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

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

Acute Kidney Injury in Critically Ill Vascular Surgery Patients is Common and Associated WithIncreased Mortality.

Introduction.Vascular surgery patients have multiple risk factors for renal dysfunction, but acute kidney injury (AKI) is poorly studied in this group. The purpose of this study was to define the incidence, risk factors and outcomes of AKI in high risk vascular patients. Methods.Critically ill vascular surgery patients admitted during January – December 2012 were retrospectively analyzed with 1-yearfollow-up. The endpoint was AKI by established RIFLE creatinine criteria. The primary analysis was between patients with or without AKI, with secondary analysis of postoperative AKI. Outcomes were inpatient and 1-year mortality, inpatient lengths of stay, and discharge renal function. Results.136 vascular surgery patients were included, representing 27% of all vascular surgery admissions during the study period. 65 (48%) developed AKI. Independent global risk factors for AKI were diabetes, increasing critical illness severity, and sepsis. Whileintraoperative blood loss and hypotension were associated with subsequent renal dysfunction, postoperative AKI rates were similar for patients undergoing aortic, carotid, endovascular, or peripheral vascular procedures, All RIFLE grades of AKI were associated with worse outcomes. Overall, patients with AKI had significantly increased short and long-term mortality, longerinpatient lengths of stay, and worse discharge renal function. Conclusions.AKI is common among critically ill vascular surgery patients. Importantly, the type of surgical procedure appears to be lessimportant than intra- and perioperative management in determining renal dysfunction. Regardless of its severity, AKI is a clinically significant complication that is associated with substantially worse patient outcomes