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1.
Front Immunol ; 13: 819058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529866

RESUMO

Vaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative approach that does not wholly depend on individuals having intact immune systems and responses. Here, we identified an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody, NC0321, which can efficiently neutralize a range of SARS-CoV-2 variants, including alpha, beta, delta, and eta. Both prophylactic and therapeutic NC0321 treatments effectively protected mice from SARS-CoV-2 infection. Notably, we adopted viral vector-mediated delivery of NC0321 IgG1 as an attractive approach to prevent SARS-CoV-2 infection. The NC0321 IgG1 expression in the proximal airway, expressed by a single direct in-vivo intranasal (I.N.) administration of a self-inactivating and recombinant lentiviral vector (rSIV.F/HN-NC0321), can protect young, elderly, and immunocompromised mice against mouse-adapted SARS-CoV-2 surrogate challenge. Long-term monitoring indicated that rSIV.F/HN-NC0321 mediated robust IgG expression throughout the airway of young and SCID mice, importantly, no statistical difference in the NC0321 expression between young and SCID mice was observed. A single I.N. dose of rSIV.F/HN-NC0321 30 or 180 days prior to SARS-CoV-2 challenge significantly reduced lung SARS-CoV-2 titers in an Ad5-hACE2-transduced mouse model, reconfirming that this vectored immunoprophylaxis strategy could be useful, especially for those individuals who cannot gain effective immunity from existing vaccines, and could potentially prevent clinical sequelae.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunoglobulina G , Camundongos , Camundongos SCID , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus
2.
Artigo em Inglês | MEDLINE | ID: mdl-35499791

RESUMO

Currently, there is a lack of studies on microplastic pollution in mountain terrains and foothills areas in Northwest China and Central Asia. Here, we collected monthly dusts samples for one year and we studied the distribution, pollution levels, and sources of microplastics in atmospheric dust fall in the Ebinur Lake Basin in Northwest China. Results showed that the average content of dust microplastic on construction land was 28.61 ± 1.13 mg/kg, followed by farmland (20.25 ± 1.56 mg/kg), forest (19.52 ± 1.06 mg/kg), and deserts (8.08 ± 0.56 mg/kg). Regarding different land use types, atmospheric dust reduction dominated on farmland (58.64%), followed by urban area (26.65%), forest (9.76%), and desert (4.95%). Regarding the shape of microplastics, the order of occurrence in dust was film (46.85%) > fiber (35.15%) > foam(12.35%) > fragment (5.65%). In this study, four colors of microplastics were found in dust, and white accounted for the largest proportion (52.15%), followed by transparent (18.65%), black (19.45%), and green (9.75%). The main components of film microplastics in atmospheric dustfall in the Ebinur Lake Basin were PE and PP, and their sources were mainly plastic products in daily life, plastic industrial packaging materials from urban enterprises, broken plastic woven bags, and PET mostly from fabric fragment emissions. The abundance of microplastics in dust was correlated with atmospheric dust pH, EC, and total salt content. The contents of seven heavy metals (Cu, Ni, Cd, Pb, Cr, Mn, and Co) adsorbed by microplastics were also correlated with pH, EC, and total salt content. Our results represent a reference for microplastics pollution prevention in mountain terrains and foothills areas in northwest China and Central Asia.

3.
Genome Res ; 32(2): 228-241, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35064006

RESUMO

The pathogenesis of COVID-19 is still elusive, which impedes disease progression prediction, differential diagnosis, and targeted therapy. Plasma cell-free RNAs (cfRNAs) carry unique information from human tissue and thus could point to resourceful solutions for pathogenesis and host-pathogen interactions. Here, we performed a comparative analysis of cfRNA profiles between COVID-19 patients and healthy donors using serial plasma. Analyses of the cfRNA landscape, potential gene regulatory mechanisms, dynamic changes in tRNA pools upon infection, and microbial communities were performed. A total of 380 cfRNA molecules were up-regulated in all COVID-19 patients, of which seven could serve as potential biomarkers (AUC > 0.85) with great sensitivity and specificity. Antiviral (NFKB1A, IFITM3, and IFI27) and neutrophil activation (S100A8, CD68, and CD63)-related genes exhibited decreased expression levels during treatment in COVID-19 patients, which is in accordance with the dynamically enhanced inflammatory response in COVID-19 patients. Noncoding RNAs, including some microRNAs (let 7 family) and long noncoding RNAs (GJA9-MYCBP) targeting interleukin (IL6/IL6R), were differentially expressed between COVID-19 patients and healthy donors, which accounts for the potential core mechanism of cytokine storm syndromes; the tRNA pools change significantly between the COVID-19 and healthy group, leading to the accumulation of SARS-CoV-2 biased codons, which facilitate SARS-CoV-2 replication. Finally, several pneumonia-related microorganisms were detected in the plasma of COVID-19 patients, raising the possibility of simultaneously monitoring immune response regulation and microbial communities using cfRNA analysis. This study fills the knowledge gap in the plasma cfRNA landscape of COVID-19 patients and offers insight into the potential mechanisms of cfRNAs to explain COVID-19 pathogenesis.


Assuntos
COVID-19 , Ácidos Nucleicos Livres , RNA/sangue , COVID-19/sangue , COVID-19/genética , Ácidos Nucleicos Livres/sangue , Síndrome da Liberação de Citocina , Humanos , SARS-CoV-2
4.
J Cell Mol Med ; 26(2): 507-514, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34889045

RESUMO

Lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (SA-AKI) is a model of clinical serious care syndrome, with high morbidity and mortality. Tacrolimus (TAC), a novel immunosuppressant that inhibits inflammatory response, plays a pivotal role in kidney diseases. In this study, LPS treated mice and cultured podocytes were used as the models of SA-AKI in vivo and in vitro, respectively. Medium- and high-dose TAC administration significantly attenuated renal function and renal pathological manifestations at 12, 24 and 48 h after LPS treatment in mice. Moreover, the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-kappa (NF-κB) signalling pathway was also dramatically inhibited by medium- and high-dose TAC administration at 12, 24 and 48 h of LPS treatment mice. In addition, TAC reversed LPS-induced podocyte cytoskeletal injury and podocyte migratory capability. Our findings indicate that TAC has protective effects against LPS-induced AKI by inhibiting TLR4/MyD88/NF-κB signalling pathway and podocyte dysfunction, providing another potential therapeutic effects for the LPS-induced SA-AKI.


Assuntos
Injúria Renal Aguda , Receptor 4 Toll-Like , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Tacrolimo/farmacologia , Receptor 4 Toll-Like/metabolismo
5.
Ther Apher Dial ; 26(1): 71-84, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34038022

RESUMO

Cardiovascular diseases (CVD) are common in maintenance hemodialysis (MHD) patients, and vascular calcification is associated with the incidence of CVD. Malnourished MHD patients are particularly prone to CVD events. Thus far, there is no clear explanation for the relationship of nutrition status with vascular calcification; therefore, we investigated the relationship between malnutrition and vascular calcification. One hundred thirty-one patients underwent laboratory testing, assessment of vascular calcification, modified quantitative subjective global assessment (MQSGA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The patients were divided into two groups based on the presence or absence of coronary artery calcification (CAC), and nutritional statuses were compared between the two groups. The MQSGA score was higher in the CAC group (mean 10.9 ± 1.81) than in the no-CAC group (mean 10.2 ± 1.51); in addition, the mean phase angle (PA) value was significantly lower in the CAC group than in the no-CAC group. Stratification according to CAC score showed that age, Kt/V, incidence of valve calcification, incidence of abdominal aortic calcification, MQSGA score, and blood cell mass were related to the severity of CAC. In addition, quartile analysis revealed that MQSGA score and PA value were related to the incidence and severity of vascular calcification. Binary regression analysis showed that MQSGA score, age, hemoglobin level, and high-density lipoprotein level were independent risk factors for dialysis-related CAC. Patients on MHD who exhibited malnutrition were more likely to have vascular calcification, especially CAC. Namely, the higher the MQSGA score, the lower the PA, and the more likely the occurrence of CAC.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Desnutrição/epidemiologia , Diálise Renal/métodos , Calcificação Vascular/epidemiologia , Adulto , Idoso , China/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Adulto Jovem
6.
Emerg Microbes Infect ; 11(1): 168-171, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34907853

RESUMO

HCoV-OC43 is one of the mildly pathogenic coronaviruses with high infection rates in common population. Here, 43 HCoV-OC43 related cases with pneumonia were reported, corresponding genomes of HCoV-OC43 were obtained. Phylogenetic analyses based on complete genome, orf1ab and spike genes revealed that two novel genotypes of HCoV-OC43 have emerged in China. Obvious recombinant events also can be detected in the analysis of the evolutionary dynamics of novel HCoV-OC43 genotypes. Estimated divergence time analysis indicated that the two novel genotypes had apparently independent evolutionary routes. Efforts should be conducted for further investigation of genomic diversity and evolution analysis of mildly pathogenic coronaviruses.


Assuntos
Resfriado Comum/epidemiologia , Infecções por Coronavirus/epidemiologia , Coronavirus Humano OC43/genética , Genoma Viral , Genótipo , Pneumonia Viral/epidemiologia , Sequência de Bases , Teorema de Bayes , Criança , Criança Hospitalizada , Pré-Escolar , China/epidemiologia , Resfriado Comum/patologia , Resfriado Comum/transmissão , Resfriado Comum/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Coronavirus Humano OC43/classificação , Coronavirus Humano OC43/patogenicidade , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Masculino , Método de Monte Carlo , Mutação , Filogenia , Pneumonia Viral/patologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Recombinação Genética
8.
Cell Discov ; 7(1): 65, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385423

RESUMO

The current COVID-19 pandemic, caused by SARS-CoV-2, poses a serious public health threat. Effective therapeutic and prophylactic treatments are urgently needed. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, which binds to the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Here, we developed recombinant human ACE2-Fc fusion protein (hACE2-Fc) and a hACE2-Fc mutant with reduced catalytic activity. hACE2-Fc and the hACE2-Fc mutant both efficiently blocked entry of SARS-CoV-2, SARS-CoV, and HCoV-NL63 into hACE2-expressing cells and inhibited SARS-CoV-2 S protein-mediated cell-cell fusion. hACE2-Fc also neutralized various SARS-CoV-2 strains with enhanced infectivity including D614G and V367F mutations, as well as the emerging SARS-CoV-2 variants, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.1 (Kappa), and B.1.617.2 (Delta), demonstrating its potent and broad-spectrum antiviral effects. In addition, hACE2-Fc proteins protected HBE from SARS-CoV-2 infection. Unlike RBD-targeting neutralizing antibodies, hACE2-Fc treatment did not induce the development of escape mutants. Furthermore, both prophylactic and therapeutic hACE2-Fc treatments effectively protected mice from SARS-CoV-2 infection, as determined by reduced viral replication, weight loss, histological changes, and inflammation in the lungs. The protection provided by hACE2 showed obvious dose-dependent efficacy in vivo. Pharmacokinetic data indicated that hACE2-Fc has a relative long half-life in vivo compared to soluble ACE2, which makes it an excellent candidate for prophylaxis and therapy for COVID-19 as well as for SARS-CoV and HCoV-NL63 infections.

9.
Cell Discov ; 7(1): 23, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850111

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

10.
Signal Transduct Target Ther ; 6(1): 155, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859163

RESUMO

Disease progression prediction and therapeutic drug target discovery for Coronavirus disease 2019 (COVID-19) are particularly important, as there is still no effective strategy for severe COVID-19 patient treatment. Herein, we performed multi-platform omics analysis of serial plasma and urine samples collected from patients during the course of COVID-19. Integrative analyses of these omics data revealed several potential therapeutic targets, such as ANXA1 and CLEC3B. Molecular changes in plasma indicated dysregulation of macrophage and suppression of T cell functions in severe patients compared to those in non-severe patients. Further, we chose 25 important molecular signatures as potential biomarkers for the prediction of disease severity. The prediction power was validated using corresponding urine samples and plasma samples from new COVID-19 patient cohort, with AUC reached to 0.904 and 0.988, respectively. In conclusion, our omics data proposed not only potential therapeutic targets, but also biomarkers for understanding the pathogenesis of severe COVID-19.


Assuntos
COVID-19/sangue , COVID-19/tratamento farmacológico , Descoberta de Drogas , Lipidômica , Proteômica , SARS-CoV-2/metabolismo , Biomarcadores/sangue , Feminino , Humanos , Masculino
11.
Front Med (Lausanne) ; 8: 585358, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33659260

RESUMO

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.

12.
Genome Med ; 13(1): 30, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618765

RESUMO

BACKGROUND: Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. METHODS: Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT). RESULTS: The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks. CONCLUSIONS: Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.


Assuntos
COVID-19/prevenção & controle , Genoma Viral/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/genética , COVID-19/virologia , Frequência do Gene , Genótipo , Haplótipos , Interações Hospedeiro-Patógeno , Humanos , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/fisiologia
13.
J Exp Med ; 218(4)2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33464307

RESUMO

Virus-specific T cells play essential roles in protection against multiple virus infections, including SARS-CoV and MERS-CoV. While SARS-CoV-2-specific T cells have been identified in COVID-19 patients, their role in the protection of SARS-CoV-2-infected mice is not established. Here, using mice sensitized for infection with SARS-CoV-2 by transduction with an adenovirus expressing the human receptor (Ad5-hACE2), we identified SARS-CoV-2-specific T cell epitopes recognized by CD4+ and CD8+ T cells in BALB/c and C57BL/6 mice. Virus-specific T cells were polyfunctional and were able to lyse target cells in vivo. Further, type I interferon pathway was proved to be critical for generating optimal antiviral T cell responses after SARS-CoV-2 infection. T cell vaccination alone partially protected SARS-CoV-2-infected mice from severe disease. In addition, the results demonstrated cross-reactive T cell responses between SARS-CoV and SARS-CoV-2, but not MERS-CoV, in mice. Understanding the role of the T cell response will guide immunopathogenesis studies of COVID-19 and vaccine design and validation.


Assuntos
COVID-19/imunologia , Epitopos de Linfócito T/imunologia , Interações Hospedeiro-Patógeno/fisiologia , Linfócitos T/imunologia , Linfócitos T/virologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Neutralizantes/sangue , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Chlorocebus aethiops , Reações Cruzadas , Mapeamento de Epitopos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Células Vero
14.
Ann Transl Med ; 8(18): 1206, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33241055

RESUMO

[This retracts the article DOI: 10.21037/atm.2019.10.113.].

15.
Ecotoxicol Environ Saf ; 202: 110976, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800235

RESUMO

In this study, we first reviewed the current research progress regarding the presence of environmental microplastics (MPs) in environment in China from 2010 to 2019. Results showed that: (1) current research has primarily focused on river and marine environments rather than soils and dusts, mainly located in eastern China, i.e., the Yangtze river, Poyang lake, Dongting lake, Yellow sea, and Bohai sea; (2) the abundance of MPs found in water bodies (sediments) of the rivers in China ranged from 3.9 to 7900 items·m-3 (19.0 × 103-13600.5 × 103 items·km-2), and 20-24300 items·kg-2 (170-5500 × 106 items·km-2) in the sediments, respectively; in lake water the range was 340-8900 items·m-3 (5 × 103-340 × 105 items·km-2) and 8 to 1200 items·m-2/25-300 items·kg-1 in the sediments, respectively; in marine water the range was 0.003-540 items·m-3 (0-380,100 item·km-2) and 1.3-14700 item·kg-1 in the sediments, respectively; in fish, shellfish, and natural planktons from ocean and freshwater, the range was 0-57 items·individuals-1 (0-168 items·g-1); (3) The absorption and toxicological effects of MPs in freshwater and oceans have mainly focused on polyethylene (PE), polypropylene (PP), and polystyrene (PS); (4) the sources of microplastics in soils and dusts primarily come from urban/town activities; for rivers and lakes (estuary), they primarily come from urban activities; for coastal waters, fishing gear and nets, and the maritime activities were the main sources.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Lagos/química , Microplásticos/análise , Rios/química , Solo/química , Poluentes Químicos da Água/análise , China , Cidades , Poeira/análise , Estuários , Oceanos e Mares , Polietileno/análise , Polipropilenos/análise , Poliestirenos/análise
16.
Vaccine ; 38(40): 6274-6279, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32747216

RESUMO

BACKGROUND: The immunogenicity and safety of the sequential schedule of Sabin strain-based inactivated poliovirus vaccine (sIPV) and bivalent oral poliovirus vaccine (bOPV) remains poorly understood in Chinese population. METHODS: A multi-center, open-label, randomized controlled trial was performed involving 648 healthy infants aged 2 months from Inner Mongolia, Shanxi, and Hebei provinces. These participants were divided into three groups: sIPV-bOPV-bOPV, sIPV-sIPV-bOPV, and sIPV-sIPV-sIPV. Doses were administered sequentially at age 2, 3, and 4 months. Neutralisation assays were tested using sera collected at 2 months and 5 months. RESULTS: A total of 569 were included in the per-protocol analysis. The seroconversion rates of poliovirus type 1 and 3 were 100% in all three groups, the seroconversion rate of poliovirus type 2 was 91.53% (173/189) (95% CI: 86.62-95.08) in the sIPV-bOPV-bOPV group, 98.38% (182/185) (95% CI: 95.33-99.66) in the sIPV-sIPV-bOPV group, and 99.49% (194/195) (95% CI: 97.18-99.99) in the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus types 1 and 3, the sIPV-bOPV-bOPV and sIPV-sIPV-bOPV groups were non-inferior to the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus type 2, the sIPV-sIPV-bOPV group was non-inferior to the sIPV-sIPV-sIPV group, and the sIPV-bOPV-bOPV group was inferior to the sIPV-sIPV-sIPV group. All three groups exhibited good safety, with two serious adverse events reported, that were unrelated to vaccine. CONCLUSIONS: In china, a new vaccination schedule that including 2 doses of IPV in the national immunization programs is essential. Trial registration ClinicalTrials.govNCT04054492.


Assuntos
Poliomielite , Poliovirus , Anticorpos Antivirais , Pré-Escolar , China , Humanos , Esquemas de Imunização , Lactente , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio Oral/efeitos adversos , Vacinação
17.
Cell ; 182(3): 734-743.e5, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32643603

RESUMO

COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/prevenção & controle , Modelos Animais de Doenças , Pandemias/prevenção & controle , Pneumonia Viral/patologia , Pneumonia Viral/prevenção & controle , Vacinação , Enzima de Conversão de Angiotensina 2 , Animais , COVID-19 , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , SARS-CoV-2 , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Organismos Livres de Patógenos Específicos , Transdução Genética , Células Vero , Carga Viral , Replicação Viral
18.
J Clin Invest ; 130(10): 5235-5244, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32634129

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus 2019 (COVID-19) pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity, and neutralization antibody response in patients with COVID-19. Two groups of patients with RT-PCR-confirmed COVID-19 were enrolled in this study: 12 severely ill patients in intensive care units who needed mechanical ventilation and 11 mildly ill patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severely ill patients had viral shedding in a variety of tissues for 20-40 days after onset of disease (8/12, 66.7%), while the majority of mildly ill patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA 10 days after onset (9/11, 81.8%). Mildly ill patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both the severe and mild groups at 9 days after onset, and remained at a high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS. High levels of neutralizing antibodies were induced after about 10 days after onset in both severely and mildly ill patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from patients with COVID-19 inhibited SARS-CoV-2 entry. Sera from convalescent patients with SARS or Middle East respiratory syndrome (MERS) did not. Anti-SARS-CoV-2 S and N IgG levels exhibited a moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in humans after SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/metabolismo , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Carga Viral , Eliminação de Partículas Virais , Adulto , Idoso , Especificidade de Anticorpos , COVID-19 , Reações Cruzadas , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Índice de Gravidade de Doença
19.
Environ Geochem Health ; 42(11): 3949-3963, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32651931

RESUMO

Heavy metals are the most important indicator for farmland soil; however, in China, few provincial and national scales of studies have been done on heavy metals. Herein, by retrieving published studies, we calculated the spatial distribution characters and evaluated the health risks of Cu, Zn, Cd, Ni, Pb, Cr, As, and Hg in the farmland soil of 146 cities in China. Results showed that (1) the range (mean) values of eight (metalloid) heavy metals were as follows in mg/kg: Cu 0.236-251.015 (44.604), Zn 0.151-1547.060 (154.203), Cd 0.014-39.100 (1.497), Ni 0.709-554.420 (41.968), Pb 0.327-495.400 (55.143), Cr 0.078-333.510 (70.093), As 0.836-60.000 (12.207), and Hg 0.008-12.190 (0.371). The coefficient of variation values of Cu, Cr, and As displayed moderate variation, and Zn, Cd, Ni, Pb, and Hg displayed high variation (142.148-364.960%). (2) the Igeo values of As, Cu, Cd, Ni, Zn, Cr, Pb, and Hg were - 4.329 to 1.837, - 7.166 to 2.888, - 3.378 to 8.070, - 5.831 to 3.780, - 9.527 to 3.797, - 10.120 to 1.866, - 6.899 to 3.667, and - 3.681 to 6.966, respectively; in many cities, there was some degree of heavy metal pollution of the farmland soil such as Zn in Pingdu, Pb in Huludao, and Hg in Tongguan, Funshun, Huludao, and Qinglong (Igeo > 3); there were no obvious spatial patterns of Cr, Ni, and As, and Zn, Cu, but Cd, Ni, Pb, and Hg mainly located in some cities in the southwest, central or eastern parts of China. (3) Health risk assessment showed that with the exception of Cd, Cr, and As by the respiration route and Ni, Cr, and As through skin exposure, the average amount of daily exposure of the eight (metalloid) heavy metals all showed values for children > adults, and the HQ and HI values were all lower than 1.0, indicating noncarcinogenic risks; calculation of carcinogenic risks showed there were no carcinogenic risks for As, Cr, Ni, and Cd; however, the value for Cr was the maximum and contributed 98.505% of the total.


Assuntos
Exposição Ambiental/efeitos adversos , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Adulto , Carcinógenos/análise , Criança , China , Cidades , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Fazendas , Humanos , Metaloides/análise , Metaloides/toxicidade , Metais Pesados/toxicidade , Medição de Risco , Poluentes do Solo/toxicidade
20.
J Virol ; 94(15)2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32434886

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-ß) were detected between these two viruses in vitro ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4+ and CD8+ T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance.IMPORTANCE MERS-CoV is an important emerging pathogen and causes severe respiratory infection in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. In this study, we showed that a clade B virus ChinaGD01 strain caused more severe disease in mice, with delayed viral clearance, increased inflammatory cytokines, and decreased antiviral T cell responses, than the early clade A virus EMC/2012. Given the differences in pathogenicity of different clades of MERS-CoV, periodic assessment of currently circulating MERS-CoV is needed to monitor potential severity of zoonotic disease.


Assuntos
Infecções por Coronavirus/virologia , Genótipo , Interações Hospedeiro-Patógeno , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Adulto , Animais , Modelos Animais de Doenças , Genoma Viral , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferon Tipo I/farmacologia , Masculino , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Filogenia , RNA Viral , Linfócitos T/imunologia , Linfócitos T/metabolismo , Virulência , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética , Sequenciamento Completo do Genoma
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