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SARS-CoV-2 proteins

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    Rapid protection from COVID-19 MESHD in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine

    Authors: Wakako Furuyama; Kyle Shifflett; Amanda N Pinksi; Amanda J Griffin; Friederike Feldmann; Atsushi Okumura; Tylisha Gourdine; Allen Jankeel; Jamie Lovaglio; Patrick W Hanley; Tina Thomas; Chad S Clancy; Ilhem Messaoudi; Andrea Marzi; Martina Turroja; Kamille A West; Kristie Gordon; Katrina G Millard; Victor Ramos; Justin Da Silva; Jianliang Xu; Robert A Colbert; Roshni Patel; Juan P Dizon; Irina Shimeliovich; Anna Gazumyan; Marina Caskey; Pamela J Bjorkman; Rafael Casellas; Theodora Hatziioannou; Paul D Bieniasz; Michel C Nussenzweig

    doi:10.1101/2021.01.19.426885 Date: 2021-01-19 Source: bioRxiv

    The ongoing pandemic of Coronavirus disease 2019 MESHD ( COVID-19 MESHD) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis MESHD virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike PROTEIN protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 MESHD pneumonia MESHD. In contrast, IN vaccination MESHD resulted in limited immunogenicity and enhanced COVID-19 MESHD pneumonia MESHD compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers MESHD, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 MESHD vaccine candidate that offers rapid protection based on the protective efficacy observed in our study.

    COVID-19 MESHD risk stratification tools should incorporate multi-ethnic age structures, multimorbidity and deprivation metrics for air pollution, household overcrowding, housing quality and adult skills 

    Authors: Marina A. Soltan; Justin Varney; Benjamin Sutton; Colin R. Melville; Sebastian T. Lugg; Dhruv Parekh; Will Carroll; Davinder Dosanjh; David R. Thickett

    doi:10.21203/rs.3.rs-149632/v1 Date: 2021-01-18 Source: ResearchSquare

    Background-Black Asian and Minority Ethnicity (BAME) patients account for 34% of critically ill COVID-19 MESHD patients despite constituting 14% of the UK population. Internationally, researchers have called for studies to understand the risk factors among ethnic subgroups. We explored the extent to which social determinants for health including individual Index of Multiple Deprivation (I MD) MESHD sub-indices are risk factors for presentation with multilobar p neumonia, MESHD Intensive Therapy Unit (ITU) admission and hospitalised outcomes disaggregated by BAME subgroup.Methods-Multi-centre cohort study of hospitalised COVID-19 MESHD patients.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Results-BAME patients with p neumonia MESHDand low CURB65 scores (0-1) had higher mortality than Caucasians (22.6% vs.9.4%; p<0.001); Africans were at highest risk (38.5%; p=0.006), followed by Caribbean (26.7%; p=0.008), Indian (23.1%; p=0.007) and Pakistani (21.2%; p=0.004). Age, sex, c irrhosis, MESHD o besity, MESHD Charlson Comorbidity (CCI) scores, presentation with m ulti-lobar pneumonia MESHDand ITU admission were independent mortality risk factors. BAME subgroups were more likely to be admitted with higher CCI scores than age, sex and deprivation matched controls and from the highest IMD sub-indices of at least one deprivation form: Indoor Living Environment (LE), Outdoor LE, Adult Skills and Wider Barriers to Housing and Services. Admission from the highest sub-indices of these deprivation forms was associated with multilobar p neumonia MESHDon presentation and ITU admission.Conclusions-BAME subgroups exhibit younger age structures resulting in CURB65 underscoring and disproportionate exposure to unscored risk factors:sex, o besity, MESHD multimorbidity and deprivation. Household overcrowding deprivation, air pollution deprivation, housing q uality deprivation and adult skills deprivation MESHDare associated with m ulti-lobar pneumonia MESHDon presentation and ITU admission. Risk tools need to reflect risk factors predominantly affecting BAME subgroups.

    Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 MESHD in the Microbial Resistant Era

    Authors: Ángel Serrano-Aroca; Kazuo Takayama; Alberto Tuñón-Molina; Murat Seyran; Sk. Sarif Hassan; Pabitra Pal Choudhury; Vladimir N. Uversky; Kenneth Lundstrom; Parise Adadi; Giorgio Palù; Alaa A. A. Aljabali; Gaurav Chauhan; Ramesh Kandimalla; Murtaza M. Tambuwala; Amos Lal; Bruce D. Uhal; Adam M. Brufsky

    id:10.20944/preprints202101.0297.v1 Date: 2021-01-15 Source: Preprints.org

    Therapeutic options for the highly pathogenic human Severe Acute Respiratory Syndrome-Coronavirus MESHD 2 (SARS-CoV-2) causing the current pandemic Coronavirus disease MESHD ( COVID-19 MESHD) are urgently needed. COVID-19 MESHD is associated with viral pneumonia MESHD and acute respiratory distress syndrome MESHD causing significant morbidity and mortality. The proposed treatments for COVID-19 MESHD, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease MESHD complex. The antibiotic resistance in pneumonia MESHD treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity MESHD to the humans are promising therapeutics against COVID-19 MESHD pneumonia MESHD complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.

    Bacterial superinfection pneumonia MESHD in SARS-CoV-2 respiratory failure MESHD

    Authors: Chiagozie O. Pickens; Catherine A. Gao; Michael J. Cuttica; Sean B. Smith; Lorenzo Pesce; Rogan Grant; Mengjia Kang; Luisa Morales-Nebreda; Avni A. Bavishi; Jason Arnold; Anna Pawlowski; Chao Qi; GR Scott Budinger; Benjamin D. Singer; Richard G. Wunderink; - NU COVID Investigators; Natalie J Thornburg; Panayampalli S Satheshkumar; Xiaowu Liang; Richard B Kennedy; Angela Yee; Michael Townsend; Joseph J Campo; Michael W Mather; Rik GH Lindeboom; Emma Dann; Ni Huang; Krzysztof Polanski; Elena Prigmore; Florian Gothe; Jonathan Scott; Rebecca P Payne; Kenneth F Baker; Aidan T Hanrath; Ina CD Schim van der Loeff; Andrew S Barr; Amada Sanchez-Gonzalez; Laura Bergamaschi; Federica Mescia; Josephine L Barnes; Eliz Kilich; Angus de Wilton; Anita Saigal; Aarash Saleh; Sam M Janes; Claire M Smith; Nusayhah Gopee; Caroline Wilson; Paul Coupland; Jonathan M Coxhead; Vladimir Y Kiselev; Stijn van Dongen; Jaume Bacardit; Hamish W King; Anthony J Rostron; A John Simpson; Sophie Hambleton; Elisa Laurenti; Paul A Lyons; Kerstin B Meyer; Marko Z Nikolic; Christopher JA Duncan; Ken Smith; Sarah A Teichmann; Menna R Clatworthy; John C Marioni; Berthold Gottgens; Muzlifah Haniffa

    doi:10.1101/2021.01.12.20248588 Date: 2021-01-15 Source: medRxiv

    BackgroundSevere community-acquired pneumonia MESHD secondary to SARS-CoV-2 is a leading cause of death MESHD. Current guidelines recommend patients with SARS-CoV-2 pneumonia MESHD receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations. MethodsWe obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia MESHD requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia MESHD ( VAP MESHD) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care. ResultsThe 179 ventilated patients with severe SARS-CoV-2 pneumonia MESHD discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days. ConclusionsWith use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia MESHD. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP MESHD in ventilated patients with SARS-CoV-2 pneumonia MESHD are higher than historically reported.

    Correlation of Computerized Tomography (CT) Severity Score for COVID-19 MESHD pneumonia MESHD with Clinical Outcomes

    Authors: Kiran Hilal; Jehanzeb Shahid; Abdullah Aameen; Russell Seth Martins; Avinash Nankani; Ainan Arshad; Haq Tu; John Bell; John Newton; Jeremy Farrar; Ian Diamond; Ruth Studley; Emma Rourke; Jodie Hay; Susan Hopkins; Derrick W Crook; Tim Peto; Philippa Matthews; David W Eyre; Nicole W Stoesser; Koen Pouwels; - the COVID-19 Infection Survey team; Roberto Bertollini

    doi:10.1101/2021.01.15.426787 Date: 2021-01-15 Source: bioRxiv

    IntroductionVarious CT severity scores have already been described in literature since the start of this pandemic. One pertinent issue with all of the previously described severity scores is their relative challenging calculation and variance in inter-observer agreement. The severity score proposed in our study is relatively simpler, easier to calculate and apart from a trained radiologist, can easily be calculated even by physicians with good inter-observer agreement. Therefore, a rapid CT severity score calculation can give a clue to physician about possible clinical outcome without being dependent on radiologist who may not be readily available especially in third world countries. ObjectiveThe objective of this study is to develop a simple CT severity score (CT-SS) with good inter-observer agreement and access its correlation with clinical outcome. MethodsThis retrospective study was conducted by the Department of Radiology and Internal Medicine, at the Aga Khan University Hospital Karachi, from April 2020 to August 2020. Non-probability consecutive sampling was used to include all patients who were positive for COVID-19 MESHD on PCR, and underwent CT chest examination at AKUH. Severity of disease was calculated in each lobe on the basis of following proposed CT severity scoring system (CT-SS). For each lobe the percentage of involvement by disease was scored - 0% involvement was scored 0, <50% involvement was scored 1 and >50% involvement was scored 2. Maximum score for one lobe was 2 and hence total maximum overall score for all lobes was 10. Continuous data was represented using mean and standard deviation, and compared using independent sample t-tests. Categorical data was represented using frequencies and percentages, and compared using Chi-squared tests. Inter-observer reliability between radiologist and COVID intensivist for the 10 point CT-SS rated on 0-10 was assessed using the Kappa statistic. A p-value < 0.05 was considered significant for all analyses. ResultsA total of 73 patients were included, the majority male (58.9%) with mean age 55.8 {+/-} 13.93 years. The CT-SS rated on 0-10 showed substantial inter-observer reliability between radiologist and intensivist with a Kappa statistic of 0.78. Patients with CT-SS 8-10 had a significantly higher ICU admission & intubation rate (53.8% vs. 23.5%) and mortality rate (35.9% vs. 11.8%; p = 0.017), as compared to those with CT-SS 0-7. ConclusionWe conclude that the described CT severity score (CT-SS) is a quick, effective and easily reproducible tool for prediction of adverse clinical outcome in patients with COVID 19 pneumonia MESHD. The tool shows good inter-observer agreement when calculated by radiologist and physician independently.

    COVID-DenseNet: A Deep Learning Architecture MESHD to Detect COVID-19 MESHD from Chest Radiology Images

    Authors: Laboni Sarker; Md. Mohaiminul Islam; Tanveer Hannan; Zakaria Ahmed

    id:202005.0151/v2 Date: 2021-01-15 Source: Preprints.org

    Coronavirus disease MESHD ( COVID-19 MESHD) is a pandemic infectious disease MESHD that has a severe risk of spreading rapidly. The quick identification and isolation of the affected persons is the very first step to fight against this virus. In this regard, chest radiology images have been proven to be an effective screening approach of COVID-19 MESHD affected patients. A number of AI based solutions have been developed to make the screening of radiological images faster and more accurate in detecting COVID-19 MESHD. In this study, we are proposing a deep learning based approach using Densenet-121 to effectively detect COVID-19 MESHD patients. We incorporated transfer learning technique to leverage the information regarding radiology image learned by another model (CheXNet) which was trained on a huge Radiology dataset of 112,120 images. We trained and tested our model on COVIDx dataset containing 13,800 chest radiography images across 13,725 patients. To check the robustness of our model, we performed both two-class and three-class classifications and achieved 96.49% and 93.71% accuracy respectively. To further validate the consistency of our performance, we performed patient-wise k-fold cross-validation and achieved an average accuracy of 92.91% for three class task. Moreover, we performed an interpretability analysis using Grad- CAM HGNC to highlight the most important image regions in making a prediction. Besides ensuring trustworthiness, this explainability can also provide new insights about the critical factors regarding COVID-19 MESHD. Finally, we developed a website that takes chest radiology images as input and generates probabilities of the presence of COVID-19 MESHD or pneumonia MESHD and a heatmap highlighting the probable infected regions. Code and models' weights are availabe.

    Dynamic Prediction of SARS-CoV-2 RT-PCR status on Chest Radiographs using Deep Learning Enabled Radiogenomics

    Authors: Wan Hang Keith Chiu; Dmytro Poplavskiy; Sailong Zhang; Philip Leong Ho Yu; Michael D Kuo; Peng Ru; Jason Garee; Keelie Thomas; Peter Mohler; Preeti Pancholi; Dan Jones; Rongjuan Pei; Shihai Zhang; Minbo Su; Yi Zhang; Jia Li; Laura Esparcia; Ana Marcos-Jimenez; Santiago Sanchez-Alonso; Irene Llorente; Joan B. Soriano; Carmen Suarez Fernandez; Rosario Garcia-Vicuna; Julio Ancochea; Jesus Sanz; Cecilia Munoz-Calleja; Rafael de la Camara; Alfonso Canabal Berlanga; Isidoro Gonzalez-Alvaro; Laura Cardenoso; John R Bradley

    doi:10.1101/2021.01.10.21249370 Date: 2021-01-15 Source: medRxiv

    Reverse Transcription-Polymerase Chain Reaction (RT-PCR) is the gold standard for diagnosis of SARS-CoV-2 infection MESHD, but requires specialized equipment and reagents and suffers from long turnaround times. While valuable, chest imaging currently only detects COVID-19 MESHD pneumonia MESHD, but if it can predict actual RT-PCR SARS-CoV-2 status is unknown. Radiogenomics may provide an effective and accurate RT-PCR-based surrogate. We describe a deep learning radiogenomics (DLR) model (RadGen) that predicts a patient's RT-PCR SARS-CoV-2 status solely from their frontal chest radiograph (CXR).

    Verifying Extra-Pulmonary Manifestation of COVID-19 MESHD in Firoozgar Hospital 2020: An Observational Study

    Authors: Azadeh Mottaghi; Maryam Roham; Mahin Jamshidi Makiani; Mitra Ranjbar; Azadeh Laali; Neda Rahimian Rahimian.n@iums.ac.ir

    doi:10.21203/rs.3.rs-147631/v1 Date: 2021-01-14 Source: ResearchSquare

    Background: COVID-19 MESHD is a new emerging disease MESHD that causes a pandemic situation in the world. Corona virus can enter into the body via several ways and it damages other organs of the body in addition to the respiratory system. This study aimed at verifying extra-pulmonary manifestation of COVID-19 MESHD.Methods: The present study was done as cross-sectional in the single center from March 1 HGNC to May 1 HGNC 2020 at Firoozgar educational hospital in Tehran, Iran. 107 patients with confirmed Covid-19 MESHD pneumonia MESHD according to WHO interim guidance were recruited in this study. Extra-pulmonary manifestations of COVID-19 MESHD were recorded. SPSS, version 26 was used for all analyses.Results: The mean (SD) and median of age was 59.3 (17.4) and 62.0 respectively and 58 (54.2%) were men. Body temperature of patients who were equal or less than 60 years was significantly higher than other patients (39.02 vs. 38.08, p=0001). The most common extra-pulmonary manifestation was GI symptoms MESHD included nausea MESHD, vomiting MESHD, abdominal pain MESHD, diarrhea MESHD, Hepatocellular LFT abnormality MESHD, Cholestatic LFT abnormality MESHD and Amylase lipase incensement (37 patients (34.6%)). Ophthalmological, cardiac, neurological and dermatological manifestations were shown in 6.5%, 6.5%, 14.9% and 14.0% of patients respectively. Conclusion: Investigating the clinical and radiological symptoms of COVID-19 MESHD showed that SARS-CoV-2 infection MESHD may also be associated with extrapulmonary symptoms. Therefore, clinicians and radiologists should be familiar with such symptoms of this disease. 

    Neonatal COVID-19 MESHD in French Guiana, a Case-Control study.

    Authors: Narcisse Elenga; Wandji Marie-Josephine; Julie Siban; Mathieu Nacher; Magalie Demar

    doi:10.21203/rs.3.rs-147493/v1 Date: 2021-01-14 Source: ResearchSquare

    BackgroundThis study aims to assess the risk of transmission of Severe Acute Respiratory Syndrome Coronavirus 2 MESHD ( SARS COV-2 MESHD) to newborns in the context of breastfeeding practice as part of routine care.MethodsIn this prospective study, we identified neonates born between May 14th and August 31st, 2020, to mothers who tested positive for SARS-CoV-2 at the time of delivery. From the cohort of 974 deliveries, we performed a nested case-control study. ResultsDuring the study period, 133 (13.7%) were positive by RT‐PCR for SARS‐CoV‐2. Among the 35 pregnant women with symptomatic COVID-19 MESHD (26.3%), cough MESHD was the most common symptom, occurring in half of the cases. Among them, 3 developed fever MESHD as other symptoms during hospitalization and 4 have progressed to critical pneumonia MESHD requiring transfer to intensive care unit. Among the neonates born from mothers with positive RT‐PCR for SARS‐CoV‐2, 32 were tested for SARS-COV-2 at 48 hours-7 days. Of them, 3 asymptomatic neonates tested positive. There were no significant differences in fetal distress, meconium-stained amniotic fluid, preterm birth, and neonatal asphyxia MESHD between the two groups Most infants were breastfed at birth, regardless of their mothers' COVID-19 MESHD status. In COVID-19 MESHD-positive pregnant women admitted to intensive care unit, the proportion of preterm births ( OR=12.5 [1.7-90.5]), fetal death MESHD in utero (OR=25.9 [2.2-305]) and admission in neonatal intensive care unit admission (OR=13.4 [3.0-60]), appeared higher than the controls. No maternal deaths were recorded.ConclusionsOur data suggest that under breastfeeding conditions with rigorous hygiene precautions and parental education, the risk of vertical transmission of the SARS-COV-2 virus is unlikely.

    Fatal neuroinvasion of SARS-CoV-2 in K18- hACE2 HGNC mice is partially dependent on hACE2 HGNC expression

    Authors: Mariano Carossino; Paige Montanaro; Devin Kenney; Hans Gertje; Kyle Grosz; Susanna Kurnick; Markus Bosmann; Mohsan Saeed; Udeni Balasuriya; Florian Douam; Nicholas Crossland; Madison M Hebert; Scott W Benzinger; Koushik T Sinha; Keith T Gagnon; Rafael Rezende; Eduardo Cilli; Guilherme Malafaia; Nicholas Thomson; Caroline Buckee; Firdausi Qadri; Tahmina Shirin

    doi:10.1101/2021.01.13.425144 Date: 2021-01-13 Source: bioRxiv

    Animal models recapitulating the distinctive features of severe COVID-19 MESHD are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 HGNC ( hACE2 HGNC) under the cytokeratin 18 promoter ( K18 HGNC- hACE2 HGNC) represent a lethal model of SARS-CoV-2 infection MESHD. However, the cause(s) and mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection MESHD for up to 14 days post-infection. Despite infection and moderate inflammation MESHD in the lungs, lethality was invariably associated with viral neuroinvasion and neuronal damage MESHD (including spinal motor neurons). Neuroinvasion occurred following virus transport through the olfactory neuroepithelium in a manner that was only partially dependent on hACE2 HGNC. Interestingly, SARS-CoV-2 tropism MESHD was overall neither widespread among nor restricted to only ACE2-expressing cells. Although our work incites caution in the utility of the K18- hACE2 HGNC model to study global aspects of SARS-CoV-2 pathogenesis, it underscores this model as a unique platform for exploring the mechanisms of SARS-CoV-2 neuropathogenesis MESHD. SUMMARY COVID-19 MESHD is a respiratory disease MESHD caused by SARS-CoV-2, a betacoronavirus. Here, we show that in a widely used transgenic mouse model of COVID-19 MESHD, lethality is invariably associated with viral neuroinvasion and the ensuing neuronal disease MESHD, while lung inflammation MESHD remains moderate.

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