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MeSH Disease


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    Corticosteroids are associated with increased survival in elderly TRANS presenting severe SARS-Cov2 infection MESHD

    Authors: Laure Gallay; Viet-Thi Tran; Elodie Perrodeau; Nicolas Vignier; Matthieu Mahevas; Francesca Bisio; Emmanuel Forestier; Xavier Lescure; Nikki Turner; Priscilla Campbell-Stokes; Michelle Balm; Hazel C Dobinson; Cameron C Grant; Shelley James; Nayyereh Aminisani; Jacqui Ralston; Wendy Gunn; Judy Bucacao; Jessica Danielewicz; Tessa Moncrieff; Andrea McNeill; Lisa Lopez; Ben Waite; Tomasz Kiedrzynski; Hannah Schrader; Rebekah Gray; Kayla Cook; Danielle Currin; Chaune Engelbrecht; Whitney Tapurau; Leigh Emmerton; Maxine Martin; Michael G Baker; Susan Taylor; Adrian Trenholme; Conroy Wong; Shirley Lawrence; Colin McArthur; Alicia Stanley; Sally Roberts; Fahimeh Ranama; Jenny Bennett; Chris Mansell; Meik Dilcher; Anja Werno; Jennifer Grant; Antje van der Linden; Ben Youngblood; Paul G Thomas; Richard J Webby

    doi:10.1101/2020.11.10.20226886 Date: 2020-11-13 Source: medRxiv

    To assess the effectiveness of corticosteroids among elderly TRANS patients with COVID-19 MESHD pneumonia MESHD pneumonia HP requiring oxygen. Design Comparative observational study based on routine care data. Baseline characteristics of patients were balanced using propensity-score inverse probability of treatment weighting. Setting Geriatric and infectious diseases wards from 36 hospitals in France and Luxembourg. Participants Adults TRANS [≥] 80 years old PCR confirmed SARS-CoV-2 infection MESHD or typical CT-scan images, requiring oxygen [≥] 3L/min and with an inflammatory syndrome MESHD (C-reactive protein [≥] 40mg/L). Measurements The primary outcome was overall survival at day 14. The secondary outcome was the proportion of patients discharged from hospital to home/rehabilitation on day 14. Adverse events were abstracted from electronic health records. Results Among the 267 patients included in the analysis, 96 were assigned to the treatment group. Median age TRANS was 86, interquartile range 83 to 90 and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. Use of corticosteroids was significantly associated with an increased survival (weighted hazard ratio [wHR] 0.66, 95% CI 0.44 to 0.97). There was no significant difference between the treatment and control groups regarding the proportion of patients discharged to home/rehabilitation at day 14 (wRR 1.11, 95% CI 0.68 to 1.81). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events while only 11 (6.4%) from the control group did. Conclusions Corticosteroids were associated with a significant increase the day-14 overall survival of patients over 80 years old hospitalized for severe COVID-19 MESHD.

    The repurposed drugs suramin and quinacrine inhibit cooperatively in vitro SARS-CoV-2 3CLpro

    Authors: Raphael J Eberle; Danilo S Olivier; Marcos S Amaral; Dieter Willbold; Raghuvir K Arni; Monika A Coronado; Andrea Benedetti; Jan Larmann; Markus A Weigand; Sean McGrath; Claudia Denkinger; Stefan Baral; Jeff Kwong; Deepali Kumar; Atul Humar; Adrienne Chan; Seham Noureldin; Joshua Booth; Rachel Hong; David Smookler; Wesam Aleyadeh; Anjali Patel; Bethany Barber; Julia Casey; Ryan Hiebert; Henna Mistry; Ingrid Choong; Colin Hislop; Deanna Santer; D. Lorne Tyrrell; Jeffrey S. Glenn; Adam J. Gehring; Harry LA Janssen; Bettina Hansen

    doi:10.1101/2020.11.11.378018 Date: 2020-11-12 Source: bioRxiv

    Since the first report of a new pneumonia disease MESHD pneumonia disease HP in December 2019 (Wuhan, China) up to now WHO reported more than 50 million confirmed cases TRANS and more than one million losses, globally. The causative agent of COVID-19 MESHD (SARS-CoV-2) has spread worldwide resulting in a pandemic of unprecedented magnitude. To date, no clinically safe drug or vaccine is available and the development of molecules to combat SARS-CoV-2 infections MESHD is imminent. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is the repurposing of clinically developed drugs, e.g., anti-parasitic drugs. The results described in this study demonstrate the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules present a competitive and non-competitive mode of inhibition, respectively, with IC50 and KD values in low M range. Using docking and molecular dynamics simulations we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin in combination with quinacrine showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. The identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 MESHD disease. Drug repositioning offers hope to the SARS-CoV-2 control.

    Recombinant ACE2 Expression is Required for SARS-CoV-2 to Infect Primary Human Endothelial Cells and Induce Inflammatory and Procoagulative Responses

    Authors: Jonas Nascimento Conde; William R. Schutt; Elena Gorbunova; Erich R. Mackow; Suprabhat Mukherjee; Kianna M. Nguyen; Ming H. Ho; Jung-Eun Shin; Jared Feldman; Blake M. Hauser; Timothy M. Caradonna; Laura M. Wingler; Aaron G. Schmidt; Debora S. Marks; Jonathan Abraham; Andrew C. Kruse; Chang C. Liu

    doi:10.1101/2020.11.10.377606 Date: 2020-11-11 Source: bioRxiv

    SARS-CoV-2 causes COVID-19 MESHD, an acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) characterized by pulmonary edema HP pulmonary edema MESHD, viral pneumonia MESHD pneumonia HP, multiorgan dysfunction, coagulopathy and inflammation MESHD. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) receptors to infect and damage ciliated epithelial cells in the upper respiratory tract. In alveoli, gas exchange occurs across an epithelial-endothelial barrier that ties respiration to endothelial cell (EC) regulation of edema HP edema MESHD, coagulation MESHD and inflammation MESHD. How SARS-CoV-2 dysregulates MESHD vascular functions to cause ARDS MESHD in COVID-19 MESHD patients remains an enigma focused on dysregulated EC responses. Whether SARS-CoV-2 directly or indirectly affects functions of the endothelium remains to be resolved and critical to understanding SARS-CoV-2 pathogenesis and therapeutic targets. We demonstrate that primary human ECs lack ACE2 receptors at protein and RNA levels, and that SARS-CoV-2 is incapable of directly infecting ECs derived from pulmonary, cardiac, brain, umbilical vein or kidney tissues. In contrast, pulmonary ECs transduced with recombinant ACE2 receptors are infected by SARS-CoV-2 and result in high viral titers (~1x107/ml), multinucleate syncytia MESHD and EC lysis. SARS-CoV-2 infection MESHD of ACE2-expressing ECs elicits procoagulative and inflammatory responses observed in COVID-19 MESHD patients. The inability of SARS-CoV-2 to directly infect and lyse ECs without ACE2 expression explains the lack of vascular hemorrhage MESHD in COVID-19 MESHD patients and indicates that the endothelium is not a primary target of SARS-CoV-2 infection MESHD. These findings are consistent with SARS-CoV-2 indirectly activating EC programs that regulate thrombosis MESHD and endotheliitis MESHD in COVID-19 MESHD patients, and focus strategies on therapeutically targeting epithelial and inflammatory responses that activate the endothelium or initiate limited ACE2 independent EC infection MESHD.

    Identification, Isolation, Propagation And Inactivation Of SARS-CoV2 Isolated From Egypt

    Authors: Mohamed Gomaa Seadawy; Kasyap Tenneti; Hung R. Vuong; Nakyung Lee; Yating Liu; Amjad Horani; Tao Huang; James B. Case; Wei Yang; Michael S. Diamond; Steven L. Brody; Joseph Dougherty; Sebla B. Kutluay; Aniket S Rali; Leo Simpson; Mehrdad Saririan; Dan Hobohm; W. Tom Stump; James A Fitzpatrick; Xuping Xie; Pei-Yong Shi; J Travis Hinson; Weng-Tein Gi; Constanze Schmidt; Florian Leuschner; Chieh-Yu Lin; Michael S Diamond; Michael J Greenberg; Kory J Lavine; Pamela J. Bjorkman; Saurabh Mehandru; Paul D. Bieniasz; Marina Caskey; Michel C. Nussenzweig

    doi:10.1101/2020.11.04.368431 Date: 2020-11-05 Source: bioRxiv

    Severe Acute Respiratory Syndrome MESHD Coronavirus 2 causes the novel pandemic Pneumonia disease MESHD Pneumonia HP disease. It is a positive single strand ssRNA virus that infect human. COVID-19 MESHD appeared in Egypt in Feb 2020. The samples were taken from patients with COVID-19 MESHD symptoms at military hospital in Egypt and transported to the main chemical laboratories under all the biosafety measures according to WHO guidelines. All samples were tested with RT-PCR. Positive samples were cultured using VeroE6 cell lines. The propagated virus was isolated and inactivated. The isolated virus was sequenced using next generation sequencing and submitted into gene bank. This study provides an isolation, propagation and inactivation methodology which is valuable for production of inactivated vaccines against SARS-CoV2 in Egypt.

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) Candidate Chest CT Features: A Systematic Review of Extracted Imaging Features from 7571 Individuals

    Authors: Javad Zahiri; Mohammad Hossein Afsharinia; Zhaleh Hekmati; Mohsen Khodarahmi; Shahrzad Hekmati; Ramin Pourghorban; Barry Rockx; Samuel H. Gellman; Christopher A. Alabi; Rik L. de Swart; ANNE MOSCONA; Matteo Porotto; Sebla B. Kutluay; Aniket S Rali; Leo Simpson; Mehrdad Saririan; Dan Hobohm; W. Tom Stump; James A Fitzpatrick; Xuping Xie; Pei-Yong Shi; J Travis Hinson; Weng-Tein Gi; Constanze Schmidt; Florian Leuschner; Chieh-Yu Lin; Michael S Diamond; Michael J Greenberg; Kory J Lavine; Pamela J. Bjorkman; Saurabh Mehandru; Paul D. Bieniasz; Marina Caskey; Michel C. Nussenzweig

    doi:10.1101/2020.11.03.20225326 Date: 2020-11-05 Source: medRxiv

    Since the outbreak of Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) causing novel coronavirus (2019-nCoV)- infected pneumonia MESHD pneumonia HP (NCIP), over 45 million affected cases have been reported worldwide. Many patients with COVID-19 MESHD have involvement of their respiratory system. According to studies in the radiology literature, chest computed tomography (CT) is recommended in suspected cases for initial detection, evaluating the disease progression and monitoring the response to therapy. The aim of this article is to review the most frequently reported imaging features in COVID-19 MESHD patients in order to provide a reliable insight into expected CT imaging manifestations in patients with positive reverse-transcription polymerase chain reaction (RT-PCR) test results, and also for the initial detection of patients with suspicious clinical presentation whose RT-PCR test results are false negative. A total of 60 out of 173 initial COVID-19 MESHD studies, comprising 7571 individuals, were identified by searching PubMed database for articles published between the months of January and June 2020. The data of these studies were related to patients from China, Japan, Italy, USA, Iran and Singapore. Among 40 reported features, presence of ground glass opacities (GGO), consolidation, bilateral lung involvement and peripheral distribution are the most frequently observed ones, reported in 100%, 91.7%, 85%, and 83.3% of articles, respectively. In a similar way, we extracted CT imaging studies of similar pulmonary syndromes outbreaks caused by other strains of coronavirus family: Middle East Respiratory Syndrome MESHD ( MERS MESHD) and Severe Acute Respiratory Syndrome MESHD (SARS). For MERS MESHD and SARS, 2 out of 21 and 5 out of 153 initially retrieved studies had CT findings, respectively. Herein, we have indicated the most common coronavirus family related and COVID-19 MESHD specific features. Presence of GGO, consolidation, bilateral lung involvement and peripheral distribution were the features reported in at least 83% of COVID-19 MESHD articles, while air bronchogram, multi-lobe involvement and linear opacity were the three potential COVID-19 MESHD specific CT imaging findings. This is necessary to recognize the most promising imaging features for diagnosis and follow-up of patients with COVID-19 MESHD. Furthermore, we identified co-existed CT imaging features.

    The N-terminal domain of spike glycoprotein mediates SARS-CoV-2 infection MESHD by associating with L-SIGN and DC-SIGN

    Authors: Wai Tuck Soh; Yafei Liu; Emi E Nakayama; Chikako Ono; Shiho Torii; Hironori Nakagami; Yoshiharu Matsuura; Tatsuo Shioda; Hisashi Arase; Reid Simon; Ivan Grishagin; Laura Brovold; Ewy A Mathé; Matthew D Hall; Samuel G Michael; Alexander G Godfrey; Jordi Mestres; Lars J Jensen; Tudor I Oprea; Isabel Crooker; Sara Y Del Valle; Guido Espana; Geoffrey Fairchild; Richard C Gerkin; Timothy C Germann; Quanquan Gu; Xiangyang Guan; Lihong Guo; Gregory R Hart; Thomas J Hladish; Nathaniel Hupert; Daniel Janies; Cliff C Kerr; Daniel J Klein; Eili Klein; Gary Lin; Carrie Manore; Lauren Ancel Meyers; John Mittler; Kunpeng Mu; Rafael C NUNez; Rachel Oidtman; Remy Pasco; Ana Pastore y Piontti Pastore y Piontti; Rajib Paul; Carl AB Pearson; Dianela Perdomo; T Alex Perkins; Kelly Pierce; Alexander N Pillai; Rosalyn Cherie Rael; Katherine Rosenfeld; Chrysm Watson Ross; Julie A Spencer; Arlin B Stoltzfus; Kok Ben Toh; Shashaank Vattikuti; Alessandro Vespignani; Lingxiao Wang; Lisa White; Pan Xu; Yupeng Yang; Osman N Yogurtcu; Weitong Zhang; Yanting Zhao; Difan Zou; Matthew Ferrari; David Pannell; Michael Tildesley; Jack Seifarth; Elyse Johnson; Matthew Biggerstaff; Michael Johansson; Rachel B Slayton; John Levander; Jeff Stazer; Jessica Salermo; Michael C Runge

    doi:10.1101/2020.11.05.369264 Date: 2020-11-05 Source: bioRxiv

    The widespread occurrence of SARS-CoV-2 has had a profound effect on society and a vaccine is currently being developed. Angiotensin-converting enzyme 2 (ACE2) is the primary host cell receptor that interacts with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Although pneumonia MESHD pneumonia HP is the main symptom in severe cases of SARS-CoV-2 infection MESHD, the expression levels of ACE2 in the lung is low, suggesting the presence of another receptor for the spike protein. In order to identify the additional receptors for the spike protein, we screened a receptor for the SARS-CoV-2 spike protein from the lung cDNA library. We cloned L-SIGN as a specific receptor for the N-terminal domain (NTD) of the SARS-CoV-2 spike protein. The RBD of the spike protein did not bind to L-SIGN. In addition, not only L-SIGN but also DC-SIGN, a closely related C-type lectin receptor to L-SIGN, bound to the NTD of the SARS-CoV-2 spike protein. Importantly, cells expressing L-SIGN and DC-SIGN were both infected by SARS-CoV-2. Furthermore, L-SIGN and DC-SIGN induced membrane fusion by associating with the SARS-CoV-2 spike protein. Serum SERO antibodies SERO from infected patients and a patient-derived monoclonal antibody SERO against NTD inhibited SARS-CoV-2 infection of L-SIGN MESHD or DC-SIGN expressing cells. Our results highlight the important role of NTD in SARS-CoV-2 dissemination through L-SIGN and DC-SIGN and the significance of having anti-NTD neutralizing antibodies SERO in antibody SERO-based therapeutics.

    Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 MESHD by Upregulating Hyaluronan via NamiRNA-Enhancer Network

    Authors: Wei Li; Shuai Yang; Peng Xu; Dapeng Zhang; Ying Tong; Lu Chen; Ben Jia; Ang Li; Daoping Ru; Baolong Zhang; Mengxing Liu; Cheng Lian; Cancan Chen; Weihui Fu; Songhua Yuan; Xiaoguang Ren; Ying Liang; Zhicong Yang; Wenxuan Li; Shaoxuan Wang; Xiaoyan Zhang; Hongzhou Lu; Jianqing Xu; Hailing Wang; Wenqiang Yu; Vattipally B Sreenu; Jay Nix; Ruth F Jarrett; Martina Beltramello; Kyriaki Nomikou; Matteo Pizzuto; Lily Tong; Elisabetta Cameroni; Natasha Johnson; Arthur Wickenhagen; Alessandro Ceschi; Daniel Mair; Paolo Ferrari; Katherine Smollett; Federica Sallusto; Stephen Carmichael; Christian Garzoni; Jenna Nichols; Massimo Galli; Joseph Hughes; Agostino Riva; Antonia Ho; Peter JM Openshaw; Kenneth Baillie; - The ISARIC4C Investigators; - COVID-19 Genomics UK (COG-UK) consortium; Suzannah J Rihn; Samantha J Lycett; Herbert W Virgin; Amalio Telenti; Davide Corti; David L Robertson; Gyorgy Snell; Lingxiao Wang; Lisa White; Pan Xu; Yupeng Yang; Osman N Yogurtcu; Weitong Zhang; Yanting Zhao; Difan Zou; Matthew Ferrari; David Pannell; Michael Tildesley; Jack Seifarth; Elyse Johnson; Matthew Biggerstaff; Michael Johansson; Rachel B Slayton; John Levander; Jeff Stazer; Jessica Salermo; Michael C Runge

    doi:10.1101/2020.11.04.361576 Date: 2020-11-05 Source: bioRxiv

    The COVID-19 MESHD pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia MESHD pneumonia HP. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences ( HIS MESHD)". HIS MESHD are also recognized in both SARS-CoV MESHD and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2 RNA directly binds to the targeted loci in human genome and further interacts with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma SERO of COVID-19 MESHD patients is tightly correlated with severity and high risk for acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) and may act as a predictor for the progression of COVID-19 MESHD. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS MESHD related ground-glass pattern in lung for COVID-19 MESHD treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS MESHD in COVID-19 MESHD patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 MESHD progression.

    U-shaped-aggressiveness of SARS-CoV-2: Period between onset of nonspecific-specific symptoms for COVID-19 MESHD. A population-based cohort study

    Authors: Dan Morgenstern-Kaplan; Bruno Buitano-Tang; Mercedes Martinez-Gil; Andrea Zaldivar-Perez Pavon; Juan O Talavera; Adrien Elena; Christopher Hein; Blake Schwendiman; Christopher Burrow; Claire Le Helloco; Clemence Lebegue; Elom A Tay; Guy Cassuto; Gilles Pialoux; Laurent Hocqueloux; thierry prazuck

    doi:10.1101/2020.10.28.20221697 Date: 2020-11-03 Source: medRxiv

    Background: Early identification of different COVID-19 MESHD clinical presentations may depict distinct pathophysiological mechanisms and guide management strategies. Objective: To determine the aggressiveness of SARS-CoV-2 MESHD using symptom progression in COVID-19 MESHD patients. Design: Historic cohort study of Mexican patients. Data from January-April 2020 were provided by the Health Ministry. Setting: Population-based. Patients registered in the Epidemiologic Surveillance System in Mexico. Participants: Subjects who sought medical attention for suspicion of COVID-19 MESHD. All patients were subjected to RT-PCR testing for SARS-CoV-2. Measurements: We measured the period between onset of nonspecific to specific symptoms for COVID-19 MESHD (PONSS) and compared it to the primary outcomes (mortality and pneumonia HP pneumonia MESHD). Results: 65,500 patients were included. Reported fatalities and pneumonia MESHD pneumonia HP were 2176 (3.32%), and 11568 (17.66%), respectively. According to the PONSS, patients were distributed as follows: 14.89% in <24 hours, 43.25% between 1-3 days, 31.87% between 4-7 days and 9.97% >7 days. The distribution for mortality and pneumonia HP pneumonia MESHD was 5.2% and 22.5% in <24 hours, 2.5% and 14% between 1-3 days, 3.6% and 19.5% between 4-7 days, 4.1% and 20.6% >7 days, respectively (p<0.001). Adjusted-risk of mortality was (OR [95% CI], p-value): <24 hours= 1.75 [1.55-1.98], p<0.001; 1-3 days= 1 (reference value); 4-7 days= 1.53 [1.37-1.70], p<0.001; >7 days= 1.67 [1.44-1.94], p<0.001. For pneumonia HP pneumonia MESHD: <24 hours= 1.49 [1.39-1.58], p<0.001; 1-3 days= 1; 4-7 days= 1.48 [1.41-1.56], p<0.001; >7 days= 1.57 [1.46-1.69], p<0.001. Limitations: Using a database fed by large numbers of people carries the risk of data inaccuracy. However, this imprecision is expected to be random and data are consistent with previous studies. Conclusion: The PONSS shows a U-shaped SARS-CoV-2 aggressiveness MESHD pattern. Further studies are needed to corroborate the time-related pathophysiology behind these findings.

    Anakinra To Prevent Respiratory Failure MESHD Respiratory Failure HP In COVID-19 MESHD

    Authors: Evdoxia Kyriazopoulou; Periklis Panagopoulos; Simeon Metallidis; George Dalekos; Garyfallia Poulakou; Nikolaos Gatselis; Eleni Karakike; Maria Saridaki; Georgia Loli; Aggelos Stefos; Danai Prasianaki; Sarah Georgiadou; Olga Tsachouridou; Vasileios Petrakis; Konstantinos Tsiakos; Maria Kosmidou; Vassiliki Lygoura; Maria Dareioti; Haralampos Milionis; Ilias C Papanikolaou; Karolina Akinosoglou; Dimitra-Melia Myrodia; Areti Gravani; Aliki Stamou; Theologia Gkavogianni; Konstantina Katrini; Theodoros Marantos; Ioannis P Trontzas; Konstantinos Syrigos; Lukas Chatzis; Stamatios Chatzis; Nikolaos Vechlidis; Christina Avgoustou; Stamatios Chalvatzis; Miltiades Kyprianou; Jos WM van der Meer; jesper eugen-olsen; Mihai Netea; Evangelos Giamarellos-Bourboulis

    doi:10.1101/2020.10.28.20217455 Date: 2020-10-29 Source: medRxiv

    Introduction The management of pneumonia MESHD pneumonia HP caused by SARS-CoV-2 should rely on early recognition of the risk for progression to severe respiratory failure MESHD respiratory failure HP ( SRF MESHD) and its prevention. We investigated if early suPAR (soluble urokinase plasminogen activator receptor)-guided anakinra treatment could prevent COVID-19 MESHD-assocated SRF. Methods In this open-label prospective trial, 130 patients admitted with SARS-CoV-2 pneumonia SARS-CoV-2 MESHD pneumonia HP SARS-CoV-2 and suPAR levels [≥]6 g/l were assigned to subcutaneous anakinra 100mg once daily for 10 days. The primary outcome was the incidence of SRF MESHD at day 14. Secondary outcomes were 30-day mortality, changes in sequential organ failure assessment (SOFA) score, of cytokine-stimulation pattern and of circulating inflammatory mediators. Equal number of propensity score-matched comparators for comorbidities, severity on admission and standard-of care (SOC) were studied. Results The incidence of SRF MESHD was 22.3% (95% CI, 16.0-30.2%) among anakinra-treated patients and 59.2% (95% CI, 50.6-67.3%; P: 4.6 x 10-8) among SOC comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46). 30-day mortality was 11.5% (95% CI, 7.1-18.2%) and 22.3% (95% CI, 16.0-30.2%) respectively (hazard ratio 0.49; 95% CI 0.25-0.97%; P: 0.041). Anakinra treatment was associated with decrease in SOFA score and in circulating interleukin (IL)-6, sCD163 and sIL2-R; the serum SERO IL-10/IL-6 ratio on day 7 was inversely associated with the change in SOFA score. Duration of stay at the intensive care unit and at hospital was shortened compared to the SOC group; the cost of hospitalization was decreased. Conclusions Early suPAR-guided anakinra treatment is associated with decrease of the risk for SRF MESHD and restoration of the pro- /anti-inflammatory balance.

    Lung transplantation for pulmonary fibrosis MESHD pulmonary fibrosis HP secondary to severe COVID-19 MESHD

    Authors: Ankit Bharat; Melissa Querrey; Nikolay S Markov; Samuel S Kim; Chitaru Kurihara; Rafael Garza-Castillon Jr.; Adwaiy Manerikar; Ali Shilatifard; Rade Tomic; Yuliya Politanska; Hiam Abdala-Valencia; Anjana V Yeldandi; Jon W Lomasney; Alexander V Misharin; GR Scott Budinger; Sarah Platt; Eve Hamilton; Andrew Barr; Lucy Venyo; Peter Wilson; Tom Bewick; Priya Daniel; Paul Dark; Adam R Jeans; Jamie McCanny; Jonathan D Edgeworth; Martin J Llewelyn; Matthias L Schmid; Tricia M McKeever; Martin Beed; Wei Shen Lim

    doi:10.1101/2020.10.26.20218636 Date: 2020-10-27 Source: medRxiv

    Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19 MESHD acute respiratory distress syndrome MESHD respiratory distress HP syndrome. Concerns limiting transplant include recurrence of SARS-CoV-2 infection MESHD in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection MESHD by pathogens associated with ventilator-induced pneumonia MESHD pneumonia HP in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report the results of the first two successful lung transplantation procedures in patients with non-resolving COVID-19 MESHD associated acute respiratory distress HP respiratory distress MESHD syndrome in the United States. We performed smFISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 MESHD pneumonia HP pneumonia MESHD. Lungs from patients with prolonged COVID-19 MESHD were free of virus but pathology showed extensive evidence of injury MESHD and fibrosis MESHD which resembled end-stage pulmonary fibrosis MESHD pulmonary fibrosis HP. Single cell RNA-Seq of the explanted native lungs from transplant and paired warm post-mortem autopsies showed similarities between late SARS-CoV-2 acute respiratory distress syndrome MESHD respiratory distress HP syndrome and irreversible end-stage pulmonary fibrosis HP pulmonary fibrosis MESHD requiring lung transplantation. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator-associated pneumonias HP pneumonias MESHD following transplantation in either patient. Our findings suggest that some patients with severe COVID-19 MESHD develop fibrotic lung disease MESHD for which lung transplantation is the only option for survival.

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