Cell Sentence Context

Table 1. Analysis of context sentence of alveolar tissue in 529 abstracts.

PMID Senteces
32170560 Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection.
32172546 Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. […] Significant proliferation of type II alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. […] The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. […] Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosiswere observed. […] Coronavirus particles in bronchial mucosal epithelia and type II alveolar epithelia were observed under electron microscope. […] Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. […] Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusion: s The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation.
32174094 本文总结重症流感病毒H1N1、高致病性禽流感病毒H5N1、SARS-CoV、MERS-CoV及2019-nCoV冠状病毒几种引起重大疫情病毒感染性疾病的病理改变,尸检肺组织均表现为弥漫性肺泡损伤(diffuse alveolar damage,DAD),但不同病毒引起的病理表现存在差异,重症流感病毒2009 H1N1病毒与受体α-2,6-SA及α-2,3-SA结合,除DAD病变外,常伴有上呼吸道、气管、支气管和细支气管的炎性病变,且较易合并细菌感染。
32215622 Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with virus nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked cytokine activation were observed within the first week of virus challenge.
32221983 Similar to SARS-CoV, SARS-CoV-2 also uses the ACE2 receptor to invade human alveolar epithelial cells.
32226695 Autopsy results of a COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS). […] HAPE itself is initially caused by an increase in pulmonary capillary pressure and induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema.
32247631 Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored.
32270184 SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages.
32271454 The therapeutic mechanisms of MXSGD on COVID-19 may primarily involve the following effects: reducing inflammation, suppressing cytokine storm, protecting the pulmonary alveolar-capillary barrier, alleviating pulmonary edema, regulating the immune response, and decreasing fever.
32275128 With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination.
32275742 Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. […] Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.
32281052 After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction.
32283217 Following the death, autopsy was performed and the histopathologic evaluations of the lungs showed evidence of viral pneumonia (viral cytopathic effect and a mild increase in alveolar wall thickness) and ARDS (hyaline membrane).
32289516 High density of macrophages and foam cells in the alveolar cavities but no obvious proliferation of pneumocyte was found.
32290839 The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients.
32291399 Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. […] In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. […] In conclusion, the postmortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients.
32291526 Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells.
32294816 The case reports 2 cases of novel coronavirus pneumonia diagnosed by concurrent bronchoalveolar lavage in our hospital, 1 case had a history of epidemiology, clinical symptoms and high imaging suspicion, but repeated negative throat swabs. […] Before the patient was discharged, the clinical symptoms disappeared, the chest CT showed significant improvement, and the pharynx swab was twice negative, reaching the discharge standard.We detected the ORF 1ab gene, the N gene and the nucleic acid of the new coronavirus in the broncho-alveolar lavage fluid of 2 patients. […] The results showed that the positive rate of bronchoalveolar lavage for detection of new coronavirus nucleic acid was high, and bronchoalveolar lavage for suspected or confirmed new coronavirus pneumonia patients with negative detection of nucleic acid in pharynx swabs but still residual lung lesions was helpful for early diagnosis, treatment and prognosis.
32299776 The pattern of COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils. […] No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent. […] In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.
32303590 In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in the absence of clinical signs and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae.
32305506 Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system, whose expression dominates on lung alveolar epithelial cells, is the human cell receptor of SARS-CoV-2, the causative agent of COVID-19.
32310915 Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges.
32311826 A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage.
32318665 Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. […] Viral antigens were detected mainly in alveolar epithelial cells and macrophages.
32323565 GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. […] Expression levels of these genes in the alveolar type II cells of elderly and young patients were comparable and, therefore, do not seem to be responsible for worse outcomes observed in coronavirus disease 2019 (COVID-19) affected elderly.
32329246 The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. […] Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state.
32331217 The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia.
32333544 Also, lung ultrasound has been shown to be more sensitive than a chest radiograph in detecting alveolar-interstitial syndrome.
32335749 Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention.
32338224 SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. […] In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8].
32339391 Similar to the recently established adipocyte-myofibroblast transition (AMT), pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes, demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of PF.
32356025 The main histologic findings observed were pneumocyte damage, alveolar hemorrhages with clustering of macrophages, prominent and diffuse neutrophilic margination within septal vessels, and interstitial inflammatory infiltrates, mainly represented by CD8+ T lymphocytes.
32356926 The SARS-CoV-2 virus enters the airway and binds, by means of the S protein on its surface to the membrane protein ACE2 in type 2 alveolar cells. […] The S protein-ACE2 complex is internalized by endocytosis leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells and in turn increasing the tissue concentration of pro-inflammatory angiotensin II by decreasing its degradation and reducing the concentration of its physiological antagonist angiotensin 1-7.
32360729 His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage and a fibrinous pneumonia. […] The presence of diffuse alveolar damage is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza.
32364264 The primary cause of death was respiratory failure with exudative diffuse alveolar damage with massive capillary congestion often accompanied by microthrombi despite anticoagulation. […] Further findings included pulmonary embolisms (n=4), alveolar haemorrhage (n=3) and vasculitis (n=1).
32365944 In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms.
32374430 The current pandemic and its pleotropic effects can be explained in part by interaction between SARS-CoV-2 spike protein S, the ACE2/L-SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC-SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells.
32374815 Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.
32375200 We hypothesise that the mechanism for this is the aggressive disease pathophysiology with an increased risk of alveolar damage and tracheobronchial injury along with the use of larger bore tracheal tubes and higher ventilation pressures.
32375845 Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation.
32380511 The typical histopathology was interstitial pneumonia with infiltration of significant macrophages and lymphocytes into the alveolar interstitium, and accumulation of macrophages in alveolar cavities. […] Viral antigens were observed in the bronchial epithelial cells, macrophages and alveolar epithelia.
32386571 Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. […] Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV.
32391666 With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination.
32392945 该文总结重症流感病毒H1N1、高致病性禽流感病毒H5N1、SARS-CoV、MERS-CoV及2019-nCoV几种引起重大疫情病毒感染性疾病的病理改变,尸检肺组织均表现为弥漫性肺泡损伤(diffuse alveolar damage,DAD),但不同病毒引起的病理表现存在差异,重症流感病毒2009 H1N1病毒与受体α-2,6-SA及α-2,3-SA结合,除DAD病变外,常伴有上呼吸道、气管、支气管和细支气管的炎性病变,且较易合并细菌感染。
32392948 The re-examination of ultrosound during the hospitalization and at discharge showed improvement in all cases and were consistent with the chest X-ray taken at the same time. Conclusions: The main changes on the pulmonary ultrasonography in neonates with COVID-19 pneumonia are increase and fusion of B-line, abnormal pleural line, and alveolar interstitial syndrome, and may coexist with small range of pulmonary consolidation.
32401577 There was no interstitial pneumonia or diffuse alveolar damage.
32402766 During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. […] Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. […] Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells.
32407552 Some authors have reported the presence of cutaneous lesions related to new COronaVirus Disease 2019 (CoViD-19) caused by SARS-CoV-2, in up to 20.4% of the cases; however, these lesions are not well characterized either clinically or histopathologically.1 Recently, it has been highlighted the finding of congested and edematous blood vessels in the alveolar septum along with hyaline thrombi, and also in the heart, liver and kidney of autopsies of 3 patients deceased due to severe infection by SARS-CoV-2.
32410003 Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19.
32412897 An autopsy of a patient in Japan with coronavirus disease indicated pneumonia lung pathology, manifested as diffuse alveolar damage. […] We detected severe acute respiratory syndrome coronavirus 2 antigen in alveolar epithelial cells and macrophages. […] Coronavirus disease is essentially a lower respiratory tract disease characterized by direct viral injury of alveolar epithelial cells.
32413619 Both Lentinan extracts reduced cytokine-induced NF-κB activation in human alveolar epithelial A549 cells, with the IHL extract proving more effective at lower doses.
32422076 Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.
32422081 Congruent with the ARDS clinical impression, autopsy findings were remarkable for extensive and markedly severe acute lung injury consistent with viral pneumonia, characterized by diffuse alveolar damage, pulmonary infarction, severe pulmonary edema, desquamation of pneumocytes with intraalveolar aggregation, and pneumocyte morphological alterations suspicious for viral cytopathic effect.
32422280 ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution.
32423449 Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC’s impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance.
32430279 Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients.
32431755 While poorly defined, this hyperinflammatory response results in diffuse alveolar damage.
32434133 Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. […] Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. […] One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia.
32434806 Suspected causes include sepsis and acute tubular necrosis resulting from renal hypoperfusion, cytokine release syndrome, direct viral invasion, renal medullary hypoxia secondary to alveolar damage, rhabdomyolysis, and cardiorenal syndrome due to viral myocarditis.
32436460 The phenomenon of a cytokine storm may be the central inducer of apoptosis of alveolar epithelial cells, which leads to rapid progression in severe group patients.
32437316 In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. […] SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues.
32437596 In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. […] Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001).
32437706 Lung biopsy showed areas of diffuse alveolar damage, characterized by extensive acute alveolitis with numerous intra-alveolar neutrophil, lymphocyte, and macrophage infiltrations.
32441805 In fact, ALI seems to be related to the inflammatory burst and release of proinflammatory mediators that induce intra-alveolar fibrin accumulation that reduces the gas exchange.
32443177 All patients presented exudative/proliferative Diffuse Alveolar Damage. […] There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. […] Fibrinous thrombi in alveolar arterioles were present in eight patients and all patients presented a high density of alveolar megakaryocytes.
32445872 Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death.
32447007 From the data available we propose a “double-hit hypothesis”: chronic exposure to PM 2.5 causes alveolar ACE-2 receptor overexpression.
32450165 The main dysfunction upon coronavirus infection is damage to alveolar and acute respiratory failure.
32450344 Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels.
32451533 Postmortem examinations revealed diffuse alveolar damage, while no viral-associated hepatic, cardiac, or renal damage was observed.
32458044 Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs.
32469732 Two radiologists (8 and 15 years of experience) reviewed all the X-ray images and evaluated the following findings: interstitial opacities, alveolar opacities (AO), AO associated with consolidation, consolidation and/or pleural effusion. […] The most common X-ray pattern is multifocal and peripheral, associated with interstitial and alveolar opacities.
32470148 Krebs von den Lungen-6 (KL-6) is mainly produced by damaged or regenerating alveolar type II pneumocytes.
32473124 Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated.
32470851 When oxLDL-trained macrophages encounter SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the lung, it causes unregulated cytokine secretion, leading to the alveolar damage.
32474064 Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are common lung disorders characterized by alveolar-capillary barrier disruption and dyspnea, which can cause substantial morbidity and mortality.
32476380 In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis.
32482538 This process is an inflammatory picture, involving an NLRP3 inflamosome-triggered cytokine storm, the main player in alveolar destruction.
32484232 Initial findings on computed tomography (CT) typically include peripheral multifocal bilateral ground-glass opacities, and correspondingly microscopic alveolar edema. […] In severe disease with acute respiratory distress syndrome, thickened interlobular septa and crazy paving pattern appear on CT, which corresponds to histologic diffuse alveolar damage with, depending on the stage of the disease, features such as edema, hyaline membranes, reactive epithelium, inflammation, and fibrosis.
32485335 A single radiologist with more than 15 years of experience in chest-imaging evaluated the presence and extent of alveolar opacities, reticulations, and/or pleural effusion. […] Lung lesions in patients with SARS-Cov2 pneumonia primarily manifested as alveolar and interstitial opacities and were mainly bilateral (60.8 %).
32486188 However, there is evidence that these receptors are abundant throughout the body, and just as abundant in cholangiocytes as alveolar cells, posing the question of possible direct liver injury.
32486534 Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. […] Type Ⅱ alveolar epithelial cells showed reactive hyperplasia and desquamation. […] Many macrophages accumulated in the alveolar cavity. […] Coronavirus particles were detected in the cytoplasm of type Ⅱ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. […] There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type Ⅱ alveolar epithelial cells.
32493030 The devastating third phase is in the gas exchange units of the lung, where ACE2 expressing alveolar type II cells and perhaps type I cells are infected. […] The loss of type II cells results in respiratory insufficiency due to the loss of pulmonary surfactant, alveolar flooding, and loss of normal repair, since type II cells are the progenitors of type I cells. […] The loss of type I and type II cells will also block normal active resorption of alveolar fluid.
32497778 Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing.
32503663 The primary endpoint of this intervention is measuring oxygenation after 5 days of inhaled (and intravenous) treatment through assessment of a change in pretreatment and post-treatment ratio of PaO2/FiO2 and through measurement of the P(A-a)O2 gradient (PAO2= Partial alveolar pressure of oxygen, PaO2=Partial arterial pressure of oxygen; FiO2= Fraction of inspired oxygen).
32504146 Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. […] Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase “acute respiratory distress syndrome” (ARDS).
32505910 Herein, we present arguments underlying our hypothesis that IL-1β and NETs, mediated via NLRP3 inflammasomes, form a feed-forward loop leading to the excessive alveolar and endothelial damage observed in severe cases of COVID-19.
32510978 Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection.
32511867 A population pharmacokinetic model was implemented to predict lung, intracellular poly/mononuclear cell (PBM/PML), and alveolar macrophage (AM) concentrations using published data and compared against preclinical EC90 for SARS-CoV-2.
32517769 These ‘pure’ cases differ in the time of presentation of symptoms, the phase of lung anatomopathological patterns (acute lung injury versus diffuse alveolar damage) and the mechanism of death.
32519302 By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS.
32519786 Our 2 patients with a confirmed influenza SARS-CoV-2virus infection had respiratory distress with lung crackles on auscultation of one or both lungs and with alveolar pulmonary edema on the chest CT-Scan.
32526058 We appreciate the opportunity to respond to the letter from Dr Thachil[1], who provided an interesting physiological explanation for coagulation-fibrinolysis balance shifts of the Broncho-alveolar haemostasis during COVID-19 infection, and speculated that the extravascular fibrinolysis would be a source of elevated D-dimers.
32526061 The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications.
32526193 All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). […] The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). […] The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.
32526206 COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively.
32526996 In addition, we made a new attempt to calculate the reduced DosePM2.5 (μg) at the bronchiolar (Br.) and alveolar-interstitial (AI) regions of the 10-year-old children after the city lockdown/self-reflection of each city.
32527257 Thus, about the pneumonia of Covid-19, we might speculate that the complicated alveolar-capillary network of lungs could be targeted by T2DM micro-vascular damage.
32530160 Histopathological changes included edema of alveoli and interstitial substance, pneumorrhagia,shedding of alveolar epithelial cells, serous and (or) fibrous exudation in the alveoli, formation of viral inclusions, formation of transparent membranes, infiltration of inflammatory cells that mainly consisted of macrophages and lymphocytes in interstitial substance and alveoli.
32532449 Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a ‘Prolific Activation of a Network-Immune-Inflammatory Crisis’, or ‘PANIC’ Attack, in the alveolar tree.
32534175 Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress.
32534467 Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome-coronavirus-2 infection often results from alveolar injury that impedes airway capacity and multi-organ failure-both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome.
32537610 Acute respiratory failure due to widespread lung inflammation progress to acute respiratory distress syndrome (ARDS) with an altered pulmonary and alveolar function that can lead to disability, prolong hospitalizations, and adverse outcomes.
32539627 Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages.
32540603 Moreover, PTX can restore the balance of the immune response, reduce damage to the endothelium and alveolar epithelial cells, improve circulation, and prevent microvascular thrombosis.
32540737 Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. […] There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury.
32542743 Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID-19)-related deaths, but recent reports also describe additional atypical findings, including vascular changes. […] Although SARS-CoV-2-positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organization, and “acute fibrinous and organizing pneumonia”-like intraalveolar fibrin deposition between the cohorts.
32544615 Mesenchymal stem cells can suppress nonproductive inflammation and improve/repair lung cells including endothelial and alveolar cells, which damaged by COVID-19 virus infection.
32552164 Early autopsy reports emphasize proximal airway and distal airspace involvement, including alveolar epithelial inflammation and capillary thickening.
32552178 Diffuse alveolar damage was the main pathologic finding in the lung tissue samples. […] Multinucleated cells in alveolar spaces and alveolar walls, atypical enlarged cells, accumulation of macrophages in alveolar spaces, and congestion of vascular channels were the other histopathologic alteration of the lung. […] Similar to the previous coronavirus infection in 2003, the main pathologic finding in the lung was diffuse alveolar damage with a pattern of organization in prolonged cases.
32553666 The postulated mechanism of viral entry is through the host ACE2 receptors that are abundantly present in type 2 alveolar cells.
32556400 In more advanced cases of pneumonia, with alveolar fillings, the perfusion was also reduced or absent in accordance with large ventilation defects.
32560746 Activated neutrophils induce inflammation and severe alveolar injury by releasing neutrophil extracellular traps (NETs). […] Dornase alfa is a FDA-approved recombinant human DNAse 1 for the treatment of cystic fibrosis, which cleaves extracellular DNA and may break up cell-free DNA, loosening sticky mucus in the distal airways and reducing NETs-induced toxicity on alveolar pneumocytes.
32561291 SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. […] Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung.
32561849 Chest imaging identified diffuse airspace disease in all patients corresponding to acute and (N = 5) or organizing (N = 2) diffuse alveolar damage (DAD) on histologic examination.
32561873 Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. […] Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process.
32565512 KL-6 was also found to be significantly correlated with oxygenation index and oxygen partial pressure difference of alveolar artery (PA-aDO2) (Both P < 0.01).
32566425 As the viral load increases within the alveolar cell, the alveolar epithelial cell will burst, releasing the newly replicated viral RNA.
32572707 The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung.
32574268 IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes.
32574272 In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells.
32574292 It is possible that protein S binds to angiotensin-converting enzyme 2 receptors and invades alveolar epithelial cells, causing direct toxic effects and an excessive immune response.
32574956 The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. […] The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. […] The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. […] Infection of Alveolar macrophage by SARS-CoV-2 might be drivers of the “cytokine storm”, which might result in damages in pulmonary tissues, heart and lung, and leading to the failure of multiple organs .
32576980 Granulocyte-macrophage colony-stimulating factor (GM-CSF), a myelopoietic growth factor and pro-inflammatory cytokine, plays a critical role in alveolar macrophage homeostasis, lung inflammation and immunological disease.
32577056 We used method of analysis of the published papers with described studies about COVID-19 connected with pharmacological issues and aspects which are included in global fighting against COVID-19 infection, and how using DMF (Nrf2 activator) in clinical trial for nCOVID-19 produce positive effects in patients for reduce lung alveolar cells damage. we are found that Nrf2 activators an important medication that’s have a role in reduce viral pathogenesis via inhibit virus entry through induce SPLI gene expression as well as inhibit TRMPSS2, upregulation of ACE2 that’s make a competition with the virus on binding site, induce gene expression of anti-viral mediators such as RIG-1 and INFs, induce anti-oxidant enzymes, also they have a role in inhibit NF-κB pathway, inhibit both apoptosis proteins and gene expression of TLRs. […] We are concluded that use DMF (Nrf2 activator) in clinical trial for nCOVID-19 positive patients to reduce lung alveolar cells damage.
32580215 Irregular and severe pneumocyte hyperplasia, interstitial thickening, oedema, pronounced protein exudates, diffuse enlargement of the alveolar walls, macrophage infiltration and fibroblastic proliferation, which is an indicator of early organisation, were detected.
32581017 Representative sections of the COVID-19 victim’s lung showed: nuclear expression of p-STAT3 (Tyr 705) in many of the alveolar pneumocytes and in occasional endothelial cells; COX-2 expression in the alveolar pneumocytes; a relative paucity of CD8+ cytotoxic lymphocytes; absence of CD56+ NK lymphoid cells; abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes; PD-L1 expression on occasional macrophages, focally on collections of alveolar pneumocytes, and on cells in the alveolar interstitium; and rare PD-1+ lymphocytes in similar regions as CD8+ lymphocytes.
32582574 We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host.
32584604 These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage.
32585295 Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death.
32590326 In the lung, the ACE2 receptor sits on the top of lung cells known as alveolar epithelial type II (AE2) cells. […] Pulmonary surfactant is believed to regulate the alveolar surface tension in mammalian lungs.
32241056 In this paper, the mechanism of destroying human alveolar epithelial cells and pulmonary tissue by 2019 novel coronavirus (2019-nCoV) was discussed firstly.
32241072 Histologically, diffuse alveolar damage (DAD) was the most characteristic finding in non-survivors with either SARS or COVID-19.
32294809 We hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis.
32597627 SARS-CoV-2 may cause severe respiratory failure due to massive alveolar damage.
32599245 Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and employed a network biology approach to generate human-virus interactome.
32600045 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been established as a cause of severe alveolar damage and pneumonia in patients with advanced Coronavirus disease (COVID-19).
32603707 Cyst formation may be explained by a focal pulmonary trauma due to mechanical ventilation and/or infection-related damage to the alveolar walls leading to pneumatoceles.
32604196 SARS-CoV-2 was detected via a pharyngeal swab and broncho-alveolar lavage.
32604407 Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction.
32605920 Histology of the lungs showed changes of diffuse alveolar damage with fibrin membrane formation, thickened alveolar walls and interstitium with lymphocytic infiltrate, and type 2 pneumocyte hyperplasia with shedding into the alveolar space.
32607684 Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. […] In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed.
32608159 COVID-19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections.
32614086 Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organising phase.
32616594 Calu-3 cells and primary human alveolar epithelial cells (hAEC) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including Calcineurin, NFAT, or MAP kinases.
32620916 Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary.
32622819 Diffuse alveolar hemorrhage (DAH) is a severe and potentially life-threatening disease manifestation.
32629875 Angiotensin converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 and other coronaviruses, is a transmembrane protein expressed by lung alveolar epithelial cells, enterocytes, and vascular endothelial cells, whose physiologic role is to induce the maturation of angiotensin I to generate angiotensin 1-7, a peptide hormone that controls vasoconstriction and blood pressure.
32629995 In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. […] In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells.
32632417 Severe cases of pneumonia requiring supplemental oxygen were more likely to exhibit bilateral alveolar or interstitial infiltrates on chest X-ray (55·6% vs. 
32634734 We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein.
32635302 The lungs are often damaged due to the presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells.
32636114 The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema.
32637738 SARS-CoV-2 was detected via a pharyngeal swab and broncho-alveolar lavage in the COVID-19 suspect.
32639031 PAR1 activation also impacts on the actions of other cell types involved in COVID-19 pathobiology, including endothelial cells, fibroblasts and pulmonary alveolar epithelial cells.
32639866 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting enzyme 2 (ACE2) binding and its functional downregulation.
32640120 The normal development of the pulmonary system is critical to transitioning from placental-dependent fetal life to alveolar-dependent newborn life. […] The organoids can also be invested with mesoderm derivatives, differentiated from the same human pluripotent stem cells, such as alveolar macrophages and vasculature.
32641343 It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane.
32642005 ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally.
32642842 The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies.
32645661 The Corona Virus Disease 2019 (COVID-19) is caused by novel coronavirus 2019-nCoV-2, leading to subsequent pulmonary interstitial fibrosis with chronic inflammatory changes, e.g., inflammatory factors repeatedly continuously stimulating and attacking the alveolar epithelial cells.
32650970 The new coronavirus SARS-CoV-2, first identified in Wuhan, China in December, 2019, can cause Severe Acute Respiratory Syndrome (SARS) with massive alveolar damage and progressive respiratory failure. […] Histological examination revealed typical changes of diffuse alveolar damage (DAD) in both the exudative and proliferative phase of acute lung injury. […] Intra-alveolar multinucleated giant cells, smudge cells and vascular thrombosis were present.
32663073 Acute alveolar damage was a consistent histopathological finding in mink that died with pneumonia.
32664116 Pathological specimens were analyzed with evidence of diffuse alveolar septum disruption, interstitium thickness, and infiltration of inflammatory cells with diffuse endothelial dysfunction and hemorrhagic thrombosis.
32666230 It has been shown that diffuse alveolar damage, signifying acute respiratory distress syndrome, is present together with atypical multinucleated cells in reported cases of the disease by Tian et al. 
32671351 Patients who maintain adequate alveolar ventilation, normocapnia, and adequate oxygenation may avoid the need for tracheal intubation.
32672430 For each patient, as gas exchange index through the alveolocapillary membrane, we determined the alveolar-arterial oxygen gradient (AaDO⁠2) and the alveolar-arterial oxygen gradient augmentation (AaDO⁠2 augmentation).
32673355 HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2’-deoxyguanosine was measured as an oxidative DNA damage marker.
32674001 ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. […] We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia.
32679425 As the main receptor of syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2) is also found to be highly expressed not only in respiratory mucosa and alveolar epithelial cells, but also in renal tubule cells, testicular Leydig cells and seminiferous tubule cells.
32681166 All 4 cases demonstrated diffuse alveolar damage within the lungs.
32682491 The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. […] The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium.
32682653 With much conflicting evidence on best practice to deliver safe treatment comprising of emergency dento-alveolar surgery, this paper describes the protocols which were undertaken to successfully set up a novel Urgent Dental Care Centre (UDCC) service within a short timeframe. […] The majority of treatment delivered in this emergency setting was surgical dento-alveolar procedures (84%). […] Preventing acute hospital admissions relies on the ability to provide safe dento-alveolar surgery.
32686248 The cybernetic model can simulate a dynamic response to the reduced pulmonary alveolar gas exchange rate, thermostat control, and mean pressure difference under a very critical condition based on equilibrium (steady state) values of the inflammatory mediators and system parameters.
32686781 SARS-CoV-2 is manifesting as a multi-dimensional disease and, recently, unique co-existing pathophysiological and clinical aspects are being defined: (i) an increased immune and inflammatory response with the activation of a cytokine storm and consequent coagulopathy, which promote both venous thromboembolic events and in situ thrombosis localized in small arterioles and pulmonary alveolar capillaries; (ii) a high intrapulmonary shunt, which often accounts for the severity of respiratory failure, due to reduced hypoxic pulmonary vasoconstriction with pulmonary neo-angiogenetic phenomena.
32689643 ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain.
32690074 Inclusion criteria - Patient over 18 years of age; - Patient with a suspected SARS-CoV-2 infection, whether or not confirmed by PCR, or close contact with a PCR-confirmed case, typical chest CT scan (unsystematic frosted glass patches with predominantly sub-pleural appearance, and at a later stage, alveolar condensation without excavation or nodules or masses) or positive serology ; - Patient with isolated sudden onset hyposmia persisting 30 days after the onset of symptoms of CoV-2 SARS infection; - Affiliate or beneficiary of a social security scheme; - Written consent to participate in the study.
32692176 Neutrophils may contribute to the diffuse alveolar inflammation seen in acute respiratory distress syndrome (ARDS) which is currently a growing challenge for intensive care units due to the outbreak of the COVID-19 pandemic.
32696264 The primary cause of SARS-CoV-2 mortality is acute respiratory distress syndrome initiated by epithelial infection and alveolar macrophage activation in the lungs.
32696665 Excessive inflammation may cause damage to the body’s tissues, thereby potentially contributing to alveolar damage and the severity of COVID-19.
32698441 In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. […] The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage.
32698853 COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. […] Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy.
32701249 Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage.
32703209 The “pomegranate sign” was characterized as follows: the increased range of GGO, the significant thickening of the interlobular septum, complicated with a small amount of punctate alveolar hemorrhage. […] The “rime sign” was characterized by numerous alveolar edemas.
32704477 One fetus had neutrophils inside alveolar spaces, suggestive of fetal infection.
32711925 Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis.
32712607 While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described.
32714336 However, in some patients, lung infection leads to the activation of alveolar macrophages and lung epithelial cells that will release proinflammatory cytokines.
32717345 ACE2 receptor is majorly expressed in the brush border of gut enterocytes along with the ciliated cells and alveolar epithelial type II cells in the lungs.
32719685 GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs).
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32722979 COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling.
32723327 Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.
32723427 All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration, and alveolar septal thickening.
32723800 Microscopic examination showed different areas with acute and organising diffuse alveolar damage and fibrosis with honeycomb-like remodelling and bronchial metaplasia.
32728817 With regard to pathophysiology, the complex nature of the acute pulmonary disease involving severe injury to the alveolar epithelium and pulmonary vascular endothelium resulting in severe respiratory failure in a proportion of patients is discussed.
32733775 Mortality generally arises from cytokine storms of uncontrolled inflammation, oxidative injury, and damage to the alveolar-capillary barrier, with secondary bacterial infection.
32734876 Microscopy of lung tissue showed diffuse alveolar damage with hyaline membranes, sparse chronic interstitial inflammation and foci of bronchopneumonia.
32736307 Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis.
32739471 In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. […] The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. […] These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space.
32740495 This virus invades alveolar epithelium and cardiomyocytes using ACE2 as a transmembrane receptor.
32750378 SARS-CoV-2 infection can result in diverse, multiorgan pathology, the most significant being in the lungs (diffuse alveolar damage in its different phases, microthrombi, bronchopneumonia, necrotizing bronchiolitis, viral pneumonia), heart (lymphocytic myocarditis), kidney (acute tubular injury), central nervous system (microthrombi, ischemic necrosis, acute hemorrhagic infarction, congestion, and vascular edema), lymph nodes (hemophagocytosis and histiocytosis), bone marrow (hemophagocytosis), and vasculature (deep vein thrombosis).
32752010 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the corona virus disease-19 which is accompanied by severe pneumonia, pulmonary alveolar collapses and which stops oxygen exchange.
32752936 The ARDS mechanism includes a diffuse alveolar damage associated disruption of alveolar capillary membrane, pulmonary edema, damaged endothelium and increased permeability.
32754041 Viremia is observed in severe cases, suggesting that in addition to type II alveolar epithelial cells, many cell types, such as vascular endothelial cells, cardiomyocytes, renal tubular cells, neuronal cells, and lymphocytes, may be damaged.
32758871 Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice.
32759311 ACE2 is expressed in numerous tissues especially the lung alveolar epithelial cells, heart, kidney and gastrointestinal tract.
32759645 Furthermore, although SARS-CoV-2 infection is characterized mainly by diffuse alveolar damage and acute respiratory failure, acute kidney injury (AKI) has developed in a high percentage of cases.
32762081 Postmortem studies have confirmed the high incidence of venous thromboembolism, but also notably revealed diffuse microvascular thrombi with endothelial swelling, consistent with a thrombotic microangiopathy, and inter-alveolar endothelial deposits of complement activation fragments.
32762443 Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release.
32763660 Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology.
32764454 The main impact upon SARS-CoV-2 infection is damage to alveolar and acute respiratory failure.
32766543 All lungs exhibited diffuse alveolar damage (DAD) with a spectrum of exudative and proliferative phases including hyaline membranes, and pneumocyte hyperplasia, with viral inclusions in epithelial cells and macrophages.
32767018 The main abnormality was diffuse alveolar damage, associated with different stages of inflammation and fibrosis.
32780299 In this review, we explored the therapeutic potential of both MSCs and exosomes in mitigating the COVID-19 induced cytokine storm as well as promoting the regeneration of alveolar tissue, attributed to the intrinsic cytokines and growth factor present in the secretome.
32784110 Bilateral diffuse alveolar damage (DAD) was found in all patients.
  1. Results: The results of the present study suggest that COVID-19 infection can cause different forms of acute respiratory distress syndrome (ARDS), due to diffuse alveolar damage and diffuse endothelial damage.
32787909 Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients.
32793615 Despite the majority of the general population displaying symptoms similar to the common cold, COVID-19 has also induced alveolar damage resulting in progressive respiratory failure with fatalities noted in 6.4% of cases.
32794245 The most important autopsy finding was fuzzily segmented diffuse alveolar damage (DAD) that expanded from the subpleural to the medial area.
32798764 Placental extract treatment is proposed as a suitable therapeutic approach consideringthe above properties which could protect against initial viral entry and acute inflammation of alveolar epithelial cells, reconstitute pulmonary microenvironment and regenerate the lung.
32799894 From these reports, we know that the virus can be found in various organs but the most striking tissue damage involves the lungs resulting almost always in diffuse alveolar damage with interstitial edema, capillary congestion, and occasional interstitial lymphocytosis, causing hypoxia, multiorgan failure, and death.
32801207 The pulmonary pathological features during the initial phase of COVID-19 are alveolar oedema, pneumocyte hyperplasia, gravitational consolidations and interstitial thickening.
32811514 Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals.
32811804 Follow-up CT showed that while the initial subpleural GGOs had improved, diffuse GGOs appeared, similar to those observed upon diffuse alveolar damage.
32815036 All lungs showed diffuse alveolar damage, thrombosis, and infarction and less frequently bronchopneumonia irrespective of Ct values.
32815517 We exemplify the capability of this approach by 3D visualization of diffuse alveolar damage (DAD) with its prominent hyaline membrane formation, by mapping the 3D distribution and density of lymphocytes infiltrating the tissue, and by providing histograms of characteristic distances from tissue interior to the closest air compartment.
32815519 Sixty-five chest X-rays were reviewed by two radiologists for alveolar and interstitial opacities and classified by severity on a scale from 0 to 3. […] Fifty-six percent of patients presented with alveolar opacities, 73% had interstitial opacities, and 23% had normal X-rays. […] The presence of alveolar or interstitial opacities was statistically correlated with age (P = 0.008) and comorbidities (P = 0.005). […] The extent of alveolar or interstitial opacities on baseline X-ray was significantly associated with the presence of endotracheal tube (P = 0.0008 and P = 0.049) or central line (P = 0.003 and P = 0.007). […] In comparison to human interpretation, the deep learning model achieved a kappa concordance of 0.51 for alveolar opacities and 0.71 for interstitial opacities.
32821902 Studies of postmortem COVID-19 lungs largely report diffuse alveolar damage (DAD) and capillary fibrin thrombi, but we have also observed other patterns.
32825954 The main pathological findings are bilateral interstitial pneumonia with diffuse alveolar damage (DAD).
32826529 Within the postmortem lung, detected viral protein and RNA were often extracellular, predominantly within hyaline membranes in patients with diffuse alveolar damage.
32831151 Exclusion criteria include pregnant and breastfeeding women, atopy or allergies to Shenfu Injection (SFI), severe underlying disease (malignant tumor with multiple metastases, uncontrolled hemopathy, cachexia, severe malnutrition, HIV), active bleeding, obstructive pneumonia caused by lung tumor, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis, continuous use of immunosuppressive drugs in last 6 months, organ transplantation, expected death within 48 hours, the patients considered unsuitable for this study by researchers.
32831518 This beta coronavirus potentially infects the alveolar cells of the lung leading to pneumonia.
32833367 In the lung, mucociliary clearance (CMC) and alveolar clearance (CA) depend on the transport of sodium through the plasma membrane of epithelial cells.
32835160 Both ACE inhibitors and ARBs induce overexpression of the angiotensin converting enzyme 2 (ACE-2) receptor, which has been identified as the main receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter into the alveolar cells of the lungs.
32835247 The lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). […] The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.
32837901 Although the exact causative mechanisms remain unknown, this observation might imply that extensive alveolar destruction due to COVID-19 may lead to bulla formation resulting in subsequent pneumothorax.
32838231 On a multivariable Cox proportional-hazard regression model at admission, creatinine, d-dimer, lactate, potassium, P/F-ratio, alveolar-arterial gradient, and ischemic heart disease were independently associated with ICU-mortality.
32839288 Lung histopathology shows features of acute and organising diffuse alveolar damage.
32842817 SARS-CoV-2 invades the pulmonary alveolar epithelial cells by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2).
32844161 Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. […] Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion.
32848014 Pulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD).
32848776 Endothelial barrier degradation and capillary leakage contribute to alveolar cell damage. […] These mechanisms are concordant with observed clinical markers in COVID-19, including high expression of inflammatory cytokines on the TNF-α/IL-6 axis, elevated neutrophil-to-lymphocyte ratio (NLR), diffuse alveolar damage via cell apoptosis in respiratory epithelia and vascular endothelia, elevated lactate dehydrogenase (LDH) and CRP, high production of neutrophil extracellular traps (NETs), depressed platelet count, and thrombosis.
32848845 Background: Covid-19 is an infectious disease caused by an invasion of the alveolar epithelial cells by coronavirus 19.
32849976 As in vitro models for such studies, lung-on-a-chip (LOAC) devices can represent key physical and physiological aspects of alveolar tissues. […] These results suggest that computer simulations can potentially inform and accelerate the design and application of LOAC devices for analyzing particulate- and microbe-alveolar interactions.
32850978 Once internalized into host cells, such as lung alveolar cells, GapmeR molecules can bind to the viral RNA.
32850989 The cardiovascular damage may be related to the imbalance of the renin-angiotensin-system (RAS) as this virus binds the Angiotensin-Converting-Enzyme 2 (ACE2), expressed on the lung alveolar epithelial cells, to enter into cells.
32851474 Hyaline membranes and destruction of the alveolar wall as well as microthrombi formation within the small blood vessels were constantly found in almost all our three cases.
32852419 In this Pictorial Essay, we review frequently encountered conditions with imaging features that overlap with those that are typical of COVID-19 (including other viral pneumonias, chronic eosinophilic pneumonia, and organizing pneumonia), and those with features that are indeterminate for COVID-19 (including hypersensitivity pneumonitis, pneumocystis pneumonia, diffuse alveolar hemorrhage, pulmonary edema, and pulmonary alveolar proteinosis).
32857175 The initially identified pulmonary damage patterns, such as diffuse alveolar damage in acute lung failure, are accompanied by new findings that draw a more complex scenario.
32860252 It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability.
32864340 Diagnostic work-up should be initiated as early as possible and should ideally include fungal cultures, galactomannan detection and Aspergillus PCR on tracheal aspirates or broncho-alveolar lavage fluid.
32865490 The main histological finding was sequential alveolar damage, apparently due in large measure to focal capillary microthrombus formation. […] Alveolar damage leads to the death of the patient either directly or by the induction of pulmonary parenchymal fibrosis.
32871592 Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and primarily manifesting as an acute respiratory failure with interstitial and alveolar pneumonia, it can also affect multiple organs.
32876222 In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. […] Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe.
32876299 It has been reported that diffuse alveolar injury caused by SARS-CoV-2 can cause alveolar rupture, produce air leakage and interstitial emphysema.
32876680 Although diffuse alveolar damage, a subtype of acute lung injury (ALI), is the most common microscopic pattern in coronavirus disease 2019 (COVID-19), other pathologic patterns have been described.
32878480 Additionally, SARS-CoV-2 receptor expression was assessed in primary human nasal, tracheal, esophageal, bronchial, and alveolar epithelial cells, as well as primary mouse alveolar type II cells exposed to elevated oxygen concentrations.
32879413 Detailed evaluation of several compartments (airways, alveolar walls, airspaces, and vasculature) was performed to determine the range of histologic features. […] Diffuse alveolar damage (DAD) was seen in 87% of cases.
32880993 And alveolar-arterial oxygen difference (A-aDO2) and oxygenation index were correlated with IgA and IgG. […] In severe COVID-19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS-CoV-2.
32881214 Natural products like ginger, turmeric, garlic, onion, cinnamon, lemon, neem, basil, and black pepper have been scientifically proven to have therapeutic benefits against acute respiratory tract infections including pulmonary fibrosis, diffuse alveolar damage, pneumonia, and acute respiratory distress syndrome, as well as associated septic shock, lung and kidney injury, all of which are symptoms associated with COVID-19 infection.
32890939 The autopsy data are few and the aspects often observed are pulmonary diffuse alveolar damage (DAD), myocarditis, acute myocardial infarction (AMI), and disseminated intravascular coagulation (DIC); these aspects are not only in COVID-19 but also in other viral infections and in sepsis.
32896206 Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs.
32903031 Alveoli are the gas-exchanging units of the lung and alveolar barrier is often a key battleground that encounters pathogens, allergens, and other insults from the environment. […] This is seen in the current COVID-19 pandemic, as alveolar epithelium is one of the major targets of SARS-COV-2, the virus that causes COVID-19. […] Alveolar type II (AT2) cells behave as tissue stem cells that repair alveoli epithelium in steady-state replacement and after injury.
32903321 Although alveolar-type (AT) 2 cells of the lung and intestinal epithelial cells expressed ACE2 as well as PT cells, AT 2 cells significantly expressed TMPRSS2 but not SLC6A19, while all 3 genes were significantly expressed in intestinal epithelial cells.
32913304 With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells.
32913696 In this way, oxygenation may be promoted by decreasing impedance and improving flow via the alveolar-capillary unit.
32915265 Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD).
32918567 The alveolar damage and the pulmonary microvascular thrombosis are the major causes of acute lung injury in COVID-19.
32920756 We can speculate that IA might have the function of restoring a functional vascular plexus consequently to extensive endothelialitis and alveolar capillary micro-thrombosis observed in Covid-19.
32922210 In severe cases the disease progresses into an Acute Respiratory Distress Syndrome (ARDS), which in turn depends on an overproduction of cytokines (IL-6, TNFα, IL-12, IL-8, CCL-2 and IL1) that causes alveolar and vascular lung damage.
32922301 TNF alpha reduces fluid absorption due to impairment of sodium and chloride transport required for building an osmotic gradient across epithelial cells, which in the airways maintains airway surface liquid helping to keep airways open and enabling bacterial clearance and aids water absorption from the alveolar spaces. […] TNF alpha can, through Rho-kinase, disintegrate the endothelial and epithelial cytoskeleton, and thus break up intercellular tight junctional proteins, breaching the intercellular barrier, which prevents flooding of the interstitial and alveolar spaces with fluid. […] Hypotheses: (1) Preservation and restoration of airway and alveolar epithelial sodium and chloride transport and the cytoskeleton dependent integrity of the cell barriers within the lung can prevent and treat COVID 19 lung disease. […] Sodium and chloride transport could be further regulated to prevent accumulation of alveolar fluid by use of Na(+)/K(+)/2Cl(-) cotransporter type 1 inhibitors, which have been associated with improved outcome in adults ventilated for acute respiratory distress syndrome (ARDS) in randomized controlled trials.
32923243 Granulomatosis with polyangiitis is a small vessel vasculitis with a wide spectrum of presentation, ranging from limited disease to life-threatening situation such as alveolar hemorrhage. […] We presented a case of granulomatosis with polyangiitis, presented with alveolar hemorrhage associated with COVID-19 infection. […] Up to our knowledge, this is the first reported case of alveolar hemorrhage secondary to granulomatosis with polyangiitis coexisting with COVID-19 infection.
32924219 Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity.
32924567 This micro-thrombotic pattern seems more specific for COVID-19 and is associated with an intense immuno-inflammatory reaction that results in diffuse occlusive thrombotic micro-angiopathy with alveolar damage and vascular angiogenesis.
32926596 While diffuse alveolar damage (DAD) is recognized to be the primary manifestation COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. […] Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organizing (25%), and/or fibrosing (43%) patterns.
32930394 We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. […] Alveolar damage was associated a prominent involvement of the vascular component in both the interstitial capillaries and in the mid-size vessels, with capillary fibrin micro-thrombi, as well as organized thrombi even in medium sized arteries, in most cases not related to sources of embolism. […] In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD).
32931069 Among the 91 severe and critical patients, 59 cases had scattered B lines, 56 cases had confluent B lines, 58 cases had alveolar-interstitial syndrome (AIS), 48 cases had lung consolidation, six cases had pleural thickening, 39 cases had pleural effusion (average depth of the pleural effusion: 1.0 ± 1.5 cm), and 20 patients developed PTX.
32932346 After 1 hour of ventilation, for each protocol, we recorded arterial blood gas, respiratory mechanics, alveolar recruitment, and hemodynamic variables. […] Alveolar recruitment was 450 ± 111 mL. […] Our data suggest that the “higher” positive end-expiratory pressure approach in patients with severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and high compliance improves oxygenation and lung aeration but may result in alveolar hyperinflation and hemodynamic alterations.
32942274 Twenty-eight patients (88%) had widespread thromboembolic disease, as well as diffuse alveolar damage (30 [94%]), diabetic nephropathy (17 [57%]) and acute tubular injury.
32944185 EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production).
32945158 Alveolar macrophages activated by SARS-CoV-2 through the TLR produce IL-1 which stimulates MCs to produce IL-6.
32945888 We evaluated all imaging for acute/chronic abnormalities including chest radiographs for interstitial or alveolar opacities, distribution/symmetry of disease, zonal predominance, and pleural abnormalities.
32946031 The clinical records of 852 patients admitted for suspect COVID-19 pneumonia, defined as respiratory symptoms or fever or certain history of contact with COVID-19 patients, plus chest CT imaging compatible with alveolar-interstitial pneumonia, were retrospectively analyzed.
32949888 However, we used more techniques and also included Angiotensin converting enzyme 2 (ACE2) (a SARS-CoV receptor, possibly the viral entry point in alveolar lung cells) and the immune system, as cytokine storm is essential in the late phase.
32951046 Coughing might have induced a sudden increase in intra-alveolar pressure, leading to the rupture of the subpleural alveoli and distal bronchus and resulting in spontaneous pneumothorax and subpleural bullae.
32955466 MMC residents with pre-SARS-CoV-2 accumulation of misfolded proteins diagnostic of AD and PD and metal-rich, magnetic nanoparticles damaging key neural organelles are an ideal host for neurotrophic SARS-CoV-2 RNA virus invading the body through the same portals damaged by nanoparticles: nasal olfactory epithelium, the gastrointestinal tract, and the alveolar-capillary portal.
32959998 Histopathological examination revealed diffuse alveolar damage, proliferation of type II pneumocytes, lymphocytes in the lung interstitium, and pulmonary microemboli.
32961040 The data generated from this project indicate that (a) human alveolar type lung cells can be simulated by DeepNEU (v5.0), (b) these simulated cells can then be infected with simulated SARS-CoV-2 virus, (c) the unsupervised learning system performed well in all simulations based on available published wet lab data, and (d) the platform identified potentially effective anti-SARS-CoV2 combinations of known drugs for urgent clinical study.
32963439 Alveolar to arterial (A-a) O2 gradient improved from a median of 170.5 mm Hg interquartile range (IQR) (127.8, 309.7) in supine position to 49.1 mm Hg IQR (45.0, 56.6) after PP.
32964918 A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by SARS-CoV-2 may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange.
32967859 A growing number of international postmortem studies identify acute and organizing diffuse alveolar damage (DAD) as the main pathologic feature of lung injury in patients with COVID-19.
32968645 Then, we speculated that the virus not only attacked alveolar epithelial cells, but also affected pulmonary vascular endothelial cells.
32968798 ACE2 is highly expressed in the bladder, ileum, kidney and liver, comparing with ACE2 expression in the lung-specific pulmonary alveolar type II cells.
32971472 In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry.
32973655 Infection typically begins in the airway epithelia with subsequent alveolar involvement, and the virus then spreads to the CNS via neuronal contacts with the recruitment of axonal transport.
32975865 Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS-CoV-2.
32978255 However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. […] In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. […] This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2.
32979316 A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). […] Here, we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture. […] We find a rapid transcriptomic change in infected cells, characterized by a shift to an inflammatory phenotype with upregulation of NF-κB signaling and loss of the mature alveolar program. […] Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells.
32979740 On histopathologic examination of the lung specimens, diffuse alveolar damage and thrombotic microangiopathy were the most common findings (80 % and 60 %, respectively).
32979742 Pathologically, the lungs show either mild congestion and alveolar exudation or acute respiratory distress syndrome (ARDS) with hyaline membrane or histopathology of acute fibrinous organizing pneumonia (AFOP) that parallels disease severity.
32981508 COVID-19 signs and symptoms indicate a progressive and irreversible failure in the oxygen transport system, secondary to pneumolysis produced by SARS-Cov-2’s alveolar-capillary membrane “attack”.
32984832 Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes.
32987179 Important histopathological findings included diffuse alveolar damage and fibrin thrombi.
32989407 Long-term pneumonia morbidity, steroid therapy, positive pressure ventilation, and extracorporeal membrane oxygenation can cause pneumothorax, leading to capillary and alveolar damage.
32989525 Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. […] Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration-32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing).
32991738 We demonstrated that ACE2 was predominantly overexpressed on the apical surface of bronchial epithelium, while reduced in alveolar epithelium, owing to the dramatically decreased abundance of alveolar type II pneumocytes in CS-exposed mouse lungs. […] Consistent with this, ACE2 was primarily significantly overexpressed in human bronchial and alveolar epithelial cells in smokers regardless of age or gender.
32991819 SARS-CoV-2 was detected in pneumocytes in alveolar septa.
32991860 Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients.
32992435 COVID-19 could present the typical two phases of diffuse alveolar damage: acute and proliferative phase on pathology.
32992843 Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner.
33011717 Although diffuse alveolar damage and respiratory failure are the key features of coronavirus disease 2019 (COVID-19), the involvement of other organs such as the kidney has also been reported.
33014070 Many studies have shown that mesenchymal stem cells (MSCs) and their exosomes (MSCs-Exo), which are isolated from allogenic bone marrow stem cells, significantly lower the risk of alveolar inflammation and other pathological conditions associated with distinct lung injuries.
33014208 This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells.
33014653 The novel coronavirus disease of 2019 (COVID-19) is caused by the binding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to angiotensin-converting enzyme 2 (ACE2) receptors present on various locations such as the pulmonary alveolar epithelium and vascular endothelium.
33015546 Extreme illness may bring about death because of enormous alveolar damage and hemorrhage along with progressive respiratory failure.
33017909 Impairment in alveolar fluid clearance due to altered functional expression of respiratory AQPs highlight their pathophysiological significance in pulmonary edema associated respiratory illness.
33017910 The receptor for corona virus and influenza A is the mucosal cell membrane protein angiotensin converting enzyme 2 (ACE2), which is abundant on the membrane of alveolar cells and enterocytes.
33024003 Protein levels of ACE2 were visualized by immunohistochemistry on paraffin-embedded lung tissue samples and quantified in alveolar and bronchial epithelium. […] In contrast, protein levels of ACE2 were significantly increased in both alveolar tissue and bronchial epithelium of patients with diabetes as compared with control subjects, independent of smoking, COPD, BMI, RAAS-inhibitor use and other potential confounders. […] To conclude, we show increased bronchial and alveolar ACE2 protein expression in patients with diabetes.
33026628 The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels.
33033561 Multipotent MSCs are able to differentiate into different types of cells of mesenchymal origin, including alveolar epithelial cells, lung epithelial cells, and vascular endothelial cells, which are severely damaged in the course of COVID-19 disease.
33033884 Studies have demonstrated that compassionate use of MSCs can reduce symptoms associated with SARS-CoV-2 infection, eliminate fluid buildup, and act as a regenerative technique for alveolar damage; all in a safe and effective way.
33037393 COVID-19 patients’ autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1.
33038391 In COVID-19, acute phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%).
33040727 Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages.
33042157 SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. […] Noteworthy, COVID-19 lung biopsies showed a higher density of CD117+ cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. […] These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. […] Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.
33043037 Mortality in COVID-19 patients predominantly results from an acute respiratory distress syndrome (ARDS), in which lungs alveolar cells undergo programmed cell death. […] A natural rise of body temperature during mild fever can naturally accumulate high cellular levels of HSP70 that can arrest apoptosis and protect alveolar lung cells from inflammatory damages.
33043235 FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages.
33045350 Ambroxol has a proven antiviral effect and a unique stimulatory action on the secretion of surfactant by alveolar type II cells, the main target of SARS-CoV-2.
32538594 Inflammatory cells damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and decreased gas exchange.
33050737 Numbers of experimental studies have previously established that hyperoxia is associated with deleterious outcomes inclusive of perturbations in immunologic responses, abnormal metabolic function, and alterations in hemodynamics and alveolar barrier function.
33052822 Angiotensin-converting enzyme 2 receptors likely serve as a key receptor for cell entry for most coronaviridae as they are present in multiple organ tissues in the body, notably neurons, and in type 2 alveolar cells in the lung.
33053145 The probable cause of SP in COVID-19 was alveolar damage.
33054759 Constantly subject to variety of damages, the alveolar epithelium injuries were recently recognized to play a vital role in the onset and development of idiopathic pulmonary fibrosis.
33059711 In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling.
33059757 MSC’s therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear.
33062077 However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.
33065046 cells in alveolar regeneration and suggest a unified model to guide future studies.
33066765 The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism.
33070537 Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries.
33070539 Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse.
33071777 The interaction unit consisting of macrophages and the alveolar epithelial cells has recently revealed as the therapeutic basis targeting ALI. […] However, little is known about its relevance with ALI, especially its protective role against ALI-induced alveolar tissue damages. […] Furthermore, we established the macrophages-alveolar epithelial cells co-culture model and firstly proved that LHQW inhibited LPS-induced ER stress and TRAIL secretion in macrophages, thereby efficiently protected epithelial cells against TRAIL-induced apoptosis.
33072084 Moreover, recently the “gut-lung axis” in bacterial and viral infections is considerably discussed for bacterial and viral infections, as the intestinal microbiota amplifies the alveolar macrophage activity having a protective role in the host defense against pneumonia.
33072337 We hypothesize the mechanism underlying the pneumomediastinum is the aggressive disease pathophysiology in COVID-19 with an incresead risk of alveolar damage.
33078028 Although SARS-CoV-2 primarily causes respiratory infection by binding to ACE2 receptors present on alveolar epithelial cells, studies have been published linking the disease to the small intestine enterocytes and its microbiome.
33081421 The expression of ACE2 is low in mucosal-associated invariant T (MAIT) cells and cannot be detected in alveolar macrophages.
33081905 Sustained high levels of cytokines cause diffuse damage to pulmonary capillary endothelial cells and alveolar epithelial cells, resulting in acute respiratory distress syndrome (ARDS).
33082395 Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection.
33082849 While follow-up studies on survivors of the severe acute respiratory syndrome (SARS) 2003 outbreak revealed increased susceptibility to infections, tumours and cardiovascular abnormalities, recent studies implicating angiopoietin 2 in induction of inflammatory intussusceptive angiogenesis and diffuse alveolar damage in COVID-19 patients raises the possibility of progression of carcinogenetic processes in patients with known malignancies.
33086222 Both clones showed strong staining in the acute phase of COVID-19 pneumonia, mostly in areas of acute diffuse alveolar damage, but were not completely congruent.
33088671 However, the dysregulation of complement cascade leads to unsolicited cytokine storm, inflammation, deterioration of alveolar lining cells, culminating in acquired respiratory destructive syndrome (ARDS).
33089047 The primary aetiology is believed to be mediated through lung alveolar injury; however, a few published reports have linked SARS-CoV-2 to significant organ dysfunction, venous thrombo-embolism, and coagulopathy.
33091590 The virus first infects the lower airway and bind with angiotensin-converting enzyme 2 (ACE2) of alveolar epithelial cells.
33092563 Computed tomography (CT) angiography of the chest revealed alveolar haemorrhage, more prominent in the left lung. […] Surprisingly, SARS-CoV-2 was eventually detected in bronchoalveolar lavage (BAL) fluid. […] Life-threatening haemoptysis is an unusual presentation of COVID-19, reflecting alveolar bleeding as a rare but possible complication.
33094537 The high mortality of severe 2019 novel coronavirus disease (COVID-19) cases is mainly caused by acute respiratory distress syndrome (ARDS), which is characterized by increased permeability of the alveolar epithelial barriers, pulmonary oedema and consequently inflammatory tissue damage. […] We focused on crucial roles of lung progenitor cells in alveolar cell regeneration and epithelial barrier re-establishment and aimed to uncover a possible mechanism of lung repair after severe SARS-CoV-2 infection. […] Bronchoalveolar lavage fluid (BALF) of COVID-19 patients was analysed by single-cell RNA-sequencing (scRNA-seq). […] The two distinct populations of progenitor cells could play crucial roles in alveolar cell regeneration and epithelial barrier re-establishment, respectively. […] The transplanted KRT5+ progenitors could long-term engraft into host lung and differentiate into HOPX+ OCLN+ alveolar barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration.
33096114 This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS. […] The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. […] The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of neutrophil extracellular traps (NETs) producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID-19 are discussed in detail.
33097094 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.
33098357 MSCs have been suggested to ameliorate the cytokine release syndrome (CRS) and protect alveolar epithelial cells by secreting many kinds of factors, demonstrating safety and possible efficacy in COVID-19 patients with acute respiratory distress syndrome (ARDS).
33101684 The lung ultrasound findings for this patient were the interstitial-alveolar damage showing bilateral, diffuse pleural line abnormalities, subpleural consolidations, white lung areas and thick, irregular vertical artifacts.
33102461 Ambroxol is reported to have anti-inflammatory, -oxidant, -viral, and -bacterial activities and has a direct impact on the production and secretion of the surfactant from the alveolar Type 2 cells.
33106832 The virus infects lung cells by binding angiotensin-converting enzyme 2 (ACE2) of cell surface, which leads to leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung, causing respiratory symptoms.
33112036 Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung.
33114061 The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage.
33122784 A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed.
33124548 Because COVID-19 is primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, the possibility of viral invasions into the other organs cannot be disregarded.
33127750 Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of respiratory failure characterized by pulmonary edema, inflammation, and hypoxemia due to reduced alveolar fluid clearance (AFC). […] Alveolar fluid clearance is required for recovery and effective gas exchange, and higher rates of AFC are associated with reduced mortality. […] Thyroid hormones play multiple roles in lung function, and L-3,5,3’-triiodothyronine (T3) has multiple effects on lung alveolar type II cells.
33128895 Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. […] The absence of ex vivo models of human alveolar epithelium is hindering an understanding of coronavirus disease 2019 (COVID-19) pathogenesis. […] Here, we report a feeder-free, scalable, chemically defined, and modular alveolosphere culture system for the propagation and differentiation of human alveolar type 2 cells/pneumocytes derived from primary lung tissue.
33130005 In this study, we focus on differentially expressed genes (DEGs), detected in SARS-CoV-2 infected cell lines including “the primary human lung epithelial cell line NHBE” and “the transformed lung alveolar cell line A549”.
33133937 Placement of middle ear tubes, primary cleft lip surgery, alveolar bone grafting, and velopharyngeal insufficiency surgery also need prioritization.
33138834 Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn’t be detected in other types of specimen in this study.
33138839 The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). […] Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. […] ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations.
33142113 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells.
33146070 This infection is characterized by a diffused alveolar damage consistent with the Acute Respiratory Disease Syndrome (ARDS).
33147445 To better understand host-virus genetic dependencies and find potential therapeutic targets for COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors required for SARS-CoV-2 viral infection of human alveolar epithelial cells.
33148089 Chest X-ray showed bilateral alveolar infiltrates in 7 (58%) and bilateral pneumonia in 3 (25%).
33148777 A stratified Cox proportional hazard for clustered data (via generalised estimating equations) and model selection algorithms were employed to identify the effect of CPAP on patients’ survival and the effect on gas exchange as measured by alveolar arterial (A-a) gradient and timing of CPAP treatment on CPAP patients’ survival.
33158808 COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%).
33159154 In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. […] We find that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. […] Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity.
33159981 BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2.
33161002 Despite major study limitations, improvement of alveolar-arterial oxygen gradient as well as vascular radiologic score after one week may account for improved pulmonary vascular perfusion and could explain the more rapid recovery of COVID-19 patients receiving tocilizumab compared to controls.
33164753 , a gene expressed in alveolar cells and with known functional association with the SARS-CoV-2 receptor ACE2.
33169014 Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi.
33173719 This human alveolar chip reproduced the key features of alveolar-capillary barrier by co-culture of human alveolar epithelium, microvascular endothelium and circulating immune cells under fluidic flow in normal and disease. […] Notably, viral infection caused the immune cell recruitment, endothelium detachment, and increased inflammatory cytokines release, suggesting the crucial role of immune cells involving in alveolar barrier injury and exacerbated inflammation.
33174599 Multiple cases of normal lung, diffuse alveolar damage, COVID-19, influenza, and bacterial and fungal infections, as well as one case of pulmonary emboli, were included.
33177276 Periodontitis, one of the most prevalent diseases worldwide, leads to alveolar bone destruction and subsequent tooth loss, and develops due to pro-inflammatory cytokine production induced by periodontopathic bacteria.
33177594 Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
33180746 Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans.
33194826 Transcriptomic analysis of human alveolar and bronchial epithelial cells confirmed that the CSF1 gene, a known target of miR-1207-5p, is over-expressed following SARS-CoV-2 infection.
33198751 Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. […] Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). […] The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
33199968 Both SARS strains show identical affinity towards the type-II alveolar pneumocytes angiotensin converting enzyme-2 (ACE-2) receptor binding domains and therefore, similar pathogenicity.
33200067 In conclusion, differences in age and comorbidities and immune response described here may be related to the SARS-CoV-2 delay in the adaptative immune response, evolution stage of diffuse alveolar damage, and progression for systemic inflammatory response syndrome.
33201071 Chest radiography and thoracic computed tomography scans revealed the bilateral patchy alveolar opacities with decreased vascular clarity that looks similar to COVID-19 radiology.
33202948 In this study, we investigated the developmental toxicity of diesel fine PM (dPM2.5) exposure during hPSC-derived alveolar epithelial cell (AEC) differentiation and three-dimensional (3D) multicellular alveolar organoid (AO) development. […] In conclusion, we demonstrated the potential alveolar development toxicity and the increase of SARS-Cov-2 susceptibility of PM2.5. […] Our findings suggest that an hPSC-based 2D and 3D alveolar induction system could be a useful in vitro platform for evaluating the adverse effects of environmental toxins and for virus research.
33216381 SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) receptor to enter the host cell and primarily target type II alveolar cells.
33217169 The prototype model captures two physiologically relevant outcomes following infection: a “healthy” immune response that appropriately defends against the virus, and an uncontrolled alveolar inflammatory response that is characteristic of acute respiratory distress syndrome.
33219111 These findings suggest that regional ventilation and alveolar airspace dimensions are relatively normal around the time of discharge, while gas-blood exchange function is diminished.
33224256 The therapeutic mechanisms of the effects of SZS on COVID-19 potentially involve four effects: suppressing cytokine storms, protecting the pulmonary alveolar-capillary barrier, regulating the immune response, and mediating cell death and survival.
33224575 The thousands of patients who died showed pneumonia and alveolar damage, but actually, according to several authors in addition to the acute respiratory distress syndrome the virus can give rise to multiorgan failure.
33226521 The diseases that COVID-19 pneumonia may mimic can be broadly classified as infectious or non-infectious diseases (pulmonary edema, hemorrhage, neoplasms, organizing pneumonia, pulmonary alveolar proteinosis, sarcoidosis, pulmonary infarction, interstitial lung diseases, and aspiration pneumonia).
33226885 The SARS-CoV-2 peripheral Spike-Fc protein binds specifically to the ACE2 receptors present on bronchial epithelial cells and alveolar pneumocytes to downmodulates its expression which leads to severe acute respiratory failure.
33231148 Alveolar recruitment maneuvers were mentioned in a few recommendations.
33236896 Focus is given to biophysical interactions between particles and the pulmonary surfactant film, the initial alveolar-capillary barrier and first-line host defense system against inhaled particles and pathogens.
33242368 In this review, we have used a bioinformatics approach to elucidate the immune response triggered by SARS-CoV-2 infection in primary human lung epithelial and transformed human lung alveolar.
33245898 The virus uses its spike proteins for entering into the host by interacting with a specific receptor called angiotensin converting enzyme-2 (ACE2) present on the surface of alveolar cells in the lungs.
33246294 ARDS is characterized by an acute and diffuse inflammatory damage into the alveolar-capillary barrier associated with a vascular permeability increase and reduced compliance, compromising gas exchange and causing hypoxemia. […] Histopathologically, this condition is known as diffuse alveolar damage which consists of permanent damage to the alveoli epithelial cells and capillary endothelial cells, with consequent hyaline membrane formation and eventually intracapillary thrombosis.
33248385 There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3.
33248470 However, replication kinetics in Vero E6 cells and primary human alveolar epithelial tissues were not affected.
33254065 Chest CT was considered positive when typical Covid-19 lesions were observed (bilateral and predominantly peripheral and sub-pleural ground glass opacities and/or alveolar consolidations).
33254171 At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD.
33257913 The cohort was characterised by high degree of alveolar consolidation, systemic inflammation and intravascular thrombosis.
33257915 Images were analysed using internationally recognised techniques which included assessment of the pleura, number of B-lines, pathology in the PLAPS (posterolateral alveolar and/or pleural syndrome) point, bedside lung ultrasound in emergency profiles, and the lung ultrasound score.
33259812 The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear.
33271063 Particularly, only this species shows SARS-CoV-2-induced severe acute diffuse alveolar damage and hyaline microthrombi in the lungs, changes described in patients who succumbed to the infection but not reproduced in any experimentally infected animal.
33274176 After inhalation, aerosols containing SARS-CoV-2 penetrate to the depths of the lungs and cause severe pneumonia, alveolar injury, and life-threatening acute respiratory distress syndrome (ARDS).
33274630 The histological characteristics found during postmortem lung tissue examination, which were indicative of diffuse alveolar damage, were proliferation of type II alveolocytes in 65.2% of cases, the appearance of hyaline membranes lining the alveoli in 64.4%, and interstitial edema in 54.2%.
33278747 We have previously hypothesized that pentoxifylline could be beneficial for the treatment of COVID-19 given its potential to restore the immune response equilibrium, reduce the impact of the disease on the endothelium and alveolar epithelial cells, and improve the circulatory function.Serum lactate dehydrogenase (LDH) and lymphocyte count are accessible biomarkers that correlate with the severity of COVID-19, the need for hospitalization, and mortality, reflecting the host immune response’s contribution to the seriousness of SARS-CoV-2 infection.
33279630 The main findings were diffuse alveolar damage and micro-angiopathies. […] Overall, the vessel lesions seemed to be more lethal than the diffuse alveolar damage.
33280254 There was no ACE2 expression on platelets and very low level of ACE2 protein expression on the surface of human primary pulmonary alveolar epithelial cells. […] Immunohistochemistry demonstrated high expressions of ACE2 on human tissue macrophages, such as alveolar macrophages, Kupffer cells within livers, and microglial cells in brain at steady state. […] The data suggest that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.
33282586 In patients with SARS-CoV1-, SARS-CoV2-, and the Middle East respiratory syndrome coronavirus (MERS-CoV)-mediated hypercoagulability, the risk of thrombosis appears to be multifactorial - direct viral cytopathological effects, a pro-inflammatory state, cytokine storm, hypoxia-inducible thrombosis, and endothelial inflammation culminating in the formation of intra-alveolar or systemic fibrin clots.
33283287 The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. […] In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self-renewing fetal lung bud tip organoids. […] These cultures were readily infected by SARS-CoV-2 with mainly surfactant protein C-positive alveolar type II-like cells being targeted.
33284956 Importantly, despite its highly protective role in disease pathogenesis, ACE2 is hijacked by SARS-CoV-2 as a cellular receptor to gain entry to alveolar epithelial cells, causing COVID-19, a severe respiratory disease in humans.
33291198 COVID-19 is typically an acute self-limited disease that can rarely be fatal with a 5.6% case mortality rate (May, 2020), mainly due to substantial damage to pulmonary alveolar structures, and subsequent respiratory failure.
33293527 To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. […] SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. […] While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. […] Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar-capillary injury during SARS-CoV-2 infection.
33297909 Especially, in COVID-19 patients, the overactivation of NF-kΒ, which is caused by the binding of coronavirus spike protein S to alveolar epithelial cells, up-regulates IL-6 and promotes its systematic circulation, causing alveolar damage and extrapulmonary injury.
33300888 Resultados: Los patrones identificados fueron alteraciones de la línea pleural por disrupción/desnivel (100%), engrosamiento pleural (100%), consolidación subpleural (90%) y derrame pleural laminar (80%), patrón B1 (60%), patrón B2 (40%) y consolidación (20%), lo que se correlaciona con los hallazgos de autopsias reportados en la literatura, caracterizados por infiltrado intersticial, colapso alveolar y condensación pulmonar.
33302976 SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure.
33304701 The CALL score and proposed factors of RAS model, namely respiratory rate, oxygen saturation at rest, alveolar arterial gradient and minimal exercise desaturation test, were calculated on the day of admission. […] However, respiratory rate of more than 30 breaths/minute (b/m) (HR: 3.03, 95%CI: 1.77-5.19), resting oxygen saturation of less than 90% (HR: 2.41, 95%CI: 1.15-5.06), and an elevated alveolar-arterial oxygen gradient (HR: 2.14, 95%CI: 1.04-4.39) were considered statistically significant high-risk predictors of disease progression and death, in the formed RAS model.
33308936 Here we propose a theory by which the main targets for SARS-CoV-2 are the Type II Alveolar Epithelial Cells and the clinical manifestations of the syndrome are a direct consequence of their involvement. […] We propose the existence of a vicious cycle by which once alveolar damage starts in AEC II cells, the inflammatory state is supported by macrophage pro-inflammatory polarization (M1), cytokines release and by the activation of the NF-κB pathway. […] If this theory is confirmed, future therapeutic efforts can be directed to target Type 2 alveolar cells and the molecular pathogenic drivers associated with their dysfunction with currently available therapeutic strategies.
33309398 The infection of cells activates proinflammatory substances, causing diffuse alveolar damage, which is the histopathological basis of ARDS. […] Severe cases have pulmonary hypoperfusion that is likely due to abnormal alveolar ventilation and perfusion.
33310781 COVID-19 causes progressive respiratory failure resulting from diffuse alveolar damage and systemic coagulopathy, thrombosis, and capillary inflammation that tie alveolar responses to EC dysfunction. […] This has prompted theories that SARS-CoV-2 directly infects ECs through ACE2 receptors, yet SARS-CoV-2 antigen has not been colocalized with ECs and prior studies indicate that ACE2 colocalizes with alveolar epithelial cells and vascular smooth muscle cells, not ECs.
33310838 The presumed pathophysiological mechanism is diffuse alveolar injury leading to alveolar rupture and air leak.
33312229 Diffuse alveolar damage (DAD) is the histopathological pattern commonly described in all the postmortem series up to date. […] Interestingly, there is an ongoing discussion about the specificity of these changes, as diffuse alveolar damage seen in other viral infections show similar features.
33313438 Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner.
33314005 Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. […] The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively.
33316027 Covid-19 has been identified as the cause of acute respiratory disease with interstitial and alveolar pneumonia, but it can affect several organs, such as kidneys, heart, blood, nervous system and digestive tract. […] The disease-causing agent (Sars-CoV-2) has a binding structure to the angiotensin-converting enzyme 2 (ACE2) receptor, enabling entry into cells that express ACE2, such as the pulmonary alveolar epithelial cells.
33316056 Debridement (day 38) showed extensive lung infarction with diffuse alveolar damage and Candida overgrowth.
33323111 Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets.
33334590 In some patients, however, the onset of the immune response results in acute lung damage with organizing pneumonia and diffuse alveolar damage. […] Other relatively common complications are spontaneous pneumothorax and pneumomediastinum due to the rupture of alveolar walls and barotrauma in mechanically ventilated patients.
33335701 Lung autopsies showed diffuse alveolar damage in two cases.
33340034 Inflammation in bronchoalveolar lavage was increased in old versus young baboons. […] Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response.
33344304 The pulmonary histological examination showed diffuse alveolar damage along with thrombotic microangiopathy affecting alveolar capillaries.
33352323 We demonstrated that systemic thrombolysis successfully improved the hemodynamics of our patient and resulted in a prominent reduction in hypercapnia, alveolar dead space, and ventilatory ratio.
33354821 The main differential diagnoses of severe COVID-19 were as follows: community-acquired pneumonia, dengue, leptospirosis causing intra-alveolar haemorrhage and cardiogenic pulmonary oedema.
33362557 Under certain circumstances, the viral infection leads to excessive and uncontrolled inflammatory response, which is associated with the massive release of inflammatory cytokines in pulmonary alveolar structures.
33372179 Hyperoxia at birth increases the severity of influenza A virus infections in adult mice by reducing the number of alveolar epithelial type 2 (AT2) cells.
33374487 Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis.
33375616 The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data.
33376694 Distinct parenchymal changes, firm thrombi in the peripheral pulmonary vessels along with diffuse alveolar damage, have been the most consistent feature of COVID-19-related lung pathology.
33376717 Diffused alveolar damage with hyaline membranes was found, as well as plurifocal fibrin microthrombi and vascular congestion in all patients’ specimens. […] COVID-19 causes progressive ARDS with onset of severe hypoxemia, underlying a dual mechanism: shunt effect through diffused alveolar damage and dead space effect through thrombotic injuries in microvascular beds.
33377671 Important findings include diffuse alveolar injury, pulmonary thrombosis and microangiopathy, as well as acute kidney injury in all cases, varying in severity.
33378773 The 25 mg BID inhalation dosing was predicted to lead to alveolar HCQ levels of 7 µM (above EC50 of ~1-5 µM), and small plasma levels of 0.18 µM (as compared to plasma levels of 3.22 µM after 200 mg BID oral dosing).
33381848 We generated an integrated host-virus genome-scale metabolic model of human alveolar macrophages and SARS-CoV-2.
33382919 Autopsy studies have confirmed thrombotic disease not only at the macrovascular scale (pulmonary emboli, venous thromboses) but also with microthrombi in alveolar capillaries and severe endothelial injury.
33387629 Monkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in the presence of various concentrations of CPZ.
33388749 Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (p < 0.01).
33389600 DD Stg were determined according to data of Apical Periodontitis Grading Scale, Radiologic Alveolar Bone Loss and Pathophysiological Process of Dental Caries obtained from dental radiological images.
33391929 It is known that COVID-19 causes dysregulated inflammation leading to diffuse alveolar damage and rupture, as well as myocarditis which may be the precipitant to the development of pneumomediastinum and pneumopericardium.
33392642 For each patient, we analysed eight post-mortem LUS parameters and the proportion of three histological patterns (normal lung, exudative diffuse alveolar damage [DAD] and fibroproliferative DAD) in eight different lung regions.
33399353 COVID-19 lung histology is most commonly diffuse alveolar damage as part of acute respiratory distress syndrome.
33403965 One case demonstrated several findings including diffuse alveolar damage, extensive fibrin thrombi in pulmonary arteries with pulmonary infarction, organising pneumonia and bronchopneumonia. […] Other findings included type 2 pneumocyte hyperplasia, intra-alveolar macrophages and squamous metaplasia.
33409846 SARS-CoV-2, by using the well-known angiotensin-converting enzyme 2 by the protein spike, as the host receptor to enter into alveolar, myocardial, and renal epithelial cells, can be disrupted by vitamin D.
33411031 This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. […] An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers.
33414457 Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier.
33416234 Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus 2-positive decedents revealed that some extent of diffuse alveolar damage in every death due to COVID-19 played some role.
33422505 Furthermore, image cytometry analysis revealed increased expression of these proteins, particularly, in the alveolar type 2 cells and macrophages, which are potential targets for SARS-CoV-2.
33429418 We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. […] We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. […] In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. […] Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. […] These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. […] Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.
33431511 Monocyte-derived macrophages recruited to the lungs, rather than tissue-resident alveolar macrophages, were most likely to be responsible for phagocytosis of infected cells and cellular debris early in infection, with their roles switching during clearance of infection.
33432484 Furthermore, they repair the renin-angiotensin-aldosterone system (RAAS) malfunction, increase alveolar fluid clearance, and reduce the chance of hypercoagulation.
33435650 That is because the S spike protein of SARS8 CoV viruses utilizes the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter alveolar epithelial cells.
33437246 The most common pattern observed is alveolar opacities with predominant peripheral distribution either unilateral or more frequently bilateral, starting from the lower and mid zones extending to the upper zones and becoming diffuse with disease progression.
33438550 COVID-19 pneumonia is a specific disease consistent with diffuse alveolar damage resulting in severe hypoxemia.
33443011 Postmortem lung pathology of a patient in Japan with severe acute respiratory syndrome coronavirus 2 infection showed diffuse alveolar damage as well as bronchopneumonia caused by Streptococcus pneumoniae infection.
33443121 ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium.
33444356 Our results confirm clinical observations on the high virus retentions observed in the extrathoracic region and the lesser fraction on the alveolar section (in the order of 5), which may shed light on physiopathology of clinical events as well on the minimal inoculum required to establish infection.
33449332 Our study found that prone position in wards improved alveolar exchange during posture and is well tolerated.
33456035 Based on the clinical observations, alveolar destruction was likely associated with hemoptysis and bulla formation. […] Therefore, we suggest the follow-up of COVID-19 patients whose clinical parameters indicate alveolar damage, even after their symptoms improve.
33459393 The histological examination showed vasculitis, microthrombus in the alveolar capillary, and small obliterated vessels.
33461602 Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract.
33464756 A systemic autopsy examination, including immunohistochemistry and ultrastructural studies, demonstrates that SARS-CoV-2 can infect multiple organs with profound adverse effect on the immune system, and the lung pathology is characterized by diffuse alveolar damage.
33468250 Measurments of lung histopathological changes and neutrophil infiltration, blood oxygen saturation, and bronchoalveolar lavge fluid (BALF) proinflammatory cytokines and coagulation related factors were performed. […] We found that Exo MSC-NTF was superior to Exo MSC in reducing LPS-induced ARDS markers, including physiological lung damage such as alveolar wall thickness, fibrin presence, and neutrophil accumulation, as well as increasing oxygenation levels. […] Furthermore, Exo MSC-NTF reversed the imbalance in the host immune response, seen as decreased IFN-γ, IL-6, TNF-α, and RANTES levels in the bronchoalveolar lavage fluid.
33471172 Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding.
33472576 We summarized the data reported in the past few months and emphasized that the main causes of death of COVID-19 patients are DAD (Diffuse Alveolar Damage) and DIC (Disseminated intravascular coagulation). […] Microvascular thrombosis may lead to microcirculation disorders and multiple organ failure lead to death.The characteristic pathological changes of DAD include alveolar epithelial and vascular endothelial injury, increased alveolar membrane permeability, large numbers of neutrophil infiltration, alveolar hyaline membrane formation, and hypoxemia and respiratory distress as the main clinical manifestations.
33473155 Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted.
33480553 Thoracic radiography and ultrasonography revealed a bronchial pattern with peribronchial cuffing and mild lung consolidation with alveolar-interstitial syndrome, respectively.
33481385 The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1.
33481950 In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. […] Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1β, IL-6, IL-12p70, IL-23, and IL-27 in serum.
33487401 Specific disorders that can cause subpleural sparing patterns include nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), pulmonary alveolar proteinosis (PAP), diffuse alveolar hemorrhage (DAH), vaping-associated lung injury (VALI), cracked lung, pulmonary edema, pneumocystis jirovecii pneumonia (PJP), pulmonary contusion, and more recently, Coronavirus disease 2019 (COVID-19) pneumonia.
33490956 We report simultaneously measured respiratory parameters (static lung compliance, alveolar dead space ventilation, and shunt fraction) in 14 patients with advanced coronavirus disease 2019-related acute respiratory distress syndrome.
33493637 Aside, organophosphates promote cytokine burst and pyroptosis in broncho-alveolar chambers leading to severe respiratory ailments.
33498225 For instance, binding of intact virions to integrins on alveolar cells could enhance viral entry.
33500377 BACKGROUND Invasive mechanical ventilation can cause pulmonary barotrauma due to elevated transpulmonary pressure and alveolar rupture.
33503244 High NET levels were present in LRT samples and persisted during the course of COVID-19, consistent with the detection of NETs in bronchi and alveolar spaces in lung tissue from fatal COVID-19 patients.
33503828 Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs.
33505220 SARS-CoV-2 also destroys the type II alveolar cells that secrete pulmonary surfactants, which normally decrease the air/tissue surface tension and block TLR4 in the lungs thus promoting ARDS and inflammation.
33507884 Here, we showed that overexpression of the NKA β1 subunit upregulates the expression of tight junction proteins, leading to increased alveolar epithelial barrier function by an ion transport-independent mechanism. […] Using a doxycycline-inducible gene expression system, we demonstrated that MRCKα and its downstream activation of myosin light chain is required for the regulation of alveolar barrier function by the NKA β1 subunit.
33508281 SARS-CoV-2 mainly causes alveolar damage ranging from mild to severe clinical respiratory manifestations.
33514373 Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. […] Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no).
33519041 decompose more easily into tiny particles on account of the accelerated collision in a complex airway, which can be deposited in the higher risk alveolar region.
33521655 In this Viewpoint, we highlight how imaging and post-mortem findings from patients with COVID-19 indicate a novel thrombosis in the pulmonary venous territory distal to the alveolar capillary bed, a territory that normally acts as a clot filtration system, which might represent an unappreciated nidus for systemic microembolism.
33526121 BODY: Both ACE inhibitors and ARBs induce overexpression of the angiotensin converting enzyme 2 (ACE-2) receptor, which has been identified as the main receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter into the alveolar cells of the lungs.
33529233 Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys.
33538189 Severe COVID-19 patients may experience cytokine release syndrome (CRS), leading to alveolar damage, pulmonary fibrinolysis, dysregulated coagulation, and pulmonary injury.
33546739 The use of corticosteroids will be recommended in patients who have had symptoms for more than 7 days and who meet all the following criteria: need for oxygen support, non-invasive or invasive mechanical ventilation, acute respiratory failure or rapid deterioration of gas exchange, appearance or worsening of bilateral alveolar-interstitial infiltrates at the radiological level.
33547007 Transbronchial lung cryobiopsy revealed pathological features of organizing pneumonia with alveolar epithelial injury, and prednisolone administration led to alleviation of respiratory symptoms and recovery of respiratory function.
33547593 The characteristic symptom of COVID-19 is respiratory distress with diffused alveolar damage, but emerging evidence suggests COVID-19 might also have neurologic consequences.
33552895 Organizing pneumonia (OP) is a sub-acute process of pulmonary tissue repair secondary to lung injury, defined histopathologically by intra-alveolar buds of granulation tissue within the lumen of distal pulmonary airspaces.
33553219 Autopsy studies demonstrate that diffuse alveolar damage, inflammatory cell infiltration, edema, proteinaceous exudates, and vascular thromboembolism in the lung as well as extrapulmonary injuries in other organs represent key pathological findings.
33557147 Knowledge about the virus is updated daily, and its RNA was isolated from several human secretions, e.g., throat, saliva, pulmonary alveolar washing, and feces.
33560382 Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages.
33560456 Progressive respiratory failure with pronounced diffuse alveolar damage has been identified as the primary cause of death in COVID-19. […] COVID-19 pneumonia shares common histopathological hallmarks with influenza (H1N1)-related ARDS, like diffuse alveolar damage (DAD) with edema, hemorrhage, and intra-alveolar fibrin deposition.
33567255 We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells.
33572417 We hypothesize that the lacking erythrocyte fragmentation and only mild platelet consumption in severe COVID-19 are due to a microangiopathy predominantly localized to the alveolar microcirculation with a low blood pressure gradient.
33572938 (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. […] In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells.
33573681 The primary outcome is the evolution of alveolar-capillary gas exchange measured by the PaO2/FiO2 ratio after two days of treatment.
33575160 The pulmonary origin of pneumoperitoneum is unusual and is associated with mechanical ventilation and alveolar leak; the air leak with subsequent dissection into other anatomical spaces is called the Macklin effect.
33575886 The most severe alterations are found in the lungs by diffuse alveolar damage as a symptom of an acute respiratory distress syndrome (ARDS), in part with fibrosis.
33575962 Considering the modulation of neutrophil recruitment of extreme relevance for respiratory distress and lung failure prevention, we propose that P2Y14 receptor inhibition by its selective antagonist PPTN could limit neutrophil recruitment and NETosis, hence limiting excessive formation of oxygen reactive species and proteolytic activation of the kallikrein-kinin system and subsequent bradykinin storm in the alveolar septa of COVID-19 patients.
33576058 Recent work establishing a human lung organoid-derived air-liquid interface model permissive to SARS-CoV-2 infection identifies alveolar type II cells as the primary cell type infected, reports an infection-induced interferon response and demonstrates the effectiveness of interferon lambda 1 treatment in dampening lung infection.
33576464 Through this mechanism, the virus infects the alveolar, esophageal epithelial, ileum, colon and other cells on which ACE2 is highly expressed, causing damage to target organs.
33585674 Oxygenation was started using an adapted snorkel mask with a PEEP valve with an alveolar recruitment function and double oxygen flow.
33586320 Given that intravenous infusion of MSCs results in a significant trapping in the lung, MSC therapy could directly mitigate inflammation, protect alveolar epithelial cells, and reverse lung dysfunction by normalizing the pulmonary microenvironment and preventing pulmonary fibrosis.
33588935 Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions.
33592054 Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. […] All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. […] In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly.