-
Hormone Molecular Biology and Clinical... Aug 2021COVID-19 is a global emergency with over 10 million cases and over 500, 000 deaths worldwide. The SARS CoV-2 is a RNA virus belonging to the family coronaviridae. It has... (Review)
Review
COVID-19 is a global emergency with over 10 million cases and over 500, 000 deaths worldwide. The SARS CoV-2 is a RNA virus belonging to the family coronaviridae. It has high infectivity. The manifestations of the disease range from asymptomatic or mild symptoms to severe pneumonia and ARDS. The CT scan of lung shows consolidation and "Ground Glass Opacities". The persons with other comorbidities are considered to be at a higher rate of acquiring the infection. Asthma and other allergies have not been identified as major risk factors for COVID-19 as the number of asthmatic patients having COVID-19 is not high enough for it to be considered so. The occurrence of COVID-19 in COPD patients can be related with smoking. The ACE-2 expression in such patients was considerably high. The relation between COVID-19 and Tuberculosis can also be reflected in terms of the stigma associated with diagnosis and treatment of such diseases in some communities, eventually increasing the chances of people's reluctance to seek medical help. Cancer patients are usually more susceptible to infections. Lung cancer is no different. Additionally, lung cancer also has strong association with smoking further increasing the risk. The risk of getting infection and its severity is high for autoimmune disorders as well as fungal infections. Currently there is no definite treatment of COVID-19. However, some of the currently used modalities are hydroxychloroquine and antiviral drugs.
Topics: COVID-19; Comorbidity; Diagnostic Imaging; Disease Management; Disease Susceptibility; Host-Pathogen Interactions; Humans; Lung; Public Health Surveillance; SARS-CoV-2; Symptom Assessment
PubMed: 34333882
DOI: 10.1515/hmbci-2020-0096 -
The Lancet. Infectious Diseases Jun 2020Tuberculosis continues to be a major threat to global health. Cavitation is a dangerous consequence of pulmonary tuberculosis associated with poor outcomes, treatment... (Review)
Review
Tuberculosis continues to be a major threat to global health. Cavitation is a dangerous consequence of pulmonary tuberculosis associated with poor outcomes, treatment relapse, higher transmission rates, and development of drug resistance. However, in the antibiotic era, cavities are often identified as the most extreme outcome of treatment failure and are one of the least-studied aspects of tuberculosis. We review the epidemiology, clinical features, and concurrent standards of care for individuals with cavitary tuberculosis. We also discuss developments in the understanding of tuberculosis cavities as dynamic physical and biochemical structures that interface the host response with a unique mycobacterial niche to drive tuberculosis-associated morbidity and transmission. Advances in preclinical models and non-invasive imaging can provide valuable insights into the drivers of cavitation. These insights will guide the development of specific pharmacological interventions to prevent cavitation and improve lung function for individuals with tuberculosis.
Topics: Antitubercular Agents; Drug Resistance, Bacterial; Humans; Lung; Tuberculosis, Pulmonary
PubMed: 32482293
DOI: 10.1016/S1473-3099(20)30148-1 -
Annual Review of Immunology Apr 2022Pulmonary granulomas are widely considered the epicenters of the immune response to (Mtb), the causative agent of tuberculosis (TB). Recent animal studies have revealed... (Review)
Review
Pulmonary granulomas are widely considered the epicenters of the immune response to (Mtb), the causative agent of tuberculosis (TB). Recent animal studies have revealed factors that either promote or restrict TB immunity within granulomas. These models, however, typically ignore the impact of preexisting immunity on cellular organization and function, an important consideration because most TB probably occurs through reinfection of previously exposed individuals. Human postmortem research from the pre-antibiotic era showed that infections in Mtb-naïve individuals (primary TB) versus those with prior Mtb exposure (postprimary TB) have distinct pathologic features. We review recent animal findings in TB granuloma biology, which largely reflect primary TB. We also discuss our current understanding of postprimary TB lesions, about which much less is known. Many knowledge gaps remain, particularly regarding how preexisting immunity shapes granuloma structure and local immune responses at Mtb infection sites.
Topics: Animals; Granuloma; Humans; Lung; Mycobacterium tuberculosis; Tuberculosis
PubMed: 35130029
DOI: 10.1146/annurev-immunol-093019-125148 -
Physiological Reviews Apr 2020Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people... (Review)
Review
Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in impairment of innate immunity and progressive loss of T cell and B cell functionality with aberrant cytokine and chemokine responses systemically as well as in the lung. HIV can be detected in the lungs of PLWH and has profound effects on cellular immune functions. In addition, HIV-related lung injury and disease can occur secondary to a number of mechanisms including altered pulmonary and systemic inflammatory pathways, viral persistence in the lung, oxidative stress with additive effects of smoke exposure, microbial translocation, and alterations in the lung and gut microbiome. Although ART has had profound effects on systemic viral suppression in HIV, the impact of ART on lung immunology still needs to be fully elucidated. Understanding of the mechanisms by which HIV-related lung diseases continue to occur is critical to the development of new preventive and therapeutic strategies to improve lung health in PLWH.
Topics: AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Anti-Inflammatory Agents; Asthma; Disease Models, Animal; HIV; HIV Infections; Host-Pathogen Interactions; Humans; Hypertension, Pulmonary; Immunocompromised Host; Lung; Lung Neoplasms; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Risk Factors
PubMed: 31600121
DOI: 10.1152/physrev.00039.2018 -
Molecular Microbiology Mar 2022Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or... (Review)
Review
Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or surrogate animal models. Although these provide important insights, they have limitations. Cell culture models fail to recapitulate cellular interactions in the lung and animal models often do not permit high-throughput analysis of drugs or pathogen isolates; hence, there is a need for improved, scalable models. Precision-cut lung slices (PCLS), small, uniform tissue slices generated from animal or human lungs are increasingly recognized and employed as an ex vivo organotypic model. PCLS retain remarkable cellular complexity and the architecture of the lung, providing a platform to investigate respiratory pathogens in a near-native environment. Here, we review the generation and features of PCLS, their use to investigate the pathogenesis of viral and bacterial pathogens, and highlight their potential to advance respiratory infection research in the future.
Topics: Animals; Communicable Diseases; Lung
PubMed: 34570407
DOI: 10.1111/mmi.14817 -
Nature Jul 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV). Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.
Topics: Angiotensin-Converting Enzyme 2; Animals; Antigens, Viral; Betacoronavirus; Bronchi; COVID-19; Coronavirus Infections; Disease Models, Animal; Epithelial Cells; Female; Humans; Immunoglobulin G; Lung; Lymphocytes; Macrophages, Alveolar; Male; Mice; Mice, Transgenic; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Receptors, Complement 3d; SARS-CoV-2; Transgenes; Virus Replication; Weight Loss
PubMed: 32380511
DOI: 10.1038/s41586-020-2312-y -
Cell Jul 2020The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to...
The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.
Topics: Aged; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Betacoronavirus; COVID-19; Cell Line; Cells, Cultured; Chlorocebus aethiops; Coronavirus Infections; Cystic Fibrosis; DNA, Recombinant; Female; Furin; Humans; Immunization, Passive; Lung; Male; Middle Aged; Nasal Mucosa; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Respiratory System; Reverse Genetics; SARS-CoV-2; Serine Endopeptidases; Vero Cells; Virulence; Virus Replication; COVID-19 Serotherapy
PubMed: 32526206
DOI: 10.1016/j.cell.2020.05.042 -
Advances in Biological Regulation Aug 2020The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and... (Review)
Review
The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options.
Topics: Acute Disease; Anticoagulants; Betacoronavirus; Biomarkers; Blood Platelets; COVID-19; Coronavirus Infections; Cytokine Release Syndrome; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Heparin; Host-Pathogen Interactions; Humans; Lung; Pandemics; Pneumonia, Viral; Pulmonary Embolism; Respiratory Insufficiency; SARS-CoV-2; Survival Analysis
PubMed: 32773098
DOI: 10.1016/j.jbior.2020.100735 -
Journal of Infection and Public Health Nov 2021Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) attacks pulmonary alveolar cells via angiotensin-converting enzyme 2 (ACE2) receptors and causes pulmonary... (Review)
Review
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) attacks pulmonary alveolar cells via angiotensin-converting enzyme 2 (ACE2) receptors and causes pulmonary infections that result in coronavirus disease (COVID-19), inducing immune responses that can result in severe pneumonia. We reviewed the clinical experiences of lung diseases during the COVID-19 pandemic to offer insights into the adaptations made by experts in the diagnosis and treatment of these comorbidities. Various lung comorbidities increase the severity of COVID-19 and associated mortality by amplifying ACE2 expression. Additionally, the COVID-19 pandemic has changed the use of routine diagnostic pulmonary imaging methods, making chest sonography scoring the most convenient, as it can be conducted bedside. Treatment protocols for SARS-CoV-2 infection and the underlying lung diseases are also affected owing to potential interactions. The optimal diagnostic methods and treatment protocols for lung diseases have been adapted worldwide to increase survival rates and attenuate acute lung injuries during the COVID-19 pandemic.
Topics: COVID-19; Humans; Lung; Pandemics; Pneumonia; SARS-CoV-2
PubMed: 34700289
DOI: 10.1016/j.jiph.2021.09.024 -
Frontiers in Immunology 2021Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical... (Review)
Review
Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease - processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.
Topics: Animals; Disease Models, Animal; Host-Parasite Interactions; Humans; Immune Evasion; Lung; Lung Diseases, Parasitic; Mice; Protozoan Vaccines; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 33953712
DOI: 10.3389/fimmu.2021.635513