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1.
NPJ Digit Med ; 5(1): 5, 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1625359

ABSTRACT

While COVID-19 diagnosis and prognosis artificial intelligence models exist, very few can be implemented for practical use given their high risk of bias. We aimed to develop a diagnosis model that addresses notable shortcomings of prior studies, integrating it into a fully automated triage pipeline that examines chest radiographs for the presence, severity, and progression of COVID-19 pneumonia. Scans were collected using the DICOM Image Analysis and Archive, a system that communicates with a hospital's image repository. The authors collected over 6,500 non-public chest X-rays comprising diverse COVID-19 severities, along with radiology reports and RT-PCR data. The authors provisioned one internally held-out and two external test sets to assess model generalizability and compare performance to traditional radiologist interpretation. The pipeline was evaluated on a prospective cohort of 80 radiographs, reporting a 95% diagnostic accuracy. The study mitigates bias in AI model development and demonstrates the value of an end-to-end COVID-19 triage platform.

2.
European Journal of Political Economy ; : 102180, 2022.
Article in English | ScienceDirect | ID: covidwho-1620645

ABSTRACT

This paper studies the role of local Chinese leaders' career incentives in decisions regarding large-scale crises such as the COVID-19 pandemic. Most local leaders were reluctant to impose lockdowns at the beginning of the pandemic, because their promotions rely on posting strong numbers for economic growth in their region, while lockdowns can suppress growth. Once the nation's top leader warned that local leaders who failed to control the disease would be removed from office, many rapidly implemented resolute measures. However, we find that local leaders with larger promotion incentives were still more likely to downplay the virus by avoiding or minimizing lockdowns.

3.
Cell ; 2022.
Article in English | EuropePMC | ID: covidwho-1601904

ABSTRACT

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses. A comprehensive analysis of sera from vaccinees, convalescent patients infected previously by multiple variants and potent monoclonal antibodies from early in the COVID-19 pandemic reveals a substantial overall reduction the ability to neutralize the SARS-CoV-2 Omicron variant, which a third vaccine dose seems to ameliorate. Structural analyses of the Omicron RBD suggest a selective pressure enabling the virus bind ACE2 with increased affinity that is offset by other changes in the receptor binding motif that facilitates immune escape.

4.
Sustainability ; 14(1):385, 2022.
Article in English | MDPI | ID: covidwho-1580460

ABSTRACT

In order to achieve the goal of carbon neutrality and explore the impact of COVID-19 on urban road carbon emission, this study applied and improved a near real-time road carbon emission estimation method for typical Chinese urban agglomeration to improve the rapid evaluation of sustainable development. As a result, we recorded the daily road carbon emission for 12 cities in the Beijing–Tianjin–Hebei (JJJ) region under the impact of the epidemic, exploring the road carbon reduction effect caused by COVID-19. Singular value decomposition method was used to analyze the temporal and spatial characteristics of road carbon emission changes among cities and to explore the urban resilience oriented to public events. The results show: (1) In the JJJ region, the carbon reduction effect caused by COVID-19 is significant, but it lasted for a short time. In the three periods—before the epidemic, strict lockdown period, and post-lockdown period for prevention and control—the total daily road carbon emissions in the 12 cities were 170,000–190,000 tons, 90,000–110,000 tons, and 160,000–180,000 tons, respectively. (2) Cities in the JJJ region showed different road carbon reduction potential under short-term administrative control. During the “strict lockdown period”(23 January–25 February 2020), the average change rate of road carbon emissions in Beijing was −78.72%, which had great potential for reduction. However, the average change rates of Xingtai and Zhangjiakou were only −7.53% and −8.66%, respectively. (3) There are spatiotemporal differences in carbon emissions of urban roads in the JJJ region under the impact of the epidemic. During the gradual reduction of COVID-19 restrictions, great differences between cities on weekends and holidays arise, showing the road carbon emissions in Beijing on weekends and holidays are far lower than that in other cities. (4) In the face of public emergencies, the larger the city is and the more complex the function of the city is, the more difficult for the city is to maintain a steady state. This study not only provides an idea for the dynamic monitoring of urban carbon emissions to improve the rapid evaluation of urban sustainable development in post- and pre-lockdown but also fills the gap in the research on the differences in the response of cities to sudden security incidents from the perspective of road carbon emissions.

5.
Vaccines (Basel) ; 9(12)2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1580390

ABSTRACT

Large clinical trials have proven the efficacy of the COVID-19 vaccine, and the number of studies about the effectiveness rapidly grew in the first half of the year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). A total of 39 studies were included, covering over 15 million participants from 11 nations. Among the general population being fully vaccinated, the VE against symptomatic SARS-CoV-2 infection was estimated at 89-97%, 92% (95% CI, 78-97%), and 94% (95% CI, 86-97%) for BNT162b2, ChAdOx1, and mRNA-1273, respectively. As for the protective effects against B.1.617.2-related symptomatic infection, the VE was 88% (95% CI, 85.3-90.1%) by BNT162b2 and 67.0% (95% CI, 61.3-71.8%) by ChAdOx1 after full vaccination. This review revealed a consistently high effectiveness of certain vaccines among the general population in real-world settings. However, scarce data on the major variants of SARS-CoV-2 and the shortness of the study time may limit the conclusions to the mRNA vaccines and ChAdOx1.

7.
Preprint | EuropePMC | ID: ppcovidwho-297096

ABSTRACT

On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced. Omicron contains a total of 30 substitutions plus deletions and an insertion in Spike, far more than any previously reported variant. The mutations include those previously identified by In-vitro evolution to contribute to high-affinity binding to ACE2, including mutations Q498R and N501Y critical in forming additional interactions in the interface. Together with increased charge complementarity between the RBD and ACE2, these substantially increase affinity and potentially virus transmissibility through increased syncytia formation. Further mutations promote immune evasion. We have studied the binding of a large panel of potent monoclonal antibodies generated from early pandemic or Beta infected cases. Mutations in Omicron will likely compromise the binding of many of these and additionally, the binding of antibodies under commercial development, however residual binding should provide protection from severe disease.

8.
Cell reports. Medicine ; 2021.
Article in English | EuropePMC | ID: covidwho-1563998

ABSTRACT

Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in people critically ill with COVID-19. Here, we present high-dimensional profiling of blood and respiratory samples from people with severe COVID-19 to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNA sequencing (RNA-seq)-based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time lead to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2-infected myeloid cells in the lower respiratory tract upregulate CXCL10, leading to a higher risk of death. Our analysis suggests a pivotal role for viral-infected myeloid cells and protracted interferon signaling in severe COVID-19. Graphical Cillo et al. identify transcriptional profiles in peripheral blood that are associated with mortality in people critically ill with COVID-19. Inflammatory monocyte signatures are correlated with CXCL10 in plasma and precede upregulation of inflammatory cytokines in blood. SARS-CoV-2-infected macrophages in the respiratory tract expressed CXCL10, linking peripheral and lung immune profiles.

9.
Int J Environ Res Public Health ; 18(23)2021 12 03.
Article in English | MEDLINE | ID: covidwho-1560757

ABSTRACT

BACKGROUND: The COVID-19 pandemic has contributed to a decline in mental health globally. Compared to the general population, university students have been identified as a group vulnerable to developing depression symptoms during the pandemic. Social isolation, a signature mental health consequence under physical-distancing regulations, is a known predictor of depression symptoms during the pandemic. Yet, more research is required to understand the mechanism that underpins the isolation-depression association and identify psychological factors that may attenuate the association. The current study aimed to understand the role of stress and resilience in the isolation-depression association among university students. METHODS: Data were collected from 1718 university students between 28 and 31 May 2020. Partial least squares structural equation modelling (PLS-SEM) was used to examine the mediating role of perceived stress and the moderating role of resilience in the isolation-depression association. RESULTS: We found that perceived stress partially mediated the association between social isolation and depression symptoms. Both the direct and indirect effects were moderated by participants' resilience levels. CONCLUSIONS: Social isolation during the pandemic may contribute to depression symptoms both directly and through elevated stress levels. As an internal strength, resilience may buffer the adverse effects of isolation and stress on depression symptoms. Targeted interventions including mindfulness and physical exercise training may provide promising results in reducing depression symptoms among university students and should be considered by university administrators particularly during times of imposed physical-distancing measures.

10.
Preprint in English | Other preprints | ID: ppcovidwho-296056

ABSTRACT

There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), high titre binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) are induced. In addition, a strong and polyfunctional T cell response was measured in these booster regimens. These data support the ongoing clinical development and testing of this new variant vaccine.

11.
Cell Rep Med ; : 100476, 2021 Dec 02.
Article in English | MEDLINE | ID: covidwho-1550143

ABSTRACT

Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in critically ill Coronavirus disease 2019 (COVID-19) patients. Here, we present high-dimensional profiling of blood and respiratory samples in severe COVID-19 patients to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNAseq based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time leads to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2 infected myeloid cells in the lower respiratory tract upregulate CXCL10, leading to a higher risk of death. Our analysis suggests a pivotal role for viral infected myeloid cells and protracted interferon signaling in severe COVID-19.

12.
Chin Med ; 16(1): 70, 2021 Aug 04.
Article in English | MEDLINE | ID: covidwho-1546786

ABSTRACT

It is well-known that Prof. Tu Youyou won the Nobel Prize in Physiology or Medicine in 2015 due to the research on artemisinin treating malaria, and this can be regarded as the milestone of modernization of Traditional medicine. This first Nobel Prize in Traditional Chinese medicine (TCM) has aroused profound impetus in the investigation of TCM and attracted global attention to the ancient books of TCM. Three new medicines for the treatment of COVID-19 derived from Chinese Classical Formula (, CCF) have been approved in 2021 due to their effectiveness for the treatment of COVID-19. This article introduced the research background of CCF pharmaceutical preparation (CCFPP), explained the ideas for the modernization of CCF and analyzed related issues involved in the development process of CCFPP, including the origin of medicinal materials, processing methods, dosages and the preparation process of CCF Material Reference. The strategy for industrialization was proposed in terms of the evaluation of the pharmaceutical properties, industrialization considerations, and clinical positioning of CCFPP. The key contents and requirements for the development CCFPP were also summarized according to the recently published registration guidance by the Center for Drug Evaluation in China. In addition, the safety issues of CCFPP were described, including the discussion on the non-clinical safety evaluation and analyzation on the international registration of Traditional herbal medicines. This article is aimed to provide references for enterprises, researchers, and relevant personnel of government departments that are engaged in the development of CCF to speed up the developing process of CCFPP.

13.
Nat Immunol ; 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1545628

ABSTRACT

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

14.
Cell Host Microbe ; 30(1): 53-68.e12, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1536483

ABSTRACT

Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

15.
Int J Mol Sci ; 22(22)2021 Nov 16.
Article in English | MEDLINE | ID: covidwho-1534087

ABSTRACT

Five novel analogs of 6-(ethyl)(4-isobutoxy-3-isopropylphenyl)amino)nicotinic acid-or NEt-4IB-in addition to seven novel analogs of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), a FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Bexarotene treatment elicits side-effects by provoking or disrupting other RXR-dependent pathways. Analogs were assessed by the modeling of binding to RXR and then evaluated in a human cell-based RXR-RXR mammalian-2-hybrid (M2H) system as well as a RXRE-controlled transcriptional system. The analogs were also tested in KMT2A-MLLT3 leukemia cells and the EC50 and IC50 values were determined for these compounds. Moreover, the analogs were assessed for activation of LXR in an LXRE system as drivers of ApoE expression and subsequent use as potential therapeutics in neurodegenerative disorders, and the results revealed that these compounds exerted a range of differential LXR-RXR activation and selectivity. Furthermore, several of the novel analogs in this study exhibited reduced RARE cross-signaling, implying RXR selectivity. These results demonstrate that modification of partial agonists such as NEt-4IB and potent rexinoids such as bexarotene can lead to compounds with improved RXR selectivity, decreased cross-signaling of other RXR-dependent nuclear receptors, increased LXRE-heterodimer selectivity, and enhanced anti-proliferative potential in leukemia cell lines compared to therapeutics such as 1.

16.
Signal Transduct Target Ther ; 6(1): 368, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1467093

ABSTRACT

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunologic Memory , Models, Immunological , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , COVID-19/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Tomography, X-Ray Computed
17.
Sensors (Basel) ; 20(21)2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-1450862

ABSTRACT

Empowered by the ubiquitous sensing capabilities of Internet of Things (IoT) technologies, smart communities could benefit our daily life in many aspects. Various smart community studies and practices have been conducted, especially in China thanks to the government's support. However, most intelligent systems are designed and built individually by different manufacturers in diverging platforms with different functionalities. Therefore, multiple individual systems must be deployed in a smart community to have a set of functions, which could lead to hardware waste, high energy consumption and high deployment cost. More importantly, current smart community systems mainly focus on the technologies involved, while the effects of human activity are neglected. In this paper, a fourth-order tensor model representing object, time, location and human activity is proposed for human-centered smart communities, based on which a unified smart community system is designed. Thanks to the powerful data management abilities of a high-order tensor, multiple functions can be integrated into our system. In addition, since the tensor model embeds human activity information, complex functions could be implemented by exploring the effects of human activity. Two exemplary applications are presented to demonstrate the flexibility of the proposed unified fourth-order tensor-based smart community system.


Subject(s)
Computers , Technology , China , Environment Design , Human Activities , Humans , Internet of Things
19.
J Agric Food Chem ; 69(41): 12197-12208, 2021 Oct 20.
Article in English | MEDLINE | ID: covidwho-1442683

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (Mpro) inhibitors are considered as potential treatments for coronavirus disease 2019, and dietary polyphenols show promise in SARS-CoV-2 Mpro inhibition based on in silico studies. In the present study, we utilize a combination of biochemical-, surface plasmon resonance-, and docking-based assays to evaluate the inhibition and binding affinities of a series of tannins and their gut microbial metabolites on SARS-CoV-2 Mpro. The tested compounds (2-50 µM) were hydrolyzable tannins, including ellagitannins (punicalagin and ellagic acid) and gallotannins (tannic acid, pentagalloyl glucose, ginnalin A, and gallic acid), and their gut microbial metabolites, urolithins and pyrogallol, respectively. They inhibited SARS-CoV-2 Mpro (by 6.6-100.0% at 50 µM) and bound directly to the Mpro protein (with dissociation constants from 1.1 × 10-6 to 5.3 × 10-5 M). This study sheds light on the inhibitory effects of tannins and their metabolites on SARS-CoV-2 Mpro.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Humans , Hydrolyzable Tannins , Molecular Docking Simulation , Peptide Hydrolases , Protease Inhibitors , SARS-CoV-2 , Surface Plasmon Resonance
20.
Front Med (Lausanne) ; 8: 699243, 2021.
Article in English | MEDLINE | ID: covidwho-1399148

ABSTRACT

Introduction: COVID-19 has overloaded worldwide medical facilities, leaving some potentially high-risk patients trapped in outpatient clinics without sufficient treatment. However, there is still a lack of a simple and effective tool to identify these patients early. Methods: A retrospective cohort study was conducted to develop an early warning model for predicting the death risk of COVID-19. Seventy-five percent of the cases were used to construct the prediction model, and the remaining 25% were used to verify the prediction model based on data immediately available on admission. Results: From March 1, 2020, to April 16, 2020, a total of 4,711 COVID-19 patients were included in our study. The average age was 63.37 ± 16.70 years, of which 1,148 (24.37%) died. Finally, age, SpO2, body temperature (T), and mean arterial pressure (MAP) were selected for constructing the model by univariate analysis, multivariate analysis, and a review of the literature. We used five common methods for constructing the model and finally found that the full model had the best specificity and higher accuracy. The area under the ROC curve (AUC), specificity, sensitivity, and accuracy of full model in train cohort were, respectively, 0.798 (0.779, 0.816), 0.804, 0.656, and 0.768, and in the validation cohort were, respectively, 0.783 (0.751, 0.815), 0.800, 0.616, and 0.755. Visualization tools of the prediction model included a nomogram and an online dynamic nomogram (https://wanghai.shinyapps.io/dynnomapp/). Conclusion: We developed a prediction model that might aid in the early identification of COVID-19 patients with a high probability of mortality on admission. However, further research is required to determine whether this tool can be applied for outpatient or home-based COVID-19 patients.

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