RESUMEN

BACKGROUND: Human metapneumovirus (HMPV) is a common respiratory pathogen that causes respiratory tract infections. In India, HMPV has been identified as one of the leading causes of morbidity and mortality in infants and young children with respiratory tract infections. The most reported sublineages of HMPV in India are B1, B2, A2b and A2c. OBJECTIVE: A retrospective study was conducted to determine the circulating genotypes of HMPV among SARI cases from January 2016 to December 2018. MATERIALS AND METHODS: Positive throat swab samples were confirmed with real-time RT-PCR. Subsequently, these samples were analysed using semi-nested conventional RT-PCR targeting the G gene, followed by sequencing and phylogenetic analysis. Clinical data analysis was also performed using SPSS 15.0 software. RESULTS: All 20 samples from the SARI cases were classified under the A2c sublineage of HMPV. Phylogenetic analysis indicated that these strains were genetically related to those circulating in Japan, China, and Croatia. Among the samples, ten showed 111-nucleotide duplications, while the other ten had 180-nucleotide duplications. CONCLUSION: Clinical analysis showed that four cases had coinfections with other pathogens. Our extensive analysis of patient samples determined that HMPV, especially the A2c genotype, significantly contributed to SARI cases within our study population, which signifies the importance of considering HMPV as a probable aetiological agent when investigating SARI outbreaks.

Asunto(s)

Genotipo , Metapneumovirus , Infecciones por Paramyxoviridae , Filogenia , Infecciones del Sistema Respiratorio , Humanos , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Lactante , Preescolar , India/epidemiología , Niño , Enfermedad Aguda , Reacción en Cadena en Tiempo Real de la Polimerasa

RESUMEN

BACKGROUND: An understanding of viral testing rates is crucial to accurately estimate the pathogen-specific hospitalisation burden. We aimed to estimate the patterns of testing for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV) and human metapneumovirus (hMPV) by geographical location, age and time in children <5 years old in Western Australia. METHODS: We conducted a population-based cohort study of children born between 1 January 2010 and 31 December 2021, utilising linked administrative data incorporating birth and death records, hospitalisations and respiratory viral surveillance testing records from state-wide public pathology data. We examined within-hospital testing rates using survival analysis techniques and identified independent predictors of testing using binary logistic regression. RESULTS: Our dataset included 46,553 laboratory tests for RSV, influenza, PIV, or hMPV from 355,021 children (52.5% male). Testing rates declined in the metropolitan region over the study period (RSV testing in infants: from 242.11/1000 child-years in 2012 to 155.47/1000 child-years in 2018) and increased thereafter. Conversely, rates increased in non-metropolitan areas (e.g., RSV in Goldfields: from 364.92 in 2012 to 504.37/1000 child-years in 2021). The strongest predictors of testing were age <12 months (adjusted odds ratio [aOR] = 2.25, 95% CI 2.20-2.31), preterm birth (<32 weeks: aOR = 2.90, 95% CI 2.76-3.05) and remote residence (aOR = 0.77, 95% CI 0.73-0.81). CONCLUSION: These current testing rates highlight the potential underestimation of respiratory virus hospitalisations by routine surveillance and the need for estimation of the true burden of respiratory virus admissions.

Asunto(s)

Infecciones del Sistema Respiratorio , Humanos , Australia Occidental/epidemiología , Lactante , Femenino , Masculino , Preescolar , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Estudios de Cohortes , Hospitalización/estadística & datos numéricos , Recién Nacido , Cohorte de Nacimiento , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/virología , Centros de Atención Terciaria/estadística & datos numéricos

RESUMEN

A disease called "hydrosalpinx fluid and egg drop syndrome" (HFEDS) was observed in four flocks of Jinding ducks (Anas platyrhynchos domesticus) in Northeast China during the years 2022 to 2023. Here, we investigated the possible involvement of avian metapneumovirus (AMPV) infection. Full-length genome sequencing and sequence analysis of two AMPV strains showed that they belong to Eurasian lineage of AMPV subtype C. Based on surface glycoprotein (G) sequence comparisons, the Eurasian lineage can be divided into two sublineages (E1 and E2), and sublineage E2 is circulating in Jinding duck populations in Northeast China.

Asunto(s)

Patos , Genoma Viral , Metapneumovirus , Infecciones por Paramyxoviridae , Filogenia , Enfermedades de las Aves de Corral , Animales , Patos/virología , Metapneumovirus/genética , Metapneumovirus/clasificación , Metapneumovirus/aislamiento & purificación , Enfermedades de las Aves de Corral/virología , Infecciones por Paramyxoviridae/veterinaria , Infecciones por Paramyxoviridae/virología , China , Genoma Viral/genética , Secuenciación Completa del Genoma

RESUMEN

Human metapneumovirus (hMPV) is a respiratory pathogen that can cause lower respiratory tract infections and pneumonia in immunocompetent adults. Pneumonia caused by hMPV is reportedly more likely to cause bronchial wall thickening and ground-glass opacity (GGO). A 44-year-old woman with no significant medical history developed fever, cough, and nausea. Computed tomography of the chest showed scattered GGOs in the right upper lobe and infiltrating shadows with air bronchograms in the left lingual and bilateral lower lobes. The patient was admitted to our hospital for further evaluation. Atypical pneumonia was suspected and lascufloxacin (LSFX) was started. Multiplex polymerase chain reaction (PCR) detected hMPV on hospital day 2 using the FilmArray Respiratory Panel 2.1. Pneumonia due to hMPV was suspected and LSFX was discontinued. The patient subsequently showed spontaneous improvement and was discharged on hospital day 6 after admission. After discharge, pneumonia continued to improve. Early detection of respiratory pathogens using multiplex PCR can help determine the appropriate treatment strategy. As hMPV can also cause lobar pneumonia, we should consider pneumonia due to hMPV in the differential diagnosis of lobar pneumonia.

Asunto(s)

Metapneumovirus , Infecciones por Paramyxoviridae , Neumonía Viral , Tomografía Computarizada por Rayos X , Humanos , Metapneumovirus/aislamiento & purificación , Metapneumovirus/genética , Adulto , Femenino , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/tratamiento farmacológico , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Neumonía Viral/tratamiento farmacológico , Reacción en Cadena de la Polimerasa Multiplex

RESUMEN

Objective: To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China. Methods: From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children's Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases. Results: A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M (Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant (P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion: The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

Asunto(s)

Genotipo , Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Humanos , Metapneumovirus/genética , Metapneumovirus/clasificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Niño , Preescolar , Lactante , China/epidemiología , Masculino , Adolescente , Femenino , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Enfermedad Aguda , Hospitalización , Recién Nacido , Filogenia

RESUMEN

Human metapneumovirus (HMPV) is a common pathogen that can cause acute respiratory tract infections and is prevalent worldwide. There is yet no effective vaccine or specific treatment for HMPV. Early, rapid, and accurate detection is essential to treat the disease and control the spread of infection. In this study, we created the One-tube assay by combining Reverse Transcription-Recombinase Polymerase Amplification (RT-RPA) with the CRISPR/Cas12a system. By targeting the nucleoprotein (N) gene of HMPV to design specific primers and CRISPR RNAs (crRNAs), combining RT-RPA and CRISPR/Cas12a, established the One-tube assay. Meanwhile, the reaction conditions of the One-tube assay were optimized to achieve rapid and visual detection of HMPV. This assay could detect HMPV at 1 copy/µL in 30 min, without cross-reactivity with nine other respiratory pathogens. We validated the detection performance using clinical specimens and showed that the coincidence rate was 98.53 %，compared to the quantitative reverse-transcription polymerase chain reaction. The One-tube assay reduced the detection time and simplified the manual operation, while maintaining the detection performance and providing a new platform for HMPV detection.

Asunto(s)

Sistemas CRISPR-Cas , Metapneumovirus , Infecciones por Paramyxoviridae , Sensibilidad y Especificidad , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Humanos , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/virología , ARN Viral/genética , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos

RESUMEN

Airborne animal viral pathogens can rapidly spread and become a global threat, resulting in substantial socioeconomic and health consequences. To prevent and control potential epidemic outbreaks, accurate, fast, and affordable point-of-care (POC) tests are essential. As a proof-of-concept, we have developed a molecular system based on the loop-mediated isothermal amplification (LAMP) technique for avian metapneumovirus (aMPV) detection, an airborne communicable agent mainly infecting turkeys and chickens. For this purpose, a colorimetric system was obtained by coupling the LAMP technique with specific DNA-functionalized AuNPs (gold nanoparticles). The system was validated using 50 different samples (pharyngeal swabs and tracheal tissue) collected from aMPV-infected and non-infected chickens and turkeys. Viral detection can be achieved in about 60 min with the naked eye, with 100% specificity and 87.88% sensitivity for aMPV. In summary, this novel molecular detection system allows suitable virus testing in the field, with accuracy and limit of detection (LOD) values highly close to qRT-PCR-based diagnosis. Furthermore, this system can be easily scalable to a platform for the detection of other viruses, addressing the current gap in the availability of POC tests for viral detection in poultry farming. KEY POINTS: •aMPV diagnosis using RT-LAMP is achieved with high sensitivity and specificity. •Fifty field samples have been visualized using DNA-nanoprobe validation. •The developed system is a reliable, fast, and cost-effective option for POCT.

Asunto(s)

Pollos , Oro , Metapneumovirus , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Infecciones por Paramyxoviridae , Enfermedades de las Aves de Corral , Sensibilidad y Especificidad , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Animales , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/economía , Pollos/virología , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/economía , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/veterinaria , Infecciones por Paramyxoviridae/virología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/diagnóstico , Oro/química , Pavos , Nanopartículas del Metal/química , Límite de Detección , Colorimetría/métodos , ADN Viral/genética

RESUMEN

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces. To identify these substitutions, we developed an AI convolutional classifier that successfully predicts complex polar interactions often overlooked by physics-based methods and visual inspection. The combination of additional processing, stabilization of interface regions and stabilization of the membrane-proximal stem, resulted in a Pre-F protein vaccine candidate without the need for a heterologous trimerization domain that exhibited high expression yields and thermostability. Cryo-EM analysis shows the complete ectodomain structure, including the stem, and a specific interaction of the newly identified cleaved C-terminus with the adjacent protomer. Importantly, the protein induces high and cross-neutralizing antibody responses resulting in near complete protection against hMPV challenge in cotton rats, making the highly stable, double-cleaved hMPV Pre-F trimer an attractive vaccine candidate.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Metapneumovirus , Proteínas Virales de Fusión , Vacunas Virales , Metapneumovirus/inmunología , Metapneumovirus/genética , Animales , Anticuerpos Neutralizantes/inmunología , Humanos , Anticuerpos Antivirales/inmunología , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/química , Proteínas Virales de Fusión/genética , Vacunas Virales/inmunología , Infecciones por Paramyxoviridae/prevención & control , Infecciones por Paramyxoviridae/inmunología , Microscopía por Crioelectrón , Ingeniería de Proteínas/métodos , Sigmodontinae , Femenino , Multimerización de Proteína , Modelos Moleculares

RESUMEN

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice. This study showed that ≥0.5 µM probenecid significantly inhibited HMPV replication in vitro, and 2-200 mg/kg probenecid prophylaxis or treatment reduced HMPV replication in BALB/c mice.

Asunto(s)

Antivirales , Metapneumovirus , Ratones Endogámicos BALB C , Infecciones por Paramyxoviridae , Probenecid , Replicación Viral , Animales , Metapneumovirus/efectos de los fármacos , Metapneumovirus/fisiología , Replicación Viral/efectos de los fármacos , Ratones , Probenecid/farmacología , Infecciones por Paramyxoviridae/tratamiento farmacológico , Infecciones por Paramyxoviridae/virología , Antivirales/farmacología , Línea Celular , Pulmón/virología , Humanos , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Femenino

RESUMEN

BACKGROUND: Human parainfluenza viruses (HPIVs) commonly cause childhood respiratory illness requiring hospitalization in Taiwan. This study aimed to investigate clinical severity and identify risk factors predisposing to severe disease in hospitalized children with HPIV infection. METHODS: We included hospitalized patients with lab-confirmed HPIV infection from 2007 to 2018 and collected their demographic and clinical characteristics. Patients with ventilator support, intravenous inotropic agents, and extracorporeal membrane oxygenation were defined as severe cases. RESULTS: There were 554 children hospitalized for HPIV infection. The median age was 1.2 years; 518 patients had non-severe HPIV infection, whereas 36 patients (6.5%) had severe HPIV infection. 266 (48%) patients had underlying diseases, and 190 patients (34.3%) had bacterial co-detection. Children with severe HPIV infection were more likely to have bacterial co-detection than those without (52.8% vs 33.0%, p = 0.02). Patients with lung patch or consolidation had more invasive bacterial co-infection or co-detection than those without patch or consolidation (43% vs 33%, p = 0.06). Patients with neurological disease (adjusted OR 4.77, 95% CI 1.94-11.68), lung consolidation/patch (adjusted OR 6.64, 95% CI 2.80-15.75), and effusion (adjusted OR 11.59, 95% CI 1.52-88.36) had significantly higher risk to have severe HPIV infection. CONCLUSION: Neurological disease and lung consolidation/patch or effusion were the most significant predictors of severe HPIV infection.

Asunto(s)

Coinfección , Hospitalización , Infecciones por Paramyxoviridae , Humanos , Masculino , Femenino , Factores de Riesgo , Lactante , Preescolar , Taiwán/epidemiología , Niño , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/complicaciones , Coinfección/epidemiología , Coinfección/virología , Coinfección/microbiología , Índice de Severidad de la Enfermedad , Niño Hospitalizado/estadística & datos numéricos , Oxigenación por Membrana Extracorpórea , Adolescente , Estudios Retrospectivos , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones Bacterianas/epidemiología

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus are responsible for acute respiratory tract infections (ARTIs) in adults. We assessed the clinical burden of RSV, hMPV and influenza virus infection among Japanese adults hospitalized with ARTIs. METHODS: The Hospitalized Acute Respiratory Tract Infection (HARTI) study was a multinational, prospective cohort study in adults with ARTIs across the 2017-2019 epidemic seasons. Enrolment in Japan began in Sept 2018 and ran until Oct 2019. The clinical diagnosis of ARTI and the decision to hospitalize the patient were made according to local standard of care practices. Viral testing was performed by reverse transcription polymerase chain reaction. RESULTS: Of the 173 adults hospitalized with ARTI during this period at the Japan sites, 7 (4.0%), 9 (5.2%), and 11 (6.4%) were positive for influenza virus, RSV, and hMPV, respectively. RSV season was observed from Oct 2018 to Jan 2019, followed by influenza from Dec 2018 to Apr 2019. hMPV was detected across both the RSV and influenza seasons. Two patients with RSV and 1 patient with hMPV required ICU admission whereas none with influenza. Use of antibiotics, bronchodilators and inhaled corticosteroids was high amongst patients with RSV and hMPV at 1, 2, and 3 months' post-discharge compared with patients with influenza, with few exceptions. CONCLUSION: These findings highlight the need for a high degree of clinical suspicion for RSV and hMPV infection in adults hospitalized with ARTIs.

Asunto(s)

Hospitalización , Gripe Humana , Infecciones por Paramyxoviridae , Infecciones por Virus Sincitial Respiratorio , Infecciones del Sistema Respiratorio , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Aguda , Estudios de Cohortes , Costo de Enfermedad , Pueblos del Este de Asia , Hospitalización/estadística & datos numéricos , Gripe Humana/epidemiología , Japón/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología

RESUMEN

BACKGROUND: Parainfluenza virus (PIV) is widely known as a causative virus of acute respiratory tract infections in children, and 4 serotypes (PIV-1-PIV-4) have been identified. The purpose of the present study was to clarify the clinical characteristics of the PIV serotypes in pediatric PIV infections in Japan. METHODS: Between April 2021 and October 2023, 8821 children aged <16 years who presented with respiratory symptoms underwent multiplex polymerase chain reaction analyses at the Department of Pediatrics, NTT Medical Center Sapporo. All 1490 cases in which PIV was detected were analyzed for their clinical characteristics by PIV serotypes. RESULTS: Of the 1490 cases, 608 were positive for a single PIV serotype: 91 (13.5%) for PIV-1, 54 (4.8%) for PIV-2, 361 (62.1%) for PIV-3 and 102 (19.6%) for PIV-4. The median ages were 3.5 years for PIV-1, 5.4 years for PIV-2, 1.9 years for PIV-3 and 2.2 years for PIV-4, with a significantly older age for PIV-2. Compared with the other serotypes, croup was significantly more common in PIV-1 and lower respiratory tract infection was significantly more common in PIV-4. Of the 608 cases with a single PIV serotype, 114 were hospitalized. The proportion of hospitalized patients was higher for PIV-4 than for the other PIV serotypes, but the difference was not significant. CONCLUSIONS: Lower respiratory tract infection was more frequent in PIV-4 than in the other PIV serotypes, and PIV-4 infection may increase the risk of hospitalization.

Asunto(s)

Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Serogrupo , Humanos , Preescolar , Japón/epidemiología , Niño , Masculino , Femenino , Lactante , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Adolescente , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Infecciones por Rubulavirus/virología , Infecciones por Rubulavirus/epidemiología , Virus de la Parainfluenza 1 Humana/genética

RESUMEN

Introduction: Community-acquired pneumonia (CAP) is a global health concern, with 25% of cases attributed to Streptococcus pneumoniae (Spn). Viral infections like influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) increase the risk of Spn, leading to severe complications due to compromised host immunity. Methods: We evaluated the efficacy of an anti-PhtD monoclonal antibody (mAb) cocktail therapy (PhtD3 + 7) in improving survival rates in three viral/bacterial coinfection models: IAV/Spn, hMPV/Spn, and RSV/Spn. Results: The PhtD3 + 7 mAb cocktail outperformed antiviral mAbs, resulting in prolonged survival. In the IAV/Spn model, it reduced bacterial titers in blood and lungs by 2-4 logs. In the hMPV/Spn model, PhtD3 + 7 provided greater protection than the hMPV-neutralizing mAb MPV467, significantly reducing bacterial titers. In the RSV/Spn model, PhtD3 + 7 offered slightly better protection than the antiviral mAb D25, uniquely decreasing bacterial titers in blood and lungs. Discussion: Given the threat of antibiotic resistance, our findings highlight the potential of anti-PhtD mAb therapy as an effective option for treating viral and secondary pneumococcal coinfections.

Asunto(s)

Anticuerpos Monoclonales , Coinfección , Streptococcus pneumoniae , Sobreinfección , Animales , Humanos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/inmunología , Streptococcus pneumoniae/inmunología , Ratones , Sobreinfección/inmunología , Sobreinfección/microbiología , Coinfección/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Metapneumovirus/inmunología , Virus de la Influenza A/inmunología , Modelos Animales de Enfermedad , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/tratamiento farmacológico , Femenino , Ratones Endogámicos BALB C , Infecciones por Paramyxoviridae/inmunología , Infecciones por Paramyxoviridae/tratamiento farmacológico , Anticuerpos Antivirales/inmunología

RESUMEN

This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory infections during 2015-2021 and assessed the impact of the coronavirus disease 2019 pandemic on hMPV infection. A single-center, retrospective cohort study was performed, including pediatric and adult patients with laboratory-confirmed hMPV. Of a total of 990 patients, 253 (25.6%), 105 (10.6%), 121 (12.2%), and 511 (51.6%) belonged to age groups 0-2, 3-17, 18-59, and ≥60 years, respectively. The highest percentage (23.0%) of patients were hospitalized during 2019 and the lowest (4.7%) during 2020. Patients < 18 years experienced high rates of comorbidities (immunodeficiencies: 14.4% and malignancies: 29.9%). Here, 37/39 (94.9%) of all bronchiolitis cases were diagnosed in patients < 2 years, whereas more patients in older age groups were diagnosed with pneumonia. A greater proportion of hMPV patients diagnosed with viral coinfection (mostly respiratory syncytial virus and adenovirus) were <18 years. The highest percentages of intensive care unit admissions were recorded among patients < 18 years. Our findings demonstrate that hMPV is an important cause of morbidity in young children and a possibly underestimated cause of morbidity among older adults.

Asunto(s)

COVID-19 , Coinfección , Hospitalización , Metapneumovirus , Infecciones por Paramyxoviridae , Humanos , Estudios Retrospectivos , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Israel/epidemiología , Persona de Mediana Edad , Niño , Masculino , Adulto , Femenino , Lactante , Adolescente , Preescolar , Hospitalización/estadística & datos numéricos , Adulto Joven , COVID-19/epidemiología , COVID-19/virología , Anciano , Coinfección/epidemiología , Coinfección/virología , Recién Nacido , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Comorbilidad , Anciano de 80 o más Años , SARS-CoV-2

RESUMEN

The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.

Asunto(s)

Genoma Viral , Filogenia , Roedores , Animales , China , Roedores/virología , Animales Salvajes/virología , Paramyxovirinae/genética , Paramyxovirinae/clasificación , Paramyxovirinae/aislamiento & purificación , ARN Viral/genética , Infecciones por Paramyxoviridae/veterinaria , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/epidemiología , Secuenciación de Nucleótidos de Alto Rendimiento , Reservorios de Enfermedades/virología , Análisis de Secuencia de ADN

RESUMEN

Respiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus, we identified recruitment of a C1q-expressing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8+ T-cell function. Production of C1q by a myeloid lineage was necessary to enhance CD8+ T-cell function. Activated and dividing CD8+ T cells expressed a C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD8+ T-cell IFN-γ production, metabolic capacity, and cell proliferation. Autopsy specimens from fatal respiratory viral infections in children exhibited diffuse production of C1q by an interstitial population. Humans with severe coronavirus disease (COVID-19) infection also exhibited upregulation of gC1qR on activated and rapidly dividing CD8+ T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD8+ T-cell function following respiratory viral infection.

Asunto(s)

Linfocitos T CD8-positivos , Monocitos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Animales , Monocitos/inmunología , Monocitos/metabolismo , Humanos , Ratones , Metapneumovirus/inmunología , COVID-19/inmunología , COVID-19/virología , COVID-19/patología , COVID-19/metabolismo , Complemento C1q/metabolismo , Complemento C1q/genética , SARS-CoV-2/inmunología , Ratones Endogámicos C57BL , Interferón gamma/metabolismo , Activación de Linfocitos/inmunología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/metabolismo , Infecciones por Paramyxoviridae/inmunología , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/metabolismo

RESUMEN

We analyzed data from a community-based acute respiratory illness study involving K-12 students and their families in southcentral Wisconsin and assessed household transmission of two common seasonal respiratory viruses - human metapneumovirus (HMPV) and human coronaviruses OC43 and HKU1 (HCOV). We found secondary infection rates of 12.2% (95% CI: 8.1%-17.4%) and 19.2% (95% CI: 13.8%-25.7%) for HMPV and HCOV, respectively. We performed individual- and family-level regression models and found that HMPV transmission was positively associated age of the index case (individual model: p = .016; family model: p = .004) and HCOV transmission was positively associated with household density (family model: p = .048). We also found that the age of the non-index case was negatively associated with transmission of both HMPV (individual model: p = .049) and HCOV (individual model: p = .041), but we attributed this to selection bias from the original study design. Understanding household transmission of common respiratory viruses like HMPV and HCOV may help to broaden our understanding of the overall disease burden and establish methods to prevent the spread of disease from low- to high-risk populations.

Asunto(s)

Infecciones por Coronavirus , Composición Familiar , Metapneumovirus , Infecciones por Paramyxoviridae , Humanos , Infecciones por Paramyxoviridae/transmisión , Infecciones por Paramyxoviridae/epidemiología , Wisconsin/epidemiología , Femenino , Adulto Joven , Masculino , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/epidemiología , Adulto , Adolescente , Niño , Coronavirus , Estaciones del Año , Persona de Mediana Edad , Preescolar , Infecciones del Sistema Respiratorio/transmisión , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología

RESUMEN

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.

Asunto(s)

Hospitalización , Gripe Humana , Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones por Virus Sincitial Respiratorio , Infecciones del Sistema Respiratorio , Índice de Severidad de la Enfermedad , Humanos , Metapneumovirus/aislamiento & purificación , Masculino , Femenino , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Persona de Mediana Edad , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/epidemiología , Gripe Humana/virología , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Adulto , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/complicaciones , Anciano , Adulto Joven , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Anciano de 80 o más Años , Adolescente

RESUMEN

BACKGROUND: Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. METHODS: In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. RESULTS: At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. CONCLUSIONS: HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.

Asunto(s)

Infecciones del Sistema Respiratorio , Humanos , Femenino , Masculino , Lactante , Preescolar , Prevalencia , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Niño , República de Corea/epidemiología , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/virología , Infecciones por Paramyxoviridae/diagnóstico , Adolescente

RESUMEN

The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Sigmodontinae , Proteínas Virales de Fusión , Vacunas Virales , Animales , Femenino , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/genética , Proteínas Virales de Fusión/química , Ratones , Vacunas Virales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Ratones Endogámicos BALB C , Infecciones por Paramyxoviridae/prevención & control , Infecciones por Paramyxoviridae/inmunología , Infecciones por Paramyxoviridae/virología , Virus de la Parainfluenza 3 Humana/inmunología , Virus de la Parainfluenza 3 Humana/genética