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Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.
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Aberrant tissue-immune interactions are the hallmark of diverse chronic lung diseases. Here, we sought to define these interactions in emphysema, a progressive disease characterized by infectious exacerbations and loss of alveolar epithelium. Single-cell analysis of human emphysema lungs revealed the expansion of tissue-resident lymphocytes (TRLs). Murine studies identified a stromal niche for TRLs that expresses Hhip, a disease-variant gene downregulated in emphysema. Stromal-specific deletion of Hhip induced the topographic expansion of TRLs in the lung that was mediated by a hyperactive hedgehog-IL-7 axis. 3D immune-stem cell organoids and animal models of viral exacerbations demonstrated that expanded TRLs suppressed alveolar stem cell growth through interferon gamma (IFNγ). Finally, we uncovered an IFNγ-sensitive subset of human alveolar stem cells that was preferentially lost in emphysema. Thus, we delineate a stromal-lymphocyte-epithelial stem cell axis in the lung that is modified by a disease-variant gene and confers host susceptibility to emphysema.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Ratones , Animales , Enfisema Pulmonar/genética , Pulmón , Linfocitos , Células MadreRESUMEN
Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.
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Linfocitos B/inmunología , COVID-19/inmunología , Monocitos/inmunología , Trastornos Respiratorios/inmunología , Sistema Respiratorio/inmunología , SARS-CoV-2/fisiología , Linfocitos T Citotóxicos/inmunología , Adulto , Anciano , COVID-19/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Celular , Inmunoproteínas , Masculino , Persona de Mediana Edad , Proteoma , Trastornos Respiratorios/etiología , Sistema Respiratorio/patologíaRESUMEN
BACKGROUND: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. METHODS: From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. RESULTS: Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant. CONCLUSIONS: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection.
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Infecciones por Enterovirus , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Virosis , Virus , Humanos , Lactante , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Washingtón/epidemiología , Virus/genética , Rhinovirus/genéticaRESUMEN
BACKGROUND: Recent developments in the domain of biomedical knowledge bases (KBs) open up new ways to exploit biomedical knowledge that is available in the form of KBs. Significant work has been done in the direction of biomedical KB creation and KB completion, specifically, those having gene-disease associations and other related entities. However, the use of such biomedical KBs in combination with patients' temporal clinical data still largely remains unexplored, but has the potential to immensely benefit medical diagnostic decision support systems. RESULTS: We propose two new algorithms, LOADDx and SCADDx, to combine a patient's gene expression data with gene-disease association and other related information available in the form of a KB, to assist personalized disease diagnosis. We have tested both of the algorithms on two KBs and on four real-world gene expression datasets of respiratory viral infection caused by Influenza-like viruses of 19 subtypes. We also compare the performance of proposed algorithms with that of five existing state-of-the-art machine learning algorithms (k-NN, Random Forest, XGBoost, Linear SVM, and SVM with RBF Kernel) using two validation approaches: LOOCV and a single internal validation set. Both SCADDx and LOADDx outperform the existing algorithms when evaluated with both validation approaches. SCADDx is able to detect infections with up to 100% accuracy in the cases of Datasets 2 and 3. Overall, SCADDx and LOADDx are able to detect an infection within 72 h of infection with 91.38% and 92.66% average accuracy respectively considering all four datasets, whereas XGBoost, which performed best among the existing machine learning algorithms, can detect the infection with only 86.43% accuracy on an average. CONCLUSIONS: We demonstrate how our novel idea of using the most and least differentially expressed genes in combination with a KB can enable identification of the diseases that a patient is most likely to have at a particular time, from a KB with thousands of diseases. Moreover, the proposed algorithms can provide a short ranked list of the most likely diseases for each patient along with their most affected genes, and other entities linked with them in the KB, which can support health care professionals in their decision-making.
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Bases del Conocimiento , Transcriptoma , Humanos , Algoritmos , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Pre-transplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay due to high-risk RVs, we examined the impact of pre-transplant RV detection on transplant outcomes in a pediatric HCT recipients. METHODS: This retrospective cohort study included myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using RT-PCR, regardless of symptoms. Post-transplant outcomes included days alive and out of hospital (DAOH) and progression to lower respiratory tract infection (LRTI). RESULTS: Among 310 patients, 134 had a RV detected in the 90 days prior to HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count less than 100/mm3, and HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus (HRV) as a virus type, and symptomatic pre-transplant upper respiratory tract infection (URTI) were associated with fewer DAOH. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to post-transplant LRTI with the same pre-transplant RV if the last positive PCR before HCT was ≤30 days compared to >30 days (p=0.007). CONCLUSION: In the setting of recommending HCT delay for high-risk RVs, symptomatic URTI, including HRV infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.
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In 2023, the Food and Drug Administration approved 2 recombinant subunit respiratory syncytial virus (RSV) vaccines based on prefusion RSV F glycoproteins for the prevention of RSV-associated lower respiratory tract disease. These vaccines were subsequently recommended for individuals ≥60 years of age using shared clinical decision-making by the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices. The development, deployment, and uptake of respiratory virus vaccines are of particular importance for solid organ recipients who are at higher risk of infectious complications and poor clinical outcomes, including from RSV-associated lower respiratory tract disease, compared to patients without immunocompromise. This review aims to summarize what is currently known about the burden of RSV disease in solid organ transplantation, to describe the currently available tools to mitigate the risk, and to highlight considerations regarding the implementation of these vaccines before and after transplantation. We also explore areas of unmet need for organ transplant recipients including questions of RSV vaccine effectiveness and safety, inequities in disease and vaccine access based on race and socioeconomic status, and expansion of coverage to immunocompromised individuals below the age of 60 years.
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Trasplante de Órganos , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Humanos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Huésped Inmunocomprometido/inmunologíaRESUMEN
BACKGROUND: This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. PATIENTS AND METHODS: The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). RESULTS: Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30 mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42-11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05-0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4-23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6-87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups. CONCLUSION: ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.
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The respiratory system is constantly exposed to viral infections that are responsible for mild to severe diseases. In this narrative review, we focalized the attention on respiratory syncytial virus (RSV), influenza virus, and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections, responsible for high morbidity and mortality in the last decades. We reviewed the human innate and adaptive immune responses in the airways following infection, focusing on a particular population: newborns and pregnant women. The recent Coronavirus disease-2019 (COVID-19) pandemic has highlighted how our interest in viral pathologies must not decrease. Furthermore, we must increase our knowledge of infection mechanisms to improve our future defense strategies.
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COVID-19 , Infecciones del Sistema Respiratorio , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/virología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Embarazo , SARS-CoV-2/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/virología , Femenino , Inmunidad Innata , Inmunidad Adaptativa , Recién Nacido , Gripe Humana/inmunología , Gripe Humana/virología , Virosis/inmunologíaRESUMEN
Neonates, particularly preterm infants, are a susceptible population to respiratory viral infections. Currently, aside from influenza, there are no antiviral medications specifically approved for the treatment of respiratory viral infections in neonates; therefore, prevention of these viral infections is particularly crucial for neonates. The Neonatal HealthCare Committee of Chinese Maternal and Child Health Association, based on domestic and international clinical evidence and combined with clinical practice experience, and after thorough discussion by relevant experts, has developed eight expert recommendations. These include preventive strategies against influenza virus, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2 infections, intended for reference in clinical practice.
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Infecciones del Sistema Respiratorio , Humanos , Recién Nacido , Infecciones del Sistema Respiratorio/prevención & control , COVID-19/prevención & control , Infecciones por Virus Sincitial Respiratorio/prevención & control , Gripe Humana/prevención & controlRESUMEN
Common respiratory diseases continue to represent a major public health problem, and much of the morbidity and mortality is due to airway inflammation and mucus production. Previous studies indicated a role for mitogen-activated protein kinase 14 (MAPK14) in this type of disease, but clinical trials are unsuccessful to date. Our previous work identified a related but distinct kinase known as MAPK13 that is activated in respiratory airway diseases and is required for mucus production in human cell-culture models. Support for MAPK13 function in these models came from effectiveness of MAPK13 versus MAPK14 gene-knockdown and from first-generation MAPK13-14 inhibitors. However, these first-generation inhibitors were incompletely optimized for blocking activity and were untested in vivo. Here we report the next generation and selection of a potent MAPK13-14 inhibitor (designated NuP-3) that more effectively downregulates type-2 cytokine-stimulated mucus production in air-liquid interface and organoid cultures of human airway epithelial cells. We also show that NuP-3 treatment prevents respiratory airway inflammation and mucus production in new minipig models of airway disease triggered by type-2 cytokine challenge or respiratory viral infection. The results thereby provide the next advance in developing a small-molecule kinase inhibitor to address key features of respiratory disease.NEW & NOTEWORTHY This study describes the discovery of a potent mitogen-activated protein kinase 13-14 (MAPK13-14) inhibitor and its effectiveness in models of respiratory airway disease. The findings thereby provide a scheme for pathogenesis and therapy of lung diseases [e.g., asthma, chronic obstructive pulmonary disease (COPD), Covid-19, postviral, and allergic respiratory disease] and related conditions that implicate MAPK13-14 function. The findings also refine a hypothesis for epithelial and immune cell functions in respiratory disease that features MAPK13 as a possible component of this disease process.
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Proteína Quinasa 14 Activada por Mitógenos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Humanos , Porcinos , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Porcinos Enanos/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Moco/metabolismo , Citocinas/metabolismo , Proteína Quinasa 13 Activada por Mitógenos/metabolismoRESUMEN
Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled chronic obstructive pulmonary disease (COPD) and relied on cigarette smoke exposure and LPS stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in COVID-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease caused by infection due to the natural pathogen Sendai virus using a mouse model of PVLD. We identify a significant decrease in myofiber size when PVLD is maximal at 49 days after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch-type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insights into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.NEW & NOTEWORTHY Our study used a mouse model of post-viral lung disease to study the impact of chronic lung disease on skeletal muscle. The model reveals a decrease in myofiber size that is selective for specific types of myofibers and an alternative mechanism for muscle atrophy that might be independent of the usual markers of protein synthesis and degradation. The findings provide a basis for new therapeutic strategies to correct skeletal muscle dysfunction in chronic respiratory disease.
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COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , COVID-19/patología , Músculo Esquelético/metabolismo , Pulmón/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Atrofia Muscular/etiología , Atrofia Muscular/metabolismoRESUMEN
BACKGROUND: Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses. RESULTS: Here, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1-/- recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7- TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection. CONCLUSIONS: This study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly.
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Ectromelia virus (ECTV) causes mousepox, a surrogate mouse model for smallpox caused by variola virus in humans. Both orthopoxviruses encode tumor necrosis factor receptor (TNFR) homologs or viral TNFR (vTNFR). These homologs are termed cytokine response modifier (Crm) proteins, containing a TNF-binding domain and a chemokine-binding domain called smallpox virus-encoded chemokine receptor (SECRET) domain. ECTV encodes one vTNFR known as CrmD. Infection of ECTV-resistant C57BL/6 mice with a CrmD deletion mutant virus resulted in uniform mortality due to excessive TNF secretion and dysregulated inflammatory cytokine production. CrmD dampened pathology, leukocyte recruitment, and inflammatory cytokine production in lungs including TNF, IL-6, IL-10, and IFN-γ. Blockade of TNF, IL-6, or IL-10R function with monoclonal antibodies reduced lung pathology and provided 60 to 100% protection from otherwise lethal infection. IFN-γ caused lung pathology only when both the TNF-binding and SECRET domains were absent. Presence of the SECRET domain alone induced significantly higher levels of IL-1ß, IL-6, and IL-10, likely overcoming any protective effects that might have been afforded by anti-IFN-γ treatment. The use of TNF-deficient mice and those that express only membrane-associated but not secreted TNF revealed that CrmD is critically dependent on host TNF for its function. In vitro, recombinant Crm proteins from different orthopoxviruses bound to membrane-associated TNF and dampened inflammatory gene expression through reverse signaling. CrmD does not affect virus replication; however, it provides the host advantage by enabling survival. Host survival would facilitate virus spread, which would also provide an advantage to the virus.
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Virus de la Ectromelia/fisiología , Interacciones Huésped-Patógeno , Receptores del Factor de Necrosis Tumoral/metabolismo , Infecciones del Sistema Respiratorio/virología , Proteínas Virales/metabolismo , Animales , Línea Celular , Chlorocebus aethiops , Femenino , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Infecciones del Sistema Respiratorio/patología , Carga ViralRESUMEN
BACKGROUND: Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. METHODS: We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019-May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. RESULTS: There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months. CONCLUSIONS: RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. CLINICAL TRIALS REGISTRATION: NCT04141917.
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COVID-19 , Infecciones por Enterovirus , Personas con Mala Vivienda , Virus , COVID-19/epidemiología , Estudios Transversales , Infecciones por Enterovirus/epidemiología , Genómica , Humanos , Pandemias , Rhinovirus/genética , Washingtón/epidemiologíaRESUMEN
Analyze clinical samples collected and determine the etiology of viral pathogens and the dynamics of their spread. Acute respiratory viral infections remain one of the key health problems worldwide. They constitute etiologically independent diseases, with similar clinical infection manifestations and a single mechanism for the transmission of pathogens. 4712 nasopharyngeal swabs were collected from people before and during the COVID-19 pandemic with acute respiratory infections that tested negative for COVID-19 and were examined in this study. The collected samples were screened by a real-time polymerase chain reaction on a Rotor-Gene Q6 plex instrument. Statistical processing of the results, tabular, and graphical data were analyzed in the MS Excel. The largest number of the nasopharyngeal swabs were collected from children under 17 years of age (60.75%). In 702 samples (9.85%) pathogens of respiratory infections of non-influenza etiology were detected, including adenovirus, bocavirus, coronavirus, metapneumovirus, paramyxovirus types I-IV, respiratory syncytial virus, and rhinovirus. At the same time, both before and during the COVID-19 pandemic, different influenza virus variants co-circulation (A/H1N1, A/H3N2, and type B) were discovered, with a predominance of viruses with the antigenic formula A/H1N1. The results of the study indicate the need for continuous monitoring of the viral pathogens spread, which will expand the existing knowledge of the viral etiology of respiratory diseases and highlight the importance of viruses in the respiratory infections occurrence.
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AIM: To establish symptoms, lung function and to evaluate subsequent exacerbations of chronic obstructive pulmonary disease (COPD) during a year after virus-induced COPD exacerbations. MATERIALS AND METHODS: Patients hospitalized with viral (n=60), bacterial (n=60) and viral-bacterial (n=60) COPD exacerbations were enrolled to single-center prospective observational study. COPD was diagnosed according spirography criteria. Viral infection was established in bronchoalveolar lavage fluid or sputum by real-time reverse transcription-polymerase chain reaction for RNA of influenza A and B virus, rhinovirus, respiratory syncytial virus and SARS-CoV-2. Symptoms, lung function, COPD exacerbations were assessed. Patients were investigated at the hospitalization onset and then 4 and 52 weeks following the discharge from the hospital. RESULTS: After 52 weeks in viral and viral-bacterial COPD exacerbations groups the rate of forced expiratory volume in one second (FEV1) decline were maximal - 71 (68; 73) ml/year and 69 (67; 72) ml/year versus 59 (55; 62) ml/year after bacterial exacerbations. Low levels of diffusion lung capacity for carbon monoxide (DLco/Va) - 52.5% (45.1%; 55.8%), 50.2% (44.9%; 56.0%) and 75.3% (72.2%; 80.1%) respectively, of 6-minute walk distance; p<0.001 in relation to bacterial exacerbations. In Cox proportional hazards regression analyses viral and viral-bacterial exacerbations were associated with increased risk of subsequent COPD exacerbations by 2.4 times independent of exacerbations rate before index event and FEV1. In linear regression models the relationships between airflow limitation and respiratory syncytial virus, rhinovirus and influenza virus infection, between low DLco/Va and rhinovirus, influenza virus and SARS-CoV-2 infection. CONCLUSION: COPD after virus-induced exacerbations were characterized by progression of airflow limitation, low DLco/Va, low 6-minute walking test distance, subsequent COPD exacerbations risk.
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COVID-19 , Gripe Humana , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , COVID-19/complicaciones , COVID-19/diagnóstico , SARS-CoV-2 , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Pulmón , Progresión de la EnfermedadRESUMEN
Respiratory viral infections are the leading cause of death worldwide. The current pandemic of coronavirus infection (COVID-19) challenged human beings for the treatment and prevention of this respiratory viral infection since its outbreak in 2019. Despite advancements in the medical field, scientists were helpless to give timely treatment and protection against this viral infection. Several drugs, whether antiviral or not, were given to the patients to reduce mortality and morbidity rate. Vaccines from various pharmaceutical manufacturers are now available to give immunization against covid-19. Still, coronavirus is continuously affecting people in the form of variants after mutation. Each new variant increases the infection risk and forces scientists to develop some innovative and effective treatments for this infection. The virus uses the host's cell machinery to grow and multiply in numbers. Therefore, scientists are facing challenges to develop antivirals that stop the virus without damaging the host cells too. The production of suitable antivirals or vaccines for the new virus would take several months, allowing the strain to cause severe damage to life. Inhalable formulation facilitates the delivery of medicinal products directly to the respiratory system without causing unwanted side effects associated with systemic absorption. Scientists are focusing on developing an inhaled version of the existing antivirals for the treatment of respiratory infections. This review focused on the inhalable formulations of antiviral agents in various respiratory viral infections including the ongoing covid-19 pandemic and important findings of the clinical studies. We also reviewed repurposed drugs that have been given through inhalation in covid-19 infection.
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Tratamiento Farmacológico de COVID-19 , Virosis , Humanos , Pandemias , SARS-CoV-2 , Antivirales/uso terapéuticoRESUMEN
Sendai virus (SeV) accessory protein C limits the generation of double-stranded RNAs, defective interfering RNAs, or both, during viral transcription and replication, thereby limiting interferon-ß production. Our recent in vitro analyses on murine macrophage cell lines demonstrated that this protein also contributes to restricting macrophage function, including the production of nitric oxide (NO) and inflammatory cytokines in addition to interferon-ß, in infected macrophages. This study showed that depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in recombinant C gene-knockout SeV (SeV∆C)-infected mice, but did not modulate disease severity in wild-type SeV-infected mice. Furthermore, the severe disease observed in macrophage-depleted, SeV∆C-infected mice was associated with exacerbated virus replication in the lungs, leading to severe airway inflammation and pulmonary edema, indicating lung injury. These results suggested that the antimacrophage activity of SeV C protein might play a critical role in modulating lung injury and associated diseases caused by SeV.
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Infecciones por Respirovirus , Virus Sendai , Animales , Interferón beta , Macrófagos/metabolismo , Ratones , Virus Sendai/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Allogeneic hematopoietic cell transplant (allo-HCT) recipients are at increased risk for respiratory viral infections (RVIs), which invoke substantial morbidity and mortality. Limited effective antiviral options and drug resistance often hamper successful RVI treatment, creating additional burden for patients and the health care system. METHODS: Using an open-source health care claims database, we examined differences in clinical outcomes, health resource utilization, and total reimbursements during the 1-year period following allo-HCT in patients with and without any RVI infection (respiratory syncytial virus, influenza, parainfluenza virus, and human metapneumovirus). RVIs were diagnosed at any time ≤1 year after allo-HCT and identified by International Classification of Disease codes. Analyses were stratified by the presence or absence of acute or chronic graft-versus-host disease (GVHD). RESULTS: The study included 13 363 allo-HCT patients, 1368 (10.2%) of whom had a diagnostic code for any RVI. A higher proportion of patients with any RVI had pneumonia ≤1 year after allo-HCT compared to patients without any RVI, with or without GVHD. Patients with any RVI had higher all-cause mortality risk, longer length of post-allo-HCT hospital stay, higher readmission rate, and higher number of hospital days after allo-HCT compared to patients without the infection (all p < .05). Total unadjusted median reimbursements were higher for those with any RVI and each specific RVI assessed than those without the specific infection, with or without GVHD. CONCLUSION: Allo-HCT patients with RVIs had significantly worse clinical outcomes and increased health resource utilization and reimbursements during the year following allo-HCT, with or without GVHD.