Clinical, radiological and pathological findings in patients with persistent lung disease following SARS-CoV-2 infection

European Respiratory Journal, Journal Year: 2022, Volume and Issue: 60(4), P. 2102411 - 2102411

Published: March 17, 2022

Some patients experience pulmonary sequelae after SARS-CoV-2 infection, ranging from self-limited abnormalities to major lung diseases. Morphological analysis of tissue may help our understanding pathogenic mechanisms and provide consistent personalised management. The aim this study was ascertain morphological immunomolecular features tissue. Transbronchial cryobiopsy carried out in with persistent symptoms computed tomography suggestive residual disease recovery infection. 164 were referred for suspected COVID-19; 10 >5% parenchymal underwent biopsy. histological pattern not homogeneous three different case clusters could be identified, which mirrored by their clinical radiological features. Cluster 1 ("chronic fibrosing") characterised post-infection progression pre-existing interstitial pneumonias. 2 ("acute/subacute injury") types grades injury, organising pneumonia fibrosing nonspecific diffuse alveolar damage. 3 ("vascular changes") vascular increase, dilatation distortion (capillaries venules) within otherwise normal parenchyma. Clusters had immunophenotypical changes similar those observed early/mild COVID-19 pneumonias (abnormal expression STAT3 hyperplastic pneumocytes PD-L1, IDO endothelial cells). This is the first correlating histological/immunohistochemical patterns pictures post-COVID disease. Different phenotypes potentially underlying have been identified.

Language: Английский

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Post-COVID-19 pulmonary fibrosis: An ongoing concern

Annals of Thoracic Medicine, Journal Year: 2023, Volume and Issue: 18(4), P. 173 - 181

Published: Oct. 1, 2023

Abstract: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 rapidly spread across the globe causing over 6 million deaths and major compromization of health facilities. The vast majority survivors post-COVID-19 are left with variable degrees sequelae including pulmonary, neurological, psychological, cardiovascular complications. Post-COVID-19 pulmonary fibrosis is one concerns arising after recovery from this pandemic. Risk factors for include age, male sex, severity COVID-19 disease. High-resolution computed tomography provides diagnostic utility to diagnose as it more details regarding pattern extent fibrosis. Emerging data showing similarities between idiopathic fibrosis, finding that needs further exploration. management depends on many but largely relies excluding other causes physiological impairment. Treatment includes immunosuppressants versus antifibrotics or both.

Language: Английский

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An Integrated Radiologic-Pathologic Understanding of COVID-19 Pneumonia

Radiology, Journal Year: 2023, Volume and Issue: 306(2)

Published: Jan. 17, 2023

This article reviews the radiologic and pathologic findings of epithelial endothelial injuries in COVID-19 pneumonia to help radiologists understand fundamental nature disease. The manifestations result from based on viral toxicity immunopathologic effects. features mild reversible involve nonspecific or an organizing pattern, while potentially fatal irreversible are characterized by diffuse alveolar damage followed fibrosis acute fibrinous pneumonia. These responses observed not specific SARS-CoV-2 but rather constitute universal Endothelial injury is a prominent feature compared with other types encompasses various vascular abnormalities at different levels, including pulmonary thromboembolism, engorgement, peripheral reduction, tree-in-bud lung perfusion abnormality. Chest CT imaging techniques (eg, quantification, dual-energy perfusion) can fully capture injuries. thus aid establishing prognosis identifying patients risk for deterioration. © RSNA, 2023

Language: Английский

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Biomarkers during COVID-19: Mechanisms of Change and Implications for Patient Outcomes

Diagnostics, Journal Year: 2022, Volume and Issue: 12(2), P. 509 - 509

Published: Feb. 16, 2022

As the COVID-19 (Coronavirus disease 19) pandemic spreads worldwide, massive numbers of patients have created a considerable healthcare burden for every country. The clinical spectrum SARS-CoV-2 infection is broad, ranging from asymptomatic to mild, moderate, severe, and critical. Most present with no or mild symptoms, but nearly one-fifth all develop severe life-threatening complications. In addition localized respiratory manifestations, cases also show extra-pulmonary complications induce multiorgan failure. Identifying, triaging, treating at risk early essential urgent. This article reviews potential prognostic value various biomarkers different stages includes information on fundamental mechanisms as well implications. Biomarkers are measurable biochemical substances used recognize indicate severity response therapeutic interventions. they provide objective suitable delivering providers means stratifying state in patients. This, turn, can be help select guide intervention efforts gauge efficacy approaches. Here, we review number that may treatment, monitor treatment efficacy, form individualized guidance based patient response. Implementation discussed here lead significantly improved quality care outcomes those infected worldwide.

Language: Английский

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Persistent Lung Injury and Prothrombotic State in Long COVID

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is investigate basis pulmonary susceptibility sequelae possibility that prothrombotic states influence long-term symptoms COVID-19. patient’s lungs remain vulnerable stage due persistent shedding virus, inflammatory environment, state, subsequent repair blood-air barrier. transformation inflammation proliferation fibrosis, hypoxia-involved vascular remodeling, endothelial cell damage, phosphatidylserine-involved hypercoagulability, continuous changes in serological markers all contribute post-discharge injury. Considering important role microthrombus arteriovenous thrombus process functional lesions organic lesions, we further study states, including activation affect COVID. Early use combined anticoagulant antiplatelet therapy a promising approach reduce incidence sequelae. Essentially, early treatment can block occurrence thrombotic events. Because impeded circulation causes large pressure imbalances over alveolar membrane infiltration plasma into cavity, inhibition events prevent hypertension, formation hyaline membranes, consolidation.

Language: Английский

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Kynurenine Pathway in Respiratory Diseases

International Journal of Tryptophan Research, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 1, 2024

The kynurenine pathway is the primary route for tryptophan catabolism and has received increasing attention as its association with inflammation immune system become more apparent. This review provides a broad overview of in respiratory diseases, from initial observations to characterization different cell types involved synthesis metabolites underlying immunoregulatory mechanisms. With focus on infections, various attempts characterize kynurenine/tryptophan (K/T) ratio an inflammatory marker are reviewed. Its implication chronic lung exacerbation by pathogens also discussed. emergence preclinical interventional studies targeting opens way future development new therapies.

Language: Английский

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Alveolar Type II Cells and Pulmonary Surfactant in COVID-19 Era

Physiological Research, Journal Year: 2021, Volume and Issue: unknown, P. S195 - S208

Published: Dec. 14, 2021

In this review, we discuss the role of pulmonary surfactant in host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. lower system, virus uses angiotensin-converting enzyme 2 (ACE2) receptor conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one SARS-CoV-2 target cells, to enter. ATII are main source surfactant. After their infection and resulting damage, consequences may be severe include injury alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired mechanics reduced oxygenation, which resembles acute distress syndrome (ARDS) other etiology. The aim review is highlight key pathogenesis form COVID-19 emphasize rational basis for exogenous therapy ARDS patients.

Language: Английский

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Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations

JCI Insight, Journal Year: 2021, Volume and Issue: 6(24)

Published: Nov. 12, 2021

Kidneys are critical target organs of COVID-19, but susceptibility and responses to infection remain poorly understood. Here, we combine SARS-CoV-2 variants with genome-edited kidney organoids clinical data investigate tropism, mechanism, therapeutics. specifically infects organoid proximal tubules among diverse cell types. Infections produce replicating virus, apoptosis, disrupted morphology, features which revealed in the context polycystic disease. Cross-validation gene expression patterns reflects proteomic signatures COVID-19 urine critically ill patients indicating interferon pathway upregulation. viral alpha, beta, gamma, kappa, delta exhibit comparable levels organoids. Infection is ameliorated ACE2–/– blocked via treatment de novo–designed spike binder peptides. Collectively, these studies clarify impact as reflected populations, enabling assessment fitness emerging therapies.

Language: Английский

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Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: Jan. 3, 2022

Abstract Background SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas well-aerated lung parenchyma results a ventilation–perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims evaluate efficacy oral sildenafil treating COVID-19 inpatients showing perfusion abnormalities sCTA. Methods Triple-blinded, randomized, placebo-controlled trial was conducted Chile tertiary-care hospital able provide on-site sCTA scans and ventilatory support when needed between August 2020 March 2021. In total, 82 eligible adults were admitted ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection performed within 24 h admission parenchyma; 42 excluded 40 participants enrolled randomized (1:1 ratio) once hospitalized. The active intervention group received (25 mg orally three times day for seven days), control identical placebo capsules same way. Primary outcomes differences oxygenation parameters measured daily during follow-up (PaO 2 /FiO ratio A-a gradient). Secondary included ICU, requirement non-invasive ventilation, invasive mechanical ventilation (IMV), mortality rates. Analysis on an intention-to-treat basis. Results Totally, (20 20 group); 33 [82.5%] male; median age 57 [IQR 41–68] years. No significant mean PaO ratios gradients found groups (repeated-measures ANOVA p = 0.67 0.69). IMV required 4 patients who none arm (logrank 0.04). Patients showed significantly shorter length stay than (9 IQR 7–12 days vs. 12 9–21 days, Conclusions statistically parameters. Sildenafil treatment could have potential therapeutic role regarding need specific patterns A large-scale is confirm these results. Trial Registration : mismatch: pilot trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .

Language: Английский

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Increased Kynurenine Indicates a Fatal Course of COVID-19

Antioxidants, Journal Year: 2021, Volume and Issue: 10(12), P. 1960 - 1960

Published: Dec. 7, 2021

(1) Background: An inefficient immune response accompanied by an overwhelming inflammatory reaction is involved in severe courses of COVID-19. Kynurenine (KYN) has important immune-modulatory functions and may contribute to a failure controlling SARS-CoV-2. The present study aims explore biomarkers that hint at fatal outcome COVID-19 early on. (2) Methods: We established cohort 148 hospitalized patients for this study. Thirty-one died due course, 117 recovered within 90 days. built biobank collecting left-over material from these whenever blood arrived the central laboratory our University hospital analysis routine markers. scientific comprised KYN, Tryptophan (TRP), KYN/TRP ratio, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), creatinine, N-terminal pro-natriuretic peptide (NTproBNP), troponin T (TnT), fibrinogen, D-Dimer, prothrombin time (PT), activated partial thromboplastin (aPTT), antithrombin (AT), C, S, factor XIII, lupus aPTT, angiotensin-2, vitamin D metabolites, telomeres all patients. Basic clinical characteristics anteceding diseases including cardiovascular, oncologic, renal, hypertension, pulmonary, metabolic (diabetes, obesity) were recorded database together with data. (3) Results: At diagnosis SARS-CoV-2 infection those who deceased days afterwards COVID-19, had significantly higher age, NTproBNP values than survived along same span. In Kaplan-Meier variables TnT, NTproBNP, creatinine showed significant influence on survival time. Gender, however, no influence. combined Cox regression KYN highest hazard ratio (1.188, 95% CI: 1.071-1.319) followed age (1.041, 1.011-1.073). ROC analysis, above cut off limit 4.82 nmol/l (as specified Youden index) sensitivity 82% (95% 66-95%) specificity 72% 65-82%) predict related death observation (4) Conclusions: promising biomarker increased risk mortality infected people already first positive verification detected persons.

Language: Английский

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