Expressions of miR-21 TGF-beta/Smad signaling pathway in peripheral blood of bronchial asthma patients complicated with respiratory virus infection

OBJECTIVE: To investigate the expressions of peripheral blood microRNA-21(miR-21) and transforming growth factor-beta(TNF-beta)/Smad signaling transduction pathway in patients with bronchial asthma complicated with respiratory virus infection. METHODS: Totally 109 patients with asthma complicated with respiratory virus infection(study group) and 104 patients without virus infection(control group) in the Third People's Hospital of Gansu Province between Feb.2019 and Feb.2021 were selected for the cross-sectional study. The basic data of the two groups were collected, and parameters including vital signs, lung function, peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins were measured. According to the guidelines, the patients of the two groups were divided into acute exacerbation phase and stable phase. The examination results of each group were compared and the levels of peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins expression of patients with asthma complicated with respiratory virus infection were analyzed. RESULTS: In study group, the proportion of respiratory virus infection among 109 patients was 33.94% for influenza virus, 23.85% for human rhinovirus, 19.27% for respiratory syncytial virus, 10.09% for parainfluenza virus, 6.42% for adenovirus, 4.59% for human coronavirus and 1.83% for human metapneumovirus respectively. The proportion of patients with acute exacerbation phase in the study group was higher than that in the control group, and the levels of peripheral blood miR-21, TGF-beta1, Smad7, pSmad2 and pSmad3 were higher than those in control group(P<0.05). The levels of miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 in peripheral blood of patients with acute exacerbation phase of asthma were higher than those of patients with stable phase of asthma(P<0.05). There were no statistical differences in peripheral blood miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 levels in asthma patients with different virus infections. CONCLUSION: Early respiratory virus infections might lead to increased expression of peripheral blood miR-21 and increased activation of TGF-beta/Smad signaling pathway in patients with asthma, which played an important role in acute attack of asthma.

Mysterious plastic bronchitis: a little-known disease in medical practice

The article presents a clinical case of a 51-year-old patient first seeking medical care with complaints of paroxysmal cough bringing up bronchial casts. The diagnosis of plastic bronchitis was verified. The disease which has not been well described in the literature, difficulty of verifying the underlying diagnosis due to polysymptomatic clinical presentation characterized by the mortality rate of 50–80%, COVID-19 coinfection, resistance to therapy, and little concern of medical specialists determine the relevance and value of this clinical case. © 2023 Authors. All rights reserved.

Mysterious plastic bronchitis: a little-known disease in medical practice

The article presents a clinical case of a 51-year-old patient first seeking medical care with complaints of paroxysmal cough bringing up bronchial casts. The diagnosis of plastic bronchitis was verified. The disease which has not been well described in the literature, difficulty of verifying the underlying diagnosis due to polysymptomatic clinical presentation characterized by the mortality rate of 50-80%, COVID-19 coinfection, resistance to therapy, and little concern of medical specialists determine the relevance and value of this clinical case.

Pathology Detector System in the Bronchopulmonary System of Asthmatic patients visualized through a radiofrequency of the chest

The arrival of COVID-19 caused devastation to humanity by spreading rapidly around the world and seriously affecting the entire health system. To date, the peculiar symptoms of COVID-19 and the problems it generates in those asthmatic people are already known, which is complicated if they have not had an adequate treatment of their disease, since bronchial asthma is one of the complex bronchopulmonary diseases and for its diagnosis some methods are used that do not provide enough information about the patient's condition, being inefficient methods, therefore, it is necessary to use tools to diagnose pathologies to patients in a comfortable way for an efficient treatment by providing the greatest amount of information about the patient's condition for continuous treatment and in addition to facilitating constant access to several patients with asthma. In view of this problem, in this article a pathology detection system was made in the bronchopulmonary system of asthmatic patients visualized through a radiofrequency of the chest, in such a way that an early diagnosis is made, and some pathological change can be detected in the patient's bronchopulmonary system, with this, an efficient treatment of the patient can be carried out. Through the development of the system, it was possible to observe that the operation was done correctly in the tests conducted, the positioning equipment will move the radiant module on the patient's body for the detection of some pathology with an accuracy of 97.86% efficiency. © 2023 IEEE.

SOME FEATURES OF THE CORONAVIRUS INFECTION COURSE IN BRONCHIAL ASTHMA PATIENTS

The outbreak of a new coronavirus infection was officially recognized by the World Health Organization as a global pandemic since March 11, 2020. The pandemic is currently gradually receding, the number of patients is also steadily decreasing. However, these circumstances are not grounds to believe that the virus has been definitively and irrevocably defeated. For this reason, the world medical community is still concerned about the coronavirus' impact on the course and outcome of various chronic bronchopulmonary diseases. Bronchial asthma has been recognized as one of the leading forms of human somatic pathology throughout the history of mankind and medicine. It is quite natural that the focus of the researchers' attention turned out to be questions about the SARS-CoV-2 virus' impact on patients suffering from bronchial asthma, starting with the peculiarities of the course of combined pathology and ending with the peculiarities of therapy and subsequent rehabilitation. The issues of coronavirus infection and bronchial asthma pathogenesis were considered. The research data on some features of the development and course of a new coronavirus infection in patients with this profile were analyzed and summarized. The low coronavirus infection prevalence among patients with an allergic bronchial asthma form compared with other phenotypes is shown among such features, data on the effect of eosinophilia on the course of infection are presented, and the basic therapy's positive effect using inhaled glucocorticosteroids and/or monoclonal antibodies (biological therapy) in severe asthma, is shown in the form of a protective effect that provides a lighter coronavirus infection course. The main features of patient management suffering from bronchial asthma in the conditions of a pandemic are the organization of stable medical control in online telemedicine once monthly, regular examinations in accordance with the severity of the course of the disease and the correction of basic therapy to achieve complete control over the course of asthma. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

Respiratory Disorders: Contemporary Issues in 2020

Respiratory system bears the major brunt of environmental insults. Respiratory infections such as pneumonias continue to threaten human health. The corona virus pandemic (COVID-19) is the most recent example of a respiratory infection threatening the human kind. Tuberculosis is one of the most ancient diseases which continue to pose as a clinical problem. Besides infections, there is a huge burden of chronic respiratory disorders in terms of morbidity and mortality. Chronic respiratory disease (CRD) is among the most common non-communicable diseases (NCDs) identified by the World Health Organization. Chronic obstructive pulmonary disease (COPD) is the third most common cause of death the world over. Respiratory allergies such as bronchial asthma, environmental, occupational and other interstitial lung diseases are other common chronic lung diseases which are increasing in incidence. Several new diagnostic and treatment modalities have been added in our armamentarium to fight against these disorders. Besides the medical and surgical treatments, some of these interventions are non-pharmacological in nature such as the pulmonary rehabilitation and patient education programmes. Newer strategies and governmental programmes constitute other important steps to control the disease-burden. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Bronchial carcinoid misdiagnosed as COVID pneumonia: a case report.

Bronchial carcinoid tumours are rare, slow-growing, malignant, Low-grade neuroendocrine tumours that arise from Enterochromaffin (Kulchitsky) cells and are usually detected typically as indolent and solitary tumours. Approximately 2% of all lung tumours are bronchial carcinoid tumours. Case presentation: The authors report a case of 55-years-old man who presented with a history of cough for 1 month and was initially diagnosed with a case of COVID-19. Then he was treated as a case of pneumonia as seen on high-resolution computed tomography. Later, contrast-enhanced computed tomography and bronchoscopy-guided biopsy were done which revealed a right lower lobe neuroendocrine tumour (carcinoid), which was successfully resected. Clinical discussion: The majority of typical carcinoids are located in the central airways leading to bronchial obstruction with recurrent pneumonia, chest pain, and wheezing. During the COVID-19 pandemic, lung cancer patients were at higher risk of being affected by COVID-19. This study emphasizes that early identification and differential diagnosis are extremely difficult in the absence of comprehensive study and workup as the clinical and imaging findings of COVID-19 may resemble lung cancer. Although hilar and mediastinal lymph nodes are the most common metastatic sites for typical carcinoids, most lymphadenopathies are caused by a reactive inflammatory reaction. Conclusion: Bronchial carcinoids are uncommon, malignant neuroendocrine tumours for which the only curative management is complete surgical resection. With full resection, the result of typical carcinoids with lymph node metastases is favourable.

Organization of immunobiological therapy for severe bronchial asthma in the Sverdlovsk region

BACKGROUND: Biologicals use in severe asthma (SA) is associated with targeted therapy (TT) availability problem. Ensuring the availability of biologicals can be resolved within the territorial compulsory medical insurance program (TCMIP) in day-stay or round-the-clock hospital. AIMS: This study aimed to develop and implement a program for immunobiological therapy (IBT) introduction for SA in Sverdlovsk Region (SR). MATERIALS AND METHODS: Program for introduction of IBT for SA was developed in SR in 2018 to provide patients with expensive biologicals within the TCMIP. Program includes the following: SA prevalence study in SR;practitioners training in differential diagnosis of SA;organization of affordable therapy for patients with SA;registration of patients with SA creation and maintenance;and selection and management of patients with SA in accordance with federal clinical guidelines. RESULT(S): Atopic phenotype in SA was detected in 5%, eosinophilic - in 2.3% of all analyzed cases of asthma (n=216). Practitioners of SR were trained in differential diagnosis of SA. Orders of the Ministry of Health of SR were issued as follows: regulating the procedure for referring patients with SA to IBT, with a list of municipal medical organizations providing IBT in a day-stay or round-the-clock hospital;approving regional registration form of patients with SA requiring biologicals use;ungrouping of clinical and statistical groups of day-stay hospital was depending on INN and dosage of biologicals;and selecting patients with SA for TT and including them in the regional register. Initiating of TT in round-the-clock hospital and continuation therapy in day-stay hospital provides a significant savings in compulsory medical insurance funds. CONCLUSION(S): IBT introduction for SA in SR is carried out within the framework of the developed program. Principle of decentralization brings highly specialized types of medical care closer to patients making it possible to provide routine medical care in "allergology-immunology" profile in the context of restrictions caused by coronavirus disease 2019 pandemic.Copyright © 2020 Pharmarus Print Media All rights reserved.

Can bronchial secretion cultures identify the etiologic agent of COVID-19-associated pulmonary aspergillosis in ICU patients? Comparison with a species-specific Aspergillus PCR in serum.

Aspergillus spp. isolated from non-BAL cultures of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) patients may reflect colonization rather than infection. Sera (n = 181) from 49 adult ICU CAPA patients (24 probable and 25 possible CAPA) with bronchial secretions (BS) culture positive for Aspergillus spp. were collected and tested for Aspergillus DNA detection by species-specific real-time PCR. Overall, 30/49 (61%) patients were PCR positive. BS culture/serum PCR agreement was moderate (21/30; 70%). Based on serum PCR positive patients, all CAPAs were due to A. fumigatus (80%), A. flavus (10%), and A. terreus (10%). No A. niger/A. nidulans or mixed infections were found despite positive BS cultures.

Discordant results were observed between bronchial secretion cultures and species-specific serum PCR (30%) with A. fumigatus being by far the most common etiological agent of CAPA (80%). No A. niger/A. nidulans or mixed infections were found despite positive cultures.

Optimized nanoparticle-mediated base editing of cystic fibrosis-causing variants

Background: Next-generation SARS-CoV-2 vaccines demonstrated that nanoparticle messenger ribonucleic acid (mRNA) delivery is effective and safe for in vivo delivery in humans. Current treatments for cystic fibrosis (CF) primarily focus on modulator drug therapies designed to correct malfunctioning CF transmembrane conductance regulator (CFTR) protein, but these modulators are ineffective for the 10% of people with CF with variants that do not allow protein production. Among these is the splice variant 3120 + 1G >A, the most common CF-causing mutation in native Africans. Gene editing would allow production of CFTR protein and enhancement of function using available CFTR modulators. We have demonstrated that electroporation of a modified CRISPR-Cas9 base editor to primary human bronchial epithelial cells carrying 3120 + 1G >A and F508del mutant alleles achieved 75% genome editing of the splice variant, resulting in approximately 40% wild-type (WT) CFTR function [1]. Here,we evaluate the effectiveness of several new nanoparticle formulations at delivering green fluorescent protein (GFP) mRNA to CF bronchial epithelial (CFBE41o-) cells. Using the optimal formulation,we then tested the efficacy correction of the 3120 + 1G >Avariant in a CFTR expression minigene (EMG) integrated into the genome of isogenic CFBE cells using mRNA and plasmid deoxyribonucleic acid (DNA) encoding adenine base editor (ABE) and guide (g)RNA. Method(s): GFP served as a reporter to evaluate transfection efficiency, cell viability, and mean fluorescence intensity (MFI) for three dosages (150, 75, 32.5 ng of mRNA), four polymer-to-mRNA to weight (w/w) ratios (60, 40, 30, 20), and four polymers (R, Y, G, B). 7-AAD served as a live/dead stain to quantify viability, with flow cytometry results analyzed using FlowJo software. CFBE cells stably expressing the 3120 + 1G >A EMG were transfected with the optimized nanoparticle formulation to deliver ABE and gRNA at two dosages (150, 75 ng) of mRNA and DNA. CFTR function in CFBE cellswas measured by short circuit current, forskolin stimulation, and inh-172 inhibition as a measure of editing efficiency. Result(s): Flow cytometry showed that polymer R achieved more than 85% GFP transfection, compared with a maximum of approximately 35% for the other three polymers at the maximum 150-ng dose, with approximately 80% viability normalized to untreated cells. In addition, polymer R achieved GFP MFI more than one order of magnitude as high as other formulations (~30 000 vs 2700 MFI) for the other three polymers at 150-ng dose and 40 w/w ratio. CFBE cells transfected with polymer R nanoparticles containing ABE and guide RNA at 75 ng and 150 ng showed mean CFTR function increase to 10 muA 6 (standard error of the mean [SEM] 1.1 muA) (~10% of WT) and 6.3 muA (SEM 0.9 muA) (~6% of WT), respectively. Greater toxicity at the higher dose could explain the larger increase in CFTR current at the lower dose. DNA-encoded ABE plasmid and gRNA showed a less robust increase in CFTR function (2.9 muA [SEM 0.4 muA] for 75-ng dose;3.0 muA [SEM 0.4 muA] for 150-ng dose), which was probably a result of the nanoparticle formulation being optimized for RNA instead of DNA cargo or the additional intracellular barriers that must be overcome for successful DNA delivery. Conclusion(s): We demonstrated that an optimized nanoparticle formulation containing ABE and gRNA can correct splicing of isogenic cells bearing the 3120 + 1G >A CFTR variant, resulting in recovery of CFTR function. In ongoing work, we are adapting these nanoparticles for RNA- and DNAencoded ABE and gRNA delivery to primary human bronchial epithelial cells.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

RNA-sequencing unravels unique host-response to infection with SARS-CoV-2

Introduction/Aim: As the causative agent of COVID-19, SARS-CoV-2 remains a global cause for concern. Compared to other highly pathogenic coronaviruses (SARS-CoV and MERS-CoV), SARS-CoV-2 exhibits stronger transmissibility but less lethality, indicating that SARS-CoV-2 displays unique characteristics, despite the partial genomic proximity. Thus, we aim to employ RNA sequencing to define transcriptional differences in epithelial responses following infection with SARS-CoV-2 compared to pathogenic SARS-CoV and MERS-CoV, and low pathogenic HCoV-229E. Method(s): Primary human bronchial epithelial cells (PBEC) were differentiated for 6 weeks at the air-liquid interface (ALI) before parallel infection by the 4 different coronaviruses (n = 4). After infection following apical application of coronaviruses at low dose (MOI 0.1), cells were harvested for bulk RNA sequencing. Gene were considered significant with a fold change (FC) > 2 and false discovery rate of FDR < 0.05. Inhibitor experiments were conducted on CALU-3 cells using DIM-C-pPhOH 10 muM (NR4A1 antagonist), Sp600125 10 muM (JNK inhibitor), T-5224 10 muM (AP-1 transcription factor inhibitor) and Cytosporone B (CsB 5 muM;NR4A1 agonist) preincubated for 1 h with these compounds and subsequently infected with SARS-CoV-2 or MERS-CoV (MOI of 1). Samples were collect 24 h later for PCR. Result(s): PCR and RNA-Seq demonstrated that all tested coronaviruses efficiently infected ALI-PBEC and replicated over 72 h (p < 0.05). RNA sequencing analysis revealed that infection with SARS-CoV, MERS-CoV and HCoV-229E resulted in largely similar transcriptional responses by the epithelial cells. However, whereas infection with these viruses was accompanied by an increased expression of genes associated with JNK/AP-1 signalling, including FOS, FOSB and NR4A1 (FC > 1, FDR < 0.05), no such increase was observed following SARS-CoV-2 infection. Further, we found that an NR4A1 antagonist reduced viral replication of MERS and SARs-CoV-2 100-fold in Calu-3 cells. Conclusion(s): In conclusion, these data suggest that SARS-CoV-2-infected ALI-PBEC exhibit a unique transcriptional response compared to other coronaviruses, which might relate to the pathogenicity of the virus.

Evaluation of lung cell populations in severe COVID-19 pneumonia

Introduction/Aim: Coronavirus disease 2019 (COVID-19) is a novel viral infection that can cause severe pneumonia and acute respiratory failure;however, the mechanism of disease progression is still unclear. The aim of this study is to evaluate inflammatory cells in the lung by analysing cell populations of bronchial aspirates of COVID-19 pneumonia. Method(s): Eligible cases were diagnosed as COVID-19, confirmed by SARS-CoV-2 PCR. All cases had developed severe COVID-19 pneumonia and undergone invasive positive pressure ventilation for the treatment of respiratory failure. Bronchial aspirates were collected during endotracheal intubation, and SARS-CoV-2 PCR was done. The populations of obtained cells from bronchial aspirates were examined by Giemsa staining and immunohistochemical staining of CD3, CD4, CD8, CD20 and CD68 antigens. Bronchial aspirates were cultured to confirm respiratory bacterial co-infections. Result(s): A total of 14 cases (median age 70;eleven male and three female) were enrolled in this study. Their bronchial aspirates were all positive for SARS-CoV-2 PCR. Bacterial co-infections were developed in 10 cases, including 6 cases of pneumonia/respiratory tract infection, 2 cases of sepsis, and 2 cases of urinary tract infection. Cell populations of bronchial aspirates with or without bacterial co-infections were as follows: neutrophils 33.0% vs. 21.5%;CD3+ mononuclear cells (MNCs) 2.5% vs. 5.8%;CD4+ MNCs 4.6% vs. 3.4%;CD8+ MNCs 3.5% vs. 5.2%;CD20+ MNCs 0.2% vs. 0.1%;CD68+ MNCs 39.7% vs. 38.8%, respectively. Conclusion(s): CD68 antigen is mainly expressed in monocytes/macrophages. CD68+ MNCs were dominant in bronchial aspirates of the cases with severe COVID-19 pneumonia. Our data suggests that CD68+ MNCs, presumably macrophages, would play an essential role during the innate immune response to acute SARS-CoV-2 infection in the lung.

Bronchial Artery Embolization Treatment During COVID-19 Pandemic: A Single-center Experience

Objective: Bronchial artery embolization (BAE) now serves as the standard treatment for hemoptysis. The aim of this study was to determine the characteristics and outcomes of the patients who undergo BAE during the coronavirus disease-2019 pandemic period. Methods: We retrospectively investigated patients that presented to the hospital with hemoptysis and received bronchial arterial embolization treatment during the pandemic period. Age, gender, history of previous diseases, and related data were collected. Results: The study was conducted with 11 patients whose 18.18% (n=2) were female and 81.81% (n=9) were male. The mean age of the patients is 61.27 +/- 10.94 and they stayed in hospital 21.18 +/- 19.59 days on average. Infection and bronchiectasis were seen as the leading cause of hemorhagee. Also, alveolar hemorrhage seen 81.8% (n=9) of the patients. Dilated bronchial arteries were seen on 72.7% (n=8) of the patients. Although 54.5% (n=6) of the patients admitted to the intensive care unit after the procedure, no complication or mortality seen in any patient during the procedure. Conclusion: Bronchial arterial embolization is an effective minimally invasive technique for treating hemoptysis. This invasive procedure could be applied safely during the pandemic period.

Galactomannan-Antigen Testing from Non-Directed Bronchial Lavage for Rapid Detection of Invasive Pulmonary Aspergillosis in Critically Ill Patients: A Proof-of-Concept Study.

Invasive pulmonary aspergillosis is associated with high mortality. For diagnosis, galactomannan-antigen in serum and bronchoalveolar lavage fluid is recommended, with higher sensitivity in bronchoalveolar lavage fluid. Because of invasiveness, bronchoalveolar lavage might be withheld due to patients' or technical limitations, leading to a delay in diagnosis while early diagnosis is crucial for patient outcome. To address this problem, we performed an analysis of patient characteristics of intubated patients with invasive pulmonary aspergillosis with comparison of galactomannan-antigen testing between non-directed bronchial lavage (NBL) and bronchoalveolar lavage fluid. A total of 32 intubated ICU patients with suspected invasive pulmonary aspergillosis could be identified. Mycological cultures were positive in 37.5% for A. fumigatus. Galactomannan-antigen in NBL (ODI 4.3 ± 2.4) and bronchoalveolar lavage fluid (ODI 3.6 ± 2.2) showed consistent results (p-value 0.697). Galactomannan-antigen testing for detection of invasive pulmonary aspergillosis using deep tracheal secretion showed comparable results to bronchoalveolar lavage fluid. Because of widespread availability in intubated patients, galactomannan-antigen from NBL can be used as a screening parameter in critical risk groups with high pretest probability for invasive aspergillosis to accelerate diagnosis and initiation of treatment. Bronchoalveolar lavage remains the gold standard for diagnosis of invasive aspergillosis to be completed to confirm diagnosis, but results from NBL remove time sensitivity.

Some features of the coronavirus infection course in bronchial asthma patients

The outbreak of a new coronavirus infection was officially recognized by the World Health Organization as a global pandemic since March 11, 2020. The pandemic is currently gradually receding, the number of patients is also steadily decreasing. However, these circumstances are not grounds to believe that the virus has been definitively and irrevocably defeated. For this reason, the world medical community is still concerned about the coronavirus' impact on the course and outcome of various chronic bronchopulmonary diseases. Bronchial asthma has been recognized as one of the leading forms of human somatic pathology throughout the history of mankind and medicine. It is quite natural that the focus of the researchers' attention turned out to be questions about the SARS-CoV-2 virus' impact on patients suffering from bronchial asthma, starting with the peculiarities of the course of combined pathology and ending with the peculiarities of therapy and subsequent rehabilitation. The issues of coronavirus infection and bronchial asthma pathogenesis were considered. The research data on some features of the development and course of a new coronavirus infection in patients with this profile were analyzed and summarized. The low coronavirus infection prevalence among patients with an allergic bronchial asthma form compared with other phenotypes is shown among such features, data on the effect of eosinophilia on the course of infection are presented, and the basic therapy's positive effect using inhaled glucocorticosteroids and/or monoclonal antibodies (biological therapy) in severe asthma, is shown in the form of a protective effect that provides a lighter coronavirus infection course. The main features of patient management suffering from bronchial asthma in the conditions of a pandemic are the organization of stable medical control in online telemedicine once monthly, regular examinations in accordance with the severity of the course of the disease and the correction of basic therapy to achieve complete control over the course of asthma.

Lung Epithelial Cells from Obese Patients Have Impaired Control of SARS-CoV-2 Infection.

Obesity is known to increase the complications of the COVID-19 coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the exact mechanisms of SARS-CoV-2 infection in obese patients have not been clearly elucidated. This study aims to better understand the effect of obesity on the course of SARS-CoV-2 infection and identify candidate molecular pathways involved in the progression of the disease, using an in vitro live infection model and RNA sequencing. Results from this study revealed the enhancement of viral load and replication in bronchial epithelial cells (NHBE) from obese subjects at 24 h of infection (MOI = 0.5) as compared to non-obese subjects. Transcriptomic profiling via RNA-Seq highlighted the enrichment of lipid metabolism-related pathways along with LPIN2, an inflammasome regulator, as a unique differentially expressed gene (DEG) in infected bronchial epithelial cells from obese subjects. Such findings correlated with altered cytokine and angiotensin-converting enzyme-2 (ACE2) expression during infection of bronchial cells. These findings provide a novel insight on the molecular interplay between obesity and SARS-CoV-2 infection. In conclusion, this study demonstrates the increased SARS-CoV-2 infection of bronchial epithelial cells from obese subjects and highlights the impaired immunity which may explain the increased severity among obese COVID-19 patients.

Airway obstruction in respiratory viral infections due to impaired mucociliary clearance.

Respiratory viral infections, such as SARS-CoV-2 or influenza, can lead to impaired mucociliary clearance in the bronchial tree due to increased mucus viscosity and its hyper-secretion. We develop in this work a mathematical model to study the interplay between viral infection and mucus motion. The results of numerical simulations show that infection progression can be characterized by three main stages. At the first stage, infection spreads through the most part of mucus producing airways (about 90% of the length) without significant changes in mucus velocity and thickness layer. During the second stage, when it passes through the remaining generations, mucus viscosity increases, its velocity drops down, and it forms a plug. At the last stage, the thickness of the mucus layer gradually increases because mucus is still produced but not removed by the flow. After some time, the thickness of the mucus layer in the small airways becomes comparable with their diameter leading to their complete obstruction.

Bronchodilator reversibility testing in long-term cough and dyspnea after Covid-19 viral infection: a trigger for asthma?

Objective: This study aims to investigate the presence of underlying chronic airway disease in individuals with chronic cough and dyspnea lasting longer than eight weeks and who had previously Coronavirus disease 2019 (COVID-19) and had no known lung disease.Methods: A total of 151 patients admitted to the respiratory diseases outpatient room with the complaint of cough and/or dyspnea that persisted for at least eight weeks following COVID-19 infection were accrued to the study. Demographic characteristics, smoking history, the severity of lung involvement on chest computed tomography in the acute phase of Covid-19 infection, and bronchodilator reversibility test results were recorded. Smoking history and forced expiratory volume in the first second (FEV1) were compared.Results: FEV1 increase ≥ 200 ml was observed in 40 (26.5%) patients. In 24 (15.9%) patients, an increase in FEV1 was found to be 200 ml and above, and the percentage of FEV1 was 12% or more. While 14 (9.3%) patients were diagnosed with asthma, 13 (8.6%) patients were diagnosed with nonreversible airflow obstruction (NRAO), and 1 (0.7%) patient was diagnosed with chronic obstructive pulmonary disease (COPD).Conclusions: COVID-19 infection may play a vital role in initiating asthma pathogenesis. It should be kept in mind that viral infection-related asthma may be the underlying cause of prolonged cough and dyspnea after COVID-19 infection.

Proteomic determinants of disease, mortality and sequelae in COVID-19 patients requiring invasive mechanical ventilation

Introduction: The molecular mechanisms linked to the pathology of severe COVID-19 and its outcomes are poorly described. Aim(s): To analyze the proteomic profile of bronchial aspirates (BAS) samples from critically ill COVID-19 patients in order to identify factors associated with the disease and its prognosis. Method(s): Multicenter study including 74 critically ill non-COVID-19 and COVID-19 patients. BAS was obtained by bronchoaspiration after invasive mechanical ventilation (IMV) initiation. Proximity extension assay (PEA) technology was used for proteomic profiling. Random forest (RF) statistical models were used to predict the variable importance. Result(s): After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-alpha showed differences between COVID-19 and non-COVID-19 patients. Reduced levels of ENTPD2 and PTN were observed in non-survivors, even after adjustment. AGR2, NQO2, IL-1alpha, OSM and TRAIL, were the top five strongest predictors for ICU mortality and were used to build a prediction model. PTN (HR=4.00) ENTPD2 (HR=2.14) and the prediction model (HR=6.25) were associated with higher risk of death. In survivors, FCRL1, NTF4 and THOP1 correlated with lung function (DLCO levels) 3-months after hospital discharge. Similar findings were observed for Flt3L and THOP1 and radiological features (TSS). The proteins identified are expressed in immune and non-immune lung cells. A poor control of viral infectivity and an inappropriate reparative response seems to be linked to the disease and fatal outcomes, respectively. Conclusion(s): In critically ill COVID-19 patients, specific proteomic profiles are associated with the pathology, mortality and lung sequelae.

RNA sequencing unravels unique host transcriptional responses to infection with SARS-CoV-2 in well differentiated primary human bronchial epithelial cells compared to other coronaviruses

As the causative agent of COVID-19, SARS-CoV-2 remains a global cause for concern. Compared to other highly pathogenic coronaviruses (SARS-CoV and MERS-CoV), SARS-CoV-2 exhibits stronger transmissibility but less lethality, indicating that SARS-CoV-2 displays unique characteristics, despite the partial genomic proximity. Thus, we aim to employ RNA sequencing to define transcriptional differences in epithelial responses following infection with SARS-CoV-2 compared to pathogenic SARS-CoV and MERS-CoV, and low pathogenic HCoV-229E. Primary human bronchial epithelial cells (PBEC) were differentiated for 6 weeks at the air-liquid interface (ALI) before parallel infection by the 4 different coronaviruses. After infection following apical application of coronaviruses at low dose, cells were harvested for bulk RNA sequencing. Results demonstrated that all tested coronaviruses efficiently infected ALI-PBEC. RNA sequencing analysis revealed that infection with SARS-CoV, MERS-CoV and HCoV-229E resulted in largely similar transcriptional responses by the epithelial cells. However, whereas infection with these viruses was accompanied by an increased expression of genes associated with JNK/AP-1 signalling, including FOS, FOSB and NR4A1, no such increase was observed following SARS-CoV-2 infection. Further, preliminary experiments indicated that an NR4A1 antagonist reduced viral replication in Calu-3 cells. In conclusion, these data suggest that SARS-CoV2-infected ALI-PBEC exhibit a unique transcriptional response compared to other coronaviruses, which might relate to the pathogenicity of the virus.