A novel pseudovirus‐based mouse model of SARS-CoV-2 infection to test COVID-19 interventions

Background The spread of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), has been characterized as a worldwide pandemic. Currently, there are few preclinical animal models that suitably represent infection, as the main point of entry to human cells is via human angiotensin-converting enzyme 2 (ACE2) which is not present in typical preclinical mouse strains. Additionally, SARS-CoV-2 is highly virulent and unsafe for use in many research facilities. Here we describe the development of a preclinical animal model using intranasal administration of ACE2 followed by non-infectious SARS-CoV-2 pseudovirus (PsV) challenge. Methods To specifically generate our SARS-CoV-2 PsV, we used a lentivirus system. Following co-transfection with a packaging plasmid containing HIV Gag and Pol, luciferase-expressing lentiviruses, and a plasmid carrying the SARS-CoV-2 spike protein, SARS-CoV-2 PsVs can be isolated and purified. To better understand and maximize the infectivity of SARS-CoV-2 PsV, we generated PsV carrying spike protein variants known to have varying human ACE2 binding properties, including 19 deletion (19del) and 19del + D614G. Results Our system demonstrated the ability of PsVs to infect the respiratory passage of mice following intranasal hACE2 transduction. Additionally, we demonstrate in vitro and in vivo manipulability of our system using recombinant receptor-binding domain protein to prevent PsV infection. Conclusions Our PsV system is able to model SARS-CoV-2 infections in a preclinical mouse model and can be used to test interventions or preventative treatments. We believe that this method can be extended to work in various mouse strains or to model infection with different coronaviruses. A simple in vivo system such as our model is crucial for rapidly and effectively responding to the current COVID-19 pandemic in addition to preparing for future potential coronavirus outbreaks.

TO STUDY THE EFFECT OF VAMANA KARMA AND NARDIYA LAXMIVILASA RASA IN THE MANAGEMENT OF DUSHTA PRATISHYAYA (ALLERGIC RHINITIS): A CASE STUDY

Background: According to Acharya Charaka nose is the gateway of head. Diseases related with upper respiratory passage affect the Prana Vata, Tarpaka Kapha, Sadhaka Pitta and Majja Dhatu. Allergic rhinitis is the most common disease of upper respiratory passage for visit to outpatient department. Prevalence of allergic rhinitis ranges from 20 to 30% in Indian population. It is an IgE-mediated immunologic response of nasal mucosa to airborne allergens and is characterized by watery nasal discharge, nasal obstruction, sneezing and itching in the nose. In Ayurveda allergic rhinitis has a high resemblance with Dushta Pratishyaya, which comes under Nasagataroga. It is described in Brihattrayee as well as Laghutrayee. Acharya Sushruta has given detailed description of DushtaPratishyaya. Aim & Objectives: To study the effect of Vamana Karma and Nardiya Laxmivilasa Rasa in the management of Dushta Pratishyaya and to find out an effective Ayuvedic management for Dushta Pratishyaya (Allergic Rhinitis). Material and Methods: The present case study is upon a 40 years old (male patient) diagnosed case of Dushta Pratishyaya with complaints of recurrent episodes of sneezing, watery nasal discharge, coughing specially at night time, throat irritation and sometimes pain in trunk region since last 2 years, at the Kayachikitsa OPD of Pt. Khushilal Sharma Govt. Ayurvedic Hospital Bhopal. The patient was treated with Vamana Karma followed by Naradiya Laxmivilasa Rasa. Duration of study is 46 Days and follow up, every 15 days for 2 months. Assessment was done on the basis of symptomatic relief after treatment. Observation: Vamana Karma and Naradiya Laxmivilasa Rasa yielded symptomatic relief after treatment. The overall effect of the treatment in patient suggested that, there is 86.66% relief in patient. Conclusion: On the basis of result obtained, it can be concluded that Vamana Karma and Naradiya Laxmivilasa Rasa can be used as an effective treatment in the management of Dushta Pratishyaya (allergic rhinitis).

Wandering airway foreign body in early infancy

Accidental impaction of objects in the respiratory passage is a life-threatening condition. A 9-month-old male infant was admitted with fever, cough and respiratory distress without history of choking. He was treated as wheezy bronchitis with appropriate therapy but, did not show response. HRCT showed an impacted foreign body in the trachea which caused a partial luminal compromise. Two attempts to remove foreign body by rigid bronchoscope failed, and tracheostomy was performed due to fall in oxygen saturation. After stabilization, again saturation was falling and air entry was absent on right hemithorax. Considering the possibility of movement of foreign body in right bronchus, bronchoscope was reintroduced and foreign body was removed in piecemeal. This process was complicated with cardiorespiratory arrest, twice from which the patient was revived. Postoperative period was uneventful. So, high index of suspicion is required to diagnose such a foreign body of the tracheobronchial tree to prevent morbidity and mortality.

Asthma as a Respiratory Disorder

This article reviews causes, symptoms and genetic basis of asthma as well as the pharmaceutical therapies currently being practiced for its treatment. Asthma is a worldwide respiratory disorder characterized by recurring conditions of inflammation and the narrowing of respiratory passage ways termed as bronchoconstriction, bronchial hyper-responsiveness, bronchospasm, chest tightening, shortness of breath, etc. About 300 million people suffer from asthma globally with 250,000 annual deaths attributed to asthma. In many populations, the main cause of an increased occurrence of asthma is the lack of awareness amonggeneral public. Smoking, allergens, microbes, pollutants, dust, chemicals, vapors, fumes, exercise etc. act as stimulants and triggers of asthma. Various gene-gene and genetic-environmental factors act together resulting in asthmatic pathogenesis. Various loci have been identified that play a potential role in this regard. Genetic polymorphism among patients makes the treatment a bit difficult as patients with similar symptoms show varied responses to the same medications and therapeutic strategies. Asthma is not completely curable; therefore, most medications aim to lower the exacerbations rather than fixing the underlying causes and mechanisms of the disease. Short and Long Acting Beta-antagonists (SABAs and LABAs) and inhaled corticosteroids (ICS) have been found to be effective against asthma. Phytomedicines and biological agents such as omalizumab are being developed currently for the modulation of asthma-related immunologic and cell-signaling mechanisms. Asthma and psychological disorders are often found to be correlated. The need arises for greater public awareness regarding asthma, improved genetic analysis techniques, assessment of underlying molecular mechanisms, optimization of current therapeutic strategies and the development of new personalized target drugs for its efficient prevention and control.

Role of Tracheostomy in Respiratory Distress: A Study of 50 Cases

ABSTRACT Tracheostomy plays a vital role in respiratory distress caused by different conditions, like respiratory passage of obstruction, head and neck tumor, surgeries, trauma patients and inflammatory conditions. Timing of the operation and postoperative care deserves more emphasis. Delay in the performance of this operation defeats the purpose of tracheostomy and if managed properly, it is a life saving procedure. The aim of the study was not only to give immediate relief to the patients of respiratory distress. But also to study age and sex distribution indication and evaluate factors associated with morbidity and mortality, intraoperative and postoperative complications associated with this procedure. This study was done on 50 cases of respiratory distress admitted in different department of Rajindra Hospital, Patiala, who underwent tracheostomy as an emergency or elective procedure. Most of the patients (24%) were of 50 to 60 years of age of which 60% were males. Emergency tracheostomy was done in most of the cases (64%). Most common complication was wound infection and granuloma formation (16%). Mortality due to primary disease (tumors of head and neck) was 34%. Followed by head injury (29%). Only one patient died of tracheostomy due to excessive bleeding. How to cite this article Sahni D. Role of Tracheostomy in Respiratory Distress: A Study of 50 Cases. Clin Rhinol An Int J 2015;8(1):20-23.

Laryngo-tracheo-bronchial foreign bodies in children

Inhalation of a foreign body into the respiratory passage can be a serious and sometimes fatal childhood accident. In this paper we analyze the management of 223 children with laryngo-tracheo-bronchial foreign bodies. Children below three years of age were found to be the most vulnerable. The majority of the patients were boys. Over a quarter of the patients did not present with a history of inhalation. Only 52 per cent reported within 24 hours of inhalation. Endoscopic removal was possible in all but nine cases. One hundred and fort eight (66.4 per cent) of the recovered foreign bodies were organic in origin, the majority of them being peanuts. In one hundred and five (47.1 per cent) the objects found their way into the right bronchial tree. There were two deaths. The modalities of diagnosis and management are discussed.