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1.
Computer Methods and Programs in Biomedicine ; : 106004, 2021.
Article | WHO COVID | ID: covidwho-1095920

ABSTRACT

Background and Objective: Coronavirus disease 2019 (COVID-19) is a highly contagious virus spreading all around the world Deep learning has been adopted as an effective technique to aid COVID-19 detection and segmentation from computed tomography (CT) images The major challenge lies in the inadequate public COVID-19 datasets Recently, transfer learning has become a widely used technique that leverages the knowledge gained while solving one problem and applying it to a different but related problem However, it remains unclear whether various non-COVID19 lung lesions could contribute to segmenting COVID-19 infection areas and how to better conduct this transfer procedure This paper provides a way to understand the transferability of non-COVID19 lung lesions and a better strategy to train a robust deep learning model for COVID-19 infection segmentation Methods: Based on a publicly available COVID-19 CT dataset and three public non-COVID19 datasets, we evaluate four transfer learning methods using 3D U-Net as a standard encoder-decoder method i) We introduce the multi-task learning method to get a multi-lesion pre-trained model for COVID-19 infection ii) We propose and compare four transfer learning strategies with various performance gains and training time costs Our proposed Hybrid-encoder Learning strategy introduces a Dedicated-encoder and an Adapted-encoder to extract COVID-19 infection features and general lung lesion features, respectively An attention-based Selective Fusion unit is designed for dynamic feature selection and aggregation Results: Experiments show that trained with limited data, proposed Hybrid-encoder strategy based on multi-lesion pre-trained model achieves a mean DSC, NSD, Sensitivity, F1-score, Accuracy and MCC of 0 704, 0 735, 0 682, 0 707, 0 994 and 0 716, respectively, with better genetalization and lower over-fitting risks for segmenting COVID-19 infection Conclusions: The results reveal the benefits of transferring knowledge from non-COVID19 lung lesions, and learning from multiple lung lesion datasets can extract more general features, leading to accurate and robust pre-trained models We further show the capability of the encoder to learn feature representations of lung lesions, which improves segmentation accuracy and facilitates training convergence In addition, our proposed Hybrid-encoder learning method incorporates transferred lung lesion features from non-COVID19 datasets effectively and achieves significant improvement These findings promote new insights into transfer learning for COVID-19 CT image segmentation, which can also be further generalized to other medical tasks

2.
Cell ; 2021.
Article | WHO COVID | ID: covidwho-1095902

ABSTRACT

Summary The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research Here we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing The trans-complementation system consists of two components: a genomic viral RNA containing ORF3 and envelope gene deletions as well as mutated transcriptional regulator sequences, and a producer cell line expressing the two deleted genes Trans-complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2 Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose Thus, the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development

3.
International Journal of Medical Sciences ; 18(6):1492-1501, 2021.
Article | WHO COVID | ID: covidwho-1089157

ABSTRACT

Objectives: As of 11 Feb 2020, a total of 1,716 medical staff infected with laboratory-confirmed the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in China had been reported The predominant cause of the infection among medical staff remains unclear We sought to explore the epidemiological, clinical characteristics and prognosis of infected medical staff

4.
Curr Med Sci ; 41(1): 14-23, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1084049

ABSTRACT

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.


Subject(s)
/epidemiology , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Olfaction Disorders/epidemiology , Taste Disorders/virology , Aged , /complications , China , Female , Humans , Male , Middle Aged , Olfaction Disorders/blood , Olfaction Disorders/virology , Recovery of Function , Retrospective Studies , Self Report , Severity of Illness Index , Taste Disorders/blood
5.
Talanta ; : 122154, 2021.
Article | WHO COVID | ID: covidwho-1078200

ABSTRACT

Infectious diseases caused by viruses such as SARS-CoV-2 and HPV have greatly endangered human health The nucleic acid detection is essential for the early diagnosis of diseases Here, we propose a method called PLCR (PfAgo coupled with modified Ligase Chain Reaction for nucleic acid detection) which utilizes PfAgo to only use DNA guides longer than 14-mer to specifically cleave DNA and LCR to precisely distinguish single-base mismatch PLCR can detect DNA or RNA without PCR at attomolar sensitivities, distinguish single base mutation between the genome of wild type SARS-CoV-2 and its mutant spike D614G, effectively distinguish the novel coronavirus from other coronaviruses and finally achieve multiplexed detection in 70 min Additionally, LCR products can be directly used as DNA guides without additional input guides to simplify primer design With desirable sensitivity, specificity and simplicity, the method can be extended for detecting other pathogenic microorganisms

6.
Nat Med ; 2021 Feb 08.
Article in English | MEDLINE | ID: covidwho-1072168

ABSTRACT

We engineered three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y + D614G from UK; and E484K + N501Y + D614G from SA. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.

7.
BMC Med ; 19(1): 40, 2021 02 05.
Article in English | MEDLINE | ID: covidwho-1067227

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories. METHODS: We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission using data from January to June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in Rt, levels of NPI intensity, time-varying changes in NPI effect, and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs. RESULTS: There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced Rt. Another three NPIs (workplace closure, income support, and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g. restrictions on 1000+ people gathering were not effective, restrictions on < 10 people gathering were). Evidence about the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Effect sizes varied depending on whether or not we included data after peak NPI intensity. CONCLUSION: Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects, and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many, although not all, actions policy-makers are taking to respond to the COVID-19 pandemic.


Subject(s)
/prevention & control , Contact Tracing/trends , Quarantine/trends , Schools/trends , /epidemiology , Contact Tracing/methods , Humans , Pandemics , Quarantine/methods , Time Factors
8.
Biomed Res Int ; 2021: 9101082, 2021.
Article in English | MEDLINE | ID: covidwho-1066963

ABSTRACT

Objective: To compare the difference of inflammatory cytokines and lymphocyte subsets between deceased patients and survivors with COVID-19. Methods: This retrospective study included 254 confirmed patients from 10 January to 11 March, 2020, at Tongji Hospital of Wuhan, China. Laboratory and immunologic features were collected and analyzed, and the main outcomes focused on inflammatory cytokines and lymphocyte subsets. Results: A trend of markedly higher levels of inflammatory cytokines as well as lower lymphocyte subset levels in deceased patients was observed compared with survivors. ROC curve analyses indicated that inflammatory cytokines and the decrease levels of T cell, Th (helper T cells) cell, Ts (suppressor T cells) cell, B cell, and NK cell along with Th/Ts ratio increase could be used to predict the death of COVID-19. Multivariate analyses showed that higher levels of IL-6, IL-8, and IL-10 remained significantly correlated with shorter survival time and that the amount of Ts cells was negatively associated with the possibility of death in COVID-19 patients. In conclusion, SARS-CoV-2 would cause lymphopenia and result in decreased lymphocyte subset cells, particularly in Ts cell counts, which further induces hyperinflammatory response and cytokine storm. IL-6, IL-8, IL-10, and Ts cell might be independent predictors for the poor outcome of COVID-19.


Subject(s)
/immunology , Cytokines/immunology , Lymphocyte Subsets/immunology , Aged , B-Lymphocytes/immunology , Biomarkers/blood , /epidemiology , China/epidemiology , Female , Humans , Kaplan-Meier Estimate , Killer Cells, Natural/immunology , Male , Middle Aged , Retrospective Studies , /isolation & purification
9.
mBio ; 12(1)2021 01 19.
Article in English | MEDLINE | ID: covidwho-1066818

ABSTRACT

The etiologic agent of COVID-19 is highly contagious and has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. In this study, we reported a replicon system which consists of four plasmids expressing the required segments of SARS-CoV-2. Our study revealed that the features for viral RNA synthesis and responses to antivirus drugs of the replicon are similar to those of wild-type viruses. Further analysis indicated that ORF6 provided potent in trans stimulation of the viral replication. Some viral variations, such as 5'UTR-C241T and ORF8-(T28144C) L84S mutation, also exhibit their different impact upon viral replication. Besides, the screening of clinically used drugs identified that several tyrosine kinase inhibitors and DNA-Top II inhibitors potently inhibit the replicon, as well as authentic SARS-CoV-2 viruses. Collectively, this replicon system provides a biosafety-worry-free platform for studying SARS-CoV-2 virology, monitoring the functional impact of viral mutations, and developing viral inhibitors.IMPORTANCE COVID-19 has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. We reported a replicon system which consists of four ordinary plasmids expressing the required segments of SARS-CoV-2. Using the replicon system, we developed three application scenarios: (i) to identify the effects of viral proteins on virus replication, (ii) to identify the effects of mutations on viral replication during viral epidemics, and (iii) to perform high-throughput screening of antiviral drugs. Collectively, this replicon system would be useful for virologists to study SARS-CoV-2 virology, for epidemiologists to monitor virus mutations, and for industry to develop antiviral drugs.

10.
Wellcome Open Res. ; (5)2020.
Article in English | ELSEVIER | ID: covidwho-1068024

ABSTRACT

Background: Several non-pharmaceutical interventions (NPIs) have been implemented across the world to control the coronavirus disease (COVID-19) pandemic. Social distancing (SD) interventions applied so far have included school closures, remote working and quarantine. These measures have been shown to have large impacts on pandemic influenza transmission. However, there has been comparatively little examination of such measures for COVID-19. Methods: We examined the existing literature, and collated data, on implementation of NPIs to examine their effects on the COVID-19 pandemic so far. Data on NPIs were collected from official government websites as well as from media sources. Results: Measures such as travel restrictions have been implemented in multiple countries and appears to have slowed the geographic spread of COVID-19 and reduced initial case numbers. We find that, due to the relatively sparse information on the differences with and without interventions, it is difficult to quantitatively assess the efficacy of many interventions. Similarly, whilst the comparison to other pandemic diseases such as influenza can be helpful, there are key differences that could affect the efficacy of similar NPIs. Conclusions: The timely implementation of control measures is key to their success and must strike a balance between early enough application to reduce the peak of the epidemic and ensuring that they can be feasibly maintained for an appropriate duration. Such measures can have large societal impacts and they need to be appropriately justified to the population. As the pandemic of COVID-19 progresses, quantifying the impact of interventions will be a vital consideration for the appropriate use of mitigation strategies.

11.
Wellcome Open Res. ; (5)2020.
Article in English | ELSEVIER | ID: covidwho-1068023

ABSTRACT

We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.

12.
Cell ; 2021.
Article | WHO COVID | ID: covidwho-1062273

ABSTRACT

Summary Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1 46 million cells The large dataset enabled us to identify that different peripheral immune subtype changes were associated with distinct clinical features including age, sex, severity, and disease stages of COVID-19 SARS-CoV-2 RNAs were found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within viral positive cells Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients Our data provide a rich resource for understanding the pathogenesis and developing effective therapeutic strategies for COVID-19

13.
Int J Infect Dis ; 104: 132-138, 2020 Dec 23.
Article in English | MEDLINE | ID: covidwho-1046388

ABSTRACT

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused a tremendous health burden and impact on the world economy. The UK Government implemented the biggest lockdown of society during peacetime in British history at the end of March 2020, aiming to contain the rapid spread of the virus. The UK lockdown was maintained for 7 weeks, but the effectiveness of the control measures in suppressing disease transmission remains incompletely understood. METHODS: A Bayesian SEIR (susceptible-exposed-infected-removed) epidemiological model was used to rebuild the local transmission dynamics of the spread of COVID-19 in nine regions of England. RESULTS: The basic reproduction number (R0) in England was found to be relatively high compared with China. The estimate of the temporally varying effective reproduction number (Rt) suggests that the control measures, especially the forced lockdown, were effective to reduce transmissibility and curb the COVID-19 epidemic. Although the overall incidence rate in the UK has declined, forecasting highlights the possibility of a second epidemic wave in several regions. CONCLUSION: This study enhances understanding of the current outbreak and the effectiveness of control measures in the UK.

14.
J Infect Public Health ; 13(12): 1840-1844, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1023642

ABSTRACT

Coronavirus disease-2019 (COVID-19) pandemic started from Wuhan, China has infected more than 6.7 million individuals and killed more than 390,000 individuals globally. Due to the higher transmissibility and infectiousness, asymptomatic infection, and lack of effective treatment options and vaccine, fatalities and morbidities are increasing day by day globally. Despite physical health consequences, COVID-19 pandemic has created stress and anxiety, as result there is an increased risk of mental illnesses both in the infected and normal individuals. To eradicate these risks, it is necessary to determine the COVID-19 zoonotic source of transmission to humans and clinical manifestations in infected individuals. Although, identification or development of the highly effective therapeutic agents is necessary, however, development of protective strategies against the COVID-19 by enhancing immune responses will be an asset in the current scenarios of the COVID-19 pandemic. In this paper, we discuss the transmission, health consequences, and potential management (therapeutic and preventive) options for COVID-19 disease.

15.
Biomed Res Int ; 2020: 3854196, 2020.
Article in English | MEDLINE | ID: covidwho-1021147

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a complex disease caused by the disturbance of genetic and environmental factors. Single-nucleotide polymorphisms (SNPs) play a vital role in the genetic dissection of complex diseases. In-depth analysis of SNP-related information could recognize disease-associated biomarkers and further uncover the genetic mechanism of complex diseases. Risk-related variants might act on the disease by affecting gene expression and gene function. Through integrating SNP disease association study and expression quantitative trait loci (eQTL) analysis, as well as functional enrichment of containing known causal genes, four risk SNPs and four corresponding susceptibility genes were identified utilizing next-generation sequencing (NGS) data of COPD. Of the four risk SNPs, one could be found in the SNPedia database that stored disease-related SNPs and has been linked to a disease in the literature. Four genes showed significant differences from the perspective of normal/disease or variant/nonvariant samples, as well as the high performance of sample classification. It is speculated that the four susceptibility genes could be used as biomarkers of COPD. Furthermore, three of our susceptibility genes have been confirmed in the literature to be associated with COPD. Among them, two genes had an impact on the significance of expression correlation of known causal genes they interact with, respectively. Overall, this research may present novel insights into the diagnosis and pathogenesis of COPD and susceptibility gene identification of other complex diseases.

17.
Preprint | SciFinder | ID: ppcovidwho-4377

ABSTRACT

A review Objective To discussandexpound the classification, origin, pathogenicity, protein target structure, vaccines and therapeutic drugs for coronavirus (CoVs) Methods After reading 159 literatures about coronavirus, we summarized and analyzed the classification, origin, pathogenicity, target structure of drug action, corresponding vaccines and therapeutic drugs development for CoVs Results CoVs is a type of pathogenic microorganism that seriously endangers human and animal health, which belongs to a RNA virus with a large amount of natural hosts The virus is prone to gene recombination and mutation, and has genetic diversity So far, new subtypes or coronaviruses are emerging continuously CoVsS protein, PLpro and 3CLpro are good targets for drug development We summarized the drugs found based on the above targets Conclusion In the past few decades, diseases caused by coronavirus have posed a great threat to global public health, for example, severe acute respiratory syndrome virus (SARS), Middle East respiratory syndrome virus (MERS) and the recently emerging new coronavirus (SARS-CoV-2) However, there is no specific therapy for SARS-CoV, MERS-CoV, SARS-CoV-2 and other HCoV infections so far Therefore, comprehensive and in-depth research on coronavirus is still a need

18.
Infect Dis Poverty ; 10(1): 5, 2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1015905

ABSTRACT

BACKGROUND: The pandemic of the coronavirus disease 2019 (COVID-19) has caused substantial disruptions to health services in the low and middle-income countries with a high burden of other diseases, such as malaria in sub-Saharan Africa. The aim of this study is to assess the impact of COVID-19 pandemic on malaria transmission potential in malaria-endemic countries in Africa. METHODS: We present a data-driven method to quantify the extent to which the COVID-19 pandemic, as well as various non-pharmaceutical interventions (NPIs), could lead to the change of malaria transmission potential in 2020. First, we adopt a particle Markov Chain Monte Carlo method to estimate epidemiological parameters in each country by fitting the time series of the cumulative number of reported COVID-19 cases. Then, we simulate the epidemic dynamics of COVID-19 under two groups of NPIs: (1) contact restriction and social distancing, and (2) early identification and isolation of cases. Based on the simulated epidemic curves, we quantify the impact of COVID-19 epidemic and NPIs on the distribution of insecticide-treated nets (ITNs). Finally, by treating the total number of ITNs available in each country in 2020, we evaluate the negative effects of COVID-19 pandemic on malaria transmission potential based on the notion of vectorial capacity. RESULTS: We conduct case studies in four malaria-endemic countries, Ethiopia, Nigeria, Tanzania, and Zambia, in Africa. The epidemiological parameters (i.e., the basic reproduction number [Formula: see text] and the duration of infection [Formula: see text]) of COVID-19 in each country are estimated as follows: Ethiopia ([Formula: see text], [Formula: see text]), Nigeria ([Formula: see text], [Formula: see text]), Tanzania ([Formula: see text], [Formula: see text]), and Zambia ([Formula: see text], [Formula: see text]). Based on the estimated epidemiological parameters, the epidemic curves simulated under various NPIs indicated that the earlier the interventions are implemented, the better the epidemic is controlled. Moreover, the effect of combined NPIs is better than contact restriction and social distancing only. By treating the total number of ITNs available in each country in 2020 as a baseline, our results show that even with stringent NPIs, malaria transmission potential will remain higher than expected in the second half of 2020. CONCLUSIONS: By quantifying the impact of various NPI response to the COVID-19 pandemic on malaria transmission potential, this study provides a way to jointly address the syndemic between COVID-19 and malaria in malaria-endemic countries in Africa. The results suggest that the early intervention of COVID-19 can effectively reduce the scale of the epidemic and mitigate its impact on malaria transmission potential.


Subject(s)
/epidemiology , Malaria/epidemiology , Malaria/therapy , /transmission , Ethiopia/epidemiology , Humans , Malaria/transmission , Markov Chains , Nigeria/epidemiology , Pandemics , Syndemic , Tanzania/epidemiology , Zambia/epidemiology
19.
Chin Med J (Engl) ; Publish Ahead of Print2021 Jan 05.
Article in English | MEDLINE | ID: covidwho-1012123
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