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1.
Clin Infect Dis ; 74(3): 479-489, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684541

ABSTRACT

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.


Subject(s)
COVID-19 , Extracellular Traps , Critical Illness , Humans , Neutrophil Activation , Neutrophils , Phenotype , SARS-CoV-2
2.
Chest ; 160(2): 652-670, 2021 08.
Article in English | MEDLINE | ID: covidwho-1491830

ABSTRACT

The COVID-19 pandemic has had devastating medical and economic consequences globally. The severity of COVID-19 is related, in a large measure, to the extent of pulmonary involvement. The role of chest CT imaging in the management of patients with COVID-19 has evolved since the onset of the pandemic. Specifically, the description of CT scan findings, use of chest CT imaging in various acute and subacute settings, and its usefulness in predicting chronic disease have been defined better. We performed a review of published data on CT scans in patients with COVID-19. A summary of the range of imaging findings, from typical to less common abnormalities, is provided. Familiarity with these findings may facilitate the diagnosis and management of this disease. A comparison of sensitivity and specificity of chest CT imaging with reverse-transcriptase polymerase chain reaction testing highlights the potential role of CT imaging in difficult-to-diagnose cases of COVID-19. The usefulness of CT imaging to assess prognosis, to guide management, and to identify acute pulmonary complications associated with SARS-CoV-2 infection is highlighted. Beyond the acute stage, it is important for clinicians to recognize pulmonary parenchymal abnormalities, progressive fibrotic lung disease, and vascular changes that may be responsible for persistent respiratory symptoms. A large collection of multi-institutional images were included to elucidate the CT scan findings described.


Subject(s)
COVID-19/diagnostic imaging , Thorax/diagnostic imaging , Tomography, X-Ray Computed , COVID-19/complications , COVID-19/therapy , Humans , Prognosis , Sensitivity and Specificity
3.
Surg Today ; 51(3): 447-451, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1453756

ABSTRACT

Accumulation of experience and advances in techniques and instruments have enabled surgeons to perform video-assisted thoracic surgery (VATS) safely for sublobar resection, including segmentectomy and wedge resection. A key to successful VATS sublobar resection is to have adequate resection margins and the appropriate use of articulated surgical staplers is essential for this purpose. The SigniaTM stapling system (Covidien Japan, Tokyo) has been used extensively in the fields of thoracic surgery. Its features include high maneuverability with fully powered articulation, rotation, clamping, and firing, which the surgeon can control with one hand. We introduce the "sliding technique" using the SigniaTM system, which allows for adjustment of the resection lines of the pulmonary parenchyma to optimize safe surgical margins with minimal stapler movement, and without repetitively moving the stapler in and out of the pleural cavity, during VATS sublobar resection.


Subject(s)
Lung Neoplasms/surgery , Lung/surgery , Margins of Excision , Pneumonectomy/instrumentation , Pneumonectomy/methods , Surgical Staplers , Surgical Stapling/instrumentation , Surgical Stapling/methods , Thoracic Surgery, Video-Assisted/instrumentation , Thoracic Surgery, Video-Assisted/methods , Humans , Safety
4.
AJR Am J Roentgenol ; 214(6): 1287-1294, 2020 06.
Article in English | MEDLINE | ID: covidwho-1408325

ABSTRACT

OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [± SD] age, 52.8 ± 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 ± 3.4) was significantly lower than that for the middle (4.5 ± 3.8) and lower (4.5 ± 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 ± 4.1) was significantly lower than that for the posterior area (7.7 ± 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (≤ 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.


Subject(s)
Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies
5.
Clin Infect Dis ; 73(5): e1089-e1098, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1398078

ABSTRACT

BACKGROUND: Long-term health sequelae of coronavirus disease 2019 (COVID-19) may be multiple but have thus far not been systematically studied. METHODS: All patients discharged after COVID-19 from the Radboud University Medical Center, Nijmegen, the Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, nonadmitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest computed tomography (CT)/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status, and quality of life (QoL). RESULTS: 124 patients (59 ±â€…14 years, 60% male) were included: 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Lung diffusion capacity was below the lower limit of normal in 42% of discharged patients. 99% of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild disease. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%), and QoL (72%). CONCLUSIONS: This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex-COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery.


Subject(s)
COVID-19 , Lung Diseases , Aged , Female , Humans , Lung , Male , Middle Aged , Quality of Life , SARS-CoV-2
6.
Rev Francoph Lab ; 2021(528): 30-35, 2021 Jan.
Article in French | MEDLINE | ID: covidwho-1386946

ABSTRACT

The histological lesions associated with an infection with the Sars-CoV-2 are mainly observed at the respiratory tract level, but not exclusively. Analyses of these lesions strongly beneficied from autopsic studies allowing us to improve the knowledge of the pathophysiology mechanisms of this emerging infectious disease. Cytological analyses, notably those obtained from broncho-alveolar lavages, poorly contribute to the Covid-19 diagnosis, but can be usefull for eliminate a couple of differential diagnoses. Although non specific, the lesions observed in the pulmonary parenchyma can be directly associated with the presence of the Sars-CoV-2 thanks to ancillary tools allowing its detection. Indeed, the presence of the virus can be detected using immunohistochemistry, in situ hybridization, molecular biology and/or electron microscopy approaches. Several uncertainties still exist concerning the direct role due to the Sars-CoV-2 in the observed lesions which can be due too to a cardiovascular failure and/or to the treatment(s) received in intensive care units. Thus, it is critical to keep going to increase our efforts for the tissue analyses, notably thanks to the autopsies of Covid-19 patients, in order to better understand the consequences of this infectious disease, and, particularly according the epidemiological factors and the different associated morbidities. An increased knowledge will participate to the further therapeutic strategies against the Covid-19. This review adresses the main histological lesions of the lung parenchyma currently described in patients infected by the Sars-CoV-2.

7.
Stem Cell Res Ther ; 11(1): 448, 2020 10 23.
Article in English | MEDLINE | ID: covidwho-1388825

ABSTRACT

Gene therapy is being investigated for a range of serious lung diseases, such as cystic fibrosis and emphysema. Recombinant adeno-associated virus (rAAV) is a well-established, safe, viral vector for gene delivery with multiple naturally occurring and artificial serotypes available displaying alternate cell, tissue, and species-specific tropisms. Efficient AAV serotypes for the transduction of the conducting airways have been identified for several species; however, efficient serotypes for human lung parenchyma have not yet been identified. Here, we screened the ability of multiple AAV serotypes to transduce lung bud organoids (LBOs)-a model of human lung parenchyma generated from human embryonic stem cells. Microinjection of LBOs allowed us to model transduction from the luminal surface, similar to dosing via vector inhalation. We identified the naturally occurring rAAV2 and rAAV6 serotypes, along with synthetic rAAV6 variants, as having tropism for the human lung parenchyma. Positive staining of LBOs for surfactant proteins B and C confirmed distal lung identity and suggested the suitability of these vectors for the transduction of alveolar type II cells. Our findings establish LBOs as a new model for pulmonary gene therapy and stress the relevance of LBOs as a viral infection model of the lung parenchyma as relevant in SARS-CoV-2 research.


Subject(s)
Dependovirus/genetics , Genetic Therapy/methods , Human Embryonic Stem Cells/cytology , Lung Diseases/therapy , Organoids/cytology , Cell Line , Dependovirus/immunology , Gene Transfer Techniques , Genetic Vectors/genetics , Humans , Lung/metabolism , Models, Biological , Parenchymal Tissue/cytology
8.
Expert Rev Respir Med ; 15(5): 635-648, 2021 05.
Article in English | MEDLINE | ID: covidwho-1369023

ABSTRACT

INTRODUCTION: The longstanding dogma that the healthy lung is sterile has been refuted by recent advances in culture-independent analyses of airway samples. The respiratory microbiome comprises all airway and lung tissue-associated microbes. These micro-organisms occur throughout the upper and lower respiratory tracts, with different populations and distinct burdens at specific sites and can be classified as pathogenic or commensal. AREAS COVERED: The majority of studies investigating the respiratory microbiome have focused on bacteria; however, emerging evidence has revealed the composition of the lung virome, the global viral communities present in the lung tissue. In this review, we searched PubMed and used keywords such as airway microbiome. We restricted outputs to English language and did not limit by any dates. We summarize the up-to-date knowledge on how the microbiome interacts with the host immune system and influences the pathogenesis of pulmonary viral infections. EXPERT OPINION: The relationship between colonizing microbes and the host is complex and various factors need to be considered in order to appreciate its pathophysiological consequences. Understanding these intricate mechanisms of interaction among the respiratory microbiome, viruses and the immune response may lead to the development of better therapies to treat or prevent respiratory viral infections.


Subject(s)
Microbiota , Virus Diseases , Viruses , Humans , Immunity , Lung
9.
Nat Med ; 27(3): 546-559, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319033

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.


Subject(s)
COVID-19/epidemiology , COVID-19/genetics , Host-Pathogen Interactions/genetics , SARS-CoV-2/physiology , Sequence Analysis, RNA/statistics & numerical data , Single-Cell Analysis/statistics & numerical data , Virus Internalization , Adult , Aged , Aged, 80 and over , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/virology , Cathepsin L/genetics , Cathepsin L/metabolism , Datasets as Topic/statistics & numerical data , Demography , Female , Gene Expression Profiling/statistics & numerical data , Humans , Lung/metabolism , Lung/virology , Male , Middle Aged , Organ Specificity/genetics , Respiratory System/metabolism , Respiratory System/virology , Sequence Analysis, RNA/methods , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Single-Cell Analysis/methods
10.
Biomolecules ; 11(6)2021 05 26.
Article in English | MEDLINE | ID: covidwho-1310053

ABSTRACT

Angiotensin-converting enzyme 2 (ACE-2) is the main cell entry receptor for severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), thus playing a critical role in causing Coronavirus disease 2019 (COVID-19). The role of smoking habit in the susceptibility to infection is still controversial. In this study we correlated lung ACE-2 gene expression with several clinical/pathological data to explore susceptibility to infection. This is a retrospective observational study on 29 consecutive COVID-19 autopsies. SARS-CoV-2 genome and ACE-2 mRNA expression were evaluated by real-time polymerase chain reaction in lung tissue samples and correlated with several data with focus on smoking habit. Smoking was less frequent in high than low ACE-2 expressors (p = 0.014). A Bayesian regression also including age, gender, hypertension, and virus quantity confirmed that smoking was the most probable risk factor associated with low ACE-2 expression in the model. A direct relation was found between viral quantity and ACE-2 expression (p = 0.028). Finally, high ACE-2 expressors more frequently showed a prevalent pattern of vascular injury than low expressors (p = 0.049). In conclusion, ACE-2 levels were decreased in the lung tissue of smokers with severe COVID-19 pneumonia. These results point out complex biological interactions between SARS-CoV-2 and ACE-2 particularly concerning the aspect of smoking habit and need larger prospective case series and translational studies.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , Lung/metabolism , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Bayes Theorem , COVID-19/virology , Female , Humans , Lung/pathology , Male , Real-Time Polymerase Chain Reaction , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Smokers
11.
J Med Virol ; 93(8): 5182-5187, 2021 08.
Article in English | MEDLINE | ID: covidwho-1298501

ABSTRACT

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.


Subject(s)
Genetic Predisposition to Disease/genetics , Lung Diseases, Interstitial/genetics , Roseolovirus Infections/genetics , Cytoskeletal Proteins/genetics , Fatal Outcome , Female , Genetic Variation , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Heterozygote , Humans , Infant, Newborn , Lung Diseases, Interstitial/therapy , Lung Diseases, Interstitial/virology , Microtubule-Associated Proteins/genetics , Mucin-5B/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Roseolovirus Infections/therapy , Roseolovirus Infections/virology , Viral Load
12.
Pulm Pharmacol Ther ; 69: 102007, 2021 08.
Article in English | MEDLINE | ID: covidwho-1267894

ABSTRACT

BACKGROUND: In the current coronavirus health crisis, inhaled bronchodilators(IB) have been suggested as a possible treatment for patients hospitalized. Patients with evidence of Covid-19 pneumonia worldwide have been prescribed these medications as part of therapy for the disease, an indication for which this medications could be ineffective taken on account the pathophysiology and mechanisms of disease progression. OBJECTIVE: The main objective was to evaluate whether there is an association between IB use and length of stay. Primary end points were the number of days that a patient stayed in the hospital and death as a final event in a time to event analysis. Pneumonia severity, oxygen requirement, involved drugs, comorbidity, historical or current respiratory diagnoses and other drugs prescribed to treat coronavirus pneumonia were also evaluated. METHODS: A descriptive, observational, cross-sectional study was performed in this tertiary hospital in Madrid (Spain). Data were obtained regarding patients hospitalized with Covid-19, excluding those who were intubated. The primary and secondary outcomes such as duration of hospitalization and death were compared in patients who received IB with those in patients who did not. RESULTS: 327 patients were evaluated, mean age was 64.4 ± 15.8 years. Median length of hospitalization stay was 10 days. Of them 292 (89.3%) overcame the disease, the remaining 35 died. Patients who had received IB did not have less mortality rate (odds ratio 0.839; 95% CI: 0.401 to 1.752) and less hospitalization period when compared with patients who did not received IB (odds ratio 1.280; 95% CI: 0.813 to 2.027). There was no significant association between IB use and recovery or death. Hypertension and diabetes were the most common comorbidities. The prevalence of chronic respiratory disease in our cohort was low (21.1%). Anticholinergics were the IB more frequently prescribed for Covid-19 pneumonia. Better response in patients treated with inhaled corticosteroids was not observed. CONCLUSION: Off-label indication of inhaled-bronchodilators for Covid-19 patients are common in admitted patients. Taken on account our results, the use of IB for coronavirus pneumonia apparently is not associated with a significantly patient's improvement. Our study confirms the hypothesis that inhaled bronchodilators do not improve clinical outcomes or reduce the risk of Covid-19 mortality. This could be due to the fact that the virus mainly affects the lung parenchyma and the pulmonary vasculature and probably not the airway. More researches are necessary in order to fill the gap in evidence for this new indication.


Subject(s)
Bronchodilator Agents , COVID-19 , Adult , Cohort Studies , Cross-Sectional Studies , Hospitalization , Humans , Inpatients , Middle Aged , Retrospective Studies , SARS-CoV-2 , Spain/epidemiology
13.
J Infect Dis ; 223(11): 1842-1854, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1258777

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients manifest with pulmonary symptoms reflected by diffuse alveolar damage (DAD), excessive inflammation, and thromboembolism. The mechanisms mediating these processes remain unclear. METHODS: We performed multicolor staining for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and lineage markers to define viral tropism and lung pathobiology in 5 autopsy cases. RESULTS: Lung parenchyma showed severe DAD with thromboemboli. Viral infection was found in an extensive range of cells including pneumocyte type II, ciliated, goblet, club-like, and endothelial cells. More than 90% of infiltrating immune cells were positive for viral proteins including macrophages, monocytes, neutrophils, natural killer (NK) cells, B cells, and T cells. Most but not all infected cells were angiotensin-converting enzyme 2 (ACE2) positive. The numbers of infected and ACE2-positive cells are associated with extensive tissue damage. Infected tissues exhibited high levels of inflammatory cells including macrophages, monocytes, neutrophils, and NK cells, and low levels of B cells but abundant T cells consisting of mainly T helper cells, few cytotoxic T cells, and no regulatory T cells. Robust interleukin-6 expression was present in most cells, with or without infection. CONCLUSIONS: In fatal COVID-19 lungs, there are broad SARS-CoV-2 cell tropisms, extensive infiltrated innate immune cells, and activation and depletion of adaptive immune cells, contributing to severe tissue damage, thromboemboli, excess inflammation, and compromised immune responses.


Subject(s)
COVID-19/pathology , Lung/pathology , SARS-CoV-2/physiology , Viral Tropism , Adult , Aged , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunity, Innate , Lung/cytology , Lung/immunology , Lung/virology , Male , Middle Aged , Pulmonary Alveoli/immunology , Pulmonary Alveoli/pathology , Pulmonary Alveoli/virology , Viral Tropism/immunology
14.
J Matern Fetal Neonatal Med ; : 1-6, 2021 Jun 06.
Article in English | MEDLINE | ID: covidwho-1258701

ABSTRACT

OBJECTIVE: To investigate whether physicians with short-term training can use a modified lung ultrasound scoring system for coronavirus disease 2019 (COVID-19) pneumonia to assess lung damage in pregnant women. METHODS: Sixteen consecutively hospitalized third-trimester pregnant women with pregnancy-induced hypertension, preeclampsia, rheumatoid arthritis or connective tissue disease were selected as the study subjects for the simulation of COVID-19 pneumonia. Two physicians (imaging and internal medicine) without ultrasonic experience performed lung examinations on pregnant women after six days of lung ultrasound training, and their consistency with examinations by the expert was assessed. In addition, 54 healthy third-trimester pregnant women and 54 healthy nonpregnant women of the same age who were continuously treated in the outpatient clinic of this hospital were selected for comparisons of abnormalities on lung ultrasound. RESULTS: (1) Third trimester pregnant women with pregnancy-induced hypertension, preeclampsia, rheumatoid arthritis or connective tissue disease had the same lung ultrasound patterns as those associated with COVID-19 pneumonia. (2) There was no statistically significant difference between the scores of the two trained doctors and the expert when the modified ultrasound scoring system was used (p > .05). (3) The evaluations of the two trained doctors and the expert showed good consistency (kappa value = 0.833-0.957). (4) The incidence of abnormal ultrasound manifestations of the pleura and lung parenchyma was higher among healthy third-trimester pregnant women than among healthy women of the same age (p < .001). CONCLUSIONS: After receiving short-term training, imaging and internal medicine physicians can use the modified lung ultrasound scoring system to evaluate pregnant women's pulmonary damage, but caution is needed to avoid false-positive results among pregnant women with suspected COVID-19 pneumonia.

15.
Pattern Recognit ; 119: 108071, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1253452

ABSTRACT

This paper aims to develop an automatic method to segment pulmonary parenchyma in chest CT images and analyze texture features from the segmented pulmonary parenchyma regions to assist radiologists in COVID-19 diagnosis. A new segmentation method, which integrates a three-dimensional (3D) V-Net with a shape deformation module implemented using a spatial transform network (STN), was proposed to segment pulmonary parenchyma in chest CT images. The 3D V-Net was adopted to perform an end-to-end lung extraction while the deformation module was utilized to refine the V-Net output according to the prior shape knowledge. The proposed segmentation method was validated against the manual annotation generated by experienced operators. The radiomic features measured from our segmentation results were further analyzed by sophisticated statistical models with high interpretability to discover significant independent features and detect COVID-19 infection. Experimental results demonstrated that compared with the manual annotation, the proposed segmentation method achieved a Dice similarity coefficient of 0.9796, a sensitivity of 0.9840, a specificity of 0.9954, and a mean surface distance error of 0.0318 mm. Furthermore, our COVID-19 classification model achieved an area under curve (AUC) of 0.9470, a sensitivity of 0.9670, and a specificity of 0.9270 when discriminating lung infection with COVID-19 from community-acquired pneumonia and healthy controls using statistically significant radiomic features. The significant features measured from our segmentation results agreed well with those from the manual annotation. Our approach has great promise for clinical use in facilitating automatic diagnosis of COVID-19 infection on chest CT images.

16.
World J Crit Care Med ; 10(3): 47-57, 2021 May 09.
Article in English | MEDLINE | ID: covidwho-1248351

ABSTRACT

BACKGROUND: Recent studies of the coronavirus disease 2019 (COVID-19) demonstrated that obesity is significantly associated with increased disease severity, clinical outcome, and mortality. The association between hepatic steatosis, which frequently accompanies obesity, and the pneumonia severity score (PSS) evaluated on computed tomography (CT), and the prevalence of steatosis in patients with COVID-19 remains to be elucidated. AIM: To assess the frequency of hepatic steatosis in the chest CT of COVID-19 patients and its association with the PSS. METHODS: The chest CT images of 485 patients who were admitted to the emergency department with suspected COVID-19 were retrospectively evaluated. The patients were divided into two groups as COVID-19-positive [CT- and reverse transcriptase-polymerase chain reaction (RT-PCR)-positive] and controls (CT- and RT-PCR-negative). The CT images of both groups were evaluated for PSS as the ratio of the volume of involved lung parenchyma to the total lung volume. Hepatic steatosis was defined as a liver attenuation value of ≤ 40 Hounsfield units (HU). RESULTS: Of the 485 patients, 56.5% (n = 274) were defined as the COVID-19-positive group and 43.5% (n = 211) as the control group. The average age of the COVID-19-positive group was significantly higher than that of the control group (50.9 ± 10.9 years vs 40.4 ± 12.3 years, P < 0.001). The frequency of hepatic steatosis in the positive group was significantly higher compared with the control group (40.9% vs 19.4%, P < 0.001). The average hepatic attenuation values were significantly lower in the positive group compared with the control group (45.7 ± 11.4 HU vs 53.9 ± 15.9 HU, P < 0.001). Logistic regression analysis showed that after adjusting for age, hypertension, diabetes mellitus, overweight, and obesity there was almost a 2.2 times greater odds of hepatic steatosis in the COVID-19-positive group than in the controls (odds ratio 2.187; 95% confidence interval: 1.336-3.580, P < 0.001). CONCLUSION: The prevalence of hepatic steatosis was significantly higher in COVID-19 patients compared with controls after adjustment for age and comorbidities. This finding can be easily assessed on chest CT images.

17.
J Ambient Intell Humaniz Comput ; : 1-24, 2021 May 25.
Article in English | MEDLINE | ID: covidwho-1244627

ABSTRACT

Different respiratory infections cause abnormal symptoms in lung parenchyma that show in chest computed tomography. Since December 2019, the SARS-COV-2 virus, which is the causative agent of COVID-19, has invaded the world causing high numbers of infections and deaths. The infection with SARS-COV-2 virus shows an abnormality in lung parenchyma that can be effectively detected using Computed Tomography (CT) imaging. In this paper, a novel computer aided framework (COV-CAF) is proposed for classifying the severity degree of the infection from 3D Chest Volumes. COV-CAF fuses traditional and deep learning approaches. The proposed COV-CAF consists of two phases: the preparatory phase and the feature analysis and classification phase. The preparatory phase handles 3D-CT volumes and presents an effective cut choice strategy for choosing informative CT slices. The feature analysis and classification phase incorporate fuzzy clustering for automatic Region of Interest (RoI) segmentation and feature fusion. In feature fusion, automatic features are extracted from a newly introduced Convolution Neural Network (Norm-VGG16) and are fused with spatial hand-crafted features extracted from segmented RoI. Experiments are conducted on MosMedData: Chest CT Scans with COVID-19 Related Findings with COVID-19 severity classes and SARS-COV-2 CT-Scan benchmark datasets. The proposed COV-CAF achieved remarkable results on both datasets. On MosMedData dataset, it achieved an overall accuracy of 97.76% and average sensitivity of 96.73%, while on SARS-COV-2 CT-Scan dataset it achieves an overall accuracy and sensitivity 97.59% and 98.41% respectively.

18.
Med Intensiva (Engl Ed) ; 44(9): 551-565, 2020 Dec.
Article in Spanish | MEDLINE | ID: covidwho-1243085

ABSTRACT

The clinical picture of SARS-CoV-2 infection (COVID-19) is characterized in its more severe form, by an acute respiratory failure which can worsen to pneumonia and acute respiratory distress syndrome (ARDS) and get complicated with thrombotic events and heart dysfunction. Therefore, admission to the Intensive Care Unit (ICU) is common. Ultrasound, which has become an everyday tool in the ICU, can be very useful during COVID-19 pandemic, since it provides the clinician with information which can be interpreted and integrated within a global assessment during the physical examination. A description of some of the potential applications of ultrasound is depicted in this document, in order to supply the physicians taking care of these patients with an adapted guide to the intensive care setting. Some of its applications since ICU admission include verification of the correct position of the endotracheal tube, contribution to safe cannulation of lines, and identification of complications and thrombotic events. Furthermore, pleural and lung ultrasound can be an alternative diagnostic test to assess the degree of involvement of the lung parenchyma by means of the evaluation of specific ultrasound patterns, identification of pleural effusions and barotrauma. Echocardiography provides information of heart involvement, detects cor pulmonale and shock states.


Subject(s)
COVID-19/diagnostic imaging , SARS-CoV-2 , Ultrasonography, Interventional/methods , Blood Vessels/diagnostic imaging , COVID-19/complications , Critical Care , Critical Illness , Echocardiography , Heart Diseases/diagnostic imaging , Heart Diseases/etiology , Heart Ventricles/diagnostic imaging , Humans , Hypertension, Pulmonary/diagnostic imaging , Intensive Care Units , Intubation, Intratracheal/methods , Lung/diagnostic imaging , Organ Size , Pleura/diagnostic imaging , Pleural Effusion/diagnostic imaging , Pneumothorax/diagnostic imaging , Pulmonary Heart Disease/diagnostic imaging , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Shock/diagnostic imaging , Transducers
19.
Heliyon ; 7(5): e07134, 2021 May.
Article in English | MEDLINE | ID: covidwho-1240373

ABSTRACT

Most COVID-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was COVID-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163 + macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothelium, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced COVID-19 ARDS.

20.
Nat Commun ; 12(1): 3010, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1237999

ABSTRACT

Resident memory T cells (TRM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, TRM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7+ T cells secreting IL-10. In convalescent patients, lung-TRM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting TRM cells as important for future protection against SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , Immunologic Memory/immunology , Lung/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Apoptosis/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , COVID-19/virology , Cell Movement/immunology , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Lung/virology , SARS-CoV-2/physiology , T-Lymphocytes/metabolism
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