scholarly journals Refocusing Functional Anatomy and Immunology of the Respiratory Mucosa in the Advent of Covid-19

2021 ◽  
Author(s):  
Humphrey Simukoko
Keyword(s):  
Respiratory Tract ◽  
Respiratory System ◽  
Mammalian Cells ◽  
Atmospheric Oxygen ◽  
Severe Disease ◽  
Pulmonary Ventilation ◽  
Functional Anatomy ◽  
Upper Respiratory Tract ◽  
Mucosal Cells ◽  
Upper Respiratory

Atmospheric oxygen is an indispensable element required in order for mammalian cells to function normally. The mammalian respiratory system, through pulmonary ventilation and gas diffusion, provides the physical mechanisms by which oxygen gains access to all body cells and through which carbon dioxide is eliminated from the body. The network of tissues and organs of the respiratory system helps the mammalian body cells to absorb oxygen from the air to enable the tissues and organs to function optimally. The advent of the coronavirus disease 2019 (Covid-19) Pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated heightened and refocused interest in the study of various aspects of the respiratory system. The SARS-CoV-2 targets the respiratory system mucosal cells and in a cascade of biological processes curtails the ability of the respiratory system to absorb and deliver oxygen to the pulmonary blood and body cells often resulting in severe disease and/or death. The mucosa and submucosa of the respiratory tract are adapted to provide both innate and adaptive immune defense mechanisms against pathogens including the SARS-CoV-2. The entire respiratory tract is covered by a mucosa that transitions in its structural and functional characteristics from the upper respiratory tract to the lower respiratory tract. This chapter provides an overview of the functional anatomy and immunology of the respiratory tract covering the mucosa from the upper respiratory tract all the way up to the alveolar epithelium. In the advent of the covid-19 pandemic, a broader perspective and understanding of the anatomy and immunology of the respiratory tract will enable general readers and researchers to fully appreciate the discourse in covid-19 research as it affects the respiratory tract.

scholarly journals New prospects for local etiotropic treatment of acute respiratory viral infections

2019 ◽  
pp. 105-108
Author(s):  
A. A. Krivopalov ◽  
V. A. Shatalov ◽  
S. V. Shervashidze
Keyword(s):  
Respiratory Tract ◽  
Respiratory System ◽  
Safety Profile ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Upper Respiratory Tract ◽  
Positive Experience ◽  
High Efficacy ◽  
Upper Respiratory ◽  
Respiratory Viral Infections

According to WHO, the respiratory system diseases are currently inside the ten most common pathologies. The modern strategy for treating influenza and ARVI gives priority to the antiviral and immunostimulating agents, but the symptomatic drugs, which include preparations based on silver and its compounds, also play an important role. The large positive experience in using silver preparations supported by numerous clinical studies shows their high efficacy and satisfactory safety profile in the treatment of infectious and inflammatory diseases of the nose and upper respiratory tract in children and adults.

scholarly journals CoViD-19: An early intervention therapeutic strategy to prevent developing a severe disease as an alternative approach to control the pandemic

2020 ◽  
Author(s):  
HAMID MERCHANT
Keyword(s):  
Early Intervention ◽  
Respiratory Tract ◽  
Therapeutic Strategy ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Antimicrobial Properties ◽  
The Body ◽  
Upper Respiratory Tract ◽  
Holistic Treatment ◽  
Upper Respiratory

While we wait for a confirmed drug or a vaccine for CoViD-19, it may be possible to intervene early to prevent the virus causing a severe disease to offer an alternative therapeutic strategy to control the pandemic. The global burden of CoViD-19 on the healthcare system can be significantly reduced by targeting CoViD-19 patients with or without symptoms who are self-isolating at home or in quarantine. If any therapeutic support can be offered to this group of patients that could attenuate the virus within the upper respiratory tract during the early stages of CoViD-19, it can give the body the time to produce enough antibodies to recover naturally from the disease before progressing into severe disease. An early intervention can, therefore, prevent the virus to get down the lower respiratory tract, reduce the number of cases with severe disease involving pneumonia and the need for hospitalisation. This article presents a simple yet holistic treatment strategy that involves inhaling steam supplemented with essential oils possessing wide spectrum antimicrobial properties in conjunction with oropharyngeal sanitisation to all those who are CoViD-19 positive or are under self-isolation due to symptoms. The approach is very simple, cheap, and effective in relieving the symptoms of the disease and is likely to reduce the viral load in the upper respiratory tract that may help recover from the infection. Since there is no vaccine or treatment yet approved to prevent or treat the CoViD-19, the importance of early intervention is invaluable in reducing the global disease burden. In the authors opinion, this strategy may be very effective to nip the infection in the bud before it gets difficult to treat and therefore, have a potential to significantly reduce the CoViD-19 associated hospitalisation.

Prenatal diagnosis of lung malformations and upper respiratory tract in fetuses with trisomy 21

2019 ◽  
Author(s):  
U.A. Strupeneva, E.S. Nekrasova, E.V. Lisina
Keyword(s):  
Early Childhood ◽  
Down Syndrome ◽  
Prenatal Diagnosis ◽  
Respiratory Tract ◽  
Respiratory System ◽  
Trisomy 21 ◽  
Upper Respiratory Tract ◽  
Children With Down Syndrome ◽  
Laryngeal Atresia ◽  
Upper Respiratory

The features of the development of the respiratory system in children with Down syndrome and related with that diseases of lungs and upper respiratory tract in children in early childhood are presented. Two cases of prenatal diagnosis of cystic adenomatous malformation type Ш and laryngeal atresia in fetuses with trisomy 21 are described.

scholarly journals Identification of Influenza A Virus PB2 Residues Involved in Enhanced Polymerase Activity and Virus Growth in Mammalian Cells at Low Temperatures

2015 ◽  
Vol 89 (15) ◽  
pp. 8042-8049 ◽  
Author(s):  
Tsuyoshi Hayashi ◽  
Saintedym Wills ◽  
Kendra A. Bussey ◽  
Toru Takimoto
Keyword(s):  
Influenza Virus ◽  
Low Temperature ◽  
Respiratory Tract ◽  
Mammalian Cells ◽  
Influenza A ◽  
Polymerase Activity ◽  
Upper Respiratory Tract ◽  
Virus Growth ◽  
Avian Origin ◽  
Upper Respiratory

ABSTRACTMutations in the polymerase genes are known to play a major role in avian influenza virus adaptation to mammalian hosts. Despite having avian origin PA and PB2, the 2009 pandemic H1N1 virus (pH1N1) can replicate well in mammalian respiratory tracts, suggesting that these proteins have acquired mutations for efficient growth in humans. We have previously shown that PA from the pH1N1 virus A/California/04/09 (Cal) strongly enhances activity of an otherwise avian polymerase complex derived from A/chicken/Nanchang/3-120/01 (Nan) in mammalian cells. However, this enhancement was observed at 37°C but not at the lower temperature of 34°C. An additional introduction of Cal PB2 enhanced activity at 34°C, suggesting the presence of unidentified residues in Cal PB2 that are required for efficient growth at low temperature. Here, we sought to determine the key PB2 residues which confer enhanced polymerase activity and virus growth in human cells at low temperature. Using a reporter gene assay, we identified novel mutations, PB2 V661A and V683T/A684S, which are involved in enhanced Cal polymerase activity at low temperature. The PB2 T271A mutation, which we previously reported, also contributed to enhanced activity. The growth of recombinant Cal containing PB2 with Nan residues 271T/661V/683V/684A was strongly reduced in human cells compared to wild-type virus at low temperature. Among the four residues, 271A and 684S are conserved in human and pH1N1 viruses but not in avian viruses, suggesting an important role in mammalian adaptation of pH1N1 virus.IMPORTANCEThe PB2 protein plays a key role in the host adaptation, cold sensitivity, and pathogenesis of influenza A virus. Despite containing an avian origin PB2 lacking the mammalian adaptive mutations 627K or 701N, pH1N1 influenza virus strains can replicate efficiently in the low temperature upper respiratory tract of mammals, suggesting the presence of unknown mutations in the pH1N1 PB2 protein responsible for its low temperature adaptation. Here, in addition to PB2 271A, which has been shown to increase polymerase activity, we identified novel PB2 residues 661A and 683T/684S in pH1N1 which confer enhanced polymerase activity and virus growth in mammalian cells especially at low temperature. Our findings suggest that the presence of these PB2 residues contributes to efficient replication of the pH1N1 virus in the upper respiratory tract, which resulted in efficient human-to-human transmission of this virus.

Indications for the Tracheoesophageal Diversion Procedure and the Laryngotracheal Separation Procedure

1988 ◽  
Vol 97 (5) ◽  
pp. 471-475 ◽  
Author(s):  
David W. Eisele ◽  
C. Thomas Yarington ◽  
Roger C. Lindeman
Keyword(s):  
Respiratory Tract ◽  
Surgical Procedures ◽  
Respiratory System ◽  
Separation Procedure ◽  
Upper Respiratory Tract ◽  
Protective Function ◽  
Laryngotracheal Separation ◽  
Intractable Aspiration ◽  
Upper Respiratory ◽  
Surgical Separation

Impaired protective function of the larynx can lead to intractable aspiration, a severe and potentially fatal disorder. If medical therapy fails to prevent intractable aspiration, surgical separation of the upper respiratory tract from the digestive tract is necessary to prevent recurrent contamination of the respiratory system in these patients. Two such surgical procedures are the tracheoesophageal diversion procedure and the laryngotracheal separation procedure. Our approach to patients with intractable aspiration and the indications for the use of these surgical procedures for the prevention of aspiration are discussed.

scholarly journals Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

2015 ◽  
Vol 90 (4) ◽  
pp. 1888-1897 ◽  
Author(s):  
Kathryn M. Edenborough ◽  
Suzanne Lowther ◽  
Karen Laurie ◽  
Manabu Yamada ◽  
Fenella Long ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Severe Disease ◽  
Upper Respiratory Tract ◽  
H5n1 Influenza Virus ◽  
Viral Spread ◽  
H5n1 Influenza ◽  
Upper Respiratory ◽  
The Brain

ABSTRACTAlthough avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease.IMPORTANCERisks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus could spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower after exposure to virus by this route than when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection, such as viremia, could help prioritize antiviral treatments for patients most at risk of succumbing to infection.

scholarly journals Features of primary morbidity of military personnel who serve in conditions of occupational hazards

2018 ◽  
Vol 20 (1) ◽  
pp. 185-189
Author(s):  
S G Grigoryev ◽  
G G Zagorodnikov ◽  
V A Sanzharevsky ◽  
P P Sivashchenko
Keyword(s):  
Respiratory Tract ◽  
Respiratory System ◽  
Military Personnel ◽  
Organophosphorus Compounds ◽  
Circulatory System ◽  
Occupational Hazards ◽  
Upper Respiratory Tract ◽  
Acute Infections ◽  
Circulatory System Diseases ◽  
Upper Respiratory

The comparative analysis of primary morbidity of officers involved in work with occupational hazards of chemical or radiation nature in 2007-2014 has been performed. It was established that the group of officers involved in work with organophosphorus compounds has significantly higher rate of respiratory system diseases and lower rate of primary morbidity of the circulatory system diseases than the officers involved in work with ionized radiation sources. It was demonstrated that the main contribution to the primary morbidity was made by the following classes: diseases of respiratory system, diseases of musculoskeletal system and connective tissue, diseases of digestive system and diseases of circulatory system. The primary morbidity for leading categories of diseases among military personnel who worked with organophosphorus compounds in two regimes (immediate activities to destroy organophosphorus compounds and support for this process (guard, medical and fire services) did not depend on the nature of work. The rate of respiratory system diseases was relatively higher among all Russian Federation Armed forces servicemen and among those who worked with highly toxic substances (mainly due to acute infections of the upper respiratory tract). For the other classes considered the primary morbidity was higher in the risk groups. Evaluation of the role of specific nosological forms showed that in a group of servicemen working with organophosphorus compounds the rates of acute infections of the upper respiratory tract of multiple and unspecified localization, other nasal and nasal sinuses diseases, dorsalgia predominated but was inferior to the incidence of chronic ischemic heart disease. In this connection it is necessary to elaborate and conduct the preventive measures against above mentioned categories of diseases and main nosological forms of these categories.

scholarly journals Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5–based COVID-19 vaccine

2021 ◽  
Vol 7 (27) ◽  
pp. eabi5246
Author(s):  
Dong An ◽  
Kun Li ◽  
Dawne K. Rowe ◽  
Maria Cristina Huertas Diaz ◽  
Emily F. Griffin ◽  
...  
Keyword(s):  
Single Dose ◽  
Respiratory Tract ◽  
Virus Replication ◽  
Severe Disease ◽  
Mucosal Vaccine ◽  
Parainfluenza Virus ◽  
Upper Respiratory Tract ◽  
Vaccine Strategy ◽  
Upper Respiratory ◽  
Parainfluenza Virus 5

Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing the SARS-CoV-2 S protein (CVXGA1), and then demonstrated that a single-dose intranasal immunization with CVXGA1 protects against lethal infection of K18-hACE2 mice, a severe disease model. CVXGA1 immunization also prevented virus infection of ferrets and blocked contact transmission. This mucosal vaccine strategy inhibited SARS-CoV-2 replication in the upper respiratory tract, thus preventing disease progression to the lower respiratory tract. A PIV5-based mucosal vaccine provides a strategy to induce protective innate and cellular immune responses and reduce SARS-CoV-2 infection and transmission in populations.

scholarly journals Combinatorial mRNA vaccination enhances protection against SARS-CoV-2 delta variant

2021 ◽  
Author(s):  
Renee L Hajnik ◽  
Jessica A Plante ◽  
Yuejin Liang ◽  
Mohamad-Gabriel Alameh ◽  
Jinyi Tang ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
T Cell Response ◽  
Antibody Activity ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Significant Control ◽  
Fold Reduction ◽  
Upper Respiratory

Emergence of SARS-CoV-2 variants of concern (VOC), including the highly transmissible delta strain, has posed challenges to current COVID-19 vaccines that principally target the viral spike protein (S). Here, we report a nucleoside-modified mRNA vaccine that expresses the more conserved viral nucleoprotein (mRNA-N). We show that mRNA-N alone was able to induce a modest but significant control of SARS-CoV-2 in mice and hamsters. Critically, by combining mRNA-N with the clinically approved S-expressing mRNA vaccine (mRNA-S-2P), we found that combinatorial mRNA vaccination (mRNA-S+N) led to markedly enhanced protection against the SARS-CoV-2 delta variant compared to mRNA-S. In a hamster model, we demonstrated that while mRNA-S alone elicited significant control of the delta strain in the lungs (~45-fold reduction in viral loads compared to un-vaccinated control), its effectiveness in the upper respiratory tract was weak, whereas combinatorial mRNA-S+N vaccination induced markedly more robust control of the delta variant infection in the lungs (~450-fold reduction) as well as in the upper respiratory tract (~20-fold reduction). Immune analyses indicated that induction of N-specific immunity as well as augmented S-specific T-cell response and neutralizing antibody activity were collectively associated the enhanced protection against SARS-CoV-2 delta strain by combinatorial mRNA vaccination. These findings suggest that the combined effects of protection in the lungs and upper respiratory tract could both reduce the risk of severe disease as well as of infection and transmission.

scholarly journals Assessment of the efficacy of SARS-CoV-2 vaccines in non-human primate studies: a systematic review

2022 ◽  
Vol 2 ◽  
pp. 4
Author(s):  
Michel Jacques Counotte ◽  
Mariana Avelino de Souza Santos ◽  
Koert J Stittelaar ◽  
Wim H M van der Poel ◽  
Jose L Gonzales
Keyword(s):  
Respiratory Tract ◽  
Severe Disease ◽  
Population Level ◽  
Diagnostic Methods ◽  
Viral Rna ◽  
Upper Respiratory Tract ◽  
Viral Shedding ◽  
Proxy Measure ◽  
Preclinical Trials ◽  
Upper Respiratory

Background: The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the rapid and successful development of vaccines to help mitigate the effect of COVID-19 and circulation of the virus. Vaccine efficacy is often defined as capacity of vaccines to prevent (severe) disease. However, the efficacy to prevent transmission or infectiousness is equally important at a population level. This is not routinely assessed in clinical trials. Preclinical vaccine trials provide a wealth of information about the presence and persistence of viruses in different anatomical sites. Methods: We systematically reviewed all available preclinical SARS-CoV-2 candidate vaccine studies where non-human primates were challenged after vaccination (PROSPERO registration: CRD42021231199). We extracted the underlying data, and recalculated the reduction in viral shedding. We summarized the efficacy of  vaccines to reduce viral RNA shedding after challenge by standardizing and stratifying the results by different anatomical sites and diagnostic methods. We considered shedding of viral RNA as a proxy measure for infectiousness. Results: We found a marked heterogeneity between the studies in the experimental design and the assessment of the outcomes. The best performing vaccine candidate per study caused only low (6 out of 12 studies), or moderate (5 out of 12) reduction of viral genomic RNA, and low (5 out of 11 studies) or moderate (3 out of 11 studies) reduction of subgenomic RNA in the upper respiratory tract, as assessed with nasal samples. Conclusions: Since most of the tested vaccines only triggered a low or moderate reduction of viral RNA in the upper respiratory tract, we need to consider that most SARS-CoV-2 vaccines that protect against disease might not fully protect against infectiousness and vaccinated individuals might still contribute to SARS-CoV-2 transmission. Careful assessment of secondary attack rates from vaccinated individuals is warranted. Standardization in design and reporting of preclinical trials is necessary.

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