Abstract：
BACKGROUND:To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS:A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS:The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1β and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS:Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.
journal_name
Eur J Clin Investjournal_title
European journal of clinical investigationauthors
Chen XJ,Li K,Xu L,Yu YJ,Wu B,He YL,Zhao WE,Li D,Luan CX,Hu L,Wang J,Ding JJ,Yu YF,Li JX,Tan ZM,Liu XF,Wei D,Zhang ZH,Guo XJ,Su C,Hu ZB,Guo YS,Chen JY,Chen Fdoi
10.1111/eci.13443subject
Has Abstractpub_date
2021-01-01 00:00:00pages
e13443issue
1eissn
0014-2972issn
1365-2362journal_volume
51pub_type
杂志文章abstract：BACKGROUND:Chronic lung diseases contribute significantly to the morbidity and mortality of the population. There are few effective treatments for many chronic lung diseases, and even fewer therapies that can arrest or reverse the progress of the disease. DESIGN:In this review, we present the current state of regenera...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2362.2012.02667.x
更新日期：2012-08-01 00:00:00
abstract：BACKGROUND:Weight loss induced by bariatric surgery is an effective method to reverse obesity and comorbidities. The aim of this prospective weight loss study was to investigate changes of body fat distribution in relation to adiponectin and its isoforms and further to investigate the influence of both body fat distrib...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.2008.01929.x
更新日期：2008-04-01 00:00:00
abstract：BACKGROUND:There is ongoing controversy whether angiotensin-converting enzyme inhibitors (ACE-I) contribute to anaemia by causing hyporesponsiveness to erythropoiesis-stimulating agents (ESA). However, it is unknown whether or not plasma levels or area under the curve (AUC) of ACE-I are associated with responsiveness t...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.2012.02699.x
更新日期：2012-10-01 00:00:00
abstract：BACKGROUND:Inactivation of the tumour suppressor gene, p53, is the commonest genetic abnormality in human cancer. The study of the type of p53 mutation in a given tumour may provide prognostic information, clues to aetiology and become useful for therapeutics. MATERIALS AND METHODS:The molecular characterisation of p5...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1046/j.1365-2362.2000.00717.x
更新日期：2000-09-01 00:00:00
abstract：:We have applied flow cytometry to the detection of activated platelets in patients with coronary heart disease. Paraformaldehyde-fixed platelets were incubated with one of the following monoclonal antibodies (MAbs): Bx-1 (anti-GP Ib), AP-2 (anti-GP IIb-IIIa complex), VH10 (anti-GMP-140, a glycoprotein of the alpha-gra...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1994.tb02426.x
更新日期：1994-02-01 00:00:00
abstract：:Polyploidization is a distinctive feature of megakaryocyte differentiation. The physiological meaning and the regulation of this process are obscure. Megakaryocyte ploidy varies in normal biology and in disease. Here we review the evidence suggesting that ploidy changes may have a role in the determination of platelet...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2362.1993.tb00711.x
更新日期：1993-01-01 00:00:00
abstract：:We recently reported that chloride-depletion metabolic alkalosis (CDMA) results in renal losses of Na, K, and water. In these studies we investigated whether CDMA (induced using a new model that avoids external changes in Na and water balance) was also associated with internal Na and water shifts out of the ECF. CDMA ...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1991.tb01370.x
更新日期：1991-06-01 00:00:00
abstract：:Activities of urea cycle enzymes were measured in the liver of starved rats 12 and 48 h after bilateral nephrectomy. Control experiments (sham-operated, starved rats) revealed that the activities of only two enzymes of the cycle are altered in the uraemic state: argininosuccinic acid synthetase (EC 6.3.4.5.), which is...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1975.tb00423.x
更新日期：1975-02-01 00:00:00
abstract：:The contribution of the kinetics of exogeneous and endogenous lipoproteins in determining the level of triglyceride in fasting plasma was assessed in a group of 19 normolipidaemic and hypertriglyceridaemic subjects. From data derived during a 9-h infusion of [15N]-glycine, we have assessed very low density lipoprotein...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1992.tb01821.x
更新日期：1992-03-01 00:00:00
abstract：:The pathogenesis of alcoholic fatty liver is unknown, but several causes have been proposed based on biochemical findings. These include the metabolism of alcohol leading to a shift in the cytosolic [NAD+]/ [NADH] ratio to reduction, which in turn causes a direct inhibition of beta-oxidation and enhanced triacylglycer...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2362.1997.1780727.x
更新日期：1997-09-01 00:00:00
abstract：BACKGROUND:Insulin has several biological functions besides glycaemic control. We investigated and compared the effects of six different commercial insulins on adipocyte cell differentiation, the lipolytic activity of differentiated cells, and the expression levels of genes involved in adipogenesis and associated with ...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.2011.02492.x
更新日期：2011-09-01 00:00:00
abstract：AIM:Observationally, low serum testosterone among men is associated with cardiovascular diseases and its risk factors, but it is unclear whether raising endogenous androgens would be protective. To clarify the role of androgens, the association of two different androgen biomarkers (serum testosterone and androstanediol...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/eci.12174
更新日期：2013-12-01 00:00:00
abstract：:Pepsinogen A (PGA) and pepsinogen C (PGC) are negatively charged, low molecular weight (LMW) proteins with a striking difference in renal handling: PGA (molecular weight 43,500 daltons) shows a high fractional excretion while the fractional excretion of PGC (molecular weight 40,500 daltons) is low, presumably due to t...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1989.tb00234.x
更新日期：1989-06-01 00:00:00
abstract：BACKGROUND:Following cisplatin-based chemotherapy, survivors of testicular cancer have a high prevalence of cardiovascular risk factors and an increased risk of cardiovascular disease. Cardiac function has not been extensively studied and no comparisons have been made with men from the general population. DESIGN:Left ...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.2005.01460.x
更新日期：2005-02-01 00:00:00
abstract：:The urinary excretion of free light immunoglobulin chains IgG, IgA, and Fcγ fragment material has been estimated in 12 healthy individuals and 7 subjects with tubular or glomerular proteinuria. Measurements were carried out by immunochemical methods after separation of concentrated urinary immunoglobulin components by...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/eci.1971.1.4.255
更新日期：1971-08-01 00:00:00
abstract：:The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min-1 kg-1), insulin (3.4, 10.3 or 68.8 pmol min-1 kg-1) or combined infusions (34 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin or 103 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin) on protein metabolism, using an infusion of [1-14...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1994.tb01094.x
更新日期：1994-05-01 00:00:00
abstract：:Many diseases with a major public health impact are the result of complex interactions between environmental factors and multiple genes. In the past decade, methods for genome analysis, in particular quantitative trait locus (QTL) analysis in animal models, were developed to identify and localize the genes responsible...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2362.2003.01089.x
更新日期：2003-02-01 00:00:00
abstract：:The esterolytic activity of mixed and parotid saliva in cystic fibrosis (CF) patients and normal subjects was determined using BAEE (alpha-Benzoyl-1-arginine-ethylester) as the substrate. Using soybean-trypsin-inhibitor the trypsin-like activity (TLA) was measured and plotted as a function of parotid flow rate. In add...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1975.tb00441.x
更新日期：1975-04-01 00:00:00
abstract：BACKGROUND:Bezafibrate reportedly lowers serum lipids and plasma fibrinogen in humans and rats, but the mechanism of this process has still to be clarified. We have addressed this problem by investigating the effects of bezafibrate on fibrinogen in the human hepatoma HepG2 cell line. METHODS:In cells cultured with and...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1046/j.1365-2362.1998.00251.x
更新日期：1998-02-01 00:00:00
abstract：:Proliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology by being involved in the development of coronary atherosclerosis and restenosis. Competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase have shown antiproliferative properties on different cell typ...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1046/j.1365-2362.1996.2550586.x
更新日期：1996-11-01 00:00:00
abstract：BACKGROUND:Stiff Person Syndrome (SPS) is a relatively rare but often overlooked autoimmune neurological disorder that targets antigens within the brain's inhibitory pathways resulting in incapacitating stiffness and spasms that impact on the patients' quality of life. Although a number of immunomodulating therapies si...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2362.2010.02340.x
更新日期：2010-11-01 00:00:00
abstract：:Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive, irreversible loss of cardiac and skeletal muscular function. Muscular enlargement in DMD is attributed to oedema, due to the increased cytoplasmic Na+ concentration. The aim of this review was to present the current experien...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,评审
doi：10.1111/eci.12843
更新日期：2017-12-01 00:00:00
abstract：:Lymphocytes were used as a cellular model for the in vitro measurements of maximal ouabain binding sites in order to assess any changes in young men at increased risk of developing essential hypertension, and to analyse whether any such changes were associated to borderline hypertension and/or heredity. Four groups we...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1989.tb00198.x
更新日期：1989-02-01 00:00:00
abstract：BACKGROUND:To investigate the clinical features of thyroid cancer in aging patients and to present the results of treatment. From this we can provide bases for earlier diagnoses and better treatment of thyroid malignancies in older patients. MATERIALS AND METHODS:In this study a retrospective analysis was performed wi...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1046/j.1365-2362.2000.00598.x
更新日期：2000-02-01 00:00:00
abstract：BACKGROUND:There is growing evidence that the predictive value of HDL cholesterol levels for cardiovascular risk stratification is limited in patients with coronary artery disease (CAD). HDL function seems to be a more sensitive surrogate of cardiovascular risk estimation than simple serum levels. Therefore, we aimed t...
journal_title：European journal of clinical investigation
pub_type： 杂志文章,多中心研究
doi：10.1111/eci.12466
更新日期：2015-07-01 00:00:00
abstract：:The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se. The authors compared non-diabetic rats (n = 9) and rats with streptozotocin-induced diabetes t...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1995.tb01976.x
更新日期：1995-12-01 00:00:00
abstract：:To assess the renal tubular damage in liver cirrhosis the fractional clearances of beta-2-microglobulin (B2m-fr.cl) and malate-dehydrogenase (MDH-fr.cl) were measured respectively in sixty-four and in forty-six out of seventy-nine patients with liver cirrhosis of different aetiology; furthermore the fractional excreti...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1981.tb01847.x
更新日期：1981-06-01 00:00:00
abstract：BACKGROUND:Parental history of type 2 diabetes (T2D) is associated with cardiometabolic risk. We aimed to investigate the associations of parental history of T2D with cardiometabolic biomarkers and to subsequently investigate to what extent these putative associations were explained by modifiable factors. MATERIALS AN...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.2012.02685.x
更新日期：2012-09-01 00:00:00
abstract：:Acute hypoglycaemia enhances intestinal sugar uptake but the mechanisms involved are unknown. Results from the present study show increased galactose movement across the brush border and basolateral membranes of isolated upper, but not mid-villus, jejunal enterocytes 45 min after intravenous administration of insulin ...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1993.tb00794.x
更新日期：1993-08-01 00:00:00
abstract：:We investigated the influence of sodium fluoride on polymorphonuclear leukocyte (PMN) adhesiveness in a healthy subject with low serum levels of fluoride. The PMN were separated from venous blood, and the percentages of adhered and unadhered cells were determined in vitro in plastic culture plates. The cells were cult...
journal_title：European journal of clinical investigation
pub_type： 杂志文章
doi：10.1111/j.1365-2362.1992.tb01426.x
更新日期：1992-10-01 00:00:00
