Intra-Host Co-Existing Strains of SARS-CoV-2 Reference Genome Uncovered by Exhaustive Computational Search.

The COVID-19 pandemic caused by SARS-CoV-2 has had a severe impact on people worldwide. The reference genome of the virus has been widely used as a template for designing mRNA vaccines to combat the disease. In this study, we present a computational method aimed at identifying co-existing intra-host strains of the virus from RNA-sequencing data of short reads that were used to assemble the original reference genome. Our method consisted of five key steps: extraction of relevant reads, error correction for the reads, identification of within-host diversity, phylogenetic study, and protein binding affinity analysis. Our study revealed that multiple strains of SARS-CoV-2 can coexist in both the viral sample used to produce the reference sequence and a wastewater sample from California. Additionally, our workflow demonstrated its capability to identify within-host diversity in foot-and-mouth disease virus (FMDV). Through our research, we were able to shed light on the binding affinity and phylogenetic relationships of these strains with the published SARS-CoV-2 reference genome, SARS-CoV, variants of concern (VOC) of SARS-CoV-2, and some closely related coronaviruses. These insights have important implications for future research efforts aimed at identifying within-host diversity, understanding the evolution and spread of these viruses, as well as the development of effective treatments and vaccines against them.

Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases.

The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed suggest that the immunological state of the lung may be indirectly influenced by elements produced by the gut microbiota. SCFAs represent valuable potential therapeutic candidates in this context.

Vitamin D-A prominent immunomodulator to prevent COVID-19 infection.

COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi.

Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease.

Advances and applications of dextran-based nanomaterials targeting inflammatory respiratory diseases

Dextran, a hydrophilic polysaccharide consists essentially of α-1,6 linked glucopyranoside residues that form the parent chain, along with α-1,2/3/4 linked residues that constitute its side chain. A considerable biocompatibility, stability under mildly acidic and basic conditions, solubility in water, non-immunogenicity, and presence of chemically modifiable –OH groups make dextran an ideal candidate for development of drug delivery vehicles and excipients. The presence of α-1,6 linkages in the parent chain provides enhanced chain mobility that determines the aqueous solubility of dextran, while its metabolism by the digestive enzymes to generate physiologically harmless degradation products validates its biocompatibility. Native dextran can be tuned for the development of pH-sensitive delivery systems by chemical modification that ensure an optimal drug concentration at the target site, and lowered dosing frequency that may ensure an overall improved patient compliance. The physicochemical properties of dextran can be changed by performing a chemical modification predominantly at the –OH group to obtain ester, ether, acetal, and dialdehyde of dextran. The review presented by us is a comprehensive account of the chemical modification strategies for native dextran and their clinical applications in containing pulmonary diseases. Furthermore, the presented review highlights the importance of nanomaterials derived from chemically modified dextran for the management of an optimal respiratory health by containing the inflammatory respiratory diseases.

Versatility of acetalated dextran in nanocarriers targeting respiratory diseases

Acetalated dextran is a chemically modified version of the FDA approved polysaccharide ‘dextran’, which serves as a perspective drug-delivery material for the pulmonary delivery of therapeutics owing to its biodegradability, sensitivity towards acidic pH for stimuli-sensitive drug release, high encapsulation efficacy, chemical conjugation with pharmaceuticals, and potency to cross the mucosal layer. Mainly, the aerosolized dry powder inhalation formulations of drug-loaded acetalated-dextran prove to be the frontrunner candidates for pulmonary delivery for the effective management of chronic respiratory diseases such as lymphangioleiomyomatosis, tularemia, and the contemporary COVID-19 pandemic. The presented communication provides a succinct account of the pulmonary drug delivery applications of acetalated dextran.

Autoantibodies and autoimmune disorders in SARS-CoV-2 infection: pathogenicity and immune regulation.

Coronavirus disease 2019 (COVID-19) is an infectious disease associated with the respiratory system caused by the SARS-CoV-2 virus. The aim of this review article is to establish an understanding about the relationship between autoimmune conditions and COVID-19 infections. Although majority of the population have been protected with vaccines against this virus, there is yet a successful curative medication for this disease. The use of autoimmune medications has been widely considered to control the infection, thus postulating possible relationships between COVID-19 and autoimmune diseases. Several studies have suggested the correlation between autoantibodies detected in patients and the severity of the COVID-19 disease. Studies have indicated that the SARS-CoV-2 virus can disrupt the self-tolerance mechanism of the immune system, thus triggering autoimmune conditions. This review discusses the current scenario and future prospects of promising therapeutic strategies that may be employed to regulate such autoimmune conditions.

A comparison of attitudes toward remote learning during the COVID-19 pandemic between students attending a Chinese and an Australian campus.

The COVID-19 pandemic has been a strong driver for moving more teaching and learning activities online. Border restrictions have had a severe impact on international students either hoping to enroll in courses offered in Australia or continue with such courses if they are already enrolled. The online learning experience is likely different between students onshore and offshore. This study took a unique opportunity to investigate any such differences in students' attitudes toward remote learning, necessitated by the pandemic, by comparing two cohorts of students, Australia versus China based. An anonymous survey using the Likert Scale and open-ended questions was available for student feedback on subject delivery. The students based in Australia expressed a preference for remote learning due to the convenience of attendance and availability of the video recordings. However, students in China had a strong preference for face-to-face sessions, with the lack of prior experience in an English-speaking learning environment and hesitance to speak with the lecturers and engage in the learning activities possible reasons for this. In quizzes, students in Australia performed better than those in China regardless of local or international student status. This difference may be due to the Australian-based students' prior experience of English-speaking environments and open-book quizzes. In conclusion, remote learning in a familiar language and learning environment is accepted by students, whereas if the teaching is delivered in a second language using unfamiliar teaching methods, remote learning will require additional scaffolding to enhance their learning experience.

Protein and peptide delivery to lungs by using advanced targeted drug delivery.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective.

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.

Is there an association between the level of ambient air pollution and COVID-19?

Epidemiological studies suggest that environmental factors (e.g., air pollution) can influence the spread and infectivity of coronavirus disease 2019 (COVID-19); however, very few papers have investigated or discussed the mechanism behind the phenomenon. Given the fact that pollution will increase as social distancing rules are relaxed, we summarized the current understanding of how air pollution may affect COVID-19 transmission and discussed several possible mechanisms. Air pollution exposure can dysregulate the human immune response and make people more susceptible to infections, and affect infectivity. For example, in response to exposure to air pollution, angiotensin-converting enzyme 2 will increase, which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This may increase the efficiency of viral infection. It is also possible that air pollution can facilitate SARS-CoV-2 spread by increasing the transmission, and potentially, SARS-CoV-2 can also survive longer when attached to a pollutant.