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SARS-CoV-2 proteins

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    COVID-19 MESHD Neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital

    Authors: Kiran Thakur; Emily H Miller; Michael D Glendinning; Osama Al Dalahmah; Matei Banu; Amelia K Boehme; Alex Boubour; Samuel Bruce; Alexander M Chong; Jan Claassen; Phyllis Faust; Gunnar Hargus; Richard Hickman; Sachin Jambawalikar; Alexander Khandji; Carla Kim; Robyn S Klein; Angela Lignelli-Dipple; Chun-Chieh Lin; Yang Liu; Michael Miller; Gul Moonis; Anna Nordvig; Jonathan Overdevest; Morgan Prust; Serge Przedborski; William Roth; Allison Soung; Kurenai Tanji; Andrew Teich; Dritan Agalliu; Anne-Catrin Uhlemann; James E. Goldman; Peter Canoll

    doi:10.1101/2021.03.16.21253167 Date: 2021-03-20 Source: medRxiv

    Many patients with SARS-CoV-2 infection MESHD develop neurological signs and symptoms, though, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological, and molecular findings of 41 consecutive patients with SARS-CoV-2 infections MESHD who died and underwent autopsy in our medical center. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit (ICU). Hospital-associated complications were common, including 8 (20%) with deep vein thrombosis MESHD/ pulmonary embolism MESHD (DVT/PE), 7 (17%) patients with acute kidney injury MESHD requiring dialysis, and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 hours of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischemic MESHD changes in all brains, both global and focal; large and small infarcts MESHD, many of which appeared hemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis MESHD of large arteries and arteriolosclerosis MESHD, though none had evidence of vasculitis MESHD. Eighteen (44%) contained pathologies of neurodegenerative diseases MESHD, not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR (qRT- PCR), RNAscope, and immunocytochemistry with primers, probes, and antibodies directed against the spike and nucleocapsid regions. qRT-PCR revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in nasal epithelia. RNAscope and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in COVID-19 MESHD brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation MESHD, perhaps with synergistic contribution from hypoxia/ischemia MESHD. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19 MESHD, might contribute to chronic neurological problems MESHD.

    Experiences of NHS Mental Healthcare Workers During the Covid-19 Pandemic MESHD: Qualitative Study

    Authors: Elisa Liberati; Natalie Richards; Janet Willars; David Scott; Nicola Boydell; Jennie Parker; Vanessa Pinfold; Graham Martin; Mary Dixon-Woods; Peter Jones

    doi:10.21203/rs.3.rs-301568/v1 Date: 2021-03-05 Source: ResearchSquare

    Background: The Covid-19 pandemic MESHD has imposed extraordinary strains on healthcare workers, but, in contrast with acute settings, relatively little attention has been given to those who work in mental health settings. We aimed to characterise the experiences of those working in English NHS secondary mental health services during the first wave of the pandemic.Methods: The design was a qualitative interview-based study. We conducted semi-structured, remote (telephone or online) interviews with 35 members of staff from NHS secondary (inpatient and community) mental health services in England. Analysis was based on the constant comparative method. Results: Participants reported wide-ranging changes in the organisation of secondary mental health care and the nature of work in response to the pandemic, including pausing of all services deemed to be “non-essential”, deployment of staff across services to new and unfamiliar roles, and moves to remote working. The quality of participants’ working life was impaired by increasing levels of daily challenge associated with trying to provide care in trying and constrained circumstances, the problems of forging new ways of working remotely, and constraints on ability to access informal support for decision-making. Participants were confronted with difficult dilemmas relating to clinical decision-making, prioritisation of care, and compromises in ability to perform the therapeutic function of their roles. Other dilemmas centred on trying to balance the risks of controlling infection with the need for human contact. Many reported features of moral injury linked to their perceived failures in providing the quality or level of care that they felt service users needed. They sometimes sought to compensate for deficits MESHD in care through increased advocacy, taking on additional tasks, or making exceptions, but this led to further personal strain.  Many experienced feelings of grief, helplessness, isolation, distress, and burnout. These problems were compounded by sometimes poor communication about service changes and by staff feeling that they could not take time off because of the potential impact on others. Some reported feeling poorly supported by organisations. Conclusions: Mental health workers faced multiple adversities during the pandemic that were highly consequential for their wellbeing. These findings help in identifying targets for support. 

    Long COVID neuropsychological deficits MESHD after severe, moderate or mild infection

    Authors: Philippe Voruz; Gilles Allali; Lamyae Benzakour; Anthony Nuber-Champier; Marine Thomasson; Isabele Jacot; Jordan Pierce; Patrice Lalive; Karl-Olof Lovblad; Olivia Brallaird; Matteo Coen; Jacques Serratrice; Jerome Pugin; Radek Ptak; Idriss Guessous; Basile Landis; Frederic Assal; Julie Anne Peron

    doi:10.1101/2021.02.24.21252329 Date: 2021-02-26 Source: medRxiv

    Background: There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD can include long-term neuropsychological deficits MESHD, even in its mild or moderate respiratory forms. Methods: Standardized neuropsychological, psychiatric MESHD, neurological and olfactory tests were administered to 45 patients (categorized according to the severity of their respiratory symptoms during the acute phase) 236.51 (SD: 22.54) days post-discharge following SARS-CoV-2 infection MESHD. Results: Deficits were found in all the domains of cognition and the prevalence of psychiatric symptoms MESHD was also high in the three groups. The severe performed more poorly on long-term episodic memory MESHD and exhibited greater anosognosia. The moderate had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction MESHD. The mild were more stressed, anxious and depressed MESHD. Conclusion: The data support the hypothesis that the virus targets the central nervous system (and notably the limbic system), and support the notion of different neuropsychological phenotypes.

    Bleeding In Head And Neck Malignancy MESHD : Institution Based Management And Review

    Authors: Elroy Saldanha; Amar Jain; Dhruv Patel; Bonny Joseph; Sandeep Ghosh; Vinod Dhakad; Sanjay Desai

    doi:10.21203/rs.3.rs-237519/v1 Date: 2021-02-12 Source: ResearchSquare

    Introduction: Squamous cell carcinoma MESHD constitutes for >90% of head and neck cancers MESHD. Acute rupture MESHD of irradiated, large vessels is life-threatening complication. The distribution of bleeding MESHD foci is diverse and can range from internal or common carotid arteries to branches of the external carotid artery. We intend to assess the management of patients presented in our institution with such acute bleeding MESHD episodes and also review the management of carotid blowout syndrome MESHD which is an oncological emergency.Methods:Retrospective observational study of 27 cases presented in our institution with acute bleeding MESHD due to head and neck cancer MESHD for period of two years. After resuscitation and necessary consents, emergency open tracheostomy MESHD was done with universal precautions. ECA/CCA ligation was done. All the patients were started on low molecular weight heparin 8 hours post surgery. Therapeutic outcomes were assessed based on simple frequencies and proportions.Results:Of the 27 cases presented in our institution, 19 of them underwent ECA ligation while 8 of them CCA ligation for the control of active bleeding MESHD. 12 of 27 patients were receiving definitive chemoradiation of which 7 of them were ongoing. Remaining 15 patients were receiving adjuvant radiotherapy following surgery.19 patients who underwent ECA ligation, had no further bleeding MESHD episodes. 8 patients who underwent CCA ligation, had only wound related complications and none of them had neurological deficits MESHD. 11 patients were operated during covid-19 MESHD period. 4 patients turned out covid positive. None of the medical personnel contacted the infection.Conclusion:Radiotherapy is one the major contributor for CBS HGNC. Endovascular procedures can be used for local tumour bleed MESHD, threatened, impending and stable acute CBS HGNC CBS MESHD. Surgical CCA ligation done in bleeds MESHD unsuccessful by endovascular procedure and in acute unstable CBS HGNC. ECA ligation is safe and effective method to control local tumor MESHD bleed. Surgical finesse, careful planning, adherence to universal precautions and institutional protocol can reduce Covid-19 MESHD transmission to medical personnel in this testing times.

    An Autoantigen Atlas from Human Lung HFL1 HGNC Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19 MESHD

    Authors: Julia Y. Wang; Wei Zhang; Michael W. Roehrl; Victor B. Roehrl; Michael H. Roehrl; Alvis Brazma; Zhichao Miao; Huanxin Su; Evandro Fei Fang; ZhangJing Zhang; Jikai Zhang; Oscar Junhong Luo; Pengchen Wang; Guobing Chen

    doi:10.1101/2021.01.24.427965 Date: 2021-01-24 Source: bioRxiv

    COVID-19 MESHD is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection MESHD, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems MESHD, fibrosis MESHD, smooth muscle dysfunction MESHD, and thrombosis MESHD. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity. The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic.

    COVID-19 MESHD severity impacts on long-term neurological manifestation after hospitalisation

    Authors: Andrea Pilotto; viviana cristillo; stefano cotti Piccinelli; Nicola Zoppi; Giulio Bonzi; Davide Sattin; Silvia Schiavolin; Alberto Raggi; Antonio Canale; Stefano Gipponi; Ilenia Libri; martina frigerio; Michela Bezzi; Matilde leonardi; alessandro padovani

    doi:10.1101/2020.12.27.20248903 Date: 2021-01-02 Source: medRxiv

    BackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalized and non-hospitalized COVID-19 MESHD patients. It is unclear whether long-term neurological symptoms MESHD and features depend on COVID-19 MESHD severity. Methodsfrom a sample of 208 consecutive non-neurological patients hospitalized for COVID-19 MESHD disease, 165 survivors were re-assessed at 6 months according to a structured standardized clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease MESHD, patients displayed a wide array of symptoms; fatigue MESHD (34%), memory/attention (31%), and sleep disorders MESHD (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities MESHD, such as hyposmia MESHD (18.0%), cognitive deficits MESHD (17.5%), postural tremor MESHD (13.8%) and subtle motor/ sensory deficits MESHD (7.6%). Older age, premorbid comorbidities and severity of COVID-19 MESHD were independent predictors of neurological manifestations in logistic regression analyses. Conclusionspremorbid vulnerability and severity of SARS-CoV-2 infection MESHD impact on prevalence and severity of long-term neurological manifestations.

    Neurological Disorders associated with COVID-19 MESHD Hospital Admissions : Experience of a Single Tertiary Healthcare Centre

    Authors: Permesh Singh Dhillon; Robert Dineen; Haley Morris; Radu Tanasescu; Esmaeil Nikfekr; Jonathan Evans; Cris S Constantinescu; Akram A Hosseini

    doi:10.1101/2020.11.22.20235184 Date: 2020-12-11 Source: medRxiv

    BackgroundEarly reports have detailed a range of neurological symptoms MESHD in patients with the SARS-CoV-2 infection MESHD. However, there is a lack of detailed description and incidence of the neurological disorders MESHD amongst hospitalized COVID-19 MESHD patients. We describe a range of neurological disorders MESHD (other than non-specific neurological symptoms), including their clinical, radiological and laboratory findings, encountered in our cohort COVID-19 MESHD patients admitted to a large tertiary institution. MethodsWe reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke MESHD admissions and Neurological multi-disciplinary MESHD team meetings for all hospitalized patients with suspected or proven COVID-19 MESHD from 17 March 2020 to 31 August 2020. ResultsTwenty-nine of 1243 COVID-19 MESHD inpatients (2.3%) presented with COVID-19 MESHD-related neurological disorders MESHD. The mean age was 68.9 +/-13.5(SD) years, age range of 34-97 years, and there were 17 males. 22 patients had confirmed, 5 were probable and 2 had suspected COVID-19 MESHD infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms MESHD at presentation included acute confusion MESHD and delirium MESHD, seizures MESHD, and new focal neurological deficits MESHD. Based on the pre-defined neurological phenotype, COVID-19 MESHD patients were grouped into four main categories. 16 patients had cerebrovascular events (13 with acute ischaemic stroke MESHD and 3 had haemorrhagic features), 7 patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy MESHD (including 2 with known Multiple Sclerosis MESHD), whilst movement and peripheral nervous system disorders MESHD were diagnosed in 3 patients each. ConclusionAlthough the exact prevalence and aetiology remains unclear, non-sporadic new onset of neurological disorders MESHD, in addition to anosmia MESHD, occurs during the acute COVID-19 MESHD-infection. Longitudinal follow-up of these patients is required to determine the long-term effects, treatment response and outcome of the SARS-CoV-2 infection MESHD.

    Predicting patients with false negative SARS-CoV-2 testing at hospital admission: A retrospective multi-center study

    Authors: Lama Ghazi; Michael Simonov; Sherry Mansour; Dennis Moledina; Jason Greenberg; Yu Yamamoto; Aditya Biswas; Francis Perry Wilson

    doi:10.1101/2020.11.30.20241414 Date: 2020-12-02 Source: medRxiv

    ImportanceFalse negative SARS-CoV-2 tests can lead to spread of infection in the inpatient setting to other patients and healthcare workers. However, the population of patients with COVID who are admitted with false negative testing is unstudied. ObjectiveTo characterize and develop a model to predict true SARS-CoV-2 infection MESHD among patients who initially test negative for COVID by PCR. DesignRetrospective cohort study. SettingFive hospitals within the Yale New Haven Health System between 3/10/2020 and 9/1/2020. Participants: Adult patients who received diagnostic testing for SARS-CoV-2 virus within the first 96 hours of hospitalization. ExposureWe developed a logistic regression model from readily available electronic health record data to predict SARS-CoV-2 positivity in patients who were positive for COVID and those who were negative and never retested. Main Outcomes and MeasuresThis model was applied to patients testing negative for SARS-CoV-2 who were retested within the first 96 hours of hospitalization. We evaluated the ability of the model to discriminate between patients who would subsequently retest negative and those who would subsequently retest positive. ResultsWe included 31,459 hospitalized adult patients; 2,666 of these patients tested positive for COVID and 3,511 initially tested negative for COVID and were retested. Of the patients who were retested, 61 (1.7%) had a subsequent positive COVID test. The model showed that higher age, vital sign abnormalities MESHD, and lower white blood cell count served as strong predictors for COVID positivity in these patients. The model had moderate performance to predict which patients would retest positive with a test set area under the receiver-operator characteristic (ROC) of 0.76 (95% CI 0.70 - 0.83). Using a cutpoint for our risk prediction model at the 90th percentile for probability, we were able to capture 35/61 (57%) of the patients who would retest positive. This cutpoint amounts to a number-needed-to-retest range between 15 and 77 patients. Conclusion and RelevanceWe show that a pragmatic model can predict which patients should be retested for COVID. Further research is required to determine if this risk model can be applied prospectively in hospitalized patients to prevent the spread of SARS-CoV-2 infections MESHD.

    Incidence, Characteristics and Clinical Relevance of Acute Stroke in Old Patients Hospitalized With COVID-19 MESHD

    Authors: Aline Mendes; François Herrmann; Laurence Genton; Christine Serratrice; Emmanuel Carrera; Maria Isabel Vargas; Gabriel Gold; Christophe Graf; Dina Zekry; Max Scheffler

    doi:10.21203/rs.3.rs-110348/v1 Date: 2020-11-17 Source: ResearchSquare

    Background: Stroke MESHD in the course of coronavirus disease MESHD ( COVID-19 MESHD) was associated with higher severity of respiratory symptoms and mortality, but little knowledge exists on older populations. We aimed to investigate the incidence, characteristics, and prognosis of acute stroke MESHD in old patients hospitalized with COVID-19 MESHD.Methods: Monocentric retrospective study of 265 older patients hospitalized with COVID-19 MESHD in geriatric wards, 11 of which having presented a stroke MESHD episode during hospitalization. Mortality rates and two-group comparisons ( stroke MESHD vs non- stroke MESHD patients) were calculated and significant variables added in logistic regression models to investigate stroke MESHD risk factors.Results: Combined ischemic MESHD and hemorrhagic stroke MESHD incidence was 4.15%. 72.7% of events occurred during acute care. Strokes MESHD presented with altered state of consciousness and/or delirium MESHD in 81.8%, followed by a focal neurological deficit MESHD in 45.5%. Ischemic stroke MESHD was more frequently unilateral (88.8%) and localized in the middle cerebral artery territory (55.5%). Smoking and a history of previous stroke MESHD increased by more than seven (OR 7.44; 95% CI 1.75-31.64; p=0.007) and five times (OR 5.19; 95% CI 1.50-17.92; p=0.009), respectively, the risk of stroke MESHD. Each additional point in body mass index (BMI) reduced the risk of stroke MESHD by 14% (OR 0.86; 95% CI 0.74-0.98; p=0.03). In-hospital mortality (32.1% vs. 27.3%; p>0.999) and institutionalization at discharge (36.4% vs. 21.1%; p=0.258) were similar between patients with and without stroke MESHD.Conclusion: Incident stroke MESHD complicating COVID-19 MESHD in old patients was associated with active smoking, previous history of stroke MESHD, and low BMI. Acute stroke MESHD did not influence early mortality or institutionalization rate at discharge.

    COVID-19 MESHD COGNITIVE DEFICITS AFTER RESPIRATORY ASSISTANCE IN THE SUBACUTE PHASE:A COVID-REHABILITATION UNIT EXPERIENCE

    Authors: Federica Alemanno; Elise Houdayer; Anna Parma; Alfio Spina; Alessandra Del Forno; Alessandra Scatolini; Sara Angelone; Luigia Brugliera; Andrea Tettamanti; Luigi Beretta; Sandro Iannaccone

    doi:10.1101/2020.11.12.20229823 Date: 2020-11-15 Source: medRxiv

    Introduction: COVID-19 MESHD complications can include neurological, psychiatric MESHD, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 MESHD on cognitive functions of patients admitted to the COVID-19 MESHD Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy). Material and Methods: 87 patients admitted to the COVID-19 MESHD Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment ( MoCA HGNC), Hamilton Rating Scale for Depression MESHD, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase: Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge. Results: Out of the 87 patients (62 Male, mean age 67.23 +/- 12.89 years), 80% had neuropsychological deficits MESHD ( MoCA HGNC and MMSE) and 40% showed mild-to-moderate depression MESHD. Group1 had higher scores than Group3 for visuospatial/executive functions (p=0.016), naming (p=0.024), short- and long-term memory (p=0.010, p=0.005), abstraction (p=0.024), and orientation (p=0.034). Group1 was younger than Groups2 and 3. Cognitive impairments MESHD correlated with patients' age. Only 18 patients presented with anosmia MESHD. Their data did not differ from the other patients. FIM (<100) did not differ between groups. Patients partly recovered at one-month follow-up and 43% showed signs of post- traumatic stress disorder MESHD. Conclusion: Patients with severe functional impairments had important cognitive and emotional deficits MESHD which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for decision-making in respiratory and neuropsychiatric assistance of COVID-19 MESHD patients in the subacute phase of the disease, and show the need for long-term support and psychological treatment of post- COVID-19 MESHD patients.

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MeSH Disease
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