Human Respiratory Tract Research Articles

Cloning and Characterization of Immunological Properties of Haemophilus influenzae Enolase.

Haemophilus influenzae is a common organism of the human upper respiratory tract; this bacterium is responsible of a wide spectrum for respiratory infections and can generate invasive diseases such as meningitis and septicemia. These infections are associated with H. influenzae encapsulated serotype b. However, the incidence of invasive disease caused by nontypeable H. influenzae (NTHi) has increased in the post-H. influenzae serotype b (Hib) vaccine era. Currently, an effective vaccine against NTHi is not available; due to this, it is important to find an antigen capable to confer protection against NTHi infection. In this study, 10 linear B cell epitopes and 13 CTL epitopes and a putative plasminogen-binding motif (252FYNKENGMY260) and the presence of enolase on the surface of different strains of H. influenzae were identified in the enolase sequence of H. influenzae. Both in silico and experimental results showed that recombinant enolase from H. influenzae is immunogenic that could induce a humoral immune response; this was observed mediating the generation of specific polyclonal antibodies anti-rNTHiENO that recognize typeable and nontypeable H. influenzae strains. The immunogenic properties and the superficial localization of enolase in H. influenzae, important characteristics to be considered as a new candidate for the development of a vaccine, were demonstrated.

Evaluation of a Filtering Facepiece Respirator and a Pleated Particulate Respirator in Filtering Ultrafine Particles and Submicron Particles in Welding and Asphalt Plant Work Environments.

Manufacturing sites, such as welding, casting, and asphalt production (fumes), generate vast numbers of ultrafine particles of <0.1 µm in size and submicron particles close to the ultrafine range (0.1–0.5 µm). Although cumulative masses of these particles are negligible in comparison to the larger particles, the health effects are more severe due to the higher penetration in the human lower respiratory tract, other body parts crossing the respiratory epithelial layers, and the larger surface area. This research investigates the effectiveness of two common commercially available N95 filtering facepieces and N95 pleated particulate respirator models against ultrafine and submicron particles. Two specific types of respirators, the N95 filtering facepiece and the N95 pleated particulate models, in both sealed and unsealed conditions to the manikin face, were tested at various commercial and academic manufacturing sites, a welding and foundry site, and an asphalt production plant. Two TSI Nanoscan SMPS nanoparticle counters were used simultaneously to collect data for particles of 10–420 nm in size from inside and outside of the respirators. While one of them represented the workplace exposure levels, the other one accounted for the exposure upon filtration through the respiratory surfaces. The results showed the particles generated by these manufacturing operations were mostly within the range of from 40 to 200 nm. Results also indicated that while the percentage of filtration levels varied based on the particle size, it remained mostly within the desired protection level of 95% for both of the N95 respirator models in sealed conditions and even for the N95 pleated particulate model in the unsealed condition. However, in the case of the N95 filtering facepiece model, unsealed respirators showed that the percentage of penetration was very high, decreasing the protection levels to 60% in some cases. Although the number of workplace airborne particle levels varied considerably, the filtration percentages were relatively consistent.

Methanolic Extract of Angelica glauca Edgew Root and Stem: A Possible Component of Herbal Medicines against Respiratory Infections

Plants are identified to produce a variety of compounds to protect themselves against a diversity of pathogens. This study assessed the antibacterial, antioxidant potential and phytochemical screening of medicinal plant Angelica glauca (Choru) root and stem extracts against respiratory tract pathogens i.e., Staphylococcus aureus MTCC 1144, Streptococcus pneumoniae MTCC 655, Streptococcus pyogenes MTCC 442, Pseudomonas aeruginosa MTCC 2474 and Klebsiella pneumoniae MTCC 4030. The plant material was collected from Tungnath 3,800m amsl of Garhwal Himalaya. Root and stem of the plants were washed, shade dried, grinded into fine powder and extracted in the organic solvents of different polarity (petroleum ether, chloroform, methanol and water). Antibacterial activities of prepared extracts were assayed using agar well diffusion and two-fold serial dilution method of MIC determination. Antioxidant potential was determined using DPPH assay and phytochemical analysis was performed using qualitative methods for different phytochemicals. Experimental outcomes revealed maximum antibacterial and antioxidant activity of methanol extract;also the maximum groups of phytochemicals were present in the methanolic extract. The methanol extract produced ZOIs of 11.0±0.54mm to 30.3±1.58mm diameters and MICs ranges were recorded between 3.12 mg/ml to 25 mg/ml against all the tested bacteria. Alkaloids, flavonoids, glycosides, tannins, steroids and saponins were present in the extracts of A. glauca. This study favors a good response towards using A. glauca as natural antioxidant in herbal medicines, either in pure form or as supplement with other herbal formulations already available in the market, to enhance their potential against respiratory tract diseases. In the present COVID-19 pandemic situation, use of A. glauca can be beneficial, as it’s methanolic extract showed promising antibacterial activity against bacterial pathogens of human respiratory tract. © 2021, Association of Pharmaceutical Teachers of India. All rights reserved.

Covid-19 Infection and Parkinsonism: Is There a Link?

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an opportunistic pathogen that infects the upper respiratory tract in humans and causes serious illness, including fatal pneumonia and neurological disorders. Several studies have reported that SARS‐CoV‐2 may worsen the symptoms of Parkinson's disease (PD), with the potential to increase mortality rates in patients with advanced disease. The potential risk of SARS‐CoV‐2 to induce PD has also been suggested because the virus can enter the brain, where it can trigger cellular processes involved in neurodegeneration. In this review, we will discuss the potential of SARS‐CoV‐2 to exacerbate and cause certain neurological disorders, including PD. We will then elucidate its impact on the brain while examining its pathways and mechanisms of action. © 2021 International Parkinson and Movement Disorder Society

A human respiratory tract-associated bacterium with an extremely small genome

Recent advances in culture-independent microbiological analyses have greatly expanded our understanding of the diversity of unculturable microbes. However, human pathogenic bacteria differing significantly from known taxa have rarely been discovered. Here, we present the complete genome sequence of an uncultured bacterium detected in human respiratory tract named IOLA, which was determined by developing a protocol to selectively amplify extremely AT-rich genomes. The IOLA genome is 303,838 bp in size with a 20.7% GC content, making it the smallest and most AT-rich genome among known human-associated bacterial genomes to our best knowledge and comparable to those of insect endosymbionts. While IOLA belongs to order Rickettsiales (mostly intracellular parasites), the gene content suggests an epicellular parasitic lifestyle. Surveillance of clinical samples provides evidence that IOLA can be predominantly detected in patients with respiratory bacterial infections and can persist for at least 15 months in the respiratory tract, suggesting that IOLA is a human respiratory tract-associated bacterium.

Improving Pulmonary Nanotherapeutics Using Helical Aerosol Streams: An In Silico Study.

The increasing prevalence of pulmonary ailments including asthma, chronic obstructive pulmonary disorder, lung tuberculosis, and lung cancer, coupled with the success of pulmonary therapy, has led to a plethora of scientific research focusing on improving the efficacy of pulmonary drug delivery systems. Recent advances in nanoscience and nano-engineering help achieve this by developing stable, potent, inhalable nanosize drug formulations that potentially increase dosages at target sites with significant therapeutic effects. In this study, we numerically analyze a novel methodology of incorporating helical air-nanoparticle streams for pulmonary nanotherapeutics, using a customized version of the open-source computational fluid dynamics (CFD) toolbox openfoam. As nanoparticles predominantly follow streamlines, helical airflow transports them in a centralized core along the human upper respiratory tract, thereby minimizing deposition and hence waste on the oropharyngeal walls, potentially also reducing the risk of drug-induced toxicity in healthy tissues. Advancing our previous study on micron-particle dynamics, helical streams are shown to improve the delivery of nanodrugs, to deeper lung regions when compared to a purely axial fluid-particle jet. For example, an optimal helical stream featuring a volumetric flow rate of 30 L/min, increased the delivery of 300-nm particles to regions beyond generation 3 by 5%, in comparison to a conventional axial jet. Results from regional deposition studies are presented to demonstrate the robustness of helical flows in pulmonary drug delivery, thus paving the way toward successful implementation of the novel methodology in nanotherapeutics.

Analyzing host-viral interactome of SARS-CoV-2 for identifying vulnerable host proteins during COVID-19 pathogenesis.

The development of therapeutic targets for COVID-19 relies on understanding the molecular mechanism of pathogenesis. Identifying genes or proteins involved in the infection mechanism is the key to shedding light on the complex molecular mechanisms. The combined effort of many laboratories distributed throughout the world has produced protein and genetic interactions. We integrated available results and obtained a host protein-protein interaction network composed of 1432 human proteins. Next, we performed network centrality analysis to identify critical proteins in the derived network. Finally, we performed a functional enrichment analysis of central proteins. We observed that the identified proteins are primarily associated with several crucial pathways, including cellular process, signaling transduction, neurodegenerative diseases. We focused on the proteins that are involved in human respiratory tract diseases. We highlighted many potential therapeutic targets, including RBX1, HSPA5, ITCH, RAB7A, RAB5A, RAB8A, PSMC5, CAPZB, CANX, IGF2R, and HSPA1A, which are central and also associated with multiple diseases.

The Relationship Between Lower Respiratory Tract Microbiome and Allergic Respiratory Tract Diseases in Children

Similar to those in the upper respiratory tract, there are microbes present in the healthy human lower respiratory tract (LRT), including the lungs and bronchus. To evaluate the relationship between LRT microbiome and allergic respiratory diseases in children, we enrolled 68 children who underwent bronchoscopy from January 2018 to December 2018 in the affiliated hospital of the Capital Institute of Pediatrics. Using the total IgE (TIgE) values, children were divided into two groups: allergy sensitivity (AS) group and non-allergy sensitivity (NAS) group. Nucleic acid was extracted from samples of bronchoalveolar lavage fluid (BALF) from the two groups of children taken during bronchoscopy treatment and the 16S rDNA gene was sequenced and analyzed. The results showed that Haemophilus, Moraxella, Streptococcus, Prevotella, Neisseria, and Rothia were detected in all patients. There was a statistically significant difference in the composition and distribution of microbiota between the AS and NAS groups (p < 0.01). Analysis of the correlation of clinical indices and microbiome showed that TIgE was positively correlated with Bacteroidetes and negatively correlated with Streptococcus. Absolute lymphocyte count showed a relationship with Streptococcus, and the absolute neutrophil count or percentage of neutrophils showed a relationship with Cardiobacterium. The LRT microbiome functioned similarly to the intestinal microbiome. That is, the decrease in microbial diversity and the change in composition could lead to an increase in allergic symptoms. The microbiome of the LRT in children, especially that of Bacteriodetes and Streptococcus, showed a correlation with respiratory allergic diseases.

Characteristics and Antibiotic Resistance of Haemophilus influenzae in Children with Lower Respiratory Tract Infection in Chengdu, China

Background: Haemophilus influenzae is an opportunistic pathogen of the human respiratory tract. Haemophilus influenzae can cause not only respiratory tract infection in children but also otitis media, epiglottitis and sinusitis. With the widespread use of antibiotics, the positive rate of β-lactamase in H. influenzae is increasing, and the rate of antimicrobial resistance is also increasing, which increases the difficulty of clinical treatment. Objectives: To study the infection characteristics of patients and the antibiotic resistance of H. influenzae in lower respiratory tract samples of children in Chengdu, so as to provide a reference for its clinical diagnosis and the rational use of antibiotics. Methods: Sputum samples of 15891 children aged 0-14 years with lower respiratory tract infection were collected. Haemophilus influenzae was cultured and identified, its drug susceptibility tested, and the results determined according to the guidelines of CLSI 2020. Results: A total of 15891 clinical isolate strains in sputum were detected for drug sensitivity from December 2018 to January 2020, of which 5488 were H. influenzae, accounting for 34.54% (5488/15891). The sex of children infected with H. influenzae was not skewed (P &gt; 0.05). The detection rate of H. influenzae was the highest in children aged 7 - 11 months, and the lowest was in the age group ≤ 28 d. The detection rate was the highest in spring and the lowest in autumn. The positive rate of β-lactamase was 92.0%, the resistance rate to ampicillin was 92.0%, the sensitivity to amoxicillin/clavulanate was 70.2%, and the sensitivity to cefotaxime, ofloxacin, tetracycline, chloramphenicol, and rifampicin was more than 90.0%. Conclusions: Children aged 7 months to 14 years were generally susceptible to H. influenzae in spring, and the positive rate of β-lactamase was high. Doctors should refer to the infection characteristics and drug resistance of H. influenzae and choose antibiotics correctly to better control the infection.

Diversity and genomic determinants of the microbiomes associated with COVID-19 and non-COVID respiratory diseases

The novel coronavirus disease 2019 (COVID-19) is a rapidly emerging and highly transmissible disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Understanding the microbiomes associated with the upper respiratory tract infection (URTI), chronic obstructive pulmonary disease (COPD) and COVID-19 diseases has clinical interest. We hypothesize that microbiome diversity and composition, and their genomic features are associated with different pathological conditions of these human respiratory tract diseases. To test this hypothesis, we analyzed 21 RNASeq metagenomic data including eleven COVID-19 (BD = 6 and China = 5), six COPD (UK = 6) and four URTI (USA = 4) samples to unravel the microbiome diversity and related genomic metabolic functions. The metagenomic data mapped to 534 bacterial, 60 archaeal and 61 viral genomes with distinct variation in the microbiome composition across the samples (COVID-19 > COPD > URTI). Notably, 94.57%, 80.0% and 24.59% bacterial, archaeal and viral genera shared between the COVID-19 and non-COVID samples, respectively. However, the COVID-19 related samples had sole association with 16 viral genera other than SARS-CoV-2. Strain-level virome profiling revealed 660 and 729 strains in COVID-19 and non-COVID samples, respectively, and of them 34.50% strains shared between the conditions. Functional annotation of the metagenomic data identified the association of several biochemical pathways related to basic metabolism (amino acid and energy), ABC transporters, membrane transport, virulence, disease and defense, regulation of virulence, programmed cell death, and primary immunodeficiency. We also detected 30 functional gene groups/classes associated with resistance to antibiotics and toxic compounds (RATC) in both COVID-19 and non-COVID microbiomes. Furthermore, we detected comparatively higher abundance of cobalt-zinc-cadmium resistance (CZCR) and multidrug resistance to efflux pumps (MREP) genes in COVID-19 metagenome. The profiles of microbiome diversity and associated microbial genomic features found in both COVID-19 and non-COVID (COPD and URTI) samples might be helpful in developing microbiome-based diagnostics and therapeutics for COVID-19 and non-COVID respiratory diseases. However, future studies might be carried out to explore the microbiome dynamics and the cross-talk between host and microbiomes employing larger volume of samples from different ethnic groups and geoclimatic conditions.

Air-liquid interface cultures of the healthy and diseased human respiratory tract: promises, challenges and future directions.

Air-liquid interface (ALI) culture models currently represent a valid instrument to recreate the typical aspects of the respiratory tract in vitro in both healthy and diseased state. They can help reducing the number of animal experiments, therefore, supporting the 3R principle. This review discusses ALI cultures and co-cultures derived from immortalized as well as primary cells, which are used to study the most common disorders of the respiratory tract, in terms of both pathophysiology and drug screening. The article displays ALI models used to simulate inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, lung cancer, and viral infections. It also includes a focus on ALI cultures described in literature studying respiratory viruses such as SARS-CoV-2 causing the global Covid-19 pandemic at the time of writing this review. Additionally, commercially available models of ALI cultures are presented. Ultimately, the aim of this review is to provide a detailed overview of ALI models currently available and to critically discuss them in the context of the most prevalent diseases of the respiratory tract.

Mechanism involved in the pathogenesis and immune response against SARS-CoV-2 infection.

SARS CoV-2, a causative agent of human respiratory tract infection, was first identified in late 2019. It is a newly emerging viral disease with unsatisfactory treatments. The virus is highly contagious and has caused pandemic globally. The number of deaths is increasing exponentially, which is an alarming situation for mankind. The detailed mechanism of the pathogenesis and host immune responses to this virus are not fully known. Here we discuss an overview of SARS CoV-2 pathogenicity, its entry and replication mechanism, and host immune response against this deadly pathogen. Understanding these processes will help to lead the development and identification of drug targets and effective therapies.

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.

It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlining molecular mechanism. N6-methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigate m6A modification of the SARS-CoV-2 gene in regulating the host cell innate immune response. Our data show that the SARS-CoV-2 virus has m6A modifications that are enriched in the 3′ end of the viral genome. We find that depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in patients with severe coronavirus disease 2019 (COVID-19). These findings will aid in the understanding of COVID-19 pathogenesis and the design of future studies regulating innate immunity for COVID-19 treatment.

Pelargonium Extract EPs 7630 in the Treatment of Human Corona Virus-Associated Acute Respiratory Tract Infections - A Secondary Subgroup-Analysis of an Open-Label, Uncontrolled Clinical Trial.

Background: Experience in treating human coronavirus (HCoV) infections might help to identify effective compounds against novel coronaviruses. We therefore performed a secondary subgroup-analysis of data from an open-label, uncontrolled clinical trial published in 2015 investigating the proanthocyanidin-rich Pelargonium sidoides extract EPs 7630 in patients with the common cold. Methods: 120 patients with common cold and at least 2 out of 10 common cold symptoms received one film-coated 20 mg tablet EPs 7630 thrice daily for 10 days in an uncontrolled, interventional multicentre trial (ISRCTN65790556). At baseline, viral nucleic acids were detected by polymerase chain reaction. Common cold-associated symptoms and treatment satisfaction were evaluated after 5 days and at treatment end. Based on the data of patients with proof of viral nucleic acids, we compared the course of the disease in patients with or without HCoV infection. Results: In 61 patients, viral nucleic acids were detected. Of these, 23 (37.7%) were tested positive for at least one HCoV (HCoV subset) and 38 (62.3%) for other viruses only (non-HCoV subset). Patients of both subsets showed a significant improvement of common cold symptoms already after 5 days of treatment, although the observed change tended to be more pronounced in the HCoV subset. At treatment end, more than 80% of patients of both groups were completely recovered or majorly improved. In both subsets, less than 22% of patients took concomitant paracetamol for antipyresis. The mean number of patients’ days off work or school/college was similar (0.9 ± 2.6 days in HCoV subset vs 1.3 ± 2.8 days in non-HCoV subset). In both groups, most patients were satisfied or very satisfied with EPs 7630 treatment. Conclusion: EPs 7630 treatment outcomes of common cold patients with confirmed HCoV infection were as favourable as in patients with other viral infections. As this trial was conducted before the pandemic, there is currently no evidence from clinical trials for the efficacy of EPs 7630 in patients with SARS-CoV-2 infection. Dedicated non-clinical studies and clinical trials are required to elucidate the potential of EPs 7630 in the early treatment of HCoV infections.

Mechanisms Underlying Pneumococcal Transmission and Factors Influencing Host-Pneumococcus Interaction: A Review.

Streptococcus pneumoniae (also called pneumococcus) is not only a commensal that frequently colonizes the human upper respiratory tract but also a pathogen that causes pneumonia, sepsis, and meningitis. The mechanism of pneumococcal infection has been extensively studied, but the process of transmission has not been fully elucidated because of the lack of tractable animal models. Novel animal models of transmission have enabled further progress in investigating pneumococcal transmission mechanisms including the processes such as pneumococcal shedding, survival in the external environment, and adherence to the nasopharynx of a new host. Herein, we present a review on these animal models, recent research findings about pneumococcal transmission, and factors influencing the host-pneumococcus interaction.

Case-Control Microbiome Study of Chronic Otitis Media with Effusion in Children Points at Streptococcus salivarius as a Pathobiont-Inhibiting Species.

ABSTRACTChronic otitis media with effusion (OME) has been associated with a shift in microbiome composition and microbial interaction in the upper respiratory tract (URT). While most studies have focused on potential pathogens, this study aimed to find bacteria that could be protective against OME through a case-control microbiome study and characterization of isolates from healthy subjects. The URT and ear microbiome profiles of 70 chronic OME patients and 53 controls were compared by 16S rRNA amplicon sequencing. Haemophilus influenzae was the most frequent classic middle ear pathobiont. However, other taxa, especially Alloiococcus otitis, were also frequently detected in the ear canal of OME patients. Streptococci of the salivarius group and Acinetobacter lwoffii were more abundant in the nasopharynx of healthy controls than in OME patients. In addition to the microbiome analysis, 142 taxa were isolated from healthy individuals, and 79 isolates of 13 different Streptococcus species were tested for their pathobiont-inhibiting potential. Of these, Streptococcus salivarius isolates showed a superior capacity to inhibit the growth of H. influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, A. otitis, and Corynebacterium otitidis. S. salivarius strains thus show potential as a probiotic for prevention or treatment of OME based on their overrepresentation in the healthy nasopharynx and their ability to inhibit the growth of respiratory pathobionts. (This study has been registered at ClinicalTrials.gov under registration no. NCT03109496.)IMPORTANCE The majority of probiotics marketed today target gastrointestinal health. This study searched for bacteria native to the human upper respiratory tract, with a beneficial potential for respiratory and middle ear health. Comparison of the microbiomes of children with chronic otitis media with effusion (OME) and of healthy controls identified Streptococcus salivarius as a health-associated and prevalent inhabitant of the human nasopharynx. However, beneficial potential should be assessed at strain level. Here, we also isolated specific S. salivarius strains from the healthy individuals in our study. These isolates showed a beneficial safety profile and efficacy potential to inhibit OME pathogens in vitro. These properties will now have to be evaluated and confirmed in human clinical studies.

Effects of yeast β-glucans for the prevention and treatment of upper respiratory tract infection in healthy subjects: a systematic review and meta-analysis.

Yeast β-glucans are known for their immune-modulating effects; however, their effects on human upper respiratory tract infections (URTIs) remain unclear. The aim of the present study was to use a systematic review and meta-analysis approach to investigate the effects of yeast β-glucans for the prevention and treatment of URTIs in healthy subjects. Databases including Pubmed, Web of Science, EMBASE and the Cochrane Library were searched and 13 RCTs investigating the effects of yeast β-glucans on the incidence, duration, and severity of URTIs in healthy subjects were included. The results showed that compared to the placebo group, yeast β-glucan could significantly reduce the incidence of URTIs (OR = 0.345, 95% CI = 0.192 to 0.620, p < 0.001), decrease the average number of URTI episodes (SMD = - 0.315, 95% CI = - 0.500 to - 0.130, p < 0.05), and decrease the duration of URTIs (SMD = - 0.312, 95% CI = - 0.561 to - 0.064, p < 0.001). Improved severity of symptoms was found in yeast β-glucan group compared to the placebo group in the majority of included studies. In addition, yeast β-glucan was well tolerated and safe in general. These findings suggest a positive effect of yeast β-glucans on human URTIs. However, due to the high heterogeneity and small number of included studies, more high-quality research and clinical trials are warranted.

Human Nasal and Lung Tissues Infected Ex Vivo with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract.

The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo, coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with a rapid increase in tissue-associated viral subgenomic mRNA and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon-stimulated genes, cytokines, and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tracts that are specific to SARS-CoV-2. The studies shed light on the role of the nasal mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV-2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19. IMPORTANCE In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here, we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues infected in parallel with SARS-CoV-2 and influenza virus, we found distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal mucosal infection model can be employed to assess the impact of viral evolutionary changes and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.

The Outbreak of Novel Coronavirus-a New Type of Threat in 2020: Genesis, Detection, Treatment, and Management

Background: COVID-19 is a new, health-threatening infectious disease in the world in 2020 and is caused by a novel coronavirus SARS-CoV-2. As of July 13, 2020, 4,881,579 active cases of COVID-19 were diagnosed, and 571,080 deaths were reported globally. In India, 301,850 active cases and 23,187 deaths were reported. To date, no effective treatment is available against the deadly virus SARS-CoV-2. Drug manufacturers, institutional laboratories, and other organizations have started developing vaccines to combat COVID-19 infection. Methods: Science Direct, Elsevier, PubMed, Scopus, and Nature databases were referred to know the current scenario of the disease. Moreover, recent data have been obtained from the World Health Organization, Centre of Disease Control, case studies, newspapers, and Worldometer reports. Data of Vaccine Centre at the London School of Hygiene &amp; Tropical Medicine, Clinicaltrials.gov, and US National Library of Medicine have also been accessed to obtain the latest information about ongoing clinical trials. Results: The primary source of the SARS-CoV-2 outbreak is connected to the Hunan seafood and live animal market in Wuhan city, Hubei Province, China. Like; SARS-CoV, and MERS-CoV, SARS-CoV- 2 is also a zoonotic virus affecting the lower respiratory tract in humans. The pathogenesis of COVID- 19 involves attachment of its Spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor in the lower respiratory tract in humans. The most common symptoms of COVID-19 are fever, cough, sore throat, fatigue, headache, myalgia, septic shock, and breathlessness. Few patients with COVID-19 infection experience diarrhea, vomiting, and abdominal pain. Currently, FDA approved drugs being used to treat COVID-19. Conclusion: This review article presents the importance of traditional Indian herbs recommended by AYUSH as precautionary and curative measures of COVID-19 until vaccines and drugs are made available. Moreover, this article discussed the origin, symptoms, mode of transmission, management, and diagnostics techniques for the detection of the SARS-CoV-2 virus.

The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways.

The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which is not observed for the other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features of the coronavirus spike (S) protein, which optimize the virus towards the human respiratory tract. First, the S proteins exhibit an intrinsic temperature preference, corresponding with the temperature of the upper or lower airways. Pseudoviruses bearing the SARS-CoV-2 spike (SARS-2-S) were more infectious when produced at 33°C instead of 37°C, a property shared with the S protein of HCoV-229E, a common cold coronavirus. In contrast, the S proteins of SARS-CoV and MERS-CoV favored 37°C, in accordance with virus preference for the lower airways. Next, SARS-2-S-driven entry was efficiently activated by not only TMPRSS2, but also the TMPRSS13 protease, thus broadening the cell tropism of SARS-CoV-2. Both proteases proved relevant in the context of authentic virus replication. TMPRSS13 appeared an effective spike activator for the virulent coronaviruses but not the low pathogenic HCoV-229E virus. Activation of SARS-2-S by these surface proteases requires processing of the S1/S2 cleavage loop, in which both the furin recognition motif and extended loop length proved critical. Conversely, entry of loop deletion mutants is significantly increased in cathepsin-rich cells. Finally, we demonstrate that the D614G mutation increases SARS-CoV-2 stability, particularly at 37°C, and, enhances its use of the cathepsin L pathway. This indicates a link between S protein stability and usage of this alternative route for virus entry. Since these spike properties may promote virus spread, they potentially explain why the spike-G614 variant has replaced the early D614 variant to become globally predominant. Collectively, our findings reveal adaptive mechanisms whereby the coronavirus spike protein is adjusted to match the temperature and protease conditions of the airways, to enhance virus transmission and pathology.