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The global prevalence of chronic obstructive pulmonary disease (COPD) has increased over the last decade and has emerged as the third leading cause of death worldwide. It is characterized by emphysema with prolonged airflow limitation. COPD patients are more susceptible to COVID-19 and increase the disease severity about four times. The most used drugs to treat it show numerous side effects, including immune suppression and infection. This review discusses a narrative opinion and critical review of COPD. We present different aspects of the disease, from cellular and inflammatory responses to cigarette smoking in COPD and signaling pathways. In addition, we highlighted various risk factors for developing COPD apart from smoking, like occupational exposure, pollutants, genetic factors, gender, etc. After the recent elucidation of the underlying inflammatory signaling pathways in COPD, new molecular targeted drug candidates for COPD are signal-transmitting substances. We further summarize recent developments in biomarker discovery for COPD and its implications for disease diagnosis. In addition, we discuss novel drug targets for COPD that could be explored for drug development and subsequent clinical management of cardiovascular disease and COVID-19, commonly associated with COPD. Our extensive analysis of COPD cause, etiology, diagnosis, and therapeutic will provide a better understanding of the disease and the development of effective therapeutic options. In-depth knowledge of the underlying mechanism will offer deeper insights into identifying novel molecular targets for developing potent therapeutics and biomarkers of disease diagnosis., Competing Interests: The authors declared they had no conflicts of interest., (Copyright © 2023 Ilma Shakeel et al.)

Introduction: The COVID-19 pandemic in India has resulted in mass destruction in the form of second wave.Indian citizens and government were badly affected and were left constrained with basic medical facilities in treating the heavy load of patients. The possibility of reemergence of virulent strains of SARS-CoV-2 still exists., Area Covered: In this article, we tend to discuss why India is at high risk to be to be affected by the other waves and what strategies could be implemented to contain the viral spread. It provides these insights with reference to the gaps and the lessons learnt from the second wave along with the possible solutions to tackle these problems that were not effectively handled during the previous episodes of viral spread. We propose strategies for implementing effective vaccination programs, focus on speeding up different ways of diagnosis, management of essential hospital aids, prevention from vaccine escape mutant strains  and implementation of COVID-appropriate behavior in rural areas of India., Expert Opinion: This article has significance to the researchers and government officials in understanding the gaps that led to COVID-19 second wave in India and provides an opportunity to improve on certain areas for handling the future waves with more vigilance. Abbreviations: COVID-19 - Coronavirus disease 2019; SARS-COV-2 - severe acute respiratory syndrome - Coronavirus 2; δ - Delta variant; δ+ - Delta plus variant; WHO - World Health Organization; RT -PCR - Reverse transcription PCR; IFN-1 - Interferon 1; VOCs - Variants of concern; HCWs - healthcare workers.

Background: Smokers and patients with COPD are highly susceptible to SARS-CoV-2 infection, leading to severe COVID-19., Methods: This cross-sectional study involved resected lung tissues from 16 patients with GOLD stage I or II COPD; of which 8 were current smokers COPD (COPD-CS), and 8 ex-smokers COPD (COPD-ES), 7 normal lung function smokers (NLFS), 9 patients with small airways disease (SAD), and 10 were never-smoking normal controls (NC). Immunostaining for ACE2, Furin, and TMPRSS2 was performed and analysed for percent expression in small airway epithelium (SAE) and counts for positively and negatively stained type 2 pneumocytes and alveolar macrophages (AMs) were done using Image ProPlus V7.0. Furthermore, primary small airway epithelial cells (pSAEC) were analysed by immunofluorescence after exposure to cigarette smoke extract (CSE)., Results: ACE2, Furin, and TMPRSS2 expression significantly increased in SAE and type 2 pneumocytes in all the subjects (except Furin for NLFS) compared to NC (p < 0.001). Similar significance was observed for ACE2 positive AM (p < 0.002), except COPD-ES, which decreased in ACE2 positive AMs (p < 0.003). Total type 2 pneumocytes and AMs significantly increased in the pathological groups compared to NC (p < 0.01), except SAD (p = 0.08). However, AMs are significantly reduced in COPD-ES (p < 0.003). Significant changes were observed for tissue co-expression of Furin and TMPRSS2 with ACE2 in SAE, type 2 pneumocytes and AMs. These markers also negatively correlated with lung function parameters, such as FEV 1 /FVC % predicted, FEF25-75%, DLCO% predicted. A strong co-localisation and expression for ACE2 (p < 0.0001), Furin (p < 0.01), and TMPRSS2 (p < 0.0001) was observed in pSAEC treated with 1% CSE than controls., Discussion: The increased expression of ACE2, TMPRSS2 and Furin, in the SAE, type 2 pneumocytes and AMs of smokers and COPD are detrimental to lung function and proves that these patient groups could be more susceptible to severe COVID-19 infection. Increased type 2 pneumocytes suggest that these patients are vulnerable to developing post-COVID-19 interstitial pulmonary fibrosis or fibrosis in general. There could be a silently developing interstitial pathology in smokers and patients with COPD. This is the first comprehensive study to report such changes., Competing Interests: Dr Josie Larby reports personal fees from GSK outside the submitted work. Dr Sukhwinder Singh Sohal reports personal fees from Chiesi outside the submitted work. The aforementioned authors report no other potential conflicts of interest in this work and all the other authors report no conflicts of interest in this work., (© 2022 Brake et al.)

Background and Objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD., Methods: We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC., Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients., Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications., (© 2021 Asian Pacific Society of Respirology.)

Introduction: COVID-19 is a recent emerging pandemic whose prognosis is still unclear. Diagnostic tools are the main players that not only indicate a possible infection but can further restrict the transmission and can determine the extent to which disease progression would occur., Areas Covered: In this paper, we have performed a narrative and critical review on different technology-based diagnostic strategies such as molecular approaches including real-time reverse transcriptase PCR, serological testing through enzyme-linked immunosorbent assay, laboratory and point of care devices, radiology-based detection through computed tomography and chest X-ray, and viral cell cultures on Vero E6 cell lines are discussed in detail to address COVID-19. This review further provides an overview of emergency use authorized immunodiagnostic and molecular diagnostic kits and POC devices by FDA for timely and efficient conduction of diagnostic tests. The majority of the literature cited in this paper is collected from guidelines on protocols and other considerations on diagnostic strategies of COVID-19 issued by WHO, CDC, and FDA under emergency authorization., Expert Opinion: Such information holds importance to the health professionals in conducting error-free diagnostic tests and researches in producing better clinical strategies by addressing the limitations associated with the available methods.

Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack. The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L, and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients. The study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers with COPD (COPD-CS) and 10 were ex-smokers with COPD (COPD-ES), 10 were normal lung function smokers, and 10 were never-smoking normal controls. Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Furthermore, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, using Image ProPlus v7.0 software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1 negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.

Purva Asrani,1 Afzal Hussain,2 Khalida Nasreen,3 Mohamed Fahad AlAjmi,2 Samira Amir,4 Sukhwinder Singh Sohal,5 Md Imtaiyaz Hassan3 1Molecular Biology and Biotechnology, ICAR- National Institute for Plant Biotechnology, New Delhi, 110012, India; 2Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India; 4Department of Chemistry, College of Science and General Studies, Alfaisal University, Riyadh, Kingdom of Saudi Arabia; 5Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, AustraliaCorrespondence: Md Imtaiyaz HassanCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, IndiaEmail mihassan@jmi.ac.inAbstract: Coronavirus disease 2019 (COVID-19) is an emerging challenging area for the researchers to buckle up against the spread and control of the virus. Since earlier times, the diagnosis has been an important procedure in estimating the fate of epidemics by indicating the extent to which disease has been spread and to the extent, further disease prognosis would occur. The absence of anti-viral therapies and vaccines for COVID-19 at present suggests early diagnosis and isolation of the patients as the only smart approach available as of now. Presently, the increasing death rates, faster rates of transmission, non-availability of vaccines, and treatment have over-pressurized the researchers, health professionals, and government officials to develop effective clinical strategies in diagnosis and to come up with guidelines to be followed during conduction of each diagnostic procedure for maintaining healthcare systems. Since the incubation period of this virus is 2– 14 days, a patient can transmit the infection without showing symptoms. Therefore, early diagnosis and isolation of susceptible individuals are the only way to limit the spread of the virus. Significance of diagnosis and triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted in this paper to make people more aware and develop better clinical strategies in the future.Keywords: COVID-19, diagnosis guidelines, specimen collection, safety consideration, SARS-COV-2

• Insights into different diagnostic techniques of SARS-CoV-2 infection have been provided. • We highlighted the importance of different diagnosis methods of COVID-19. • Emerging drugs used in the treatment of COVID-19 are also discussed. The most important aspect of controlling COVID-19 is its timely diagnosis. Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. This review highlights the underlying mechanisms, advancements, and clinical limitations for each of the diagnostic techniques authorized by the Food and Drug Administration (USA). Significance of diagnosis triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted to make medical and research community more informed so that better clinical strategies are developed. We have discussed here the clinical manifestations and hospital outcomes along with the underlying mechanisms for several drugs administered to COVID-19 prophylaxis. In addition to favourable clinical outcomes, the challenges, and the future directions of management of COVOD-19 are highlighted. Having a comprehensive knowledge of the diagnostic approaches of SARS-CoV-2, and its pathogenesis will be of great value in designing a long-term strategy to tackle COVID-19. [ABSTRACT FROM AUTHOR]