RESUMO
Childhood obesity is widely recognized as a risk factor for numerous health conditions, particularly cardiovascular disease. However, it remains unclear whether childhood adiposity directly affects the risk of COVID-19 in later life. We aimed to investigate the causal effects of early life adiposity on COVID-19 susceptibility and severity. We used genetic instruments from large-scale genome-wide association studies to examine the relationships between birth weight, childhood and adulthood adiposity indicators (including body mass index [BMI], obesity, and body size), and COVID-19 outcomes. Univariable and multivariable Mendelian randomization (MR) analyses were used to obtain the causal estimates. Univariable MR analyses found that childhood BMI and obesity were positively associated with COVID-19 risk and severity in adulthood, however, the significant associations were attenuated to null after further adjusting for adulthood adiposity indicators in multivariable MR analyses. In contrast, our analysis revealed strong evidence of a genetically predicted effect of childhood obesity on COVID-19 hospitalization (OR 1.08, 95% CI: 1.01-1.15, p = 2.12E-2), which remained robust even after adjusting for adulthood obesity and potential lifestyle confounders. Our results highlight the importance of promoting healthy weight management throughout life to reduce the risk of COVID-19.
Assuntos
Adiposidade , Índice de Massa Corporal , COVID-19 , Análise da Randomização Mendeliana , Humanos , COVID-19/genética , COVID-19/epidemiologia , COVID-19/virologia , Adiposidade/genética , Fatores de Risco , Estudo de Associação Genômica Ampla , Obesidade Infantil/genética , Obesidade Infantil/epidemiologia , SARS-CoV-2/genética , Suscetibilidade a Doenças , Adulto , Masculino , Criança , Feminino , Índice de Gravidade de Doença , Obesidade/genética , Obesidade/complicações , Hospitalização/estatística & dados numéricos , Predisposição Genética para Doença , Peso ao NascerRESUMO
Influenza circulation was significantly affected in 2020-21 by the COVID-19 pandemic. During this time, few influenza cases were recorded. However, in the summer of 2021-22, an increase in atypical influenza cases was observed, leading to the resurgence of influenza in the southernmost state of Brazil, Rio Grande do Sul (RS). The present study aimed to identify the circulation of FLUAV, FLUBV and SARS-CoV-2 and characterize the influenza genomes in respiratory samples using high-throughput sequencing technology (HTS). Respiratory samples (n = 694) from patients in RS were selected between July 2021 and August 2022. The samples were typed using reverse transcriptase real-time PCR (RT-qPCR) and showed 32% (223/694) of the samples to be positive for SARS-CoV-2, 7% for FLUAV (H3) (49/694). FLUBV was not detected. RT-qPCR data also resulted in FLUAV and SARS-CoV-2 co-infections in 1.7% (4/223) of samples tested. Whole genome sequencing of FLUAV produced 15 complete genomes of the H3N2 subtype, phylogenetically classified in the 3C.2a1b.2a.2a.3 subclade and revealing the dominance of viruses in the southern region of Brazil. Mutation analysis identified 72 amino acid substitutions in all genes, highlighting ongoing genetic evolution with potential implications for vaccine effectiveness, viral fitness, and pathogenicity. This study underscores limitations in current surveillance systems, advocating for comprehensive data inclusion to enhance understanding of influenza epidemiology in southern Brazil. These findings contribute valuable insights to inform more effective public health responses and underscore the critical need for continuous genomic surveillance.
Assuntos
COVID-19 , Genoma Viral , Influenza Humana , Filogenia , SARS-CoV-2 , Humanos , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pessoa de Meia-Idade , Adulto , Feminino , Genoma Viral/genética , Masculino , Adulto Jovem , Idoso , Adolescente , Surtos de Doenças , Sequenciamento Completo do Genoma , Criança , Pré-Escolar , Lactente , Coinfecção/epidemiologia , Coinfecção/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Idoso de 80 Anos ou mais , GenômicaRESUMO
A low-cost, lab-made polytetrafluoroethylene micro-cell, equipped with three electrodes, wasd eveloped for the impedimetric detection of SARS-CoV-2. The gold working electrode was modified with a double-ended thiolated poly-adenine probe, which was conjugated with magnetic Fe3O4@Au nanoparticles (Fe3O4@Au-(S-polyA-S)-Au). After the loop-mediated isothermal amplification (LAMP) of viral RNA, the single-guide RNA (sgRNA), specifically bound to the SARS-CoV-2 target sequence, activates Cas12a. Cas12a then cleaved the immobilized probe. As a result, the magnetic Fe3O4@Au nanoparticles were released and adsorbed onto the gold electrode surface, using an external magnet. This process increased the physical surface area of the gold electrode, facilitating redox ion ([FeIII/II(CN)6]3-/4-) electron transfer. The decrease in the charge transfer resistance was utilized for SARS-CoV-2 detection. Our LAMP-CRISPR/Cas12a-based impedimetric biosensor, powered by Fe3O4@Au-(S-polyA-S)-Au, demonstrated impressive capabilities, including a remarkable detection limit of 0.8 aM (0.48 copies/µL) and a linear range of 0.01 to 36.06 fM.
Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Ouro , Técnicas de Amplificação de Ácido Nucleico , RNA Viral , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Técnicas Biossensoriais/métodos , Ouro/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , RNA Viral/análise , COVID-19/diagnóstico , COVID-19/virologia , Limite de Detecção , Eletrodos , Poli A/química , Proteínas Associadas a CRISPR , Nanopartículas de Magnetita/química , Endodesoxirribonucleases/química , Nanopartículas Metálicas/química , Proteínas de Bactérias , Técnicas de Diagnóstico MolecularRESUMO
The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.
Assuntos
COVID-19 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hospitalização , Humanos , COVID-19/genética , COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , SARS-CoV-2/genética , Feminino , Masculino , Loci Gênicos , Fatores de Risco , Polimorfismo de Nucleotídeo Único , Pessoa de Meia-Idade , Idoso , América Latina/epidemiologiaRESUMO
Single-cell RNA sequencing (scRNA-seq) technologies can generate transcriptomic profiles at a single-cell resolution in large patient cohorts, facilitating discovery of gene and cellular biomarkers for disease. Yet, when the number of biomarker genes is large, the translation to clinical applications is challenging due to prohibitive sequencing costs. Here, we introduce scPanel, a computational framework designed to bridge the gap between biomarker discovery and clinical application by identifying a sparse gene panel for patient classification from the cell population(s) most responsive to perturbations (e.g. diseases/drugs). scPanel incorporates a data-driven way to automatically determine a minimal number of informative biomarker genes. Patient-level classification is achieved by aggregating the prediction probabilities of cells associated with a patient using the area under the curve score. Application of scPanel to scleroderma, colorectal cancer, and COVID-19 datasets resulted in high patient classification accuracy using only a small number of genes (<20), automatically selected from the entire transcriptome. In the COVID-19 case study, we demonstrated cross-dataset generalizability in predicting disease state in an external patient cohort. scPanel outperforms other state-of-the-art gene selection methods for patient classification and can be used to identify parsimonious sets of reliable biomarker candidates for clinical translation.
Assuntos
COVID-19 , Análise de Célula Única , Humanos , COVID-19/genética , COVID-19/virologia , Análise de Célula Única/métodos , Biologia Computacional/métodos , Transcriptoma , RNA-Seq/métodos , Neoplasias Colorretais/genética , Neoplasias Colorretais/classificação , Perfilação da Expressão Gênica/métodos , SARS-CoV-2/genética , Análise de Sequência de RNA/métodos , Software , Análise da Expressão Gênica de Célula ÚnicaRESUMO
BACKGROUND: This retrospective observational matched cohort study assessed the differences in critical infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the omicron-predominant period of the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the vaccine effectiveness of bivalent mRNA vaccine compared to unvaccinated individuals. METHODS: We collected COVID-19 case data from the Korean COVID-19 vaccine effectiveness cohort. We calculated the probability of critical COVID-19 cases by comparing the vaccinated and unvaccinated groups. RESULTS: The risk of being critically infected due to SAR-CoV-2 infection was 5.96 times higher (95% confidence interval, 5.63-6.38) among older individuals who were unvaccinated compared to those who received the bivalent COVID-19 vaccine. CONCLUSION: Our findings indicate that the bivalent vaccine reduces the disease burden of the SARS-CoV-2 omicron variant, particularly among the older population. Further studies are warranted to determine the effectiveness of booster doses of vaccines for SARS-CoV-2 infection.
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Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , República da Coreia/epidemiologia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Eficácia de Vacinas , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among polycystic ovary syndrome (PCOS) is significantly higher than in the general population. However, the mechanisms underlying this remain obscure. This study aimed to explore the mechanisms by identifying the genetic signature of SARS-CoV-2 infection in PCOS. In the present study, a total of 27 common differentially expressed genes (DEGs) were selected for subsequent analyses. Functional analyses showed that immunity and hormone-related pathways collectively participated in the development and progression of PCOS and SARS-CoV-2 infection. Under these, 7 significant hub genes were identified, including S100A9, MMP9, TLR2, THBD, ITGB2, ICAM1, and CD86 by using the algorithm in Cytoscape. Furthermore, hub gene expression was confirmed in the validation set, PCOS clinical samples, and mouse model. Immune microenvironment analysis with the CIBERSORTx database demonstrated that the hub genes were significantly correlated with T cells, dendritic cells, mast cells, B cells, NK cells, and eosinophils and positively correlated with immune scores. Among the hub genes, S100A9, MMP9, THBD, ITGB2, CD86, and ICAM1 demonstrated potential as possible diagnostic markers for COVID-19 and PCOS. In addition, we established the interaction networks of ovary-specific genes, transcription factors, miRNAs, drugs, and chemical compounds with hub genes with NetworkAnalyst. This work uncovered the common pathogenesis and genetic signature of PCOS and SARS-CoV-2 infection, which might provide a theoretical basis and innovative ideas for further mechanistic research and drug discovery of the comorbidity of the two diseases.
Assuntos
COVID-19 , Biologia Computacional , Síndrome do Ovário Policístico , SARS-CoV-2 , Feminino , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/virologia , COVID-19/genética , COVID-19/virologia , Humanos , SARS-CoV-2/genética , Animais , Camundongos , Biologia Computacional/métodos , Redes Reguladoras de Genes , Modelos Animais de Doenças , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Influenza outbreaks have occurred frequently these years, especially in the summer of 2022 when the number of influenza cases in southern provinces of China increased abnormally. However, the exact evidence of the driving factors involved in the prodrome period is unclear, posing great difficulties for early and accurate prediction in practical work. METHODS: In order to avoid the serious interference of strict prevention and control measures on the analysis of influenza influencing factors during the COVID-19 epidemic period, only the impact of meteorological and air quality factors on influenza A (H3N2) in Xiamen during the non coronavirus disease 2019 (COVID-19) period (2013/01/01-202/01/24) was analyzed using the distribution lag non-linear model. Phylogenetic analysis of influenza A (H3N2) during 2013-2022 was also performed. Influenza A (H3N2) was predicted through a random forest and long short-term memory (RF-LSTM) model via actual and forecasted meteorological and influenza A (H3N2) values. RESULTS: Twenty nine thousand four hundred thirty five influenza cases were reported in 2022, accounting for 58.54% of the total cases during 2013-2022. A (H3N2) dominated the 2022 summer epidemic season, accounting for 95.60%. The influenza cases in the summer of 2022 accounted for 83.72% of the year and 49.02% of all influenza reported from 2013 to 2022. Among them, the A (H3N2) cases in the summer of 2022 accounted for 83.90% of all A (H3N2) reported from 2013 to 2022. Daily precipitation(20-50 mm), relative humidity (70-78%), low (≤ 3 h) and high (≥ 7 h) sunshine duration, air temperature (≤ 21 °C) and O3 concentration (≤ 30 µg/m3, > 85 µg/m3) had significant cumulative effects on influenza A (H3N2) during the non-COVID-19 period. The daily values of PRE, RHU, SSD, and TEM in the prodrome period of the abnormal influenza A (H3N2) epidemic (19-22 weeks) in the summer of 2022 were significantly different from the average values of the same period from 2013 to 2019 (P < 0.05). The minimum RHU value was 70.5%, the lowest TEM value was 16.0 °C, and there was no sunlight exposure for 9 consecutive days. The highest O3 concentration reached 164 µg/m3. The range of these factors were consistent with the risk factor range of A (H3N2). The common influenza A (H3N2) variant genotype in 2022 was 3 C.2a1b.2a.1a. It was more accurate to predict influenza A (H3N2) with meteorological forecast values than with actual values only. CONCLUSION: The extreme weather conditions of sustained low temperature and wet rain may have been important driving factors for the abnormal influenza A (H3N2) epidemic. A low vaccination rate, new mutated strains, and insufficient immune barriers formed by natural infections may have exacerbated this epidemic. Meteorological forecast values can aid in the early prediction of influenza outbreaks. This study can help relevant departments prepare for influenza outbreaks during extreme weather, provide a scientific basis for prevention strategies and risk warnings, better adapt to climate change, and improve public health.
Assuntos
COVID-19 , Vírus da Influenza A Subtipo H3N2 , Influenza Humana , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , China/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Estações do Ano , Filogenia , Epidemias , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infections. Some of these infections are linked to specific clinical and immunological subgroups of GBS, suggesting a potential correlation between viral infections and the development of GBS. However, observational studies have several limitations, including the presence of confounding factors. METHOD: We explored the potential correlation between HIV, SARS-CoV-2, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, hepatitis B virus, and influenza virus with GBS using a two-sample Mendelian randomization approach. The data was derived from published summary statistics from genome-wide association studies (GWAS). After removing linkage disequilibrium, selecting strong instrumental variables and addressing confounding factors, we would conduct a two-sample Mendelian randomization analysis along with sensitivity testing and the MR-Steiger directional test. RESULT: HIV may have a causal association with GBS (IVW: p = 0.010, OR [95% CI] 1.240 [1.052-1.463]), while no such relationship exists with COVID-19 (IVW: p = 0.275, OR [95% CI] 0.831[0.596-1.159]), varicella (IVW: p = 0.543, OR [95% CI] 0.919 [0.701-1.206]), herpes zoster (IVW: p = 0.563, OR [95% CI] 0.941 [0.766-1.156]), HSV (IVW: p = 0.280, OR [95% CI] 1.244 [0.837-1.851]), EBV (IVW: p = 0.218, OR [95% CI] 0.883 [0.724-1.076]), HBV (IVW: p = 0.179, OR [95% CI] 1.072 [0.969-1.187]), or influenza virus (IVW: p = 0.917, OR [95% CI] 0.971 [0.553-1.703]). We did not find any abnormal SNPs, pleiotropy, or heterogeneity, nor is there any reverse causation. CONCLUSION: Our study results indicate a causal relationship between HIV and GBS, providing new research directions for the etiology of GBS.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome de Guillain-Barré , Análise da Randomização Mendeliana , Viroses , Humanos , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/virologia , Viroses/genética , Viroses/complicações , Fatores de Risco , Polimorfismo de Nucleotídeo Único/genética , SARS-CoV-2/genéticaRESUMO
Introduction: The immune response regulates the severity of COVID-19 (sCOVID-19). This study examined the cause-and-effect relationship between immune cell traits (ICTs) and the risk of severe COVID-19. Additionally, we discovered the potential role of plasma metabolome in modulating this risk. Methods: Employing data from a genome-wide association study (GWAS), we conducted a two-sample Mendelian randomization (MR) assessment of 731 genetic ICTs and sCOVID-19 (5,101 cases, 1,383,241 controls) incidence. The MR analysis was utilized to further quantitate the degree of plasma metabolome-mediated regulation of immune traits in sCOVID-19. Results: The inverse variance weighted method recognized 2 plasma metabolites (PMs) responsible for casual associations between immune cells and sCOVID-19 risk. These included Tridecenedioate (C13:1-DC) which regulated the association between CD27 on IgD- CD38br (OR 0.804, 95% CI 0.699-0.925, p = 0.002) and sCOVID-19 risk (mediated proportion: 18.7%); arginine to citrulline ratio which controlled the relationship of CD39 on monocyte (OR 1.053, 95% CI 1.013-1.094, p = 0.009) with sCOVID-19 risk (mediated proportion: -7.11%). No strong evidence that genetically predicted sCOVID-19 influenced the aforementioned immune traits. Conclusion: In this study, we have successfully identified a cause-and-effect relationship between certain ICTs, PMs, and the likelihood of contracting severe COVID-19. Our findings can potentially improve the accuracy of COVID-19 prognostic evaluation and provide valuable insights into the underlying mechanisms of the disease.
Assuntos
COVID-19 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Metaboloma , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Índice de Gravidade de Doença , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To verify the use and identify advantages of molecular methods for congenital infections diagnosis in cerebrospinal fluid of neonates. DATA SOURCE: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under CRD42021274210. The literature search was performed in databases: PubMed, Virtual Health Library/ Latin American and Caribbean Center on Health Sciences Information (VHL/BIREME), Scopus, Web of Science, Excerpta Medica database (EMBASE), Cochrane, ProQuest, and EBSCOhost. The search was carried out from August to October 2021 and updated in December 2022, respecting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The selection sequence was: 1) Duplicate title removal; 2) Examination of titles and abstracts; 3) Full-text retrieval of potentially relevant reports; and 4) Evaluation of the full text according to eligibility criteria by two independent authors. Inclusion criteria considered randomized and non-randomized control trials, longitudinal, cross-sectional, and peer-reviewed studies in humans, published in English, Spanish, Italian, and Portuguese, with newborns up to 28 days old who had congenital neuroinfections by toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH), and others such as Treponema pallidum, Zika, parvovirus B-19, varicella zoster, Epstein-Barr, and SARS-CoV2, diagnosed by polymerase chain reaction (PCR). Two evaluators extracted the following information: author, year of publication, nationality, subjects, study type, methods, results, and conclusion. DATA SYNTHESIS: The most studied pathogen was herpes simplex. Several articles reported only nonspecific initial symptoms, motivating the collection of cerebrospinal fluid and performing PCR for etiological investigation. CONCLUSIONS: Molecular methods are effective to detect pathogen genomes in cerebrospinal fluid, which can impact clinical evolution and neurological prognosis.
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COVID-19 , Humanos , Recém-Nascido , COVID-19/diagnóstico , COVID-19/líquido cefalorraquidiano , SARS-CoV-2/genética , Herpes Simples/diagnóstico , Herpes Simples/líquido cefalorraquidiano , Herpes Simples/congênito , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/líquido cefalorraquidianoRESUMO
It is estimated that there are 544.9 million people suffering from chronic respiratory diseases in the world, which is the third largest chronic disease. Although there are various clinical treatment methods, there is no specific drug for chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF). Therefore, it is urgent to clarify the pathological mechanism and medication development. Single-cell transcriptome data of human and mouse from GEO database were integrated by "Harmony" algorithm. The data was standardized and normalized by using "Seurat" package, and "SingleR" algorithm was used for cell grouping annotation. The "Findmarker" function is used to find differentially expressed genes (DEGs), which were enriched and analyzed by using "clusterProfiler", and a protein interaction network was constructed for DEGs, and four algorithms are used to find the hub genes. The expression of hub genes were analyzed in independent human and mouse single-cell transcriptome data. Bulk RNA data were used to integrate by the "SVA" function, verify the expression levels of hub genes and build a diagnostic model. The L1000FWD platform was used to screen potential drugs. Through exploring the similarities and differences by integrated single-cell atlas, we found that the lung parenchymal cells showed abnormal oxidative stress, cell matrix adhesion and ubiquitination in COPD, corona virus disease 2019 (COVID-19), ILD and IPF. Meanwhile, the lung resident immune cells showed abnormal Toll-like receptor signals, interferon signals and ubiquitination. However, unlike acute pneumonia (COVID-19), chronic pulmonary disease shows enhanced ubiquitination. This phenomenon was confirmed in independent external human single-cell atlas, but unfortunately, it was not confirmed in mouse single-cell atlas of bleomycin-induced pulmonary fibrosis model and influenza virus-infected mouse model, which means that the model needs to be optimized. In addition, the bulk RNA-Seq data of COVID-19, ILD and IPF was integrated, and we found that the immune infiltration of lung tissue was enhanced, consistent with the single-cell level, UBA52, UBB and UBC were low expressed in COVID-19 and high expressed in ILD, and had a strong correlation with the expression of cell matrix adhesion genes. UBA52 and UBB have good diagnostic efficacy, and salermide and SSR-69071 can be used as their candidate drugs. Our study found that the disorder of protein ubiquitination in chronic pulmonary diseases is an important cause of pathological phenotype of pulmonary fibrosis by integrating scRNA-Seq and bulk RNA-Seq, which provides a new horizons for clinicopathology, diagnosis and treatment.
Assuntos
RNA-Seq , Ubiquitina , Humanos , Animais , Camundongos , Ubiquitina/metabolismo , Ubiquitina/genética , Análise de Célula Única/métodos , Transcriptoma , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas , Doença Crônica , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/metabolismo , SARS-CoV-2/genética , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Análise da Expressão Gênica de Célula ÚnicaRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection typically relies on reverse transcription-polymerase chain reaction (RT-PCR) technology. However, there is a certain rate of missed detection of SARS-CoV-2 in nasopharyngeal samples, particularly among immunosuppressed individuals. METHODS: In this case, SARS-CoV-2 was detected in nasopharyngeal swabs and bronchoalveolar lavage fluid (BALF) using RT-PCR. Pulmonary imaging was performed using computed tomography (CT). Patient clinical data were retrieved from the Laboratory Information System (LIS). RESULTS: SARS-CoV-2 was negative in two nasopharyngeal tests of the patient, but was finally detected in BALF, confirming that the lung lesions were infected by SARS-CoV-2. CONCLUSIONS: In the post-epidemic era, it is necessary to use BALF to identify SARS-CoV-2 infection in cases where other factors have been ruled out in immunosuppressed individuals with pulmonary infections, especially when the nasopharyngeal test yields a negative result.
Assuntos
Líquido da Lavagem Broncoalveolar , COVID-19 , Nasofaringe , SARS-CoV-2 , Humanos , Líquido da Lavagem Broncoalveolar/virologia , COVID-19/diagnóstico , COVID-19/virologia , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Tomografia Computadorizada por Raios X , Masculino , Teste de Ácido Nucleico para COVID-19 , Pessoa de Meia-Idade , Feminino , Hospedeiro ImunocomprometidoRESUMO
Horseshoe bats (genus Rhinolophus, family Rhinolophidae) represent an important group within chiropteran phylogeny due to their distinctive traits, including constant high-frequency echolocation, rapid karyotype evolution, and unique immune system. Advances in evolutionary biology, supported by high-quality reference genomes and comprehensive whole-genome data, have significantly enhanced our understanding of species origins, speciation mechanisms, adaptive evolutionary processes, and phenotypic diversity. However, genomic research and understanding of the evolutionary patterns of Rhinolophus are severely constrained by limited data, with only a single published genome of R. ferrumequinum currently available. In this study, we constructed a high-quality chromosome-level reference genome for the intermediate horseshoe bat ( R. affinis). Comparative genomic analyses revealed potential genetic characteristics associated with virus tolerance in Rhinolophidae. Notably, we observed expansions in several immune-related gene families and identified various genes functionally associated with the SARS-CoV-2 signaling pathway, DNA repair, and apoptosis, which displayed signs of rapid evolution. In addition, we observed an expansion of the major histocompatibility complex class II (MHC-II) region and a higher copy number of the HLA- DQB2 gene in horseshoe bats compared to other chiropteran species. Based on whole-genome resequencing and population genomic analyses, we identified multiple candidate loci (e.g., GLI3) associated with variations in echolocation call frequency across R. affinis subspecies. This research not only expands our understanding of the genetic characteristics of the Rhinolophus genus but also establishes a valuable foundation for future research.
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Quirópteros , Ecolocação , Genoma , Animais , Quirópteros/genética , Quirópteros/virologia , Quirópteros/fisiologia , SARS-CoV-2/fisiologia , SARS-CoV-2/genética , Cromossomos/genéticaRESUMO
BACKGROUND: The Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses. METHODS: This paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference. RESULTS: The model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15-0.29) and transmission rate of 5.0 (95% CI 2.4-6.6) for the Omicron variant. CONCLUSIONS: The study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/transmissão , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , Philadelphia/epidemiologiaRESUMO
Long COVID is a poorly understood condition characterized by persistent symptoms following the acute phase of COVID-19, including fatigue, cognitive impairment, and joint pain. Acupuncture, a key component of traditional Chinese medicine treatment, has shown potential in alleviating long COVID symptoms. However, the molecular mechanisms underlying its therapeutic effects remain largely unknown. In this study, we employed bioinformatics approaches to explore the potential molecular mechanisms of acupuncture's therapeutic effects on long COVID symptoms. We screened protein targets of active ingredients produced by the body after acupuncture and identified potential therapeutic targets of long COVID. Protein-protein interaction networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify key targets and pathways. Our findings provide valuable insights into the potential molecular mechanisms of acupuncture's therapeutic effects on long COVID symptoms and may contribute to the development of targeted therapies for managing this challenging condition.
Assuntos
Terapia por Acupuntura , COVID-19 , Biologia Computacional , Ontologia Genética , Mapas de Interação de Proteínas , SARS-CoV-2 , Humanos , Terapia por Acupuntura/métodos , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , COVID-19/terapia , COVID-19/genética , COVID-19/virologia , SARS-CoV-2/genética , Síndrome de COVID-19 Pós-Aguda , Medicina Tradicional Chinesa/métodosRESUMO
Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on a platform that streamlines biosensor discovery and unlocks directed nanosensor evolution through genetically encodable fluorogenic amino acids (FgAAs). Building on the classical knowledge-based semisynthetic approach, we engineer ~15 kDa nanosensors that recognize specific proteins, peptides, and small molecules with up to 100-fold fluorescence increases and subsecond kinetics, allowing real-time and wash-free target sensing and live-cell bioimaging. An optimized genetic code expansion chemistry with FgAAs further enables rapid (~3 h) ribosomal nanosensor discovery via the cell-free translation of hundreds of candidates in parallel and directed nanosensor evolution with improved variant-specific sensitivities (up to ~250-fold) for SARS-CoV-2 antigens. Altogether, this platform could accelerate the discovery of fluorogenic nanosensors and pave the way to modify proteins with other non-standard functionalities for diverse applications.
Assuntos
Aminoácidos , Técnicas Biossensoriais , Corantes Fluorescentes , SARS-CoV-2 , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Humanos , SARS-CoV-2/genética , COVID-19/virologia , Nanotecnologia/métodos , Peptídeos/metabolismo , Peptídeos/química , Peptídeos/genéticaRESUMO
Human coronaviruses (hCoVs) infect millions of people every year. Among these, MERS, SARS-CoV-1, and SARS-CoV-2 caused significant morbidity and mortality and their emergence highlights the risk of possible future coronavirus outbreaks. Therefore, broadly-active anti-coronavirus drugs are needed. Pharmacological inhibition of the hCoV protease Nsp5 (3CLpro) is clinically beneficial as shown by the wide and effective use of Paxlovid (nirmatrelvir, ritonavir). However, further treatment options are required due to the risk of drug resistance. To facilitate the assessment of coronavirus protease function and its pharmacological inhibition, we developed an assay allowing rapid and reliable quantification of Nsp5 activity under biosafety level 1 conditions. It is based on an ACE2-Gal4 transcription factor fusion protein separated by a Nsp5 recognition site. Cleavage by Nsp5 releases the Gal4 transcription factor, which then induces the expression of Gaussia luciferase. Our assay is compatible with Nsp5 proteases from all hCoVs and allows simultaneous measurement of inhibitory and cytotoxic effects of the tested compounds. Proof-of-concept measurements confirmed that nirmatrelvir, GC376 and lopinavir inhibit SARS-CoV-2 Nsp5 function. Furthermore, the assay accurately predicted the impact of Nsp5 mutations on catalytic activity and inhibitor sensitivity. Overall, the reporter assay is suitable for evaluating viral protease activity.
Assuntos
Proteases 3C de Coronavírus , Luciferases , Humanos , Luciferases/metabolismo , Luciferases/genética , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/antagonistas & inibidores , Genes Reporter , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , Antivirais/farmacologia , Células HEK293RESUMO
The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02-0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56-0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5-0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07-1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97-1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95-1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.
Assuntos
COVID-19 , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Idoso , Adulto , Receptor 7 Toll-Like/genética , TYK2 Quinase/genética , Genótipo , Predisposição Genética para Doença , 2',5'-Oligoadenilato Sintetase/genéticaRESUMO
Recent studies suggest an increased risk of reinfection with the SARS-CoV-2 Omicron variant compared with previous variants, potentially due to an increased ability to escape immunity specific to older variants, high antigenic divergence of Omicron from earlier virus variants as well as its altered cell entry pathway. The present study sought to investigate epidemiological evidence for differential SARS-CoV-2 reinfection intervals and incidence rates for the Delta versus Omicron variants within Wales. Reinfections in Wales up to February 2022 were defined using genotyping and whole genome sequencing. The median inter-infection intervals for Delta and Omicron were 226 and 192 days, respectively. An incidence rate ratio of 2.17 for reinfection with Omicron compared to Delta was estimated using a conditional Poisson model, which accounted for several factors including sample collection date, age group, area of residence, vaccination and travel status. These findings are consistent with an increased risk of reinfection with the Omicron variant, and highlight the value of monitoring emerging variants that have the potential for causing further waves of cases.