The COVID-19 pandemic is expanding at an unprecedented rate. As a result, diagnostic services are stretched to their limit, and there is a clear need for the provision of additional diagnostic capacity. Academic laboratories, many of which are closed due to governmental lockdowns, may be in a position to support local screening capacity by adapting their current laboratory practices. Here, we describe the process of developing a SARS-Cov2 diagnostic workflow in a conventional academic Containment Level 2 laboratory. Our outline includes simple SARS-Cov2 deactivation upon contact, the method for a quantitative real-time reverse transcriptase PCR detecting SARS-Cov2, a description of process establishment and validation, and some considerations for establishing a similar workflow elsewhere. This was achieved under challenging circumstances through the collaborative efforts of scientists, clinical staff, and diagnostic staff to mitigate to the ongoing crisis. Within 14 days, we created a validated COVID-19 diagnostics service for healthcare workers in our local hospital. The described methods are not exhaustive, but we hope may offer support to other academic groups aiming to set up something comparable in a short time frame.
The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation. ; This work was supported by funds from the Wellcome Trust WT090323MA and MRC G1000236. MR/L018373/1. This work was also supported by a Wellcome Trust Principal Research Fellowship (WT101835) to PJL and a Wellcome Trust Senior Fellowship (108070/Z/15/Z) to MPW and a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140). JAP was supported by NIH/NIDDK grant K01 DK098285. BV was supported by projects MEYS – NPS I – LO1413 and Czech Science Foundation P206/12/G151. ER was supported by MH CZ-DRO (MMCI, 00209805). CC and JT were supported by grant G0901682 from the MRC and funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 695551), with partial funding from the National Institute of Health Cambridge Biomedical Research Centre.
Understanding 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. ; DA is a Wellcome Clinical PhD Fellow and gratefully supported by the Wellcome Trust (Grant number: 222903/Z/21/Z). BW receives funding from the University of Cambridge and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) at the Cambridge University Hospitals NHS Foundation Trust. IG is a Wellcome Senior Fellow and is supported by the Wellcome Trust (Grant number: 207498/Z/17/Z and 206298/B/17/Z). EMH is supported by a UK Research and Innovation (UKRI) Fellowship: MR/S00291X/1. CJRI acknowledges Medical Research Council (MRC) funding (ref: MC_UU_00002/11). NJM is supported by the MRC (CSF MR/P008801/1) and NHSBT (WPA15-02). AJP gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); their research was funded by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10352, also Quadram Institute Bioscience BBSRC funded Core Capability Grant (project number BB/CCG1860/1). LdP and OGP were supported by the Oxford Martin School. This research was supported by the NIHR Cambridge BRC. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The COVID-19 Genomics UK Consortium is supported by funding from the MRC part of UK Research & Innovation (UKRI), the National Institute of Health Research and Genome Research Limited, operating as the Wellcome Sanger Institute. The Cambridge Covid-19 testing Centre is funded by the Department of Health and Social Care, UK Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Understanding 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. ; DA is a Wellcome Clinical PhD Fellow and gratefully supported by the Wellcome Trust (Grant number: 222903/Z/21/Z). BW receives funding from the University of Cambridge and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC) at the Cambridge University Hospitals NHS Foundation Trust. IG is a Wellcome Senior Fellow and is supported by the Wellcome Trust (Grant number: 207498/Z/17/Z and 206298/B/17/Z). EMH is supported by a UK Research and Innovation (UKRI) Fellowship: MR/S00291X/1. CJRI acknowledges Medical Research Council (MRC) funding (ref: MC_UU_00002/11). NJM is supported by the MRC (CSF MR/P008801/1) and NHSBT (WPA15-02). AJP gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); their research was funded by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10352, also Quadram Institute Bioscience BBSRC funded Core Capability Grant (project number BB/CCG1860/1). LdP and OGP were supported by the Oxford Martin School. This research was supported by the NIHR Cambridge BRC. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The COVID-19 Genomics UK Consortium is supported by funding from the MRC part of UK Research & Innovation (UKRI), the National Institute of Health Research and Genome Research Limited, operating as the Wellcome Sanger Institute. The Cambridge Covid-19 testing Centre is funded by the Department of Health and Social Care, UK Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
