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  • 1
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-3)
    Abstract: The development of lung fibrosis is a major concern in patients recovered from severe COVID-19 pneumonia. This study aimed to document the evolution of diffuse alveolar damage (DAD) to the fibrosing pattern and define the transcriptional programs involved. Morphological, immunohistochemical and transcriptional analysis were performed in lung samples obtained from autopsy of 33 severe COVID-19 patients (median illness duration: 36 days). Normal lung and idiopathic pulmonary fibrosis (IPF) were used for comparison. Twenty-seven patients with DAD and disease evolution of more than 2 weeks had fibrosis. Pathways and genes related with collagen biosynthesis and extracellular matrix (ECM) biosynthesis and degradation, myofibroblastic differentiation and epithelial to mesenchymal transition (EMT) were overexpressed in COVID-19. This pattern had similarities with that observed in IPF. By immunohistochemistry, pathological fibroblasts (pFBs), with CTHRC1 and SPARC expression, increased in areas of proliferative DAD and decreased in areas of mature fibrosis. Immunohistochemical analysis demonstrated constitutive expression of cadherin-11 in normal epithelial cells and a similar pattern of cadherin and catenin expression in epithelial cells from both normal and COVID-19 samples. Transcriptomic analysis revealed downregulation of the Hippo pathway, concordant with the observation of YAP overexpression in hyperplastic alveolar epithelial cells. Progression to fibrosis in severe COVID-19 is associated with overexpression of fibrogenic pathways and increased in CTHRC1- and SPARC-positive pFBs. Whereas the Hippo pathway seemed to be implicated in the response to epithelial cell damage, EMT was not a major process implicated in COVID-19 mediated lung fibrosis.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 2
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2021-10-15)
    Abstract: The role of SARS-CoV-2 as a direct cause in the cardiac lesions in patients with severe COVID-19 remains to be established. Our objective is to report the pathological findings in cardiac samples of 30 patients who died after a prolonged hospital stay due to Sars-Cov-2 infection. We performed macroscopic, histological and immunohistochemical analysis of the hearts of 30 patients; and detected Sars-Cov-2 RNA by RT-PCR in the cardiac tissue samples. The median age of our cohort was 69.5 years and 76.6% were male. The median time between symptoms onset and death was 36.5 days. The main comorbidities were arterial hypertension (13 patients, 43.3%), dyslipidemia (11 patients, 36.7%), cardiovascular conditions (8 patients, 26.7%), and obesity (8 patients, 26.7%). Cardiovascular conditions included ischemic cardiopathy in 4 patients (13.3%), hypertrophic cardiomyopathy in 2 patients (6.7%) and valve replacement and chronic heart failure in one patient each (3.3%). At autopsy, the most frequent histopathological findings were coronary artery atherosclerosis (8 patients, 26.7%), left ventricular hypertrophy (4 patients, 13.3%), chronic epicardial inflammation (3 patients, 10%) and adipose metaplasia (2 patients, 6.7%). Two patients showed focal myocarditis, one due to invasive aspergillosis. One additional patient showed senile amyloidosis. Sars-Cov-2 RNA was detected in the heart of only one out of 30 patients, who had the shortest disease evolution of the series (9 days). However, no relevant cardiac histological alterations were identified. In present series, cardiac pathology was only modest in most patients with severe COVID-19. At present, the contribution of a direct effect of SARS-CoV-2 on cardiac lesions remains to be established.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2781496-8
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  • 3
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-1-31)
    Abstract: The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9–108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of & lt;2 weeks, but in none of the 23 adult patients with an illness duration of & gt;2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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