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1.
Viruses ; 14(7)2022 Jun 25.
Article in English | MEDLINE | ID: covidwho-1911655

ABSTRACT

Infectious Bronchitis virus (IBV) continues to cause significant economic losses for the chicken industry despite the use of many live IBV vaccines around the world. Several authors have suggested that vaccine-induced partial protection may contribute to the emergence of new IBV strains. In order to study this hypothesis, three passages of a challenge IBV were made in SPF chickens sham inoculated or vaccinated at day of age using a live vaccine heterologous to the challenge virus. All birds that were challenged with vaccine heterologous virus were positive for viral RNA. NGS analysis of viral RNA in the unvaccinated group showed a rapid selection of seven genetic variants, finally modifying the consensus genome of the viral population. Among them, five were non-synonymous, modifying one position in NSP 8, one in NSP 13, and three in the Spike protein. In the vaccinated group, one genetic variant was selected over the three passages. This synonymous modification was absent from the unvaccinated group. Under these conditions, the genome population of an IBV challenge virus evolved rapidly in both heterologous vaccinated and non-vaccinated birds, while the genetic changes that were selected and the locations of these were very different between the two groups.


Subject(s)
Bronchitis , Communicable Diseases , Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Viral Vaccines , Animals , Chickens , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Evolution, Molecular , Infectious bronchitis virus/genetics , RNA, Viral/genetics , Vaccines, Attenuated , Viral Vaccines/genetics
2.
Biomed Pharmacother ; 152: 113254, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1889242

ABSTRACT

Sang Xing decoction (SXD) is a typical prescription for treating "warm dryness" in traditional Chinese medicine (TCM), which is equivalent to respiratory diseases such as acute bronchitis in modern medicine. However, its mechanism of action remains unclear. In this study, the representative components of SXD were characterized using liquid chromatography-tandem mass spectrometry (LC-MS). The key targets, signaling pathways, and metabolic pathways associated with SXD in the treatment of acute bronchitis were identified via network prediction and metabolomics. A rat model of acute bronchitis was also established using mixed smoke, systematic in vivo experiments such as histopathological analyses, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunohistochemistry and western blotting were conducted to evaluate the network prediction results. An in-depth analysis of the targeted quantitative results was performed using the SIMCA software and MetaboAnalyst website. The results revealed that 50 active compounds and 45 key targets were screened and clustered with 20 approved drugs. The NF-κB signaling pathway, oxidative stress, and glutamine metabolism were associated with the therapeutic mechanism of SXD in acute bronchitis. In vivo experiments showed that SXD may maintain the production of inflammatory factors by regulating the PI3K/Akt/NF-κB signaling pathway, improving the metabolism of glutamine and glutamate to reduce oxidative stress, and inhibiting apoptosis. Simultaneously, the possibility of using SXD as an adjuvant drug for COVID-19 treatment was also revealed. This research will lay the foundation for the modern clinical application of SXD and promote the promotion and innovation of TCM.


Subject(s)
Bronchitis , COVID-19 , Drugs, Chinese Herbal , Animals , Bronchitis/drug therapy , COVID-19/drug therapy , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Glutamine , Humans , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases , Rats , Smoke
4.
Cells ; 11(9)2022 04 21.
Article in English | MEDLINE | ID: covidwho-1818055

ABSTRACT

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton's jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.


Subject(s)
Bronchitis , COVID-19 , Mesenchymal Stem Cells , Wharton Jelly , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Bronchitis/metabolism , Chickens , Humans , Immunologic Factors/metabolism , Mesenchymal Stem Cells/metabolism , SARS-CoV-2 , Secretome , Wharton Jelly/metabolism
5.
Virus Genes ; 58(3): 203-213, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1766911

ABSTRACT

Infectious bronchitis virus (IBV) and avian influenza virus (AIV) are two major respiratory infections in chickens. The coinfection of these viruses can cause significant financial losses and severe complications in the poultry industry across the world. To examine transcriptome profile changes during the early stages of infection, differential transcriptional profiles in tracheal tissue of three infected groups (i.e., IBV, AIV, and coinfected) were compared with the control group. Specific-pathogen-free chickens were challenged with Iranian variant-2-like IBV (IS/1494), UT-Barin isolates of H9N2 (A/chicken/Mashhad/UT-Barin/2017), and IBV-AIV coinfection; then, RNA was extracted from tracheal tissue. The Illumina RNA-sequencing (RNA-seq) technique was employed to investigate changes in the Transcriptome. Up- and downregulated differentially expressed genes (DEGs) were detected in the trachea transcriptome of all groups. The Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology databases were examined to identify possible relationships between DEGs. In the experimental groups, upregulated genes were higher compared to downregulated genes. A more severe immune response was observed in the coinfected group; further, cytokine-cytokine receptor interaction, RIG-I-like receptor signaling, Toll-like receptor signaling, NOD-like receptor signaling, Janus kinase/signal transducer, and activator of transcription, and apoptotic pathways were important upregulated genes in this group. The findings of this paper may give a better understanding of transcriptome changes in the trachea during the early stages of infection with these viruses.


Subject(s)
Bronchitis , Coinfection , Coronavirus Infections , Infectious bronchitis virus , Influenza A Virus, H9N2 Subtype , Influenza in Birds , Poultry Diseases , Animals , Bronchitis/genetics , Bronchitis/veterinary , Chickens , Gene Expression Profiling , Infectious bronchitis virus/genetics , Influenza A Virus, H9N2 Subtype/genetics , Influenza in Birds/genetics , Iran , Poultry Diseases/genetics , RNA , Trachea , Transcriptome/genetics
6.
Viruses ; 14(3)2022 02 27.
Article in English | MEDLINE | ID: covidwho-1744919

ABSTRACT

Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the early phase. Only a limited number of international exacerbation cohorts were studied. Here, we have established a local pediatric exacerbation study in Germany consisting of children with asthma or chronic, recurrent bronchitis and analyzed the viriome within the nasopharyngeal swab specimens derived from the entire cohort (n = 141). Interestingly, 41% of exacerbated children had a positive test result for human rhinovirus (HRV)/human enterovirus (HEV), and 14% were positive for respiratory syncytial virus (RSV). HRV was particularly prevalent in asthmatics (56%), wheezers (50%), and atopic (66%) patients. Lymphocytes were decreased in asthmatics and in HRV-infected subjects, and patients allergic to house dust mites were more susceptible to HRV infection. Our study thus confirms HRV infection as a strong 'biomarker' of exacerbated asthma. Further longitudinal studies will show the clinical progress of those children with a history of an RSV or HRV infection. Vaccination strategies and novel treatment guidelines against HRV are urgently needed to protect those high-risk children from a serious course of disease.


Subject(s)
Asthma , Bronchitis , Enterovirus Infections , Enterovirus , Picornaviridae Infections , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Virus Diseases , Viruses , Asthma/epidemiology , Biomarkers , Child , Humans , Infant , Respiratory Tract Infections/epidemiology , Rhinovirus
7.
Semin Respir Crit Care Med ; 43(2): 243-247, 2022 04.
Article in English | MEDLINE | ID: covidwho-1637081

ABSTRACT

Although few studies evaluated the incidence of hospital-acquired pneumonia (HAP) or ventilator-associated tracheobronchitis in COVID-19 patients, several studies evaluated the incidence of ventilator-associated pneumonia (VAP) in these patients. Based on the results of a large multicenter European study, VAP incidence is higher in patients with SARS-CoV-2 pneumonia (36.1%), as compared with those with influenza pneumonia (22.2%), or no viral infection at intensive care unit (ICU) admission (16.5%). Potential explanation for the high incidence of VAP in COVID-19 patients includes long duration of invasive mechanical ventilation, high incidence of acute respiratory distress syndrome, and immune-suppressive treatment. Specific risk factors for VAP, including SARS-CoV-2-related pulmonary lesions, and bacteria-virus interaction in lung microbiota might also play a role in VAP pathogenesis. VAP is associated with increased mortality, duration of mechanical ventilation, and ICU length of stay in COVID-19 patients. Further studies should focus on the incidence of HAP especially in ICU non-ventilated patients, better determine the pathophysiology of these infections, and evaluate the accuracy of currently available treatment guidelines in COVID-19 patients.


Subject(s)
Bronchitis , COVID-19 , Pneumonia, Ventilator-Associated , Tracheitis , Bronchitis/epidemiology , Bronchitis/etiology , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Hospitals , Humans , Intensive Care Units , Pneumonia, Ventilator-Associated/epidemiology , Respiration, Artificial/adverse effects , SARS-CoV-2 , Tracheitis/epidemiology , Tracheitis/etiology , Ventilators, Mechanical
8.
Pediatr Pulmonol ; 57(2): 529-537, 2022 02.
Article in English | MEDLINE | ID: covidwho-1490884

ABSTRACT

BACKGROUND AND OBJECTIVES: Plastic bronchitis (PB) is a condition characterized by the formation of thick airway casts leading to acute and often life-threatening airway obstruction. PB occurs mainly in pediatric patients with congenital heart disease (CHO) who have undergone staged surgical palliation (Glenn, Fontan), but can also occur after chemical inhalation, H1N1, severe COVID-19, sickle cell disease, severe asthma, and other diseases. Mortality risk from PB can be up to 40%-60%, and no treatment guideline exist. The objectives herein are to develop a standardized evaluation, classification, and treatment guideline for PB patients presenting with tracheobronchial casts, based on our experience with PB at the Children's Hospital of Colorado in Denver. METHODS: We describe 11 patients with CHO-associated PB (post-Fontan [n = 9], pre-Fontan [n = 2]) who presented with their initial episodes. We utilized histopathological analysis of tracheobronchial casts to guide treatment in these patients, utilizing our hospital-wide guideline document and classification system. RESULTS: We found that 100% of post-Fontan PB patients had fibrinous airway casts, while pre-Fontan PB casts were fibrinous only in one of two patients (50%). Utilizing histopathology as a guide to therapy, PB patients with fibrin airway casts were treated with airway-delivered fibrinolytics and anticoagulants, as well as aggressive airway clearance and other supportive care measures. These therapies resulted in successful cast resolution and improved survival in post-Fontan PB patients. CONCLUSION: We have shown an improved outcome in PB patients whose treatment plan was based on Denver's PB classification schema and standardized treatment guideline based on tracheobronchial cast histopathology.


Subject(s)
Airway Obstruction , Bronchitis , COVID-19 , Fontan Procedure , Influenza A Virus, H1N1 Subtype , Airway Obstruction/etiology , Airway Obstruction/therapy , Bronchitis/diagnosis , Bronchitis/therapy , Child , Fibrin , Humans , SARS-CoV-2
10.
Pulm Med ; 2021: 6680232, 2021.
Article in English | MEDLINE | ID: covidwho-1334599

ABSTRACT

INTRODUCTION: The SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test is useful for diagnosing COVID-19, and the RT-PCR positive rate is an important indicator for estimating the incidence rate and number of infections. COVID-19 pneumonia is also associated with characteristic findings on chest CT, which can aid in diagnosis. METHODS: We retrospectively evaluated patient background characteristics, the number of cases, the positivity rate, and chest CT findings for positive and negative cases in 672 patients who underwent RT-PCR for suspected COVID-19 at our hospital between April 3 and August 28, 2020. In addition, we compared trends in the positive rates at approximately weekly intervals with trends in the number of new infections in Machida City, Tokyo. RESULTS: The study included 323 men and 349 women, with a median age of 46 years (range: 1 month-100 years). RT-PCR findings were positive in 37 cases, and the positive rate was 5.51%. Trends in the positive rate at our hospital and the number of new COVID-19 cases in the city were similar during the study period. Among patients with positive results, 15 (40.5%) had chest CT findings, and 14 had bilateral homogeneous GGOs. Among patients with negative results, 190 had chest CT findings at the time of examination, and 150 were diagnosed with bacterial pneumonia or bronchitis, with main findings consisting of consolidations and centrilobular opacities. Only 11 of these patients exhibited bilateral homogeneous GGOs. CONCLUSION: Bilateral homogeneous GGOs are characteristic of COVID-19 pneumonia and may aid in the diagnosis of COVID-19.


Subject(s)
COVID-19/diagnostic imaging , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Bronchitis/diagnostic imaging , COVID-19/diagnosis , Child , Child, Preschool , Female , Hospitals, Municipal , Humans , Infant , Male , Middle Aged , Pneumonia, Bacterial/diagnostic imaging , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Tokyo , Young Adult
11.
BMJ Open Qual ; 10(3)2021 07.
Article in English | MEDLINE | ID: covidwho-1295223

ABSTRACT

BACKGROUND: Antibiotics are not recommended for treatment of acute uncomplicated bronchitis (AUB), but are often prescribed (85% of AUB visits within the Veterans Affairs nationally). This quality improvement project aimed to decrease antibiotic prescribing for AUB in community-based outpatient centres from 65% to <32% by April 2020. METHODS: From January to December 2018, community-based outpatient clinics' 6 months' average of prescribed antibiotics for AUB and upper respiratory infections was 63% (667 of 1054) and 64.6% (314 of 486) when reviewing the last 6 months. Seven plan-do-study-act (PDSA) cycles were implemented by an interprofessional antimicrobial stewardship team between January 2019 and March 2020. Balancing measures were a return patient phone call or visit within 4 weeks for the same complaint. Χ2 tests and statistical process control charts using Western Electric rules were used to analyse intervention data. RESULTS: The AUB antibiotic prescribing rate decreased from 64.6% (314 of 486) in the 6 months prior to the intervention to 36.8% (154 of 418) in the final 6 months of the intervention. No change was seen in balancing measures. The largest reduction in antibiotic prescribing was seen after implementation of PDSA 6 in which 14 high prescribers were identified and targeted for individualised reviews of encounters of patients with AUB with an antimicrobial steward. CONCLUSIONS: Operational implementation of successful stewardship interventions is challenging and differs from the traditional implementation study environment. As a nascent outpatient stewardship programme with limited resources and no additional intervention funding, we successfully reduced antibiotic prescribing from 64.6% to 36.8%, a reduction of 43% from baseline. The most success was seen with targeted education of high prescribers.


Subject(s)
Antimicrobial Stewardship , Bronchitis , Anti-Bacterial Agents/therapeutic use , Bronchitis/drug therapy , Humans , Outpatients , Practice Patterns, Physicians'
12.
J Med Virol ; 93(3): 1512-1519, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196466

ABSTRACT

As coronavirus disease 2019 (COVID-19) crashed into the influenza season, clinical characteristics of both infectious diseases were compared to make a difference. We reported 211 COVID-19 patients and 115 influenza patients as two separate cohorts at different locations. Demographic data, medical history, laboratory findings, and radiological characters were summarized and compared between two cohorts, as well as between patients at the intensive care unit (ICU) andnon-ICU within the COVID-19 cohort. For all 326 patients, the median age was 57.0 (interquartile range: 45.0-69.0) and 48.2% was male, while 43.9% had comorbidities that included hypertension, diabetes, bronchitis, and heart diseases. Patients had cough (75.5%), fever (69.3%), expectoration (41.1%), dyspnea (19.3%), chest pain (18.7%), and fatigue (16.0%), etc. Both viral infections caused substantial blood abnormality, whereas the COVID-19 cohort showed a lower frequency of leukocytosis, neutrophilia, or lymphocytopenia, but a higher chance of creatine kinase elevation. A total of 7.7% of all patients possessed no abnormal sign in chest computed tomography (CT) scans. For both infections, pulmonary lesions in radiological findings did not show any difference in their location or distribution. Nevertheless, compared to the influenza cohort, the COVID-19 cohort presented more diversity in CT features, where certain specific CT patterns showed significantly more frequency, including consolidation, crazy paving pattern, rounded opacities, air bronchogram, tree-in-bud sign, interlobular septal thickening, and bronchiolar wall thickening. Differentiable clinical manifestations and CT patterns may help diagnose COVID-19 from influenza and gain a better understanding of both contagious respiratory illnesses.


Subject(s)
COVID-19/diagnosis , Influenza, Human/diagnosis , Lung/diagnostic imaging , Lung/pathology , Adult , Aged , Bronchitis/complications , Comorbidity , Diabetes Complications/complications , Diagnosis, Differential , Female , Heart Diseases/complications , Humans , Hypertension/complications , Length of Stay/statistics & numerical data , Male , Middle Aged , SARS-CoV-2 , Thorax/diagnostic imaging , Tomography, X-Ray Computed
13.
BMJ Open Respir Res ; 8(1)2021 03.
Article in English | MEDLINE | ID: covidwho-1119320

ABSTRACT

BACKGROUND: Air pollution may affect the risk of respiratory infection, though research has focused on uncommon infections or infections in children. Whether ambient air pollutants increase the risk of common acute respiratory infections among adults is uncertain, yet this may help understand whether pollutants influence spread of pandemic respiratory infections like COVID-19. OBJECTIVE: To estimate the association between ambient air pollutant exposures and respiratory infections in adults. METHODS: During five study examinations over 12 years, 6536 participants in the multiethnic study of atherosclerosis (MESA) reported upper respiratory tract infections, bronchitis, pneumonia or febrile illness in the preceding 2 weeks. Using a validated spatiotemporal model, we estimated residential concentrations of ambient PM2.5, NOx and NO2 for the 2-6 weeks (short-term) and year (long-term) prior to each examination. RESULTS: In this population aged 44-84 years at baseline, 10%-32% of participants reported a recent respiratory infection, depending on month of examination and study region. PM2.5, NOx and NO2 concentrations over the prior 2-6 weeks were associated with increased reporting of recent respiratory infection, with risk ratios (95% CIs) of 1.04 (1.00 to 1.09), 1.15 (1.10 to 1.20) and 1.21 (1.10 to 1.33), respectively, per increase from 25th to 75th percentile in residential pollutant concentration. CONCLUSION: Higher short-term exposure to PM2.5 and traffic-related pollutants are associated with increased risk of symptomatic acute respiratory infections among adults. These findings may provide an insight into the epidemiology of COVID-19.


Subject(s)
Air Pollution/adverse effects , Air Pollution/statistics & numerical data , Atherosclerosis/ethnology , Atherosclerosis/epidemiology , COVID-19/ethnology , COVID-19/epidemiology , Cross-Cultural Comparison , Respiratory Tract Infections/ethnology , Respiratory Tract Infections/epidemiology , Acute Disease , Adult , Aged , Aged, 80 and over , Bronchitis/epidemiology , Bronchitis/ethnology , Correlation of Data , Cross-Sectional Studies , Female , Fever/epidemiology , Fever/ethnology , Humans , Male , Middle Aged , Odds Ratio , Pneumonia/epidemiology , Pneumonia/ethnology , Risk , Spatio-Temporal Analysis , United States
14.
PLoS One ; 15(12): e0243694, 2020.
Article in English | MEDLINE | ID: covidwho-971781

ABSTRACT

INTRODUCTION: Respiratory tract diseases are the major cause of morbidity and mortality in children under the age of 5 years, constituting the highest rate of hospitalization in this age group. OBJECTIVES: To determine the prevalence of hospitalizations for respiratory diseases in childhood in the last 5 years and to assess the impact of social isolation due to COVID-19 on the seasonal behavior of these diseases. METHODS: A cross-sectional clinical study was carried out, with a survey of all patients aged 0 to 17 years who were admitted with a diagnosis of respiratory diseases between January 2015 and July 2020. The database was delivered to the researchers anonymized. The variables used for analysis were date of admission, date of discharge, length of stay, age, sex and diagnosis. In order to make the analysis possible, the diagnoses were grouped into upper respiratory infection (URI), asthma / bronchitis, bronchiolitis and pneumonia. RESULTS: 2236 admissions were included in the study. Children under 5 years old account for 81% of hospitalizations for respiratory disease in our population. In the adjusted model, an average reduction of 38 hospitalizations was observed in the period of social isolation (coefficient: -37.66; 95% CI (- 68.17; -7.15); p = 0.016). CONCLUSION: The social isolation measures adopted during the COVID-19 pandemic dramatically interfered with the seasonality of childhood respiratory diseases. This was reflected in the unexpected reduction in the number of hospitalizations in the pediatric population during this period.


Subject(s)
Asthma/therapy , Bronchitis/therapy , COVID-19 , Hospitalization , Respiratory Tract Infections/therapy , SARS-CoV-2 , Seasons , Adolescent , Asthma/epidemiology , Bronchitis/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Child , Child, Preschool , Cross-Sectional Studies , Female , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Male , Respiratory Tract Infections/epidemiology , Social Isolation
15.
Am J Hum Genet ; 108(1): 194-201, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-971875

ABSTRACT

Given the coronavirus disease 2019 (COVID-19) pandemic, investigations into host susceptibility to infectious diseases and downstream sequelae have never been more relevant. Pneumonia is a lung disease that can cause respiratory failure and hypoxia and is a common complication of infectious diseases, including COVID-19. Few genome-wide association studies (GWASs) of host susceptibility and severity of pneumonia have been conducted. We performed GWASs of pneumonia susceptibility and severity in the Vanderbilt University biobank (BioVU) with linked electronic health records (EHRs), including Illumina Expanded Multi-Ethnic Global Array (MEGAEX)-genotyped European ancestry (EA, n= 69,819) and African ancestry (AA, n = 15,603) individuals. Two regions of large effect were identified: the CFTR locus in EA (rs113827944; OR = 1.84, p value = 1.2 × 10-36) and HBB in AA (rs334 [p.Glu7Val]; OR = 1.63, p value = 3.5 × 10-13). Mutations in these genes cause cystic fibrosis (CF) and sickle cell disease (SCD), respectively. After removing individuals diagnosed with CF and SCD, we assessed heterozygosity effects at our lead variants. Further GWASs after removing individuals with CF uncovered an additional association in R3HCC1L (rs10786398; OR = 1.22, p value = 3.5 × 10-8), which was replicated in two independent datasets: UK Biobank (n = 459,741) and 7,985 non-overlapping BioVU subjects, who are genotyped on arrays other than MEGAEX. This variant was also validated in GWASs of COVID-19 hospitalization and lung function. Our results highlight the importance of the host genome in infectious disease susceptibility and severity and offer crucial insight into genetic effects that could potentially influence severity of COVID-19 sequelae.


Subject(s)
COVID-19/complications , COVID-19/genetics , Host-Pathogen Interactions/genetics , Pneumonia, Viral/complications , Pneumonia, Viral/genetics , Bronchitis/genetics , COVID-19/pathology , COVID-19/physiopathology , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Databases, Genetic , Electronic Health Records , Female , Genome-Wide Association Study , Genotype , Hemoglobins/genetics , Humans , Inpatients , Linkage Disequilibrium , Male , Outpatients , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Polymorphism, Single Nucleotide/genetics , Principal Component Analysis , Pulmonary Disease, Chronic Obstructive/genetics , Reproducibility of Results , United Kingdom
17.
Microb Pathog ; 149: 104560, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-857004

ABSTRACT

Infectious Bronchitis (IB) is an economically important avian disease that considerably threatens the global poultry industry. This is partly, as a result of its negative consequences on egg production, weight gain as well as mortality rate.The disease is caused by a constantly evolving avian infectious bronchitis virus whose isolates are classified into several serotypes and genotypes that demonstrate little or no cross protection. In order to curb the menace of the disease therefore, broad based vaccines are urgently needed. The aim of this study was to develop a recombinant DNA vaccine candidate for improved protection of avian infectious bronchitis in poultry. Using bioinformatics and molecular cloning procedures, sets of monovalent and bivalent DNA vaccine constructs were developed based on the S1 glycoprotein from classical and variants IBV strains namely, M41 and CR88 respectively. The candidate vaccine was then encapsulated with a chitosan and saponin formulated nanoparticle for enhanced immunogenicity and protective capacity. RT-PCR assay and IFAT were used to confirm the transcriptional and translational expression of the encoded proteins respectively, while ELISA and Flow-cytometry were used to evaluate the immunogenicity of the candidate vaccine following immunization of various SPF chicken groups (A-F). Furthermore, histopathological changes and virus shedding were determined by quantitative realtime PCR assay and lesion scoring procedure respectively following challenge of various subgroups with respective wild-type IBV viruses. Results obtained from this study showed that, groups vaccinated with a bivalent DNA vaccine construct (pBudCR88-S1/M41-S1) had a significant increase in anti-IBV antibodies, CD3+ and CD8+ T-cells responses as compared to non-vaccinated groups. Likewise, the bivalent vaccine candidate significantly decreased the oropharyngeal and cloacal virus shedding (p < 0.05) compared to non-vaccinated control. Chickens immunized with the bivalent vaccine also exhibited milder clinical signs as well as low tracheal and kidney lesion scores following virus challenge when compared to control groups. Collectively, the present study demonstrated that bivalent DNA vaccine co-expressing dual S1 glycoprotein induced strong immune responses capable of protecting chickens against infection with both M41 and CR88 IBV strains. Moreso, it was evident that encapsulation of the vaccine with chitosan-saponin nanoparticle further enhanced immune responses and abrogates the need for multiple booster administration of vaccine. Therefore, the bivalent DNA vaccine could serve as efficient and effective alternative strategy for the control of IB in poultry.


Subject(s)
Chitosan/immunology , Coronavirus Infections/veterinary , Infectious bronchitis virus/immunology , Poultry Diseases/immunology , Saponins/immunology , Vaccines, DNA/immunology , Viral Vaccines/immunology , Animals , Antibodies, Viral/immunology , Bronchitis/immunology , Bronchitis/prevention & control , Bronchitis/veterinary , CD8-Positive T-Lymphocytes/immunology , Chickens , Chitosan/chemistry , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Cross Protection , Immunity, Cellular , Immunization, Secondary/veterinary , Immunogenicity, Vaccine , Nanoparticles/chemistry , Poultry Diseases/prevention & control , Saponins/chemistry , Vaccination/veterinary , Vaccines, DNA/chemistry , Vaccines, DNA/genetics , Viral Vaccines/chemistry , Viral Vaccines/genetics
18.
Transbound Emerg Dis ; 67(2): 884-893, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-797115

ABSTRACT

Infectious bronchitis virus (IBV) causes respiratory diseases in chickens and poses an economic threat to the poultry industry worldwide. Despite vaccine use, there have been field outbreaks of IBV in Taiwan. This study aimed to characterize the emerging IBV variants circulating in Taiwan. The analysis of the structural protein genes showed that these variants emerged through frequent recombination events among Taiwan strains, China strains, Japan strains and vaccine strains. Cross-neutralization tests revealed that two of the variants exhibited novel serotypes. Clinicopathological assessment showed that two of the variants caused high fatality rates of 67% and 20% in one-day-old SPF chicks, and all the variants possessed multiorgan tropisms, including trachea, proventriculus and urogenital tissues. Furthermore, the commercial live-attenuated Mass-type vaccine conferred poor protection against these variants. This study identified novel genotypes, serotypes and pathotypes of emerging IBV variants circulating in Taiwan. There is an urgent need for effective countermeasures against these variant strains.


Subject(s)
Bronchitis/veterinary , Chickens/virology , Coronavirus Infections/veterinary , Disease Outbreaks/veterinary , Infectious bronchitis virus/genetics , Poultry Diseases/virology , Animals , Bronchitis/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Genetic Variation , Infectious bronchitis virus/immunology , Infectious bronchitis virus/physiology , Poultry Diseases/epidemiology , Proventriculus/virology , Specific Pathogen-Free Organisms , Taiwan/epidemiology , Trachea/virology , Viral Tropism
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