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1.
Am J Obstet Gynecol ; 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1926160

ABSTRACT

BACKGROUND: Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated. OBJECTIVE: To examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics. STUDY DESIGN: We prospectively followed 3,858 pre-menopausal women in the Nurses' Health Study 3 (NHS3) living in the United States or Canada who received biannual follow-up questionnaires between January 2011 and December 2021, and completed additional monthly and quarterly surveys related to the COVID-19 pandemic between April 2020 and November 2021. History of positive SARS-CoV-2 test, COVID-19 vaccination status, and vaccine type were self-reported in surveys conducted in 2020 and 2021. Current menstrual cycle length and regularity "pre-COVID" (reported at baseline between 2011-2016) and "post-COVID" (reported in late 2021). Pre- to post-COVID change in menstrual cycle length and regularity was calculated between reports. Logistic or multinomial logistic regression models were used to assess the associations between (1) SARS-CoV-2 infection and (2) COVID-19 vaccination and change in menstrual cycle characteristics. RESULTS: The median age at baseline and end of follow-up were 33 years (range=21-51) and 42 years (range=27-56), respectively, with a median follow-up time of 9.2 years. We documented 421 (10.9%) SARS-CoV-2 infections and 3,527 (91.4%) vaccinations during follow-up. Vaccinated women had a higher risk of increased cycle length compared to those unvaccinated (OR=1.54, 95% CI=1.04-2.27), after adjusting for sociodemographic and behavioral factors. These associations were similar after additionally accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0-6 months: OR=1.72, 95% CI=1.08-2.73; 7-9 months: OR=1.49, 95% CI=1.00-2.23; >9 months: OR=1.44, 95% CI=0.93-2.22) and among women whose cycles were short, long or irregular before vaccination (OR=2.87, 95% CI=1.54-5.35; OR=1.03, 95% CI=0.60-1.75 for women with normal length, regular cycles before vaccination). mRNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics. CONCLUSIONS AND RELEVANCE: COVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long or irregular before vaccination. These results underscore the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms.

2.
Current psychology (New Brunswick, N.J.) ; : 1-10, 2022.
Article in English | EuropePMC | ID: covidwho-1898355

ABSTRACT

Prior measures on rationality overlook the individual differences in the weight people place on social rationality versus individual rationality. The current research develops and validates an individual-collective dilemma task (ICDT) to distinguish different rationality types. It was translated from a reality that, at the beginning of the ongoing COVID-19 outbreak, a global shortage of face masks occurred because of the jumping demand for masks as a precautionary measure. The ICDT asked participants to decide how many masks to buy in front of a shortfall of masks, which facilitated coping with a hypothetical epidemic outbreak. Based on the number of masks they selected, three rationality groups emerged. Individual rationalists preferred self-interest goals to goals of social interests;social rationalists prioritized social-interest goals;balancers assigned equal weight to both goals. The ICDT showed sound test–retest reliability and criterion-related, discriminant, and convergent validity. The present research contributes to the literature on rationality assessment and offers policy-makers a valid and reliable tool to understand the distribution of rationalists among the public. Supplementary Information The online version contains supplementary material available at 10.1007/s12144-022-03338-x.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321467

ABSTRACT

Mice are not susceptible to wildtype SARS-CoV-2 infection. Emerging SARS-CoV-2 variants including B.1.1.7, B.1.351, P.1, and P.3 contain mutations in spike, which have been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that they may have evolved to expand species tropism to rodents. Here, we investigated the capacity of B.1.1.7 and other emerging SARS-CoV-2 variants in infecting mouse (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Our results show that B.1.1.7 and P.3, but not B.1 or wildtype SARS-CoV-2, can utilize mouse and rat ACE2 for virus entry in vitro. High infectious virus titers, abundant viral antigen expression, and pathological changes are detected in the nasal turbinate and lung of B.1.1.7-inocluated mice and rats. Together, these results reveal that the current predominant circulating SARS-CoV-2 variant, B.1.1.7, has gained the capability to expand species tropism to rodents.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316481

ABSTRACT

Coronaviruses have repeatedly crossed species barriers to cause epidemics 1 . “Pan-coronavirus” antivirals targeting conserved viral components involved in coronavirus replication, such as the extensively glycosylated spike protein, can be designed. Here we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high-mannose found on viral proteins but seldom on healthy human cells 2 , potently inhibits the highly virulent MERS-CoV, pandemic SARS-CoV-2 and its variants, and other human-pathogenic coronaviruses at nanomolar concentrations. MERS-CoV-infected human DPP4-transgenic mice treated by H84T-BanLec have significantly higher survival, lower viral burden, and reduced pulmonary damage. Similarly, prophylactic or therapeutic H84T-BanLec is effective against SARS-CoV-2 in hamsters. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Time-of-drug-addition assay shows that H84T-BanLec targets virus entry. Real-time structural analysis with high-speed atomic force microscopy depicts multi-molecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity, and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modelling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the activity against SARS-CoV-2 variants and the lack of resistant mutants. The broad-spectrum H84T-BanLec should be clinically evaluated in respiratory viral infections including COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316018

ABSTRACT

Purpose: Accurate segmentation of lung and infection in COVID-19 CT scans plays an important role in the quantitative management of patients. Most of the existing studies are based on large and private annotated datasets that are impractical to obtain from a single institution, especially when radiologists are busy fighting the coronavirus disease. Furthermore, it is hard to compare current COVID-19 CT segmentation methods as they are developed on different datasets, trained in different settings, and evaluated with different metrics. Methods: To promote the development of data-efficient deep learning methods, in this paper, we built three benchmarks for lung and infection segmentation based on 70 annotated COVID-19 cases, which contain current active research areas, e.g., few-shot learning, domain generalization, and knowledge transfer. For a fair comparison among different segmentation methods, we also provide standard training, validation and testing splits, evaluation metrics and, the corresponding code. Results: Based on the state-of-the-art network, we provide more than 40 pre-trained baseline models, which not only serve as out-of-the-box segmentation tools but also save computational time for researchers who are interested in COVID-19 lung and infection segmentation. We achieve average Dice Similarity Coefficient (DSC) scores of 97.3\%, 97.7\%, and 67.3\% and average Normalized Surface Dice (NSD) scores of 90.6\%, 91.4\%, and 70.0\% for left lung, right lung, and infection, respectively. Conclusions: To the best of our knowledge, this work presents the first data-efficient learning benchmark for medical image segmentation and the largest number of pre-trained models up to now. All these resources are publicly available, and our work lays the foundation for promoting the development of deep learning methods for efficient COVID-19 CT segmentation with limited data.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308523

ABSTRACT

SARS-CoV-2 has affected over 9 million patients with more than 460,000 deaths in about 6 months. Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells, which are not previously reported, may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we reported key host and viral determinants that were essential for efficient SARS-CoV-2 infection in the human lung. First, we identified heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Second, we demonstrated that while cell surface sialic acids significantly restricted SARS-CoV infection, SARS-CoV-2 could largely overcome sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissue explants. Third, we demonstrated that the inserted furin-like cleavage site in SARS-CoV-2 spike was required for efficient virus replication in human lung but not intestine tissues. Overall, these findings contributed to our understanding on efficient SARS-CoV-2 infection of human lungs.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324830

ABSTRACT

Highly pathogenic coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1,2 , Middle East respiratory syndrome coronavirus (MERS-CoV) 3,4 , and SARS-CoV-1 5 vary in their transmissibility and pathogenicity. However, infection by all three viruses result in substantial apoptosis in cell culture 6-8 and in patient samples 9-11 , suggesting a potential link between apoptosis and the pathogenesis of coronaviruses. To date, the underlying mechanism of how apoptosis modulates coronavirus pathogenesis is unknown. Here we show that a cysteine-aspartic protease of the apoptosis cascade, caspase-6, serves as an essential host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid (N) proteins, generating N fragments that serve as interferon (IFN) antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates the lung pathology and body weight loss of SARS-CoV-2-infected golden Syrian hamsters and improves the survival of mouse-adapted MERS-CoV (MERS-CoV MA )-infected human DPP4 knock-in (hDPP4 KI) mice. Overall, our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate their replication. These results further suggest caspase-6 as a potential target of intervention for the treatment of highly pathogenic coronavirus infections including COVID-19 and MERS.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323775

ABSTRACT

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. 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. 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.

9.
Emerg Microbes Infect ; 11(1): 519-531, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1642257

ABSTRACT

ABSTRACTHost circular RNAs (circRNAs) play critical roles in the pathogenesis of viral infections. However, how viruses modulate the biogenesis of host proviral circRNAs to facilitate their replication remains unclear. We have recently shown that Middle East respiratory syndrome coronavirus (MERS-CoV) infection increases co-expression of circRNAs and their cognate messenger RNAs (mRNAs), possibly by hijacking specific host RNA binding proteins (RBPs). In this study, we systemically analysed the interactions between the representative circRNA-mRNA pairs upregulated upon MERS-CoV infection and host RBPs. Our analysis identified heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a key host factor that governed the expression of numerous MERS-CoV-perturbed circRNAs, including hsa_circ_0002846, hsa_circ_0002061, and hsa_circ_0004445. RNA immunoprecipitation assay showed that hnRNP C could bind physically to these circRNAs. Specific knockdown of hnRNP C by small interfering RNA significantly (P < 0.05 to P < 0.0001) suppressed MERS-CoV replication in human lung adenocarcinoma (Calu-3) and human small airway epithelial (HSAEC) cells. Both MERS-CoV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increased the total and phosphorylated forms of hnRNP C to activate the downstream CRK-mTOR pathway. Treatment of MERS-CoV- (IC50: 0.618 µM) or SARS-CoV-2-infected (IC50: 1.233 µM) Calu-3 cells with the mTOR inhibitor OSI-027 resulted in significantly reduced viral loads. Collectively, our study identified hnRNP C as a key regulator of MERS-CoV-perturbed circRNAs and their cognate mRNAs, and the potential of targeting hnRNP C-related signalling pathways as an anticoronaviral strategy.


Subject(s)
Heterogeneous-Nuclear Ribonucleoprotein Group C , Middle East Respiratory Syndrome Coronavirus , RNA, Circular/genetics , SARS-CoV-2 , Virus Replication , COVID-19 , Cognition , Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics , Humans , Middle East Respiratory Syndrome Coronavirus/physiology , RNA, Messenger/genetics , SARS-CoV-2/physiology
10.
Nature ; 603(7902): 693-699, 2022 03.
Article in English | MEDLINE | ID: covidwho-1641975

ABSTRACT

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population1. Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies2-10, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.


Subject(s)
COVID-19/pathology , COVID-19/virology , SARS-CoV-2/pathogenicity , Virus Replication , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/immunology , Caco-2 Cells , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Virulence
11.
EBioMedicine ; 73: 103643, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1482542

ABSTRACT

BACKGROUND: Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance. METHODS: We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays. FINDINGS: Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles. INTERPRETATION: Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Subject(s)
COVID-19/pathology , SARS-CoV-2/physiology , Viral Tropism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/virology , Female , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neutralization Tests , Nucleocapsid Proteins/immunology , Nucleocapsid Proteins/metabolism , RNA, Viral/analysis , RNA, Viral/metabolism , Rats , Rats, Sprague-Dawley , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Turbinates/pathology , Turbinates/virology , Virus Internalization
12.
Nat Commun ; 12(1): 134, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-1387323

ABSTRACT

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/transmission , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment , Animals , Caco-2 Cells , Cell Line, Tumor , Chlorocebus aethiops , Cricetinae , Furin/metabolism , HEK293 Cells , Heparitin Sulfate/metabolism , Humans , Intestinal Mucosa/metabolism , Intestines/virology , Lung/pathology , Lung/virology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/pathology , Vero Cells , Virus Internalization , Virus Replication/physiology
13.
Sci Adv ; 7(25)2021 06.
Article in English | MEDLINE | ID: covidwho-1276873

ABSTRACT

Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2- and SARS-CoV-induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2-inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.


Subject(s)
Antiviral Agents/pharmacology , Apoptosis/drug effects , COVID-19/drug therapy , Coronavirus Infections/drug therapy , eIF-2 Kinase/metabolism , Adenine/analogs & derivatives , Adenine/pharmacology , Angiotensin-Converting Enzyme 2/genetics , Animals , Apoptosis/physiology , COVID-19/etiology , COVID-19/pathology , Cell Line , Coronavirus Infections/etiology , Coronavirus Infections/pathology , Dipeptidyl Peptidase 4/genetics , Epithelial Cells/virology , Female , Humans , Indoles/pharmacology , Lung/virology , Male , Mice, Transgenic , eIF-2 Kinase/antagonists & inhibitors , eIF-2 Kinase/genetics
14.
J Colloid Interface Sci ; 600: 613-619, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1275439

ABSTRACT

Surface contact with virus is ubiquitous in the transmission pathways of respiratory diseases such as Coronavirus Disease 2019 (COVID-19), by which contaminated surfaces are infectious fomites intensifying the transmission of the disease. To date, the influence of surface wettability on fomite formation remains elusive. Here, we report that superhydrophobicity prevents the attachment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces by repelling virus-laden droplets. Compared to bare surfaces, superhydrophobic (SHPB) surfaces exhibit a significant reduction in SARS-CoV-2 attachment of up to 99.99995%. We identify the vital importance of solid-liquid adhesion in dominating viral attachment, where the viral activity (N) is proportional to the cube of solid-liquid adhesion (A), N âˆ A3. Our results predict that a surface would be practically free of SARS-CoV-2 deposition when solid-liquid adhesion is ≤1 mN. Engineering surfaces with superhydrophobicity would open an avenue for developing a general approach to preventing fomite formation against the COVID-19 pandemic and future ones.


Subject(s)
COVID-19 , Pandemics , Fomites , Humans , SARS-CoV-2
15.
Front Public Health ; 9: 610280, 2021.
Article in English | MEDLINE | ID: covidwho-1247935

ABSTRACT

Background: The COVID-19 global pandemic has posed unprecedented challenges to health care systems all over the world. The speed of the viral spread results in a tsunami of patients, which begs for a reliable screening tool using readily available data to predict disease progression. Methods: Multicenter retrospective cohort study was performed to develop and validate a triage model. Patient demographic and non-laboratory clinical data were recorded. Using only the data from Zhongnan Hospital, step-wise multivariable logistic regression was performed, and a prognostic nomogram was constructed based on the independent variables identifies. The discrimination and calibration of the model were validated. External independent validation was performed to further address the utility of this model using data from Jinyintan Hospital. Results: A total of 716 confirmed COVID-19 cases from Zhongnan Hospital were included for model construction. Men, increased age, fever, hypertension, cardio-cerebrovascular disease, dyspnea, cough, and myalgia are independent risk factors for disease progression. External independent validation was carried out in a cohort with 201 cases from Jinyintan Hospital. The area under the curve (AUC) was 0.787 (95% confidence interval [CI]: 0.747-0.827) in the training group and 0.704 (95% CI: 0.632-0.777) in the validation group. Conclusions: We developed a novel triage model based on basic and clinical data. Our model could be used as a pragmatic screening aid to allow for cost efficient screening to be carried out such as over the phone, which may reduce disease propagation through limiting unnecessary contact. This may help allocation of limited medical resources.


Subject(s)
COVID-19 , Humans , Logistic Models , Male , Retrospective Studies , SARS-CoV-2 , Triage
16.
Comput Methods Programs Biomed ; 202: 106004, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1118366

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.


Subject(s)
COVID-19 , Image Processing, Computer-Assisted , Lung/diagnostic imaging , Lung/physiopathology , Tomography, X-Ray Computed , Algorithms , Databases, Factual , Humans , SARS-CoV-2
17.
Lancet Microbe ; 1(1): e14-e23, 2020 05.
Article in English | MEDLINE | ID: covidwho-1087358

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82 000 laboratory-confirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus-host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown. METHODS: We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student's t test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA. FINDINGS: SARS-CoV-2 infected and replicated to comparable levels in human Caco2 cells and Calu3 cells over a period of 120 h (p=0·52). By contrast, SARS-CoV infected and replicated more efficiently in Caco2 cells than in Calu3 cells under the same multiplicity of infection (p=0·0098). SARS-CoV-2, but not SARS-CoV, replicated modestly in U251 (neuronal) cells (p=0·036). For animal species cell tropism, both SARS-CoV and SARS-CoV-2 replicated in non-human primate, cat, rabbit, and pig cells. SARS-CoV, but not SARS-CoV-2, infected and replicated in Rhinolophus sinicus bat kidney cells. SARS-CoV-2 consistently induced significantly delayed and milder levels of cell damage than did SARS-CoV in non-human primate cells (VeroE6, p=0·016; FRhK4, p=0·0004). INTERPRETATION: As far as we know, our study presents the first quantitative data for tropism, replication kinetics, and cell damage of SARS-CoV-2. These data provide novel insights into the lower incidence of diarrhoea, decreased disease severity, and reduced mortality in patients with COVID-19, with respect to the pathogenesis and high transmissibility of SARS-CoV-2 compared with SARS-CoV. FUNDING: May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, Respiratory Viral Research Foundation, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, The Hong Kong Hainan Commercial Association South China Microbiology Research Fund, The Jessie & George Ho Charitable Foundation, Perfect Shape Medical, The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, The Theme-Based Research Scheme of the Research Grants Council, Sanming Project of Medicine in Shenzhen, and The High Level-Hospital Program, Health Commission of Guangdong Province, China.


Subject(s)
COVID-19 , SARS Virus , Animals , Caco-2 Cells , Diarrhea , Humans , Kinetics , Rabbits , SARS-CoV-2 , Swine , Tropism
18.
Med Phys ; 48(3): 1197-1210, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1070776

ABSTRACT

PURPOSE: Accurate segmentation of lung and infection in COVID-19 computed tomography (CT) scans plays an important role in the quantitative management of patients. Most of the existing studies are based on large and private annotated datasets that are impractical to obtain from a single institution, especially when radiologists are busy fighting the coronavirus disease. Furthermore, it is hard to compare current COVID-19 CT segmentation methods as they are developed on different datasets, trained in different settings, and evaluated with different metrics. METHODS: To promote the development of data-efficient deep learning methods, in this paper, we built three benchmarks for lung and infection segmentation based on 70 annotated COVID-19 cases, which contain current active research areas, for example, few-shot learning, domain generalization, and knowledge transfer. For a fair comparison among different segmentation methods, we also provide standard training, validation and testing splits, evaluation metrics and, the corresponding code. RESULTS: Based on the state-of-the-art network, we provide more than 40 pretrained baseline models, which not only serve as out-of-the-box segmentation tools but also save computational time for researchers who are interested in COVID-19 lung and infection segmentation. We achieve average dice similarity coefficient (DSC) scores of 97.3%, 97.7%, and 67.3% and average normalized surface dice (NSD) scores of 90.6%, 91.4%, and 70.0% for left lung, right lung, and infection, respectively. CONCLUSIONS: To the best of our knowledge, this work presents the first data-efficient learning benchmark for medical image segmentation, and the largest number of pretrained models up to now. All these resources are publicly available, and our work lays the foundation for promoting the development of deep learning methods for efficient COVID-19 CT segmentation with limited data.


Subject(s)
COVID-19/diagnostic imaging , Image Processing, Computer-Assisted/methods , Lung/diagnostic imaging , Machine Learning , Tomography, X-Ray Computed , Benchmarking , Humans
19.
Adv Funct Mater ; : 2008452, 2020 Nov 25.
Article in English | MEDLINE | ID: covidwho-967839

ABSTRACT

The world-wide spreading of coronavirus disease (COVID-19) has greatly shaken human society, thus effective and fast-speed methods of non-daily-life-disturbance sterilization have become extremely significant. In this work, by fully benefitting from high-quality AlN template (with threading dislocation density as low as ≈6×108 cm-2) as well as outstanding deep ultraviolet (UVC-less than 280 nm) light-emitting diodes (LEDs) structure design and epitaxy optimization, high power UVC LEDs and ultra-high-power sterilization irradiation source are achieved. Moreover, for the first time, a result in which a fast and complete elimination of SARS-CoV-2 (the virus causes COVID-19) within only 1 s is achieved by the nearly whole industry-chain-covered product. These results advance the promising potential in UVC-LED disinfection particularly in the shadow of COVID-19.

20.
Cell Mol Gastroenterol Hepatol ; 11(3): 771-781, 2021.
Article in English | MEDLINE | ID: covidwho-808973

ABSTRACT

BACKGROUND AND AIMS: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. METHODS: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. RESULTS: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. CONCLUSION: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immunity, Innate/immunology , Intestinal Mucosa/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Aged , Aged, 80 and over , Female , Humans , In Vitro Techniques , Male , Middle Aged , SARS Virus/pathogenicity , Virus Replication/immunology , Virus Replication/physiology
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