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1.
Radiology ; 295(3): 200463, 2020 06.
Article in English | MEDLINE | ID: covidwho-1723927

ABSTRACT

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).


Subject(s)
Coronavirus Infections/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/virology , Pneumonia, Viral/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/virology , Lung Diseases/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Radiography, Thoracic/methods , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Young Adult
2.
Clin Exp Pharmacol Physiol ; 49(4): 483-491, 2022 04.
Article in English | MEDLINE | ID: covidwho-1691664

ABSTRACT

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.


Subject(s)
Acute Lung Injury/etiology , Blood Coagulation Disorders/etiology , COVID-19/pathology , Cytokine Release Syndrome/etiology , Hemorrhage/etiology , Lipopolysaccharides/adverse effects , Lung Diseases/etiology , Receptor, Angiotensin, Type 1/metabolism , STAT Transcription Factors/metabolism , Signal Transduction , Acute Lung Injury/pathology , Animals , Blood Coagulation Disorders/pathology , COVID-19/etiology , Cytokine Release Syndrome/pathology , Disease Models, Animal , Hemorrhage/pathology , Janus Kinases , Lung Diseases/pathology , Male , Rats , Rats, Wistar
3.
Sci Rep ; 11(1): 23205, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1545647

ABSTRACT

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Lung Diseases/pathology , Matrix Metalloproteinase 9/metabolism , SARS-CoV-2/drug effects , Viral Load , Adenosine Monophosphate/adverse effects , Aged , Alanine/adverse effects , Antibody Formation , Antimalarials/adverse effects , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/virology , Female , Hospitalization , Humans , Lung Diseases/chemically induced , Lung Diseases/enzymology , Lung Diseases/virology , Male , Middle Aged , Severity of Illness Index
4.
Int J Mol Sci ; 22(18)2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1403613

ABSTRACT

The importance of a healthy microbiome cannot be overemphasized. Disturbances in its composition can lead to a variety of symptoms that can extend to other organs. Likewise, acute or chronic conditions in other organs can affect the composition and physiology of the gut microbiome. Here, we discuss interorgan communication along the gut-lung axis, as well as interactions between lung and coronary heart diseases and between cardiovascular disease and the gut microbiome. This triangle of organs, which also affects the clinical outcome of COVID-19 infections, is connected by means of numerous receptors and effectors, including immune cells and immune-modulating factors such as short chain fatty acids (SCFA) and trimethlamine-N-oxide (TMAO). The gut microbiome plays an important role in each of these, thus affecting the health of the lungs and the heart, and this interplay occurs in both directions. The gut microbiome can be influenced by the oral uptake of probiotics. With an improved understanding of the mechanisms responsible for interorgan communication, we can start to define what requirements an 'ideal' probiotic should have and its role in this triangle.


Subject(s)
COVID-19 , Coronary Disease , Gastrointestinal Microbiome/drug effects , Lung Diseases , Probiotics/administration & dosage , Animals , COVID-19/microbiology , COVID-19/pathology , Coronary Disease/microbiology , Coronary Disease/pathology , Humans , Lung Diseases/microbiology , Lung Diseases/pathology
5.
Int J Mol Sci ; 22(5)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1389392

ABSTRACT

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.


Subject(s)
Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/physiology , Lung Diseases/physiopathology , Lung/physiology , Alveolar Epithelial Cells/cytology , Animals , COVID-19/physiopathology , Humans , Immunity, Innate , Ions/metabolism , Lung/anatomy & histology , Lung Diseases/etiology , Lung Diseases/pathology , Pulmonary Surfactant-Associated Proteins/metabolism , Regeneration
6.
Cells ; 10(7)2021 06 26.
Article in English | MEDLINE | ID: covidwho-1389304

ABSTRACT

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.


Subject(s)
Lab-On-A-Chip Devices , Lung Diseases/pathology , Lung/physiology , Regeneration/physiology , Respiratory Mucosa/cytology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Cells, Cultured , Extracellular Matrix/physiology , Humans , Lung/cytology , Lung/pathology , Lung Diseases/physiopathology , Lung Diseases/therapy , Models, Biological , Respiratory Mucosa/pathology , Respiratory Mucosa/physiology , SARS-CoV-2/pathogenicity , Tissue Culture Techniques/instrumentation , Tissue Culture Techniques/methods
7.
Pathol Oncol Res ; 27: 1609900, 2021.
Article in English | MEDLINE | ID: covidwho-1369742

ABSTRACT

Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 post-mortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.


Subject(s)
COVID-19/pathology , Laboratories/statistics & numerical data , Lung Diseases/pathology , Aged , Aged, 80 and over , Autopsy , COVID-19/complications , COVID-19/virology , Cohort Studies , Female , Humans , Lung Diseases/complications , Lung Diseases/virology , Male , Middle Aged , SARS-CoV-2
8.
Life Sci ; 283: 119871, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1336712

ABSTRACT

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.


Subject(s)
Influenza, Human/immunology , Interleukin-13/immunology , Lung Diseases/immunology , Chronic Disease , Humans , Inflammation/immunology , Inflammation/pathology , Influenza, Human/pathology , Lung Diseases/pathology , Mucus/immunology
9.
Addiction ; 116(9): 2559-2571, 2021 09.
Article in English | MEDLINE | ID: covidwho-1334376

ABSTRACT

This narrative review provides a summary of the impact of tobacco smoking on the respiratory system and the benefits of smoking cessation. Tobacco smoking is one of the leading preventable causes of death world-wide and a major risk factor for lung cancer and chronic obstructive pulmonary disease. Smoking is also associated with an increased risk of respiratory infections and appears to be related to poorer outcomes among those with COVID-19. Non-smokers with second-hand smoke exposure also experience significant adverse respiratory effects. Smoking imposes enormous health- and non-health-related costs to societies. The benefits of smoking cessation, in both prevention and management of respiratory disease, have been known for decades and, to this day, cessation support remains one of the most important cost-effective interventions that health professionals can provide to people who smoke. Cessation at any age confers substantial health benefits, even in smokers with established morbidities. As other treatments for chronic respiratory disease advance and survival rates increase, smoking cessation treatment will become even more relevant. While smoking cessation interventions are available, the offer of these by clinicians and uptake by patients remain limited.


Subject(s)
Lung Diseases/complications , Lung Diseases/pathology , Smoking Cessation , Tobacco Use Disorder/complications , Tobacco Use Disorder/pathology , Humans , Lung/pathology , Lung Diseases/prevention & control , Tobacco Use Disorder/therapy
10.
Nat Commun ; 12(1): 4314, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1310804

ABSTRACT

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.


Subject(s)
Lung Diseases/genetics , SARS-CoV-2/physiology , Transcriptome , Virus Internalization , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/genetics , COVID-19/pathology , Chronic Disease , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Immunity, Innate/genetics , Inflammation/genetics , Lung/metabolism , Lung/pathology , Lung Diseases/pathology , SARS-CoV-2/pathogenicity , Virus Replication/genetics
11.
PLoS One ; 16(7): e0246270, 2021.
Article in English | MEDLINE | ID: covidwho-1302006

ABSTRACT

During infectious disease, pathogen load drives inflammation and immune response that together contribute to tissue injury often resulting in organ dysfunction. Pulmonary failure in SARS-CoV2-infected hospitalized COVID-19 patients is one such prominent example. Intervention strategies require characterization of the host-pathogen interaction by accurately assessing all of the above-mentioned disease parameters. To study infection in intact mammals, mice are often used as essential genetic models. Due to humane concerns, there is a constant unmet demand to develop studies that reduce the number of mice utilized while generating objective data. Here, we describe an integrated method of evaluating lung inflammation in mice infected with Pseudomonas aeruginosa or murine gammaherpesvirus (MHV)-68. This method conserves animal resources while permitting evaluation of disease mechanisms in both infection settings. Lungs from a single euthanized mouse were used for two purposes-biological assays to determine inflammation and infection load, as well as histology to evaluate tissue architecture. For this concurrent assessment of multiple parameters from a single euthanized mouse, we limit in-situ formalin fixation to the right lung of the cadaver. The unfixed left lung is collected immediately and divided into several segments for biological assays including determination of pathogen titer, assessment of infection-driven cytokine levels and appearance of cell death markers. In situ fixed right lung was then processed for histological determination of tissue injury and confirmation of infection-driven cell death patterns. This method reduces overall animal use and minimizes inter-animal variability that results from sacrificing different animals for different types of assays. The technique can be applied to any lung disease study in mice or other mammals.


Subject(s)
Herpesviridae Infections/pathology , Lung Diseases/pathology , Lung/pathology , Pseudomonas Infections/pathology , Animals , Gammaherpesvirinae , Mice , Pseudomonas aeruginosa
12.
Life Sci ; 281: 119718, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1271709

ABSTRACT

AIMS: Hypoxia, a pathophysiological condition, is profound in several cardiopulmonary diseases (CPD). Every individual's lethality to a hypoxia state differs in terms of hypoxia exposure time, dosage units and dependent on the individual's genetic makeup. Most of the proposed markers for CPD were generally aim to distinguish disease samples from normal samples. Although, as per the 2018 GOLD guidelines, clinically useful biomarkers for several cardio pulmonary disease patients in stable condition have yet to be identified. We attempt to address these key issues through the identification of Dynamic Network Biomarkers (DNB) to detect hypoxia induced early warning signals of CPD before the catastrophic deterioration. MATERIALS AND METHODS: The human microvascular endothelial tissues microarray datasets (GSE11341) of lung and cardiac expose to hypoxia (1% O2) for 3, 24 and 48 h were retrieved from the public repository. The time dependent differentially expressed genes were subjected to tissue specificity and promoter analysis to filtrate the noise levels in the networks and to dissect the tissue specific hypoxia induced genes. These filtered out genes were used to construct the dynamic segmentation networks. The hypoxia induced dynamic differentially expressed genes were validated in the lung and heart tissues of male rats. These rats were exposed to hypobaric hypoxia (simulated altitude of 25,000 or PO2 - 282 mm of Hg) progressively for 3, 24 and 48 h. KEY FINDINGS: To identify the temporal key genes regulated in hypoxia, we ranked the dominant genes based on their consolidated topological features from tissue specific networks, time dependent networks and dynamic networks. Overall topological ranking described VEGFA as a single node dynamic hub and strongly communicated with tissue specific genes to carry forward their tissue specific information. We named this type of VEGFAcentric dynamic networks as "V-DNBs". As a proof of principle, our methodology helped us to identify the V-DNBs specific for lung and cardiac tissues namely V-DNBL and V-DNBC respectively. SIGNIFICANCE: Our experimental studies identified VEGFA, SLC2A3, ADM and ENO2 as the minimum and sufficient candidates of V-DNBL. The dynamic expression patterns could be readily exploited to capture the pre disease state of hypoxia induced pulmonary vascular remodelling. Whereas in V-DNBC the minimum and sufficient candidates are VEGFA, SCL2A3, ADM, NDRG1, ENO2 and BHLHE40. The time dependent single node expansion indicates V-DNBC could also be the pre disease state pathological hallmark for hypoxia-associated cardiovascular remodelling. The network cross-talk and expression pattern between V-DNBL and V-DNBC are completely distinct. On the other hand, the great clinical advantage of V-DNBs for pre disease predictions, a set of samples during the healthy condition should suffice. Future clinical studies might further shed light on the predictive power of V-DNBs as prognostic and diagnostic biomarkers for CPD.


Subject(s)
Heart Diseases/metabolism , Hypoxia/metabolism , Lung Diseases/metabolism , Vascular Endothelial Growth Factor A/metabolism , Animals , Biomarkers/metabolism , Clinical Deterioration , Gene Expression Regulation , Heart Diseases/etiology , Heart Diseases/pathology , Humans , Hypoxia/complications , Hypoxia/genetics , Lung Diseases/etiology , Lung Diseases/pathology , Male , Rats , Rats, Sprague-Dawley
13.
Biomed Phys Eng Express ; 7(4)2021 05 20.
Article in English | MEDLINE | ID: covidwho-1225585

ABSTRACT

Segmenting lesion regions of Coronavirus Disease 2019 (COVID-19) from computed tomography (CT) images is a challenge owing to COVID-19 lesions characterized by high variation, low contrast between infection lesions and around normal tissues, and blurred boundaries of infections. Moreover, a shortage of available CT dataset hinders deep learning techniques applying to tackling COVID-19. To address these issues, we propose a deep learning-based approach known as PPM-Unet to segmenting COVID-19 lesions from CT images. Our method improves an Unet by adopting pyramid pooling modules instead of the conventional skip connection and then enhances the representation of the neural network by aiding the global attention mechanism. We first pre-train PPM-Unet on COVID-19 dataset of pseudo labels containing1600 samples producing a coarse model. Then we fine-tune the coarse PPM-Unet on the standard COVID-19 dataset consisting of 100 pairs of samples to achieve a fine PPM-Unet. Qualitative and quantitative results demonstrate that our method can accurately segment COVID-19 infection regions from CT images, and achieve higher performance than other state-of-the-art segmentation models in this study. It offers a promising tool to lay a foundation for quantitatively detecting COVID-19 lesions.


Subject(s)
COVID-19/complications , Deep Learning , Image Processing, Computer-Assisted/methods , Lung Diseases/pathology , Neural Networks, Computer , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed/methods , Algorithms , COVID-19/virology , Humans , Lung Diseases/diagnostic imaging , Lung Diseases/virology , Specimen Handling
14.
JAMA ; 325(15): 1525-1534, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1222575

ABSTRACT

Importance: Little is known about long-term sequelae of COVID-19. Objective: To describe the consequences at 4 months in patients hospitalized for COVID-19. Design, Setting, and Participants: In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit. Exposures: Survival of hospitalization for COVID-19. Main Outcomes and Measures: Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography. Results: Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale "role limited owing to physical problems" (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%). Conclusions and Relevance: Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.


Subject(s)
COVID-19/complications , Hospitalization , Lung Diseases/etiology , Lung/pathology , Aged , Anxiety/etiology , COVID-19/psychology , Cognition Disorders/etiology , Cohort Studies , Depression/etiology , Dyspnea/etiology , Fatigue/etiology , Female , Follow-Up Studies , Humans , Lung/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/pathology , Male , Middle Aged , Tomography, X-Ray Computed
16.
Cell ; 184(8): 1990-2019, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1163481

ABSTRACT

The population is aging at a rate never seen before in human history. As the number of elderly adults grows, it is imperative we expand our understanding of the underpinnings of aging biology. Human lungs are composed of a unique panoply of cell types that face ongoing chemical, mechanical, biological, immunological, and xenobiotic stress over a lifetime. Yet, we do not fully appreciate the mechanistic drivers of lung aging and why age increases the risk of parenchymal lung disease, fatal respiratory infection, and primary lung cancer. Here, we review the molecular and cellular aspects of lung aging, local stress response pathways, and how the aging process predisposes to the pathogenesis of pulmonary disease. We place these insights into context of the COVID-19 pandemic and discuss how innate and adaptive immunity within the lung is altered with age.


Subject(s)
Aging , Cellular Senescence , Lung Diseases , Lung , Adaptive Immunity , Aged , Aging/immunology , Aging/pathology , COVID-19/immunology , COVID-19/pathology , Humans , Lung/immunology , Lung/pathology , Lung Diseases/immunology , Lung Diseases/pathology , Oxidative Stress
17.
Pathol Res Pract ; 221: 153419, 2021 May.
Article in English | MEDLINE | ID: covidwho-1157674

ABSTRACT

Sars-Cov-2 infection is still a healthcare emergency and acute respiratory distress failure with Diffuse Alveolar Damage (DAD) features is the main causes of patients' death. Pathogenic mechanisms of the disease are not clear yet, but new insights are necessary to improve therapeutic management, to prevent fatal irreversible multi-organ damage and to adequately follow up those patients who survive. Here we investigated, by histochemistry and immunohistochemistry, a wide number of mapped lung specimens taken from whole body autopsies of 7 patients dead of COVID-19 disease. Our data confirm morphological data of other authors, and enlarge recent reports of the literature suggesting that Endothelial-Mesenchymal Transition might be central to COVID-19 lung fibrosing lesions. Furthermore, based upon recent acquisition of new roles in immunity and vascular pathology of the CD31 molecule, we hypothesize that this molecule might be important in the development and treatment of COVID-19 pulmonary lesions. These preliminary findings need further investigations to shed light on the complexity of Sars-Cov-2 disease.


Subject(s)
COVID-19/pathology , Epithelial-Mesenchymal Transition , Lung Diseases/pathology , Lung Diseases/virology , Aged , Female , Humans , Male , Middle Aged , SARS-CoV-2
18.
Mil Med Res ; 8(1): 22, 2021 03 24.
Article in English | MEDLINE | ID: covidwho-1150431

ABSTRACT

Evidence shows that pulmonary problems in coronavirus disease 2019 (COVID-19) may set off from vascular injury that progresses to physiological disturbances through a compromised gas exchange, following an infection with the severe acute respiratory syndrome coronavirus 2. In this process, inefficient gas exchange in the alveolar could precipitate silent nonclinical hypoxemia. Unfortunately, patients with "silent hypoxemia" do not necessarily experience any breathing difficulty (dyspnea) at the early stage of COVID-19 while the disease progresses. As a result, several asymptomatic, presymptomatic and patients with mild symptoms may escape quarantine measure and thus continue to spread the virus through contacts. Therefore, early diagnosis of "silent hypoxemia", which attracts no clinical warnings, could be an important diagnostic measure to prevent acute respiratory distress syndrome from the risk of pulmonary failure among the presymptomatic and as a screening tool in the asymptomatic who are hitherto potential spreaders of the virus.


Subject(s)
COVID-19/transmission , Lung Diseases/virology , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/pathology , Disease Progression , Humans , Lung Diseases/pathology , Oximetry , SARS-CoV-2
19.
Syst Rev ; 10(1): 77, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1136248

ABSTRACT

BACKGROUND: Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of different rapid tests for exertional desaturation and draw on this evidence base to provide guidance in the context of acute Covid-19. MAIN RESEARCH QUESTIONS: 1. What exercise tests have been used to assess exertional hypoxia at home or in an ambulatory setting in the context of Covid-19 and to what extent have they been validated? 2. What exercise tests have been used to assess exertional hypoxia in other lung conditions, to what extent have they been validated and what is the applicability of these studies to acute Covid-19? METHOD: AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases were searched to September 2020. Studies where participants had Covid-19 or another lung disease and underwent any form of exercise test which was compared to a reference standard were eligible. Risk of bias was assessed using QUADAS 2. A protocol for the review was published on the Medrxiv database. RESULTS: Of 47 relevant papers, 15 were empirical studies, of which 11 described an attempt to validate one or more exercise desaturation tests in lung diseases other than Covid-19. In all but one of these, methodological quality was poor or impossible to fully assess. None had been designed as a formal validation study (most used simple tests of correlation). Only one validation study (comparing a 1-min sit-to-stand test [1MSTST] with reference to the 6-min walk test [6MWT] in 107 patients with interstitial lung disease) contained sufficient raw data for us to calculate the sensitivity (88%), specificity (81%) and positive and negative predictive value (79% and 89% respectively) of the 1MSTST. The other 4 empirical studies included two predictive studies on patients with Covid-19, and two on HIV-positive patients with suspected pneumocystis pneumonia. We found no studies on the 40-step walk test (a less demanding test that is widely used in clinical practice to assess Covid-19 patients). Heterogeneity of study design precluded meta-analysis. DISCUSSION: Exertional desaturation tests have not yet been validated in patients with (or suspected of having) Covid-19. A stronger evidence base exists for the diagnostic accuracy of the 1MSTST in chronic long-term pulmonary disease; the relative intensity of this test may raise safety concerns in remote consultations or unstable patients. The less strenuous 40-step walk test should be urgently evaluated.


Subject(s)
COVID-19/blood , Exercise Test , Exercise , Lung Diseases/diagnosis , Oxygen/blood , Physical Exertion , COVID-19/pathology , COVID-19/virology , Dyspnea , Exercise Test/adverse effects , Humans , Hypoxia , Lung Diseases/blood , Lung Diseases/pathology , Lung Diseases/virology , Predictive Value of Tests , SARS-CoV-2 , Sensitivity and Specificity
20.
Hepatology ; 74(3): 1674-1686, 2021 09.
Article in English | MEDLINE | ID: covidwho-1103301

ABSTRACT

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.


Subject(s)
Hypertension, Portal/complications , Liver Cirrhosis/complications , Liver Transplantation/mortality , Lung Diseases/complications , Adult , Asthma/diagnosis , Asthma/epidemiology , Asthma/mortality , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Child , Cystic Fibrosis , End Stage Liver Disease/complications , Hepatopulmonary Syndrome/diagnosis , Hepatopulmonary Syndrome/epidemiology , Hepatopulmonary Syndrome/mortality , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Liver Transplantation/methods , Lung Diseases/epidemiology , Lung Diseases/pathology , Lung Diseases/physiopathology , Mass Screening , Patient Selection/ethics , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Respiratory Function Tests/methods , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sarcoidosis/diagnosis , Sarcoidosis/epidemiology , Sarcoidosis/mortality , Survival Rate/trends , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/epidemiology , Telangiectasia, Hereditary Hemorrhagic/mortality , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/epidemiology , alpha 1-Antitrypsin Deficiency/mortality
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