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1.
BMC Med Imaging ; 22(1): 149, 2022 08 26.
Article in English | MEDLINE | ID: covidwho-2038671

ABSTRACT

BACKGROUND: Soft tissue sarcoma is a rare and highly heterogeneous tumor in clinical practice. Pathological grading of the soft tissue sarcoma is a key factor in patient prognosis and treatment planning while the clinical data of soft tissue sarcoma are imbalanced. In this paper, we propose an effective solution to find the optimal imbalance machine learning model for predicting the classification of soft tissue sarcoma data. METHODS: In this paper, a large number of features are first obtained based on [Formula: see text]WI images using the radiomics methods.Then, we explore the methods of feature selection, sampling and classification, get 17 imbalance machine learning models based on the above features and performed extensive experiments to classify imbalanced soft tissue sarcoma data. Meanwhile, we used another dataset splitting method as well, which could improve the classification performance and verify the validity of the models. RESULTS: The experimental results show that the combination of extremely randomized trees (ERT) classification algorithm using SMOTETomek and the recursive feature elimination technique (RFE) performs best compared to other methods. The accuracy of RFE+STT+ERT is 81.57% , which is close to the accuracy of biopsy, and the accuracy is 95.69% when using another dataset splitting method. CONCLUSION: Preoperative predicting pathological grade of soft tissue sarcoma in an accurate and noninvasive manner is essential. Our proposed machine learning method (RFE+STT+ERT) can make a positive contribution to solving the imbalanced data classification problem, which can favorably support the development of personalized treatment plans for soft tissue sarcoma patients.


Subject(s)
Machine Learning , Sarcoma , Soft Tissue Neoplasms , Algorithms , Humans
3.
Psychol Health Med ; : 1-7, 2022 Sep 08.
Article in English | MEDLINE | ID: covidwho-2008427

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has been assumed to affect mental health of college students. The present cross-sectional study was conducted to examine levels of knowledge and anxiety about COVID-19, as well as attitude towards the back-to-school arrangement among college students in China in May 2020. A total of 716 students (312 males, 404 females) were included. Only 38.1% of the participants showed good knowledge about COVID-19. Moderate and severe anxiety was observed among 7.6% of the students. There were 15.6% of the participants opposing the back-to-school arrangement. Female students had more risk of having anxiety symptoms and negative attitude towards the back-to-school arrangement (p < 0.05). In addition, the level of anxiety was positively associated with the negative attitude towards the back-to-school arrangement (r = 0.11, p < 0.05). We therefore suggest that health education and psychological interventions should be given to college students, especially females and those without health-related backgrounds during the COVID-19 pandemic.

4.
Chin Geogr Sci ; 32(5): 824-833, 2022.
Article in English | MEDLINE | ID: covidwho-2007247

ABSTRACT

Depending on various government policies, COVID-19 (Corona Virus Disease-19) lockdowns have had diverse impacts on global aerosol concentrations. In 2022, Changchun, a provincial capital city in Northeast China, suffered a severe COVID-19 outbreak and implemented a very strict lockdown that lasted for nearly two months. Using ground-based polarization Light Detection and Ranging (LiDAR), we detected real-time aerosol profile parameters (EC, extinction coefficient; DR, depolarization ratio; AOD, aerosol optical depth), as well as air-quality and meteorological indexes from 1 March to 30 April in 2021 and 2022 to quantify the effects of lockdown on aerosol concentrations. The period in 2022 was divided into three stages: pre-lockdown (1-10 March), strict lockdown (11 March to 10 April), and partial lockdown (11-30 April). The results showed that, during the strict lockdown period, compared with the pre-lockdown period, there were substantial reductions in aerosol parameters (EC and AOD), and this was consistent with the concentrations of the atmospheric pollutants PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10 (particulate matter with an aerodynamic diameter ≤ 10 µm), and the O3 concentration increased by 8.3%. During the strict lockdown, the values of EC within 0-1 km and AOD decreased by 16.0% and 11.2%, respectively, as compared to the corresponding period in 2021. Lockdown reduced the conventional and organized emissions of air pollutants, and it clearly delayed the time of seasonal emissions from agricultural burning; however, it did not decrease the number of farmland fire points. Considering meteorological factors and eliminating the influence of wind-blown dust events, the results showed that reductions from conventional organized emission sources during the strict lockdown contributed to a 30% air-quality improvement and a 22% reduction in near-surface extinction (0-2 km). Aerosols produced by urban epidemic prevention and disinfection can also be identified using the EC. Regarding seasonal sources of agricultural straw burning, the concentrated burning induced by the epidemic led to the occurrence of heavy pollution from increased amounts of atmospheric aerosols, with a contribution rate of 62%. These results indicate that there is great potential to further improve air quality in the local area, and suggest that the comprehensive use of straw accompanied by reasonable planned burning is the best way to achieve this.

5.
Economic Analysis and Policy ; 2022.
Article in English | ScienceDirect | ID: covidwho-1996116

ABSTRACT

As an innovative and convenient micro-mobility service, dockless bicycle-sharing systems (DBSSs) are essential to achieving green recovery of the transportation sector in post-COVID-19 world. DBSS green externalities on climate change have attracted the attention of scholars and have revealed different roles in carbon mitigation in different studies. In this study, Shanghai is employed as a case city to analyze DBSS green externalities. The direct carbon emissions reduced by DBSS cycling are calculated and the indirect carbon mitigation by a DBSS in promoting use of low-carbon public transport is estimated. The carbon consumption of DBSS from the perspective of life-cycle assessment is also valued. The results show that DBSSs have much greater carbon mitigation potential in promoting the use of low-carbon public transport than do cycling routes. The production, maintenance, and rebalance of DBSSs may produce a large number of carbon emissions and even offset their green benefits. The application of (electric) e-bikes and the integration of DBSSs and public transportation should be the key issue for policy makers to promote the green recovery of the transport sector. This study calls for further studies to demonstrate the green externality of DBSSs based on the detailed operation dataset.

6.
Lancet Microbe ; 3(5): e348-e356, 2022 05.
Article in English | MEDLINE | ID: covidwho-1984300

ABSTRACT

Background: The memory immune response is crucial for preventing reinfection or reducing disease severity. However, the robustness and functionality of the humoral and T-cell response to SARS-CoV-2 remains unknown 12 months after initial infection. The aim of this study is to investigate the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection. Methods: In this longitudinal cohort study, we recruited participants who had recovered from COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020. Patients received a follow-up visit between Dec 16, 2020, and Jan 27, 2021. We evaluated the presence of IgM, IgA, and IgG antibodies against the SARS-CoV-2 nucleoprotein, Spike protein, and the receptor-binding domain 12 months after initial infection, using ELISA. Neutralising antibodies against the original SARS-CoV-2 strain, and the D614G, beta (B.1.351), and delta (B.1.617.2) variants were analysed using a microneutralisation assay in a subset of plasma samples. We analysed the magnitude and breadth of the SARS-CoV-2-specific memory T-cell responses using the interferon γ (IFNγ) enzyme-linked immune absorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) assay. The antibody response and T-cell response (ie, IFN-γ, interleukin-2 [IL-2], and tumour necrosis factor α [TNFα]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms. Findings: We enrolled 1096 patients, including 289 (26·4%) patients with moderate initial disease, 734 (67·0%) with severe initial disease, and 73 (6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG (899 [82·0%]), S-IgG (1043 [95·2%]), RBD-IgG (1032 [94·2%]), and neutralising (115 [81·6%] of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 (72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection. Interpretation: SARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time. Funding: Chinese Academy of Medical Sciences, National Natural Science Foundation, and UK Medical Research Council.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/epidemiology , Cohort Studies , Cytokines , Humans , Immunoglobulin G , Longitudinal Studies , T-Lymphocytes
7.
J Med Virol ; 94(12): 5746-5757, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1976742

ABSTRACT

We evaluated and compared humoral immune responses after inactivated coronavirus disease 2019 (COVID-19) vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after 2 doses of inactivated COVID-19 vaccination. Among 392 severe acute respiratory syndrome coronavirus 2-naïve individuals, the seroconversion rate increased significantly from 51.8% (median antispike protein pan-immunoglobulins [S-Igs] titer: 0.8 U/ml) after the first dose to 96% (median S-Igs titer: 79.5 U/ml) after the second dose. Thirty-two percent of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S-Igs titers of 596.7, 1176, 1086.5, and 1828 U/ml for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Prospective Studies , SARS-CoV-2 , Vaccination , Vaccines, Inactivated
8.
Respir Res ; 23(1): 188, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1938326

ABSTRACT

BACKGROUND: Assessing the humoral immunity of patients with underlying diseases after being infected with SARS-CoV-2 is essential for adopting effective prevention and control strategies. The purpose of this study is to analyze the seroprevalence of people with underlying diseases and the dynamic change features of anti-SARS-CoV-2 antibodies. METHODS: We selected 100 communities in Wuhan using the probability-proportional-to-size sampling method. From these 100 communities, we randomly selected households according to a list provided by the local government. Individuals who have lived in Wuhan for at least 14 days since December 2019 and were ≥ 40 years old were included. From April 9-13, 2020, community staff invited all selected individuals to the community healthcare center in batches by going door-to-door or telephone. All participants completed a standardized electronic questionnaire simultaneously. Finally, 5 ml of venous blood was collected from all participants. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. During the period June 11-13, 2020 and October 9-December 5, 2020, all family members of a positive family and matched negative families were followed up twice. RESULTS: The seroprevalence of anti-SARS-CoV-2 antibodies in people with underlying diseases was 6.30% (95% CI [5.09-7.52]), and that of people without underlying diseases was 6.12% (95% CI [5.33-6.91]). A total of 313 people were positive for total antibodies at baseline, of which 97 had underlying disease. At the first follow-up, a total of 212 people were positive for total antibodies, of which 66 had underlying disease. At the second follow-up, a total of 238 people were positive for total antibodies, of which 68 had underlying disease. A total of 219 participants had three consecutive serum samples with positive total antibodies at baseline. The IgG titers decreased significantly with or without underlying diseases (P < 0.05) within the 9 months at least, while the neutralizing antibody titer remained stable. The titer of asymptomatic patients was lower than that of symptomatic patients (baseline, P = 0.032, second follow-up, P = 0.018) in the underlying diseases group. CONCLUSION: Our research focused on the serological changes of people with and without underlying diseases in a state of single natural infection. Regardless of the underlying diseases, the IgG titer decreased significantly over time, while there was no significant difference in the decline rate of IgG between with and without underlying diseases. Moreover, the neutralizing antibody titer remained relatively stable within the 9 months at least.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Immunoglobulin G , Longitudinal Studies , Seroepidemiologic Studies
9.
J Mol Biol ; 434(3): 167243, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1851574

ABSTRACT

Brain organoids are self-organized three-dimensional aggregates generated from pluripotent stem cells. They exhibit complex cell diversities and organized architectures that resemble human brain development ranging from neural tube formation, neuroepithelium differentiation, neurogenesis and gliogenesis, to neural circuit formation. Rapid advancements in brain organoid culture technologies have allowed researchers to generate more accurate models of human brain development and neurological diseases. These models also allow for direct investigation of pathological processes associated with infectious diseases affecting the nervous system. In this review, we first briefly summarize recent advancements in brain organoid methodologies and neurodevelopmental processes that can be effectively modeled by brain organoids. We then focus on applications of brain organoids to investigate the pathogenesis of neurotropic viral infection. Finally, we discuss limitations of the current brain organoid methodologies as well as applications of other organ specific organoids in the infectious disease research.


Subject(s)
Brain , Central Nervous System Viral Diseases , Organoids , Brain/growth & development , Brain/virology , Central Nervous System Viral Diseases/virology , Humans , Neurogenesis , Organoids/virology
10.
BMC Pregnancy Childbirth ; 22(1): 412, 2022 May 16.
Article in English | MEDLINE | ID: covidwho-1846811

ABSTRACT

OBJECTIVE: To understand the use of online antenatal education classes accessed via the Mother and Child Health Handbook app during the COVID-19 pandemic in order to provide a basis and suggestions for optimizing Internet education during pregnancy under public health emergencies. METHODS: We compared and analyzed the use of online antenatal education classes via the Mother and Child Health Handbook app in Hangzhou in 2019 and 2020 (during the COVID-19 pandemic). RESULTS: Between January 1, 2019, and December 31, 2020, a total of 229,794 pregnant women created files and registered for the app, including 124,273 women in 2019 and 105,521 women in 2020. More pregnant women participated in online antenatal education learning (n = 36,379/34.5% vs. 29,226/23.5%, p = 0.000) in 2020 than in 2019. The proportion of pregnant women in the 18-34-year-old group who participated in online learning was higher than that in the advanced age group, and the difference was statistically significant (2019: 24.3% vs. 18.8%, p = 0.000) (2020: 35.7% vs. 27.4%, p = 0.000). More pregnant women accessed online antenatal education during early pregnancy (n = 13,463/37.0% vs. 9088/31.1%, p = 0.000) in 2020 than in 2019. Similar percentages of pregnant women participated in online antenatal education during mid-pregnancy (n = 15,426/52.8% vs. 19,269/53.0%, p = 0.639) in 2019 and 2020. Fewer pregnant women accessed online antenatal education during late pregnancy (n = 10,246/28.2% vs. 9476/32.4%, p = 0.000) in 2020 than in 2019. Fewer pregnant women choose to take 'Puerperal Health' courses in 2020 than in 2019 (early pregnancy: 36.20% vs. 42.79%, p = 0.000; mid-pregnancy: 41.65% vs. 48.19%, p = 0.000; late pregnancy: 55.31% vs. 58.41%, p = 0.000). Fewer pregnant women choose to take 'Psychological Adjustment' courses in 2020 than in 2019 (early pregnancy: 21.59% vs. 29.60%, p = 0.000; mid-pregnancy: 26.20% vs. 40.50%, p = 0.000; late pregnancy: 12.79% vs. 42.53%, p = 0.000). More pregnant women choose to study 'Nutrition and Exercise' in 2020 than in 2019 (early pregnancy: 44.48% vs. 25.95%, p = 0.000; mid-pregnancy: 47.77% vs. 40.75%, p = 0.000; late pregnancy: 55.94% vs. 42.99%, p = 0.000). "Pregnancy Care and Fetal Development" was the most selected course by pregnant women in early pregnancy (2019: 67.50%; 2020: 71.39%) and middle pregnancy (2019: 67.01%; 2020: 82.05%), and the proportion in 2020 was higher than it was in 2019. "Baby care" was the most selected course by pregnant women in late pregnancy, and the proportion in 2020 was higher than it was in 2019 (78.31% vs. 72.85%). CONCLUSION: During the COVID-19 pandemic, online antenatal education was well-used by pregnant women. More women participated in the online antenatal education modules during the COVID-19 pandemic than during 2019.The proportion of choosing different courses for pregnant women before and after the COVID-19 epidemic varied, and the learning course needs of pregnant women in different trimesters were different.


Subject(s)
COVID-19 , Education, Distance , Mobile Applications , Prenatal Education , Adolescent , Adult , Child , Female , Humans , Pandemics , Pregnancy , Pregnant Women/psychology , Prenatal Care , Young Adult
11.
Biosaf Health ; 4(3): 186-192, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1821155

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses containing the spike protein from the original strain (SARS-CoV-2-WH01). The cytotoxicity of these compounds was determined. Furthermore, we identified six compounds with strong antagonistic activity against the WH01 pseudovirus, and low cytotoxicity was identified. These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2 (Delta) and B.1.1.529 (Omicron), the two most prevalent circulating strains. These assays demonstrated that two phenothiazine compounds, trifluoperazine 2HCl and thioridazine HCl, inhibit the infection of Delta and Omicron pseudoviruses. Finally, we discovered that these two compounds were highly effective against authentic SARS-CoV-2 viruses, including the WH01, Delta, and Omicron strains. Our study identified potential broad-spectrum SARS-CoV-2 inhibitors and provided insights into the development of novel therapeutics.

13.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331897

ABSTRACT

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

14.
Cell ; 185(10): 1728-1744.e16, 2022 05 12.
Article in English | MEDLINE | ID: covidwho-1767964

ABSTRACT

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta , Mice , RNA, Circular/genetics , SARS-CoV-2/genetics , Vaccines, Synthetic/genetics , mRNA Vaccines
15.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722617

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , SARS-CoV-2 , Tomography, X-Ray , Treatment Outcome
16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324519

ABSTRACT

Since the outbreak of 2019 novel coronavirus (2019-nCoV) at the hardest-hit city of Wuhan, the fast-moving spread has killed over three hundred people and infected more than ten thousands in China1. There are more than one hundred cases outside of China, affecting a dozen of countries globally2. The genome sequence of 2019-nCoV has been reported and fast diagnostic kits, effective treatment as well as preventive vaccines are rapidly being developed3. Initial fast-growing confirmed cases triggered lock-down of Wuhan as well as nearby cities in Hubei Province. Mathematical models have been proposed by scientists around the world to project the numbers of infected cases in the coming days 4,5. However, major factors such as transportation and cultural customs have not been weighed enough. Our model is not set out for precise prediction of the number of infected cases, rather, it is meant for a glance of the dynamics under a public epidemic emergency situation and of different contributing factors. We hope that our model and simulation would provide more insights and perspective information to public health authorities around the globe for better informed prevention and containment solution.

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319974

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has caused global pandemic. Here we profiled the humoral response against SARS-CoV-2 by measuring immunoglobulin (Ig) A, IgM and IgG against nucleocapsid, spike proteins and IgM, IgG antibodies against receptor-binding domain (RBD) of the spike protein along with total neutralizing antibodies. We tested 279 plasma samples collected from 176 COVID-19 patients. We demonstrate more severe cases have a late onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to the disease severity. The appearance time and titers of neutralizing antibodies showed significant positive correlation to the antibodies against spike protein. Our results suggest late onset of antibody response as a risk factor for disease severity, however there is a limited role of antibody titers in predicting disease severity of COVID-19.

18.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319973

ABSTRACT

Background: The pandemic of Coronavirus disease 2019 (COVID-19) is ongoing globally, which is a big challenge for public health. Alteration of human microbiota had been observed in COVID-19. However, it is unknown how the microbiota is associated with the fatality in COVID-19.Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients recruited in the LOTUS clinical trial (Registration number: ChiCTR2000029308) (including 39 deceased patients), and 95 healthy controls from the same geographic area.Findings: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota. Streptococcus was enriched in recovered patients, whereas potential pathogens, including Candida and Enterococcus, were more abundant in deceased patients. Moreover, the microbiota dominated by Streptococcus was more stable than that dominated by other species. In contrast, the URT microbiota in deceased patients showed a more significant alteration and became more deviated from the norm after admission. The abundance of Streptococcus on admission, particularly that of S. parasanguis, was identified as a strong predictor of fatality by Cox and L1 regularized logistic regression analysis, thus could be used as a potential prognostic biomarker of COVID-19.Interpretation Alteration of the URT microbiota was observed in COVID-19 patients and was associated with the fatality rate. A higher abundance of Streptococcus, especially S. parasanguis, on admission in oropharyngeal swabs predicts a better outcome. The generalization of the results in other populations and underlying mechanisms need further investigations.Trial Registration: Participants were enrolled in ChiCTR2000029308.Funding: This study was funded in part by the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10103004, 2018ZX10301401), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-2-XX, 2016-I2M-1-014, 2018-I2M-1-003), The Non-profit Central Research Institute Fund of CAMS (2020HY320001, 2019PT310029), Beijing Advanced Innovation Center for Genomics (ICG), and Beijing Advanced Innovation Center for Structural Biology (ICSB).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the Institutional Review Board of Jin Yin-Tan Hospital (KY2020-02.01). Written informed consent was obtained from all patients or their legal representatives if they were too unwell to provide consent.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318459

ABSTRACT

Since beginning of this century, there have already been three zoonotic outbreaks caused by beta coronaviruses (CoV), SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly identified 2019-nCoV in late 2019, Wuhan, China. As to Feb 10 th , 2020, there are over 40,000 confirmed cases and over 900 deaths. However, little is known about the biology of this newly emerged virus. Here we developed a lentiviral based pseudovirus system for S protein of 2019-nCoV to study virus entry in BSL2 settings. First, we confirmed that human angiotensin converting enzyme 2 (hACE2) is the main entry receptor for 2019-nCoV. Second, we found that 2019-nCoV S protein mediated entry on 293/hACE2 cells was mainly through endocytosis, and PIKfyve, TPC2, and cathepsin L are critical for virus entry. Third, 2019-nCoV S protein is less stable than SARS-CoV, and it could trigger protease-independent and receptor dependent cell-cell fusion, which might help virus rapidly spread from cell to cell. Finally and more importantly, polyclonal anti-SARS S1 antibodies T62 effectively inhibited entry of SARS-CoV S pseudovirions, but almost had no effect on entry of 2019-nCoV S pseudovirions. Further studies using sera from one recovered SARS-CoV patient and five 2019-nCoV patients showed that there was only limited cross-neutralization activities between SARS-CoV and 2019-nCoV sera, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for 2019-nCoV.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315953

ABSTRACT

Background: Covid-19 vaccine research and development is progressing and expected to be put into use in a predictable time, we aimed to learn the awareness and acceptance of the new vaccine by healthcare workers (HCWs) in Beijing, China. Methods: : A cross-sectional survey was conducted to investigate HCWs including doctors, nurses and technicians from sixty hospitals in Beijing to obtain the perception of COVID-19 epidemic and the attitudes towards vaccination before before the completion of vaccine phase III clinical trials. Multivariate analysis was applied to evaluate the associated factors with intention to get vaccination. Results: : A total of 8040 HCWs was recruited. 67.1% reported they would get vaccination, others said unsure or would not. Half of the HCWs were unsure whether the outbreak in China would come back and the global epidemic would last for a long time. 67.6% agreed the epidemic can be prevented by vaccination. Positive associated factors with willingness to get vaccination were mainly included epidemic situation prognosis, perception of disease severity, self infection risk and disease can be prevented by vaccine, etc. Two positive factors of “wanted the vaccine free of charge” (OR:5.807, 95%CI:5.083-6.635, P<0.001) and “believed vaccine approved for license have been fully evaluated in clinical trials” (OR:4.485, 95%CI:3.849-5.227, P<0.001) were strongly associated with willingness to get vaccination, while two factors of “highest academic degree” (OR:0.840, 95%CI:0.772-0.914, P<0.001) and “professional ranks and titles” (OR:0.930, 95%CI:0.865-1.000, P=0.049) were negative associated . Conclusions: : A little above moderate willingness to get COVID-19 vaccination was found among HCWs in Beijing before the vaccine being licensed. Free vaccination strategy should be considered to implement, effective measures should be taken to remove barriers and convey correct information through appropriate ways to enhance the acceptance of COVID-19 vaccination among HCWs in China.

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