unit, colour-coded by sequence type. Circles represent residents;addition signs represent healthcare workers. Blue lines represent identified high-risk exposures. Node labels represent floor and unit identifiers;2 units per floor. Conclusion. We demonstrate the complex genomic epidemiology of a multi-unit LTCF outbreak, putting into evidence the importance of a multi-faceted approach to limit transmission. This analysis highlights the utility of using WGS to uncover unsuspected transmission routes, such as HCW contact outside work, which can prompt new infection control measures.

Prevalence and predictors of post-traumatic stress disorder in patients with cured coronavirus disease 2019 (COVID-19) one month post-discharge Prevalencia y predictores de TEPT en pacientes recuperados de COVID-19 un mes después del alta 新型冠状病毒肺炎患者 (COVID-19) 出院一个月后创伤后应激障碍的患病率和预测因素

Background: Coronavirus disease 2019 (COVID-19) can place an immense psychological strain on the infected patient. The psychological distress can linger after the initial recovery from the infection. Objective: This study aimed to evaluate the prevalence and predictors of provisional post-traumatic stress disorder (PTSD) in patients with cured COVID-2019. Methods: The baseline survey was conducted from 10 to 25 February 2020 in patients with COVID-19 in a designated hospital. Demographic and clinical characteristics were acquired, and depression and anxiety levels were assessed, using the 9-item Patient Health Questionnaire and 7-item Generalized Anxiety Disorder scale, respectively. A follow-up survey was conducted 1 month post-discharge. PTSD symptoms were measured by the Impact of Event Scale-6 (IES-6) and patients’ perception of supportive care during hospitalization was investigated using a self-developed questionnaire. Results: In total, 114 patients completed both the baseline and follow-up surveys. Of these, 41 (36.0%) met the cut-off score for provisional PTSD diagnosis according to the IES-6. Female gender [odds ratio (OR) = 4.69, 95% confidence interval (CI) 1.54–14.37], educational level of high school or below (OR = 15.49, 95% CI 1.13–212.71), higher anxiety levels (OR = 1.34, 95% CI 1.12–1.61) and lower perceptions of emotional support during hospitalization (OR = 0.41, 95% CI 0.17–0.96) predicted a higher risk for provisional PTSD. Conclusions: PTSD is commonly seen in patients with COVID-19 1 month post-discharge. Female patients, and patients with lower educational levels, higher anxiety levels and lower perceptions of emotional support during hospitalization may be more likely to develop PTSD in the near future. Enhancing emotional support during hospitalization could help to prevent PTSD in patients with COVID-19. HIGHLIGHTS More than one-third ofpatients met the diagnostic criteria of probable PTSD 1 month post-discharge. Providing timely emotional support during hospitaliza-tion may be one of the key measures for preventing PTSD in patients with COVID-19.

Understanding the characteristics of COVID-19 misinformation communities through graphlet analysis

Online social networks serve as a convenient way to connect, share, and promote content with others. As a result, these networks can be used with malicious intent, causing disruption and harm to public debate through the sharing of misinformation. However, automatically identifying such content through its use of natural language is a significant challenge compared to our solution which uses less computational resources, language-agnostic and without the need for complex semantic analysis. Consequently alternative and complementary approaches are highly valuable. In this paper, we assess content that has the potential for misinformation and focus on patterns of user association with online social media communities (subreddits) in the popular Reddit social media platform, and generate networks of behaviour capturing user interaction with different subreddits. We examine these networks using both global and local metrics, in particular noting the presence of induced substructures (graphlets) assessing 7,876,064 posts from 96,634 users. From subreddits identified as having potential for misinformation, we note that the associated networks have strongly defined local features relating to node degree - these are evident both from analysis of dominant graphlets and degree-related global metrics. We find that these local features support high accuracy classification of subreddits that are categorised as having the potential for misinformation. Consequently we observe that induced local substructures of high degree are fundamental metrics for subreddit classification, and support automatic detection capabilities for online misinformation independent from any particular language.

Decreases in out of hospital cardiac arrest (OHCA) outcome metrics persist when known COVID patients are excluded from analysis.

OBJECTIVE: A decline in OHCA performance metrics during the pandemic has been reported in the literature but the cause is still not known. The Montgomery County Fire and Rescue Service (MCFRS) observed a decline in both the rate of return of spontaneous circulation (ROSC) and the proportion of resuscitations that resulted in cerebral performance category (CPC) 1 or 2 discharge of the patient beginning in March of 2020. This study examines whether the decline in these performance metrics persists when known COVID positive patients are excluded from the analysis. METHODS: Two samples of OHCA patients for similar time periods (one year apart) before and after the start of the COVID pandemic were developed. A database of known COVID positive patients among EMS encounters was used to identify and exclude COVID positive patients. OHCA outcomes in these two groups were then compared using a Chi-square test and Fisher's exact test for difference in proportions and Analysis of Variance (ANOVA) for difference in means. A two-stage multivariable logistic regression model was used to develop odds ratios for achieving ROSC and CPC 1 or 2 discharge in each period. RESULTS: After excluding known COVID patients, 32.5% of the patients in the pre-COVID period achieved ROSC compared to 25.1% in the COVID period (p = 0.007). 6% of patients in the pre-COVID period were discharged with CPC 1 or 2 compared to 3.2% from the COVID era (p = 0.026). Controlling for all available patient characteristics, patients undergoing OHCA resuscitation prior to be beginning of the pandemic were 1.2 times more likely to achieve ROSC and 1.6 times more likely to be discharged with CPC 1 or 2 than non-COVID patients in the pandemic era sample. CONCLUSIONS: When known COVID patients are excluded, pre-pandemic OHCA resuscitation patients were more likely to achieve ROSC and CPC 1 or 2 discharge. The prevalence of known COVID positive patients among all OHCA resuscitations during the pandemic was not sufficient to fully account for the marked decrease in both ROSC and CPC 1 or 2 discharges. Other causative factors must be sought.

Cross-sectional cycle threshold values reflect epidemic dynamics of COVID-19 in Madagascar (preprint)

As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (Ct) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-Ct value infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on Ct value, suggesting that Ct value can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population level Ct distribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional Ct distributions across three regions in Madagascar. We find that Ct-derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of Ct values could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting.

Prevalence and predictors of post-traumatic stress disorder in patients with cured coronavirus disease 2019 (COVID-19) one month post-discharge.

Background: Coronavirus disease 2019 (COVID-19) can place an immense psychological strain on the infected patient. The psychological distress can linger after the initial recovery from the infection. Objective: This study aimed to evaluate the prevalence and predictors of provisional post-traumatic stress disorder (PTSD) in patients with cured COVID-2019. Methods: The baseline survey was conducted from 10 to 25 February 2020 in patients with COVID-19 in a designated hospital. Demographic and clinical characteristics were acquired, and depression and anxiety levels were assessed, using the 9-item Patient Health Questionnaire and 7-item Generalized Anxiety Disorder scale, respectively. A follow-up survey was conducted 1 month post-discharge. PTSD symptoms were measured by the Impact of Event Scale-6 (IES-6) and patients' perception of supportive care during hospitalization was investigated using a self-developed questionnaire. Results: In total, 114 patients completed both the baseline and follow-up surveys. Of these, 41 (36.0%) met the cut-off score for provisional PTSD diagnosis according to the IES-6. Female gender [odds ratio (OR) = 4.69, 95% confidence interval (CI) 1.54-14.37], educational level of high school or below (OR = 15.49, 95% CI 1.13-212.71), higher anxiety levels (OR = 1.34, 95% CI 1.12-1.61) and lower perceptions of emotional support during hospitalization (OR = 0.41, 95% CI 0.17-0.96) predicted a higher risk for provisional PTSD. Conclusions: PTSD is commonly seen in patients with COVID-19 1 month post-discharge. Female patients, and patients with lower educational levels, higher anxiety levels and lower perceptions of emotional support during hospitalization may be more likely to develop PTSD in the near future. Enhancing emotional support during hospitalization could help to prevent PTSD in patients with COVID-19.

Antecedentes: El COVID-19 ha supuesto una inmensa carga psicológica para el paciente infectado. El malestar psicológico puede persistir aún después de la recuperación inicial de la infección.Objetivos: Este estudio tuvo como objetivo evaluar la prevalencia y los factores predictores del trastorno de estrés postraumático (TEPT) provisional en pacientes recuperados de COVID-2019.Métodos: El cuestionario inicial se realizó en pacientes con el COVID-19 desde el 10 de febrero del 2020 hasta el 25 de febrero del 2020 en un hospital designado. Se consideraron las variables demográficas y clínicas, además, se evaluaron los niveles de depresión y ansiedad mediante el cuestionario de salud del paciente de 9 elementos y el cuestionario del trastorno de ansiedad generalizada de 7 elementos, respectivamente. Un cuestionario de seguimiento fue realizado un mes después del alta. Los síntomas de TEPT fueron medidos por el Cuestionario de Eventos de Impacto 6 (IES-6 por sus siglas en ingles) y el nivel de percepción de los pacientes sobre el cuidado de soporte durante la hospitalización fue investigado utilizando un cuestionario auto-administrado.Resultados: Ciento catorce pacientes completaron tanto el cuestionario inicial como el de seguimiento. Cuarenta y un (36.0%) pacientes cumplieron con el punto de corte para el diagnóstico provisional de TEPT según el IES-6. El sexo femenino (OR = 4.69, 95% CI: 1.54-14.37), un nivel de educación secundaria o inferior (OR = 15.49, 95% CI: 1.13-212.71), niveles elevados de ansiedad (OR = 1.34, 95% CI: 1.12-1.61) y una menor percepción de soporte emocional durante la hospitalización (OR = 0.41, 95% CI: 0.17-0.96) fueron factores predictores de riesgo elevado para el desarrollo provisional de TEPT.Conclusiones: El TEPT es observado con frecuencia en pacientes con COVID-19 un mes después del alta. Las pacientes de sexo femenino, los pacientes con un nivel de educación bajo, los pacientes con un nivel elevado de ansiedad y una menor percepción de apoyo emocional durante la hospitalización podrían tener mayor probabilidad de desarrollar TEPT en el futuro cercano. El reforzamiento del apoyo emocional durante la hospitalización podría ayudar a prevenir el TEPT en pacientes con COVID-19.

Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories.

As the coronavirus disease 2019 (COVID-19) pandemic second wave is emerging, it is of the upmost importance to screen the population immunity in order to keep track of infected individuals. Consequently, immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and positive predictive values are needed to obtain an accurate epidemiological picture. As more data accumulate about the immune responses and the kinetics of neutralizing-antibody (nAb) production in SARS-CoV-2-infected individuals, new applications are forecast for serological assays such as nAb activity prediction in convalescent-phase plasma from recovered patients. This multicenter study, involving six hospital centers, determined the baseline clinical performances, reproducibility, and nAb level correlations of 10 commercially available immunoassays. In addition, three lateral-flow chromatography assays were evaluated, as these devices can be used in logistically challenged areas. All assays were evaluated using the same patient panels in duplicate, thus enabling accurate comparison of the tests. Seven immunoassays examined in this study were shown to have excellent specificity (98 to 100%) and good to excellent positive predictive values (82 to 100%) when used in a low (5%)-seroprevalence setting. We observed sensitivities as low as 74% and as high as 95% at ≥15 days after symptom onset. The determination of optimized cutoff values through receiver operating characteristic (ROC) curve analyses had a significant impact on the diagnostic resolution of several enzyme immunoassays by increasing the sensitivity significantly without a large trade-off in specificity. We found that spike-based immunoassays seem to be better correlates of nAb activity. Finally, the results reported here will add to the general knowledge of the interlaboratory reproducibility of clinical performance parameters of immunoassays and provide new evidence about nAb activity prediction.

Diagnostic, Prognostic, and Therapeutic Use of Radiopharmaceuticals in the Context of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) outbreak has devastated the healthcare systems and economies of over 200 countries in just a few months. The etiological agent of COVID-19, SARS-CoV-2, is a highly contagious virus that can be transmitted by asymptomatic and symptomatic carriers alike. While in vitro testing techniques have allowed for population-wide screening, prognostic tools are required to assess the disease severity and therapeutic response, contributing to improve the patient clinical outcomes. Moreover, no specific antiviral against COVID-19 exists at the time of publication, severely limiting treatment against the infection. Hence, there is an urgent clinical need for innovative therapeutic strategies that may contribute to manage the COVID-19 outbreak and prevent future pandemics. Herein, we critically examine recent diagnostic, prognostic, and therapeutic advancements for COVID-19 in the field of radiopharmaceuticals. First, we summarize the gold standard techniques used to diagnose COVID-19, including in vitro assays and imaging techniques, and then discuss how radionuclide-based nuclear imaging provides complementary information for prognosis and treatment management of infected patients. Second, we introduce new emerging types of radiotherapies that employ radioimmunoconjugates, which have shown selective cytotoxic response in oncological studies, and critically analyze how these compounds could be used as therapeutic agents against SARS-CoV-2. Finally, this Perspective further discusses the emerging applications of radionuclides to study the behavior of pulmonary SARS-CoV-2 aerosol particles.

Impact of the COVID-19 Pandemic on Manual Therapy Service Utilization within the Australian Private Healthcare Setting.

The COVID-19 pandemic has impacted a wide range of health services. This study aimed to quantify the impact of the COVID-19 pandemic on manual therapy service utilization within the Australian private healthcare setting during the first half of 2020. Quarterly data regarding the number and total cost of services provided were extracted for each manual therapy profession (i.e., chiropractic, osteopathy, and physiotherapy) for the period January 2015 to June 2020 from the Australian Prudential Regulation Authority. Time series forecasting methods were used to estimate absolute and relative differences between the forecasted and observed values of service utilization. An estimated 1.3 million (13.2%) fewer manual therapy services, with a total cost of AUD 84 million, were provided within the Australian private healthcare setting during the first half of 2020. Reduction in service utilization was considerably larger in the second quarter (21.7%) than in the first quarter (5.7%), and was larger in physiotherapy (20.6%) and osteopathy (12.7%) than in chiropractic (5.2%). The impact varied across states and territories, with the largest reductions in service utilization observed in New South Wales (17.5%), Australian Capital Territory (16.3%), and Victoria (16.2%). The COVID-19 pandemic has had a profound impact on manual therapy service utilization in Australia. The magnitude of the decline in service utilization varied considerably across professions and locations. The long-term consequences of this decline in manual therapy utilization remain to be determined.

Design, Expression, Purification, and Characterization of a YFP-Tagged 2019-nCoV Spike Receptor-Binding Domain Construct.

2019-nCoV is the causative agent of the serious, still ongoing, worldwide coronavirus disease (COVID-19) pandemic. High quality recombinant virus proteins are required for research related to the development of vaccines and improved assays, and to the general understanding of virus action. The receptor-binding domain (RBD) of the 2019-nCoV spike (S) protein contains disulfide bonds and N-linked glycosylations, therefore, it is typically produced by secretion. Here, we describe a construct and protocol for the expression and purification of yellow fluorescent protein (YFP) labeled 2019-nCoV spike RBD. The fusion protein, in the vector pcDNA 4/TO, comprises an N-terminal interferon alpha 2 (IFNα2) signal peptide, an eYFP, a FLAG-tag, a human rhinovirus 3C protease (HRV3C) cleavage site, the RBD of the 2019-nCoV spike protein and a C-terminal 8x His-tag. We stably transfected HEK 293 cells. Following expansion of the cells, the fusion protein was secreted from adherent cells into serum-free medium. Ni-NTA immobilized metal ion affinity chromatography (IMAC) purification resulted in very high protein purity, based on analysis by SDS-PAGE. The fusion protein was soluble and monodisperse, as confirmed by size-exclusion chromatography (SEC) and negative staining electron microscopy. Deglycosylation experiments confirmed the presence of N-linked glycosylations in the secreted protein. Complex formation with the peptidase domain of human angiotensin-converting enzyme 2 (ACE2), the receptor for the 2019-nCoV spike RBD, was confirmed by SEC, both for the YFP-fused spike RBD and for spike RBD alone, after removal of YFP by proteolytic cleavage. Possible applications for the fusion protein include binding studies on cells or in vitro, fluorescent labeling of potential virus-binding sites on cells, the use as an antigen for immunization studies or as a tool for the development of novel virus- or antibody-detection assays.

China's mental health support in response to COVID-19: progression, challenges and reflection.

The continued spread of the coronavirus disease 2019 (COVID-19) has a serious impact on everyone across the globe, both physically and psychologically. In addition to proactive measures addressing physical survival needs and health protection, China has launched a mental health support system to cope with the widespread psychological stress during the pandemic and its aftermath. In this debate, the authors attempted to depict and reflect upon the overall framework of China's mental health support, with particular reference to the psychological intervention in response to COVID-19 over the last few months. Although a lot of effort has been made to meet the mental health needs, the accessibility, acceptability and effectiveness of the support system still have much room for improvement. Therefore, it is very important to re-think the predicament and challenge on ways of enhancing public mental health emergency responses in China. The concepts of universality, timeliness and scientific rigour were proposed as a possible reform in preparation for large-scale natural or man-made disasters in the coming future.

EMDR Therapy Treatment of Grief and Mourning in Times of COVID-19 (Coronavirus)

Death of a loved one is universally distressing. The stressful conditions of COVID-19 can compound the trauma of a loss. Consequently, the mourner has to deal with: (a) the loss of a loved one;(b) potential complications of grief and mourning caused by COVID-19 (e.g., sudden and unexpected death, a loved one's suffering, inability to be physically present to offer comfort or say good-bye, social distancing interfering with funeral and religious ceremonies);and (c) personal disruption caused by COVID-19 (e.g., disruption of employment and daily living routines, fears related to safety and uncertainty). Further, grief can be complicated by prior unresolved losses and trauma, including attachment-based trauma, which would also need to be identified and treated. This article presents a framework for treatment of grief and mourning with eye movement desensitization and reprocessing (EMDR) therapy. EMDR treatment, guided by the Adaptive Information Processing model, can be informed by other frameworks, including attachment theory and the Dual Process Model, which are described. A case example is presented to illustrate treatment of a client whose father died due to COVID-19.

Characteristics of Newborns Born to SARS-CoV-2-Positive Mothers: A Retrospective Cohort Study.

OBJECTIVE: The novel virus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to a terrifying pandemic. The range of illness severity among children is variable. This study aims to assess the characteristics of newborns born to SARS-CoV-2-positive women compared with those mothers who tested negative. STUDY DESIGN: This was a retrospective cohort study performed at Brookdale Hospital Medical Center in New York City from March to May 2020. Electronic medical records of mother-baby dyads were reviewed. RESULTS: Seventy-nine mothers tested for SARS-CoV-2 were included, out of which 18.98% of mothers tested SARS-CoV-2 positive. We found a significant association between symptoms and SARS-CoV-2 status. We observed a significant association between newborns of SARS-CoV-2 positive and SARS-CoV-2 negative mothers regarding skin-to-skin contact (p < 0.001). Both groups showed significant differences regarding isolation (p < 0.001). Interestingly, regarding SARS-CoV-2 infection in newborns, only one newborn tested SARS-CoV-2 positive and was unstable in the neonatal intensive care unit (NICU). With the multivariable logistic regression model, babies of SARS-CoV-2 positive mothers were three times as likely to have desaturations in comparison to newborns from negative mothers. Also, newborns of SARS-CoV-2-positive mothers were four times more likely to have poor feeding, compared with newborns of SARS-CoV-2-negative mothers. Finally, babies of SARS-CoV-2-positive mothers were ten times more likely to be symptomatic at the 2-week follow-up. CONCLUSION: SARS-CoV-2 has caused major morbidity and mortality worldwide. Neonates born to mothers with confirmed or suspected SARS-CoV-2 are most of the time asymptomatic. However, neonatal critical illness due to SARS-CoV-2 is still a possibility; thus, isolation precautions (such as avoiding skin-to-skin contact and direct breastfeeding) and vertical transmission should be studied thoroughly. In addition, testing these newborns by nasopharyngeal swab at least at 24 hours after birth and monitoring them for the development of symptoms for 14 days after birth is needed. KEY POINTS: · For SARS-CoV-2-positive mothers, reducing transmission of infection to newborns is crucial.. · Newborns of SARS-CoV-2-positive mothers are usually asymptomatic and may not be easily infected.. · Critical illness in the newborn may still happen, so monitoring is needed..

Psychometric property study of the posttraumatic stress disorder checklist for DSM-5 (PCL-5) in Chinese healthcare workers during the outbreak of corona virus disease 2019.

BACKGROUND: Previous studies about the reliability and validity of the updated PCL version for the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (PCL-5) have only been evaluated in certain samples of the population, which lacks in the sample of Healthcare Workers. Our study focused on the factor structure, reliability and validity of the PCL-5 among Chinese Healthcare Workers during the Outbreak of Corona Virus Disease 2019. METHODS: We conducted an online survey of frontline healthcare workers using the PCL-5 for PTSD. Total of 212 frontline healthcare providers were included in this study. RESULTS: The findings showed that PCL-5 is a reliable instrument in our sample. The total and subscale scores showed good internal consistency. The convergent and discriminant validity of the PCL-5 were also well demonstrated. Our result showed a better fit with the seven-factor hybrid model compared with other models and supported that the PCL-5 Chinese version can be used as a reliable screening tool to conduct psychological screening for Chinese healthcare workers. LIMITATION: We could not examine other aspects of reliability and validity like test-retest reliability or criterion validity. We didn't use the gold-standard structured interview for PTSD in our study. Besides, most of our samples were young people who had access to the internet. Not all professional levels and seniorities were presented because our sample had a lower mean income and educational level. CONCLUSION: Our study shows that the Chinese PCL-5 has good validity and reliability in frontline healthcare workers during the outbreak.