Corpus overview


MeSH Disease

Human Phenotype


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    Stroke MESHD Stroke HP increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs

    Authors: Vikramjeet Singh; Alexander Beer; Andreas Kraus; Xiaoni Zhang; Jinhua Xue; Dirk M Hermann; Matthias Gunzer

    doi:10.1101/2020.06.24.162941 Date: 2020-06-24 Source: bioRxiv

    BackgroundThe newly emerged severe acute respiratory syndrome MESHD coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease MESHD. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection MESHD of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke MESHD stroke HP are particularly susceptible to severe courses of SARS-CoV-2 infection MESHD, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke MESHD stroke HP induce lymphocytopenia and systemic inflammation MESHD that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation MESHD following stroke MESHD stroke HP can specifically modulate ACE2 expression in the lung has not been investigated. MethodsMice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1{beta} were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry. ResultsStrikingly, 24 h after stroke MESHD stroke HP, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke MESHD stroke HP. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1{beta} in the lungs. Higher gene expression of cytokines IL-6 and IL-1{beta} was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood SERO and spleen as an indicator of sterile tissue injury-induced immunosuppression. ConclusionsWe demonstrate significantly augmented ACE2 levels and inflammation MESHD in murine lungs after experimental stroke MESHD stroke HP. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke MESHD stroke HP represent a high-risk group for the development of severe SARS-CoV-2 infections MESHD. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions. HighlightsBrain tissue injury increases ACE2 levels in the lungs Brain injury MESHD induces pro-inflammatory cytokine expression in the lungs Brain injury MESHD causes parenchymal inflammation MESHD and systemic lymphopenia MESHD lymphopenia HP

    Bipallidal Lesions in a COVID-19 Patient: A Case Report and Brief Review of Literature

    Authors: Sudhat Ashok; Kalyan Shastri; L. Beryl Guterman; Lee R. Guterman

    doi:10.21203/ Date: 2020-06-09 Source: ResearchSquare

    BackgroundAltered mentation in COVID-19 patients can be a function of any number of metabolic abnormalities associated with the infection MESHD. Here we present the case of an encephalopathic COVID-19 patient with bilateral globus pallidus lesions. While imaging abnormalities involving basal ganglia have been reported in encephalitis MESHD encephalitis HP caused by neuroinvasive flaviviruses, the bipallidal lesions noted here likely resulted from hypoxic-ischemic brain injury MESHD.Case PresentationA 51-year-old African American woman was found unresponsive at home by her fiancé. She had been complaining of shortness of breath and cough MESHD cough HP for three days. She is a former smoker with past medical history of hypertension MESHD hypertension HP, nephropathy HP, and bipolar disorder. Upon examination, she was alert but nonverbal, following commands inconsistently, and unable to move extremities against gravity. After several minutes, she was able to state her name but kept repeating it in response to all questions. Chest radiograph revealed bilateral lung infiltrates. CT of the head showed hypodensities in bilateral globus pallidi. A non-contrast MRI of the brain showed symmetric restricted diffusion and FLAIR hyperintense signal changes in bilateral globus pallidi. Abnormal SWI signal seen in bilateral globus pallidi likely represents mineralization or hemosiderin. There were no striatal or thalamic lesions. Major intracranial arteries were widely patent.The patient later tested positive for 2019-nCoV using real-time PCR assay, and was transferred to our COVID-19 designated hospital campus. Thereafter, she had waxing and waning mentation. Repeat CT imaging 11 days after the first scan demonstrated resolution of the bipallidal hypodensities. The patient was recently discharged to a subacute rehab facility but is still experiencing confusion MESHD confusion HP.ConclusionsAs we come across neurological manifestations of COVID-19, we believe neuroimaging is likely to play an important role in establishing if central nervous system involvement is invariably due to indirect mechanisms such as metabolic or hypoxic-ischemic brain injury MESHD or if direct neuroinvasive disease MESHD is a possibility, as with certain viruses.

    Analysis of ACE2 Genetic Variability Among Populations Highlights A Possible Link With COVID19-Related Neurological Complications 

    Authors: Claudia Strafella; Valerio Caputo; Andrea Termine; Shila Barati; Stefano Gambardella; Paola Borgiani; Carlo Caltagirone; Giuseppe Novelli; Emiliano Giardina; Raffaella Cascella

    doi:10.21203/ Date: 2020-05-14 Source: ResearchSquare

    The Angiotensin-converting enzyme 2 (ACE2) has been recently recognized as the entry receptor of the novel pathogenic Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-Cov-2). The presence of structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection MESHD and COVID19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of Single Nucleotide Variants (SNVs), Copy Number Variations (CNVs) and expression Quantitative Loci (eQTLs) in a cohort of 268 individuals representative of the Italian general population. The analysis identified 5 SNVs (rs35803318, rs41303171, rs774469453, rs773676270, rs2285666) which displayed a significantly different frequency distribution in the Italian cohort compared to the worldwide populations. The analysis of eQTLs located in and targeting ACE2, revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between the genetic variability of ACE2 and the neurological complications in patients with COVID19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury MESHD.

    Early postmortem brain MRI findings in COVID-19 non-survivors

    Authors: Tim Coolen; Valentina Lolli; Niloufar Sadeghi; Antonin Rovai; Nicola Trotta; Fabio S Taccone; Jacques Creteur; Sophie Henrard; Jean-Christophe Goffard; Olivier Dewitte; Gilles Naeije; Serge Goldman; Xavier De Tiege

    doi:10.1101/2020.05.04.20090316 Date: 2020-05-08 Source: medRxiv

    Importance: The severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress HP in patients with coronavirus disease MESHD 2019 (COVID-19). Brain magnetic resonance imaging (MRI) data in COVID-19 patients are scarce due to difficulties to obtain such examination in infected unstable patients during the COVID-19 outbreak. Objective: To investigate the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. Design: Prospective, case series study with postmortem brain MRI obtained early (<24h) after death MESHD. Setting: Monocentric study. Participants: From 31/03/2020 to 24/04/2020, consecutive decedents who fulfilled the following inclusion criteria were included: death MESHD <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. Main Outcome(s) and Measure(s): Signs of acute brain injury MESHD and MRI signal abnormalities along the olfactory tract and brainstem were searched independently by 3 neuroradiologists, then reviewed with neurologists and clinicians. Results: Among the 62 patients who died from COVID-19 during the inclusion period, 19 decedents fulfilled inclusion criteria. Subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy HP syndrome MESHD (PRES, one decedent), and nonspecific deep white matter changes (one decedent) were observed. Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality. Conclusions and Relevance: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. The absence of brainstem MRI abnormalities does not support a brain-related contribution to respiratory distress HP in COVID-19.

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MeSH Disease
Human Phenotype

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