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1.
Eur J Gastroenterol Hepatol ; 33(1S Suppl 1): e368-e374, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1764695

ABSTRACT

BACKGROUND/AIMS: In this meta-analysis, we aimed to evaluate the prognostic value of fibrosis-4 index (FIB-4) in COVID-19. METHODS: We performed a comprehensive literature search of PubMed, Embase, and Scopus databases on 26 November 2020. FIB-4 was calculated by [age (years) × AST (IU/L)]/[platelet count (109/L) × âˆšALT (U/L)]. A value above cutoff point was considered high and a value below cutoff point was considered low. The main outcome was mortality, the association between high FIB-4 and mortality was reported in odds ratio (OR). Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic OR (DOR), area under the curve (AUC) were generated. RESULTS: There were 963 patients from five studies included in this systematic review and meta-analysis. Meta-analysis showed that high FIB-4 was associated with increased mortality [OR 3.96 (2.16-7.27), P < 0.001; I2: 41.3%]. High FIB-4 was associated mortality with a sensitivity of 0.56 (0.40-0.70), specificity of 0.80 (0.72-0.86), PLR 2.8 (1.8-4.2), NLR 0.55 (0.39-0.78), DOR 5 (2-10), and AUC of 0.77 (0.73-0.81). Fagan's nomogram indicated that for a pre-test probability (mortality) of 30%, a high FIB-4 was associated with 54% post-test probability and a low FIB-4 was associated with 19%, respectively. The funnel-plot analysis was asymmetrical, trim-and-fill analysis by imputation of a study on the left side using linear estimator resulted in an OR of 3.48 (1.97-6.14). Egger's test showed no indication of small-study effects (P = 0.881). CONCLUSION: High FIB-4 was associated with mortality in patients with COVID-19.


Subject(s)
COVID-19 , Area Under Curve , Fibrosis , Humans , Platelet Count , SARS-CoV-2
2.
Turk J Med Sci ; 51(SI-1): 3359-3371, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1726151

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a disease named as COVID-19, which is composed of multi systemic manifestations with a pulmonary system predominance. As the time passes, we are dealing more and more with a wide variety of effects and complications of the disease in survivors as far as with concerns about the clinical outcome and the timeline of symptoms in different patients. Since the lungs are the most involved organs and the post-COVID prolonged and persistent effects are mainly related to the pulmonary system, it is crucial to define and predict the outcome and to determine the individuals that can progress to fibrosis and loss of function of lungs. This review summarizes the current literature regarding the pulmonary complications in post-COVID syndrome and the management of these conditions.


Subject(s)
COVID-19/complications , Fibrosis , Lung/physiopathology , Severe Acute Respiratory Syndrome/complications , COVID-19/epidemiology , COVID-19/therapy , Humans , Pandemics , SARS-CoV-2 , Syndrome
3.
Int J Chron Obstruct Pulmon Dis ; 17: 101-115, 2022.
Article in English | MEDLINE | ID: covidwho-1630608

ABSTRACT

Background: Smokers and patients with COPD are highly susceptible to SARS-CoV-2 infection, leading to severe COVID-19. Methods: This cross-sectional study involved resected lung tissues from 16 patients with GOLD stage I or II COPD; of which 8 were current smokers COPD (COPD-CS), and 8 ex-smokers COPD (COPD-ES), 7 normal lung function smokers (NLFS), 9 patients with small airways disease (SAD), and 10 were never-smoking normal controls (NC). Immunostaining for ACE2, Furin, and TMPRSS2 was performed and analysed for percent expression in small airway epithelium (SAE) and counts for positively and negatively stained type 2 pneumocytes and alveolar macrophages (AMs) were done using Image ProPlus V7.0. Furthermore, primary small airway epithelial cells (pSAEC) were analysed by immunofluorescence after exposure to cigarette smoke extract (CSE). Results: ACE2, Furin, and TMPRSS2 expression significantly increased in SAE and type 2 pneumocytes in all the subjects (except Furin for NLFS) compared to NC (p < 0.001). Similar significance was observed for ACE2 positive AM (p < 0.002), except COPD-ES, which decreased in ACE2 positive AMs (p < 0.003). Total type 2 pneumocytes and AMs significantly increased in the pathological groups compared to NC (p < 0.01), except SAD (p = 0.08). However, AMs are significantly reduced in COPD-ES (p < 0.003). Significant changes were observed for tissue co-expression of Furin and TMPRSS2 with ACE2 in SAE, type 2 pneumocytes and AMs. These markers also negatively correlated with lung function parameters, such as FEV1/FVC % predicted, FEF25-75%, DLCO% predicted. A strong co-localisation and expression for ACE2 (p < 0.0001), Furin (p < 0.01), and TMPRSS2 (p < 0.0001) was observed in pSAEC treated with 1% CSE than controls. Discussion: The increased expression of ACE2, TMPRSS2 and Furin, in the SAE, type 2 pneumocytes and AMs of smokers and COPD are detrimental to lung function and proves that these patient groups could be more susceptible to severe COVID-19 infection. Increased type 2 pneumocytes suggest that these patients are vulnerable to developing post-COVID-19 interstitial pulmonary fibrosis or fibrosis in general. There could be a silently developing interstitial pathology in smokers and patients with COPD. This is the first comprehensive study to report such changes.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Alveolar Epithelial Cells , Cross-Sectional Studies , Fibrosis , Humans , Macrophages, Alveolar , Pulmonary Disease, Chronic Obstructive/diagnosis , SARS-CoV-2 , Smokers , Up-Regulation
4.
Curr Opin Nephrol Hypertens ; 31(1): 36-46, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1612725

ABSTRACT

PURPOSE OF REVIEW: Severe COVID-19 disease is often complicated by acute kidney injury (AKI), which may transition to chronic kidney disease (CKD). Better understanding of underlying mechanisms is important in advancing therapeutic approaches. RECENT FINDINGS: SARS-CoV-2-induced endothelial injury initiates platelet activation, platelet-neutrophil partnership and release of neutrophil extracellular traps. The resulting thromboinflammation causes ischemia-reperfusion (I/R) injury to end organs. Severe COVID-19 induces a lipid-mediator storm with massive increases in thromboxane A2 (TxA2) and PGD2, which promote thromboinflammation and apoptosis of renal tubular cells, respectively, and thereby enhance renal fibrosis. COVID-19-associated AKI improves rapidly in the majority. However, 15-30% have protracted renal injury, raising the specter of transition from AKI to CKD. SUMMARY: In COVID-19, the lipid-mediator storm promotes thromboinflammation, ischemia-reperfusion injury and cytotoxicity. The thromboxane A2 and PGD2 signaling presents a therapeutic target with potential to mitigate AKI and transition to CKD. Ramatroban, the only dual antagonist of the thromboxane A2/TPr and PGD2/DPr2 signaling could potentially mitigate renal injury in acute and long-haul COVID. Urgent studies targeting the lipid-mediator storm are needed to potentially reduce the heavy burden of kidney disease emerging in the wake of the current pandemic.


Subject(s)
Acute Kidney Injury , COVID-19 , Renal Insufficiency, Chronic , Thrombosis , Acute Kidney Injury/etiology , COVID-19/complications , Fibrosis , Humans , Inflammation , Kidney/pathology , Lipids , Renal Insufficiency, Chronic/pathology , SARS-CoV-2 , Thrombosis/pathology
5.
Cell Stem Cell ; 29(2): 217-231.e8, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1586459

ABSTRACT

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/complications , Fibrosis , Humans , Kidney , Organoids/pathology
7.
Nat Cell Biol ; 23(12): 1314-1328, 2021 12.
Article in English | MEDLINE | ID: covidwho-1559292

ABSTRACT

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.


Subject(s)
COVID-19/genetics , Lung/metabolism , Transcriptome/genetics , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , COVID-19/metabolism , Fibrosis/metabolism , Fibrosis/pathology , Fibrosis/virology , Humans , Lung/pathology , Lung/virology , Proteomics/methods , SARS-CoV-2/pathogenicity
8.
Viruses ; 13(12)2021 12 02.
Article in English | MEDLINE | ID: covidwho-1554803

ABSTRACT

The SARS-CoV-2 virus's ability to induce hypercytokinemia and cause multiple organ failure makes it imperative to find effective treatments. To understand the mechanism of viral infection and its effects on organ tissues, we analyzed multiple single-cell and bulk RNAseq data from COVID-19 patients' organ samples. Various levels of severity of infection were accounted for, with comparative analyses between mild, moderate, and severely infected patients. Our analysis uncovered an upregulation of the innate immune response via several inflammatory genes, IL-2, IL-6, IL-8, IL-17A, and NF-κB. Consequently, we found that the upregulation of these downstream effects can lead to organ injury. The downregulated pathways such as eukaryotic initiation factor 2 (eIF2) and eIF4-mediated host translation, were found to lead to an increased viral translation. We also found that the loss of inhibitory peptides can suppress an overactive innate immune response via NF-κB and interleukin-mediated pathways. Investigation of viral-host protein mapping showed that the interaction of viral proteins with host proteins correlated with the down- and upregulation of host pathways such as decreased eIF2-mediated host translation and increased hypertrophy and fibrosis. Inflammation was increased via the stimulation of pro-inflammatory cytokines and suppression of host translation pathways that led to reduced inflammatory inhibitors. Cardiac hypertrophy and organ fibrosis were the results of increased inflammation in organs of severe and critical patients. Finally, we identified potential therapeutic targets for the treatment of COVID-19 and its deleterious effects on organs. Further experimental investigation would conclusively determine the effects of COVID-19 infection on organs other than the lungs and the effectiveness of the proposed therapeutic targets.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Immunity, Innate , Inflammation/immunology , Sequence Analysis, RNA , Single-Cell Analysis , COVID-19/genetics , Cytokine Release Syndrome , Cytokines/genetics , Fibrosis/immunology , Gene Expression , Humans , Lung/immunology , SARS-CoV-2 , Severity of Illness Index
9.
Int J Mol Sci ; 22(23)2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1542585

ABSTRACT

Pulmonary fibrosis is a chronic, fibrotic lung disease affecting 3 million people worldwide. The ACE2/Ang-(1-7)/MasR axis is of interest in pulmonary fibrosis due to evidence of its anti-fibrotic action. Current scientific evidence supports that inhibition of ACE2 causes enhanced fibrosis. ACE2 is also the primary receptor that facilitates the entry of SARS-CoV-2, the virus responsible for the current COVID-19 pandemic. COVID-19 is associated with a myriad of symptoms ranging from asymptomatic to severe pneumonia and acute respiratory distress syndrome (ARDS) leading to respiratory failure, mechanical ventilation, and often death. One of the potential complications in people who recover from COVID-19 is pulmonary fibrosis. Cigarette smoking is a risk factor for fibrotic lung diseases, including the idiopathic form of this disease (idiopathic pulmonary fibrosis), which has a prevalence of 41% to 83%. Cigarette smoke increases the expression of pulmonary ACE2 and is thought to alter susceptibility to COVID-19. Cannabis is another popular combustible product that shares some similarities with cigarette smoke, however, cannabis contains cannabinoids that may reduce inflammation and/or ACE2 levels. The role of cannabis smoke in the pathogenesis of pulmonary fibrosis remains unknown. This review aimed to characterize the ACE2-Ang-(1-7)-MasR Axis in the context of pulmonary fibrosis with an emphasis on risk factors, including the SARS-CoV-2 virus and exposure to environmental toxicants. In the context of the pandemic, there is a dire need for an understanding of pulmonary fibrotic events. More research is needed to understand the interplay between ACE2, pulmonary fibrosis, and susceptibility to coronavirus infection.


Subject(s)
Angiotensin I/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Fibrosis/metabolism , Peptide Fragments/metabolism , /metabolism , Cannabis , Cigarette Smoking , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Inflammation , Lung/pathology , Pandemics , Respiration, Artificial , Respiratory Distress Syndrome , Respiratory Insufficiency/metabolism , Risk Factors , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
10.
Respir Physiol Neurobiol ; 297: 103813, 2022 03.
Article in English | MEDLINE | ID: covidwho-1521498

ABSTRACT

This study was aimed to explore the precise dose of corticosteroid therapy in critical COVID-19. A total of forty-five critical COVID-19 patients were enrolled. The process of critical COVID-19 was divided into alveolitis and fibrosis stages. Most nonsurvivors died in fibrosis phase. Nonsurvivors had more dyspnea symptoms, fewer days of hospitalization, shorter duration of alveolitis and fibrosis. High-dose daily corticosteroid therapy (≥150 mg/d) was associated with shorter survival time and lower lymphocyte count in fibrosis phase. Moreover, a high cumulative dose (≥604 mg) was tied to longer duration of virus shedding, lower oxygenation index (OI), higher incidence of tracheal intubation, fewer lymphocytes and higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH). In alveolitis phase, the low-to-moderate-dose daily corticosteroid therapy and a small cumulative dose reduced lymphocytes. In conclusion, low-to-moderate dose corticosteroids may be beneficial in the fibrosis phase. High-dose corticosteroid therapy in the fibrosis phase aggravates the severity of critical COVID-19.


Subject(s)
COVID-19/drug therapy , Glucocorticoids/administration & dosage , Lung/diagnostic imaging , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Aged , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/physiopathology , Critical Illness , Female , Fibrosis , Glucocorticoids/therapeutic use , Humans , L-Lactate Dehydrogenase/metabolism , Lung/pathology , Lung/physiopathology , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Prednisolone/administration & dosage , Prednisolone/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Survival Rate , Tomography, X-Ray Computed , Virus Shedding
11.
Thorax ; 76(12): 1242-1245, 2021 12.
Article in English | MEDLINE | ID: covidwho-1518155

ABSTRACT

The risk factors for development of fibrotic-like radiographic abnormalities after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalisation remains unclear. At 4 months after hospitalisation, fibrotic-like patterns were more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission and leucocyte telomere length are independent risk factors for fibrotic-like radiographic abnormalities. These fibrotic-like changes correlate with lung function, cough and measures of frailty, but not with dyspnoea.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Telomere , COVID-19/complications , Dyspnea , Fibrosis , Humans , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/virology , Telomere/genetics
12.
Int J Biochem Cell Biol ; 141: 106090, 2021 12.
Article in English | MEDLINE | ID: covidwho-1509589

ABSTRACT

Fibrosis is a key feature of chronic lung diseases and occurs as a consequence of aberrant wound healing. TGFß1 plays a major role in promoting fibrosis and is the primary target of current treatments that slow, but do not halt or reverse the progression of disease. Accumulating evidence suggests that additional mechanisms, including excessive airway contraction, inflammation and infections including COVID-19, can contribute to fibrosis. This review summarises experimental and clinical studies assessing the potential beneficial effects of novel drugs that possess a unique suite of complementary actions to oppose contraction, inflammation and remodelling, along with evidence that they also limit fibrosis. Translation of these promising findings is critical for the repurposing and development of improved therapeutics for fibrotic lung diseases.


Subject(s)
Lung , Transforming Growth Factor beta1 , COVID-19 , Fibrosis , Humans , Lung/pathology
13.
Front Immunol ; 12: 740260, 2021.
Article in English | MEDLINE | ID: covidwho-1506482

ABSTRACT

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor ß1 (TGF-ß1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-ß1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-ß1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-ß1 mRNA performed at the time of first medical contact.


Subject(s)
COVID-19/physiopathology , Heart Ventricles/pathology , Myocardium/pathology , Pulmonary Fibrosis/physiopathology , SARS-CoV-2/physiology , Adult , Aged , COVID-19/immunology , Female , Fibrosis , Heart Ventricles/metabolism , Humans , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-1 Receptor-Like 1 Protein/metabolism , Male , Middle Aged , Myocardium/metabolism , Neuropilin-1/genetics , Neuropilin-1/metabolism , Pulmonary Fibrosis/immunology , Risk , Severity of Illness Index , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Viral Load
14.
J Am Soc Nephrol ; 32(1): 69-85, 2021 01.
Article in English | MEDLINE | ID: covidwho-1496661

ABSTRACT

BACKGROUND: In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. METHODS: We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. RESULTS: We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. CONCLUSIONS: These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.


Subject(s)
Cicatrix/physiopathology , Kidney/physiopathology , Macrophages/cytology , Neutrophils/cytology , Pyelonephritis/metabolism , Animals , Escherichia coli , Female , Fibrosis/microbiology , Fibrosis/physiopathology , Inflammation , Kidney/microbiology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Neutrophils/metabolism , Phagocytosis , Pyelonephritis/microbiology , Pyelonephritis/physiopathology , Urinary Tract Infections/microbiology , Urinary Tract Infections/physiopathology
15.
J Autoimmun ; 125: 102741, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482678

ABSTRACT

The COVID-19 pandemic is still raging across the world and vaccination is expected to lead us out of this pandemic. Although the efficacy of the vaccines is beyond doubt, safety still remains a concern. We report a case of a 65-year-old woman who experienced acute severe autoimmune hepatitis two weeks after receiving the first dose of Moderna-COVID-19 vaccine. Serum immunoglobulin G was elevated and antinuclear antibody was positive (1:100, speckled pattern). Liver histology showed a marked expansion of the portal tracts, severe interface hepatitis and multiple confluent foci of lobular necrosis. She started treatment with prednisolone, with a favorable clinical and analytical evolution. Some recent reports have been suggested that COVID-19 vaccination can lead to the development of autoimmune diseases. It is speculated that the vaccine can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. Therefore, healthcare providers must remain vigilant during mass COVID-19 vaccination.


Subject(s)
/adverse effects , COVID-19/prevention & control , Hepatitis, Autoimmune/etiology , Jaundice/etiology , Vaccination/adverse effects , Antibodies, Antinuclear/blood , Bilirubin/blood , Female , Fibrosis/pathology , Hepatitis, Autoimmune/immunology , Humans , Jaundice/diagnosis , Liver/enzymology , Middle Aged , Molecular Mimicry/immunology , Prednisolone/therapeutic use , SARS-CoV-2/immunology
16.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477960

ABSTRACT

A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.


Subject(s)
COVID-19/pathology , Lung/physiology , Regeneration , COVID-19/virology , Epigenomics , Fibrosis , Humans , Immune System/metabolism , MicroRNAs/metabolism , SARS-CoV-2/isolation & purification , Signal Transduction
17.
Cells ; 10(10)2021 10 15.
Article in English | MEDLINE | ID: covidwho-1470800

ABSTRACT

Pulmonary epithelial cells are widely considered to be the first line of defence in the lung and are responsible for coordinating the innate immune response to injury and subsequent repair. Consequently, epithelial cells communicate with multiple cell types including immune cells and fibroblasts to promote acute inflammation and normal wound healing in response to damage. However, aberrant epithelial cell death and damage are hallmarks of pulmonary disease, with necrotic cell death and cellular senescence contributing to disease pathogenesis in numerous respiratory diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and coronavirus disease (COVID)-19. In this review, we summarise the literature that demonstrates that epithelial damage plays a pivotal role in the dysregulation of the immune response leading to tissue destruction and abnormal remodelling in several chronic diseases. Specifically, we highlight the role of epithelial-derived damage-associated molecular patterns (DAMPs) and senescence in shaping the immune response and assess their contribution to inflammatory and fibrotic signalling pathways in the lung.


Subject(s)
COVID-19/immunology , Epithelium/immunology , Idiopathic Pulmonary Fibrosis/immunology , Lung/immunology , Alarmins , Animals , Cellular Senescence , Coculture Techniques , Epithelial Cells/cytology , Epithelial Cells/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , Fibrosis/metabolism , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Immunity , Inflammation/metabolism , Ligands , Necroptosis , Necrosis/pathology , Pulmonary Disease, Chronic Obstructive , SARS-CoV-2 , Signal Transduction
18.
Radiology ; 303(2): 444-454, 2022 May.
Article in English | MEDLINE | ID: covidwho-1450625

ABSTRACT

Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up. Materials and Methods Adult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used. Results Eighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95-141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360-366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%-40%). Conclusion CT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up. ClinicalTrials.gov identifier: NCT04459351. © RSNA, 2022 Online supplemental material is available for this article.


Subject(s)
COVID-19 , Patient Discharge , COVID-19/diagnostic imaging , Dyspnea , Fibrosis , Hospitals , Humans , Lung/diagnostic imaging , Tomography, X-Ray Computed
20.
Chembiochem ; 22(15): 2516-2520, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1400765

ABSTRACT

The outbreak of SARS-CoV-2 has been an extraordinary event that constituted a global health emergency. As the novel coronavirus is continuing to spread over the world, the need for therapeutic agents to control this pandemic is increasing. αV ß6 Integrin may be an intriguing target not only for the inhibition of SARS-CoV-2 entry, but also for the diagnosis/treatment of COVID-19 related fibrosis, an emerging type of fibrotic disease which will probably affect a significant part of the recovered patients. In this short article, the possible role of this integrin for fighting COVID-19 is discussed on the basis of recently published evidence, showing how its underestimated involvement may be interesting for the development of novel pharmacological tools.


Subject(s)
COVID-19/virology , Fibrosis/virology , Integrin beta Chains/metabolism , SARS-CoV-2/isolation & purification , COVID-19/metabolism , COVID-19/pathology , Fibrosis/metabolism , Fibrosis/pathology , Humans
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