SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study.

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.This report was produced by members of the COG-UK-HOCI Variant substudy consortium. COG-UK-HOCI is part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Structural and inhibition studies on Human Flap Endonuclease

Flap endonuclease 1 (FEN1) is a paradigm of structure-specific metallonuclease family that selectively catalyzes the removal of single-stranded 5ʹ-flaps, occurring in vivo primarily in Okazaki fragment maturation and DNA repair. Enzymatic malfunction of FEN1 has dramatic consequences for eukaryotic genome stability. Since overexpression of FEN1 has been reported in multiple cancers, FEN1 inhibition is proposed to have a therapeutic potential. Without any clinical trials related to FEN1 inhibition registered to date, small molecule inhibitors are now recognized as possible leads for the development of novel anticancer drugs. Aiming at the identification of small molecule FEN1 inhibitors at an in silico stage, a dual approach of virtual and physical screening was followed. Manipulation of active site metal charges led to a well-performing docking strategy under +2 active site metal charges that can effectively predict the great majority of in vitro confirmed hits and used for cost-effective FEN1 inhibitor identification. In addition, following a collaborative hit expansion study an inhibitor of HsFEN1 with IC50 of ∼1.7 μM was identified for future inhibitor development studies, expanding the reported to date range of FEN1 inhibitors. Crystallographic analyses also led to two HsFEN1:product DNA complex structures supporting the dsDNA substrate’s ability to bend 100°, “trapping” of the 1-nt long 3ʹ-flap and positioning of 5ʹ-flap towards the active site because of HsFEN1 binding at the DNA bend. The presence of CaCl2 allowed some enzymatic activity and facilitated crystallization of a product complex whose structure was determined at 2.3 Å. Whilst this project focuses on human FEN1, microbial FEN inhibitors identified by the University of Sheffield (UoS) spin-out DeFENition Ltd primarily for antibiotics development were examined within the context of the current thesis for their induced cytotoxicity. Although structure-activity relationships fell outside the scope of the current thesis, this first ever collected cytotoxicity dataset provided key information for future toxicity studies and downstream compound development

Ο βαθμός αποδοχής του διαιτολογίου διαβήτη από τους νοσηλευόμενους ασθενείς

Εισαγωγή: Η διαχείριση του ΣΔ εξαρτάται σε μεγάλο βαθμό από την ικανότητα του ασθενούς να ασκήσει αυτοφροντίδα στην καθημερινή του ζωή. Η τήρηση μιας ισορροπημένης διατροφής αποτελεί κρίσιμη πτυχή της αυτοφροντίδας, για αυτό η διατροφική εκπαίδευση των ατόμων με ΣΔ θα πρέπει να αποτελεί προτεραιότητα. Σκοπός: Η διερεύνηση της αποδοχής του ενδονοσοκομειακού φαγητού από τους νοσηλευόμενους διαβητικούς ασθενείς, των πεποιθήσεων τους ως προς την διατροφή που πρέπει να ακολουθούν αλλά και η αξιολόγηση των γνώσεων τους ως προς την διατροφική διαχείριση της νόσου. Υλικό και μέθοδος: Μελετήθηκαν 138 νοσηλευόμενα άτομα με ΣΔ, εκ των οποίων οι 78 (56,5%) ήταν άντρες και οι 60 (43,5%) γυναίκες. Οι συμμετέχοντες συμπλήρωσαν ένα ερωτηματολόγιο 10 ερωτήσεων που διαμορφώθηκε για τους σκοπούς της μελέτης. Απαραίτητη προϋπόθεση για την συμμετοχή τους ήταν η νοσηλεία τους για τουλάχιστον 3 ημέρες και η κατανάλωση διαιτολογίου από τα άτομα με διαβήτη. Για τη στατιστική ανάλυση χρησιμοποιήθηκε το στατιστικό λογισμικό SPSS v.23.0. Αποτελέσματα: Η μέση ηλικία των συμμετεχόντων ήταν 69.6 ± 12,1 έτη. Παρατηρήθηκε ότι οι 9 συμμετέχοντες είχαν ΣΔτ1 (6,5%) και οι 129 είχαν ΣΔτ2 (93,5%), εκ των οποίων οι 111 (80,4%) είχαν διάρκεια ΣΔ άνω των 5 ετών. Οι 70 (50,7%) συμμετέχοντες δήλωσαν ότι το προσφερόμενο ενδονοσοκομειακό φαγητό συνάδει με τις διατροφικές οδηγίες, που είχαν λάβει στο παρελθόν για την διαχείριση του ΣΔ, ενώ παράλληλα πίστευαν ότι τους βοηθούσε στη γλυκαιμική ρύθμιση. Οι 40 (29%) θεωρούσαν ότι τα αμυλούχα τρόφιμα δεν έχουν θέση στην διατροφή του ατόμου με ΣΔ, εκ των οποίων οι 14 (10,1%) δήλωσαν ως πιο επιβαρυντικό αμυλούχο τρόφιμο το ρύζι για το γλυκαιμικό έλεγχο. Συμπεράσματα : Ένα μεγάλο ποσοστό ασθενών έχουν ικανοποιητικό επίπεδο γνώσης, σχετικά με τις ισχύουσες διατροφικές οδηγίες και τη σημασία της σωστής διατροφής στην αποτελεσματική γλυκαιμική ρύθμιση. Η μελέτη έδειξε επίσης τη μεγάλη ανάγκη για εξειδικευμένο επιστημονικό προσωπικό στα νοσοκομεία με ευθύνη την εκπαίδευση αλλά και το σχεδιασμό κατάλληλων γευμάτων για τους ασθενείς με ΣΔ.Introduction: Management of diabetes mellitus (DM) largely depends on the patient’s ability to participate and receive self-management education and support (DSMES). Maintaining a balanced and healthy diet is the main therapeutic goal of DM. Therefore, nutritional patient’s education should always be considered a priority of DM management. Objectives: This study aims to assess the level of acceptance of food provided in hospital among inpatient diabetics, their beliefs about the diet they should follow according to their disease and their awareness of nutritional management of DM. Methods: 138 diabetic inpatients participated in the study, 78 (56,5%) men and 60 (43,5%) women. Data was collected using a 10-item questionnaire, which was designed for the purposes of the study. Inclusion criteria were the hospitalization of the diabetic patients for at least 3 days and the consumption of hospital meals for diabetics during their hospitalization. SPSS version 23 was used for statistical analysis. Results: The mean age of the participants was 69.6 ±12.1 years. Among 138 participants, 9 (6.5%) were diagnosed with Type 1 DM and 129 (93.5%) with Type 2 DM. The duration of DM was more than five years in 111 (80,4%) of the total participants. 70 (50.7%) of the participants think that hospital dietary plan is following the dietary guidelines they had received in the past for the management of DM. The same percentage of participants believed that hospital diet for DM helped them in glycemic control. In conclusion, about 40 (29%) participants answered that starchy foods have no place in diabetic diet and 14 (10.1%) of them stated that, according to their opinion, rice has the most harmful effect in glycemic control among all the starchy food. Conclusion: A high percentage of patients had a satisfactory level of awareness of current dietary guidelines and the importance of balanced nutrition in effective glycemic control. The study revealed also the urgent necessity for specialized scientific staff in hospitals, which will be responsible for the education of diabetic patients and the dietary planning of appropriate meals for inpatients with DM

Σύνθεση και χαρακτηρισμός του συμπλόκου [RhL1Cl3(MeOH)] με τον οργανικό υποκαταστάτη L1 = 2-(2-Πυριδυλ) Κινολίνη

Η παρούσα εργασία έχει ως αντικείμενο τη σύνθεση και τον χαρακτηρισμό του συμπλόκου [RhL1Cl3(MeOH)], με τον οργανικό υποκαταστάτη L1 = 2-(2-ΠΥΡΙΔΥΛ) ΚΙΝΟΛΙΝΗ. Μελετήθηκε η αγώγιμότητά του, η διαλυτότητά του σε δια΄φορους διαλύτες και λήφθηκαν φάσματα NMR, IR και UV.The present work is dedicated to the synthesis and characterization of the complex [RhL1Cl3(MeOH)] with the organic substituent L1- 2-(2-pyridyl) quinoline. Its conductivity, solubility in various solvents was studied and NMR, IR and UV spectra were obtained