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Pathology, Research and Practice Sep 2020The novel coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), first appeared in December 2019, in Wuhan, China... (Review)
Review
The novel coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), first appeared in December 2019, in Wuhan, China and evolved into a pandemic. As Angiotensin-Converting Enzyme 2 (ACE2) is one of the potential target receptors for SARS-CoV-2 in human body, which is expressed in different tissues, multiple organs might become affected. In the initial phase of the current pandemic, a handful of post-mortem case-series revealed COVID-19-related pathological changes in various organs. Although pathological examination is not a feasible method of diagnosis, it can elucidate pathological changes, pathogenesis of the disease, and the cause of death in COVID-19 cases. Herein, we thoroughly reviewed multiple organs including lung, gastrointestinal tract, liver, kidney, skin, heart, blood, spleen, lymph nodes, brain, blood vessels, and placenta in terms of COVID-19-related pathological alterations. Also, these findings were compared with SARS and MERS infection, wherever applicable. We found a diverse range of pathological changes, some of which resemble those found in SARS and MERS.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; China; Coronavirus Infections; Humans; Lung; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2
PubMed: 32825963
DOI: 10.1016/j.prp.2020.153097 -
American Journal of Physiology. Lung... Aug 2020In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early... (Review)
Review
In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage, and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronavirus infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Coronavirus Infections; Cytokines; DNA Damage; Heart Injuries; Host Microbial Interactions; Humans; Hypoxia; Inflammation Mediators; Lung; Lung Diseases; Mitochondria; Myocardium; Oxidative Stress; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pulmonary Circulation; Pulmonary Embolism; Receptors, Virus; Risk Factors; SARS-CoV-2; Vasculitis
PubMed: 32551862
DOI: 10.1152/ajplung.00195.2020 -
Surgical Infections Dec 2016Coccidioidomycosis, commonly called "valley fever," "San Joaquin fever," "desert fever," or "desert rheumatism," is a multi-system illness caused by infection with... (Review)
Review
BACKGROUND
Coccidioidomycosis, commonly called "valley fever," "San Joaquin fever," "desert fever," or "desert rheumatism," is a multi-system illness caused by infection with Coccidioides fungi (C. immitis or C. posadasii). This organism is endemic to the desert Southwest regions of the United States and Mexico and to parts of South America. The manifestations of infection occur along a spectrum from asymptomatic to mild self-limited fever to severe disseminated disease.
METHODS
Review of the English-language literature.
RESULTS
There are five broad indications for surgical intervention in patients with coccidioidomycosis: Tissue diagnosis in patients at risk for co-existing pathology, perforation, bleeding, impingement on critical organs, and failure to resolve with medical management. As part of a multidisciplinary team, surgeons may be responsible for the care of infected patients, particularly those with severe disease.
CONCLUSION
This review discusses the history, microbiology, epidemiology, pathology, diagnosis, and treatment of coccidioidomycosis, focusing on situations that may be encountered by surgeons.
Topics: Adult; Antifungal Agents; Coccidioidomycosis; Female; Humans; Lung; Male; Middle Aged
PubMed: 27740893
DOI: 10.1089/sur.2016.148 -
Seminars in Immunology Dec 2014Mycobacterium tuberculosis (Mtb) infects about one-third of the world's population, with a majority of infected individuals exhibiting latent asymptomatic infection,... (Review)
Review
Mycobacterium tuberculosis (Mtb) infects about one-third of the world's population, with a majority of infected individuals exhibiting latent asymptomatic infection, while 5-10% of infected individuals progress to active pulmonary disease. Research in the past two decades has elucidated critical host immune mechanisms that mediate Mtb control. Among these, chemokines have been associated with numerous key processes that lead to Mtb containment, from recruitment of myeloid cells into the lung to activation of adaptive immunity, formation of protective granulomas and vaccine recall responses. However, imbalances in several key chemokine mediators can alter the delicate balance of cytokines and cellular responses that promote mycobacterial containment, instead precipitating terminal tissue destruction and spread of Mtb infection. In this review, we will describe recent insights in the involvement of chemokines in host responses to Mtb infection and Mtb containment (the good), chemokines contributing to inflammation during TB (the bad), and the role of chemokines in driving cavitation and lung pathology (the ugly).
Topics: Chemokines; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immunity, Innate; Latent Tuberculosis; Lung; Lymphocytes; Mycobacterium tuberculosis; Myeloid Cells; Signal Transduction; Th1-Th2 Balance; Tuberculosis, Pulmonary
PubMed: 25444549
DOI: 10.1016/j.smim.2014.09.004 -
Current Genetics Feb 2016Many bacterial pathogens have evolved ingenious ways to escape from the lung during pneumonia to cause bacteremia. Unfortunately, the clinical consequences of this... (Review)
Review
Many bacterial pathogens have evolved ingenious ways to escape from the lung during pneumonia to cause bacteremia. Unfortunately, the clinical consequences of this spread to the bloodstream are frequently dire. It is therefore important to understand the molecular mechanisms used by pathogens to breach the lung barrier. We have recently shown that Pseudomonas aeruginosa, one of the leading causes of hospital-acquired pneumonia, utilizes the type III secretion system effector ExoS to intoxicate pulmonary epithelial cells. Injection of these cells leads to localized disruption of the pulmonary-vascular barrier and dissemination of P. aeruginosa to the bloodstream. We put these data in the context of previous studies to provide a holistic model of P. aeruginosa dissemination from the lung. Finally, we compare P. aeruginosa dissemination to that of other bacteria to highlight the complexity of bacterial pneumonia. Although respiratory pathogens use distinct and intricate strategies to escape from the lungs, a thorough understanding of these processes can lay the foundation for new therapeutic approaches for bacterial pneumonia.
Topics: Animals; Bacteremia; Cross Infection; Humans; Lung; Pneumonia, Bacterial; Pseudomonas Infections; Pseudomonas aeruginosa; Type III Secretion Systems; Virulence; Virulence Factors
PubMed: 26407972
DOI: 10.1007/s00294-015-0522-x -
The Journal of Infectious Diseases Jun 2021
Review
Topics: Anti-Infective Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Humans; Lung; Microbiota; Pneumonia
PubMed: 33330898
DOI: 10.1093/infdis/jiaa702 -
Journal of Immunology (Baltimore, Md. :... Apr 2023Fatty acid-binding protein 4 (FABP4) is a critical immune-metabolic modulator, mainly expressed in adipocytes and macrophages, secreted from adipocytes in association...
Fatty acid-binding protein 4 (FABP4) is a critical immune-metabolic modulator, mainly expressed in adipocytes and macrophages, secreted from adipocytes in association with lipolysis, and plays essential pathogenic roles in cardiovascular and metabolic diseases. We previously reported Chlamydia pneumoniae infecting murine 3T3-L1 adipocytes and causing lipolysis and FABP4 secretion in vitro. However, it is still unknown whether C. pneumoniae intranasal lung infection targets white adipose tissues (WATs), induces lipolysis, and causes FABP4 secretion in vivo. In this study, we demonstrate that C. pneumoniae lung infection causes robust lipolysis in WAT. Infection-induced WAT lipolysis was diminished in FABP4-/- mice or FABP4 inhibitor-pretreated wild-type mice. Infection by C. pneumoniae in wild-type but not FABP4-/- mice induces the accumulation of TNF-α- and IL-6-producing M1-like adipose tissue macrophages in WAT. Infection-induced WAT pathology is augmented by endoplasmic reticulum (ER) stress/the unfolded protein response (UPR), which is abrogated by treatment with azoramide, a modulator of the UPR. C. pneumoniae lung infection is suggested to target WAT and induce lipolysis and FABP4 secretion in vivo via ER stress/UPR. FABP4 released from infected adipocytes may be taken up by other neighboring intact adipocytes or adipose tissue macrophages. This process can further induce ER stress activation and trigger lipolysis and inflammation, followed by FABP4 secretion, leading to WAT pathology. A better understanding of the role of FABP4 in C. pneumoniae infection-induced WAT pathology will provide the basis for rational intervention measures directed at C. pneumoniae infection and metabolic syndrome, such as atherosclerosis, for which robust epidemiologic evidence exists.
Topics: Animals; Mice; Adipose Tissue, White; Chlamydophila pneumoniae; Fatty Acid-Binding Proteins; Lung; Chlamydophila Infections; Pneumonia, Bacterial
PubMed: 36883861
DOI: 10.4049/jimmunol.2200601 -
Blood Advances Aug 2023Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2-infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs.
Topics: Animals; Mice; COVID-19; Inflammation; Lung; SARS-CoV-2
PubMed: 37307197
DOI: 10.1182/bloodadvances.2022009430 -
Clinical Microbiology and Infection :... Mar 2024Imaging is a key diagnostic modality for suspected invasive pulmonary or sinus fungal disease and may help to direct testing and treatment. Fungal diagnostic guidelines... (Review)
Review
BACKGROUND
Imaging is a key diagnostic modality for suspected invasive pulmonary or sinus fungal disease and may help to direct testing and treatment. Fungal diagnostic guidelines have been developed and emphasize the role of imaging in this setting. We review and summarize evidence regarding imaging for fungal pulmonary and sinus disease (in particular invasive aspergillosis, mucormycosis and pneumocystosis) in immunocompromised patients.
OBJECTIVES
We reviewed data on imaging modalities and findings used for diagnosis of invasive fungal pulmonary and sinus disease.
SOURCES
References for this review were identified by searches of PubMed, Google Scholar, Embase and Web of Science through 1 April 1 2023.
CONTENT
Computed tomography imaging is the method of choice for the evaluation of suspected lung or sinus fungal disease. Although no computed tomography radiologic pattern is pathognomonic of pulmonary invasive fungal disease (IFD) the halo sign firstly suggests an angio-invasive pulmonary aspergillosis while the Reversed Halo Sign is more suggestive of pulmonary mucormycosis in an appropriate clinical setting. The air crescent sign is uncommon, occurring in the later stages of invasive aspergillosis in neutropenic patients. In contrast, new cavitary lesions should suggest IFD in moderately immunocompromised patients. Regarding sinus site, bony erosion, peri-antral fat or septal ulceration are reasonably predictive of IFD.
IMPLICATIONS
Imaging assessment of the lung and sinuses is an important component of the diagnostic work-up and management of IFD in immunocompromised patients. However, radiological features signs have sensitivity and specificity that often vary according to underlying disease states. Periodic review of imaging studies and diagnostic guidelines characterizing imaging findings may help clinicians to consider fungal infections in clinical care thereby leading to an earlier confirmation and treatment of IFD.
Topics: Humans; Mucormycosis; Lung; Aspergillosis; Invasive Pulmonary Aspergillosis; Invasive Fungal Infections; Immunocompromised Host
PubMed: 37604274
DOI: 10.1016/j.cmi.2023.08.013 -
Seminars in Diagnostic Pathology Nov 2017Fungal pneumonias can be a diagnostic problem. However, their recognition is important as they can pose a significant health risk, especially in the immunocompromised... (Review)
Review
Fungal pneumonias can be a diagnostic problem. However, their recognition is important as they can pose a significant health risk, especially in the immunocompromised host. While many of these infections are accompanied by necrotizing or non-necrotizing granulomas, some might be characterized by cellular interstitial pneumonia, intra-alveolar frothy material or only minimal inflammatory change. Much of the tissue reaction is dependent on the immune status of the patient and the type of fungal organism. While many of the fungi can be identified in tissue, especially if using histochemical stains such as Grocott's Methenamine Silver (GMS) stain and/or Periodic Acid Schiff (PAS) stain, in some cases, these stains are negative and the organisms can only be identified in cultures or using special techniques such as PCR or fungal serology. Some fungi can be accurately identified in tissue based on morphologic features; others require culture for exact classification. Knowledge about immune status, geographic region and social history of the patient are helpful in identifying the fungus and, therefore, detailed clinical and travel histories are important. In this manuscript we aim to describe the most common fungal infections that occur in the lung, their morphologic features, and differential diagnoses.
Topics: Biopsy; Fungi; Host-Pathogen Interactions; Humans; Immunocompromised Host; Lung; Lung Diseases, Fungal; Microbiological Techniques; Opportunistic Infections; Predictive Value of Tests
PubMed: 28684133
DOI: 10.1053/j.semdp.2017.06.002