Novel coronavirus-like particles targeting cells lining the respiratory tract

<div><p>Virus like particles (VLPs) produced by the expression of viral structural proteins can serve as versatile nanovectors or potential vaccine candidates. In this study we describe for the first time the generation of HCoV-NL63 VLPs using baculovirus system. Major structural proteins of HCoV-NL63 have been expressed in tagged or native form, and their assembly to form VLPs was evaluated. Additionally, a novel procedure for chromatography purification of HCoV-NL63 VLPs was developed. Interestingly, we show that these nanoparticles may deliver cargo and selectively transduce cells expressing the ACE2 protein such as ciliated cells of the respiratory tract. Production of a specific delivery vector is a major challenge for research concerning targeting molecules. The obtained results show that HCoV-NL63 VLPs may be efficiently produced, purified, modified and serve as a delivery platform. This study constitutes an important basis for further development of a promising viral vector displaying narrow tissue tropism.</p></div

Potential Role of Platelets in COVID‐19: Implications for Thrombosis

For the past 150 years, platelets have been recognized as the major blood component that mediates hemostasis and thrombosis. In more recent years, however, we have come to appreciate that platelets also perform profound immune functions during infection with various pathogens. We now recognize that platelets can also mediate a response to various RNA viruses such as influenza and that many viral infections, including the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can affect platelet count. Thrombocytopenia and increased coagulation have been independently associated with increased mortality. This article provides a perspective on the potential roles of platelets during COVID‐19

Emerging Respiratory Viral Pathogens

Respiratory disease is arguably the most important health concern for the production animal industry [1-3]. Respiratory problems accounted for the highest mortality both in the swine and beef industries [1, 4]. Respiratory pathogens remain the most vital for swine and bovine research and disease monitoring [2, 5-7]. As pathogens, in particular viral pathogens, mutate, novel disease-causing viruses emerge, and there becomes an increasing concern and need for identification with control perimeters. One frequently identified disease syndrome is Porcine Respiratory Disease Complex (PRDC). PRDC is characterized by pneumonia of mixed respiratory infections with contributions from the environment and management practices. The main pathogens associated with PRDC include viruses, such as swine influenza virus (SIV), porcine respiratory and reproductive virus (PRRSV), and porcine circovirus 2 (PCV2), and bacteria, such as Mycoplasma hyopneumoniae, Pasteurella multocida, Streptococcus suis, Bordetella bronchiseptica, and Actinobacillus suis. Viral and bacterial pathogens can be classified as primary pathogens, capable of subverting host defense mechanisms and establishing infection on their own, or opportunistic pathogens [8]. Often, coinfections and superinfections with primary and/ or opportunistic pathogens occur with PRDC. The bovine counterpart to PRDC is Bovine Respiratory Disease (BRD). Like PRDC, BRD is a general term for a complex multi-factorial disease that encompasses upper and lower respiratory tract diseases. BRD is caused by stress, viral infection, and/ or bacterial infection with contributions from environmental factors (in particular transportation) and host characteristics (such as age, immune status, and genetics) [2, 9]. Bacterial and viral agents that are implicated in BRD include bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine herpesvirus 1 (BoHV-1), parainfluenza 3 virus (PI3V), bovine coronavirus (BCoV), Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, and Histophilus somni [10]. BRD is a costly disease of beef cattle with NAHMS Beef Feedlot 2011 Study reporting the direct cost of treatment for respiratory disease in feedlot cattle at $23.60 USD per case, resulting in a total cost of$54.12 million, not including production loses due to morbidity and mortality [2, 4]. With rising costs of food, the morbidity and mortality associated with respiratory diseases is economically disastrous. Many diagnostic panels are available for common respiratory pathogens for both swine and cattle. Although these panels are helpful, emerging, novel, variant, and underdiagnosed pathogens are often missed. Monitoring for these pathogens, often using metagenomic sequencing, can aid in their control and prevention. Once identified, research can begin on prevalence, pathogenesis, and control and prevention of these pathogens. This review is focused on the discovery of respiratory viral pathogens

SARS-CoV-2 infection, COVID-19 pathogenesis, and exposure to air pollution: What is the connection?

Exposure to air pollutants has been previously associated with respiratory viral infections, including influenza, measles, mumps, rhinovirus, and respiratory syncytial virus. Epidemiological studies have also suggested that air pollution exposure is associated with increased cases of SARS-CoV-2 infection and COVID-19–associated mortality, although the molecular mechanisms by which pollutant exposure affects viral infection and pathogenesis of COVID-19 remain unknown. In this review, we suggest potential molecular mechanisms that could account for this association. We have focused on the potential effect of exposure to nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM) since there are studies investigating how exposure to these pollutants affects the life cycle of other viruses. We have concluded that pollutant exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability. We believe that exposure to pollutants skews adaptive immune responses toward bacterial/allergic immune responses, as opposed to antiviral responses. Exposure to air pollutants could also predispose exposed populations toward developing COIVD-19–associated immunopathology, enhancing virus-induced tissue inflammation and damage

POST COVID PNEUMONIA: MODERN THERAPEUTIC APPROACH BY PULMONARY DRUG DELIVERY DEVICE

Streptococcus pneumonia (also known as pneumococcal) is a commensal that colonizes the upper respiratory tract and a pathogen that causes intrusive illnesses like otitis media, pneumonia, sepsis, and meningitis. In India, the Invasive Bacterial Infection Surveillance (IBIS) organization and South Asian Pneumococcal Alliance (SAPNA) have been associated with assortment of significant information in regards to serotype dissemination and antimicrobial obstruction of pneumococcal diseases for over 12 years. COVID 19 Patients are much more prone towards this infection, if untreated at appropriate time. So development of New Device are immense Important which contributes rapid and Proper Drug Delivery to lungs. Research must be carried out in the field of Novel Drug Delivery System for target delivery of Drugs like Antibiotic, Bronchodiator and Corticosteroid to Respiratory Tract. The present Review article focus Different grade of Pneumococcal Infection and Infection associated with Post COVID Condition. The article also highlights new devices which helpful for Pulmonary drug delivery which is vital during COVID Associated Pneumococcal Infection

Viral pathogens and acute lung injury: investigations inspired by the SARS epidemic and the 2009 H1N1 influenza pandemic.

Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage

Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1\u3b2, IL-6, IL-15 and TNF-\u3b1

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1\u3b2, IL-6, IL-10, IL-15, TNF-\u3b1, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1\u3b2 in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-\u3b1 showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes

Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1\u3b2, IL-6, IL-15 and TNF-\u3b1

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1\u3b2, IL-6, IL-10, IL-15, TNF-\u3b1, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1\u3b2 in lung samples obtained from the COVID-19 group (p\u2009&lt;\u20090.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p\u2009&lt;\u20090.001). TNF-\u3b1 showed a higher immunoreactivity in the COVID-19 group than in the control group (p\u2009&lt;\u20090.001). CD8\u2009+\u2009T cells where more numerous in the lung samples obtained from the COVID-19 group (p\u2009&lt;\u20090.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes

DPP4 in MERS-CoV Transmission and Pathogenesis

MERS-CoV is a virus that commonly infects dromedary camels in the Arabian Peninsula and Africa. This virus spreads effectively in this species and merely causes mild upper respiratory tract infection. However, since late 2012s, it is known that MERS-CoV could also cause pneumonia in humans and has been causing multiple outbreaks. The clinical manifestation of MERS-CoV infection in humans ranges from asymptomatic to fatal. MERS-CoV attaches to a host protein called dipeptidyl peptidase-4 (DPP4) to infect host cell. This thesis describes our effort to understand the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis. We found that the localization of DPP4 and α2,3-sialic acids, an attachment factor for MERS-CoV, varies between species. We also found that DPP4 expression in the human lungs could be upregulated due to several insults. These results indicate that DPP4 and other host factors could explain the inter- and intraspecies variations in MERS-CoV transmission and pathogenesis. Further characterization of these host determinants could offer insight into this virus epidemiology and help us identify the most vulnerable individuals to protect against MERS-CoV infection, for example by using vaccination

Hamster models of COVID-19 pneumonia reviewed: How human can they be?

The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate the development and testing of therapies and vaccines. In contrast to other rodents, hamsters are naturally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the Syrian hamster (Mesocricetus auratus) rapidly developed into a popular model. It recapitulates many characteristic features as seen in patients with a moderate, self-limiting course of the disease such as specific patterns of respiratory tract inflammation, vascular endothelialitis, and age dependence. Among 4 other hamster species examined, the Roborovski dwarf hamster (Phodopus roborovskii) more closely mimics the disease in highly susceptible patients with frequent lethal outcome, including devastating diffuse alveolar damage and coagulopathy. Thus, different hamster species are available to mimic different courses of the wide spectrum of COVID-19 manifestations in humans. On the other hand, fewer diagnostic tools and information on immune functions and molecular pathways are available than in mice, which limits mechanistic studies and inference to humans in several aspects. Still, under pandemic conditions with high pressure on progress in both basic and clinically oriented research, the Syrian hamster has turned into the leading non-transgenic model at an unprecedented pace, currently used in innumerable studies that all aim to combat the impact of the virus with its new variants of concern. As in other models, its strength rests upon a solid understanding of its similarities to and differences from the human disease, which we review here