An important component of the UK's early response to the COVID-19 pandemic was increasing SARS-CoV-2 testing capacity across the National Health Service (NHS). At the time, we and others advocated for the repurposing of academic centres to deliver laboratory capacity for testing and screening of asymptomatic health-care workers, to prevent the transmission of SARS-CoV-2.1Black JRM Bailey C Przewrocka J Dijkstra KK Swanton C COVID-19: the case for health-care worker screening to prevent hospital transmission.Lancet. 2020; 395: 1418-1420Summary Full Text Full Text PDF PubMed Scopus (300) Google Scholar In response to a pressing need for testing across London in March, 2020, the Francis Crick Institute rapidly repurposed its laboratory facilities in partnership with University College London Hospitals (UCLH) and the Health Services Laboratory, to create the Crick COVID Testing Pipeline (CCTP). The CCTP provided 680 602 occupational RT-PCR tests from April, 2020, to April, 2022.2Aitken J Ambrose K Barrell S et al.Scalable and robust SARS-CoV-2 testing in an academic center.Nat Biotechnol. 2020; 38: 927-931Crossref PubMed Scopus (22) Google Scholar Same-day results were provided: median turnaround time was 533 min (IQR 456–654; 8·9 h [7·6–10·9]) from receipt to result reporting. All SARS-CoV-2 positive samples were reported to the NHS Test and Trace service, viral genomes were sequenced in-house and submitted to the COVID-19 Genome UK Consortium, and protocols were rapidly shared.2Aitken J Ambrose K Barrell S et al.Scalable and robust SARS-CoV-2 testing in an academic center.Nat Biotechnol. 2020; 38: 927-931Crossref PubMed Scopus (22) Google Scholar The CCTP provided both asymptomatic screening and diagnostic testing for staff in eight NHS trusts and 98 local care homes and rehabilitation facilities up until May, 2021, when NHS testing capacity was realised, covering boroughs with high rates of COVID-19 including Brent, Harrow, Barnet, and Ealing (figure A). Testing was expanded to the Francis Crick Institute in June, 2020, to support essential clinical and research work and continued until May, 2022, under an institutional COVID-19 secure policy.2Aitken J Ambrose K Barrell S et al.Scalable and robust SARS-CoV-2 testing in an academic center.Nat Biotechnol. 2020; 38: 927-931Crossref PubMed Scopus (22) Google Scholar Here, we performed an analysis of testing data with a view to understanding both the effect of hospital trust screening policies and the Francis Crick Institute's in-person work policy to inform future pandemic planning. Overall, 7316 positive infections were detected from 680 602 tests (1%) between April 1, 2020, and April 14, 2022 (figure B). Across the CCTP, the rolling 7-day incidence (7-day mean number of positive tests per 1000 tests taken per site) showed that infections in health-care workers mirrored the incidence of national trends (figure C).3Vöhringer HS Sanderson T Sinnott M et al.Genomic reconstruction of the SARS-CoV-2 epidemic in England.Nature. 2021; 600: 506-511Crossref PubMed Scopus (44) Google Scholar We captured variants of concern (figure D–E)—often ahead of their designation by WHO (figure F)—whereby alpha (B.1.1.7) was first detected 33 days before, delta (B.1.617.2) 27 days before, and omicron (BA.1) 5 days following its designation. We first explored the interactions across the CCTP between positive test rates, viral loads, and different testing policies adopted by NHS trusts between 2020 and 2021 (appendix pp 10–11). We compared the 7-day rolling infection incidence between sites (appendix pp 10–11) and found, as expected, that the incidence was highest when testing was predominantly offered to symptomatic staff, including at sites managed by the London Northwest University Hospitals NHS Trust and The Royal Free Hospital NHS Trust. However, despite a low 7-day rolling infection incidence, 40·8% of all positive tests were from UCLH and Royal Marsden Hospitals; both sites offered asymptomatic testing to support the delivery of COVID-19 secure cancer and surgical services. These sites detected a substantial number of additional infections. To investigate the differences between sites operating symptomatic and asymptomatic testing policies, we calculated an incidence for each site by adjusting for the organisation size (defined by the number of employees stated in their 2020–21 annual reports), and then calculated an incidence rate ratio (IRR) for each site over the first 4 months of testing, defined as the daily incidence of positive tests for each site, divided by the daily incidence estimates for London's population.4Greater London AuthorityCoronavirus (COVID-19) weekly update.https://data.london.gov.uk/dataset/coronavirus--covid-19--casesDate accessed: November 1, 2022Google Scholar We compared the IRR between primarily symptomatic and asymptomatic testing sites, including those following NHS guidelines to create COVID-19 secure clinical areas.5UK Health Security AgencyInfection prevention and control for seasonal respiratory infections in health and care settings (including SARS-CoV-2) for winter 2021 to 2022.https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/covid-19-guidance-for-maintaining-services-within-health-and-care-settings-infection-prevention-and-control-recommendationsDate accessed: November 3, 2021Google Scholar During the first 4 months of testing, the incidence of cases at NHS sites (UCLH and Royal Marsden Hospitals) that offered primarily asymptomatic SARS-CoV-2 testing was 7·5 and 13 times respectively that of the London population (appendix pp 10–11) and NHS sites continued to report positive tests consistently above 5 times the background population symptomatic rate until the second week of July, 2020 (appendix pp 3–4). Asymptomatic screening is designed to detect early infections, reducing transmission with self isolation.1Black JRM Bailey C Przewrocka J Dijkstra KK Swanton C COVID-19: the case for health-care worker screening to prevent hospital transmission.Lancet. 2020; 395: 1418-1420Summary Full Text Full Text PDF PubMed Scopus (300) Google Scholar We compared the distribution of PCR cycle threshold (Ct) value between the two types of sites as a well recognised proxy measure of viral load and thus, infectiousness.6Killingley B Mann AJ Kalinova M et al.Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.Nat Med. 2022; 28: 1031-1041Crossref PubMed Scopus (190) Google Scholar We found the median Ct was lower (corresponding with a higher viral load) in symptomatic test sites (Ct 21·2 [IQR 8·06], n=1458), compared with asymptomatic sites (Ct 25·7 [10·1], n=3322, p<0·0001; appendix pp 3–4). Ct values typically peak just before or around symptom onset and symptomatic-only testing might be biased towards the post-peak period; therefore, asymptomatic testing might further detect a subset of people with infectious virus at or before the Ct peak.6Killingley B Mann AJ Kalinova M et al.Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.Nat Med. 2022; 28: 1031-1041Crossref PubMed Scopus (190) Google Scholar To capture peak Ct values and control for different Ct ranges across sites with different testing policies, we compared the cumulative occurrence of positive tests between asymptomatic and symptomatic sites in a subset of swabs with a Ct value of less than 15 (appendix pp 10–11). Within this subset, we found that asymptomatic sites identified infections at lower Ct values, suggesting enhanced detection of these highly infectious individuals. We then analysed the Francis Crick Institute, whereby to support a rapid return to in-person working, we implemented a COVID-19 secure workplace policy.7de Quetteville H How Sir Paul Nurse got 1200 scientists safely back to work with the 'easy' test and trace method.https://www.telegraph.co.uk/health-fitness/mind/sir-paul-nurse-got-1200-scientists-safely-back-work-easy-test/Date: Aug 10, 2020Date accessed: November 3, 2021Google Scholar With an asymptomatic testing policy, entry to the institute was contingent on negative testing within the previous 8 days, internal contact tracing following positive tests, distancing, and face coverings were enforced by social compliance. The institute remained open, while the weekly test positivity remained less than 1%. Analysis of building occupancy data showed mean 7-day occupancy was maintained at over 60% of peak attendance for the overwhelming majority of days (356 [84%] of 423 days; appendix pp 10–11), reaching 75% peak attendance by September, 2020. The 1% threshold was met on Oct 22, 2020, following the spread of the EU1 variant (B.1.177), and again on Dec 8, 2021, as a result of the omicron variant (BA.1, appendix pp 5–6). The Francis Crick Institute implemented a stricter testing protocol resulting in flatter peaks of infection in employees than were otherwise observed within our local borough of Camden (appendix pp 10–11). Taken together, we show that it was possible to repurpose laboratory facilities and integrate existing clinical and laboratory expertise to set up a comprehensive testing facility in an academic institution at pace,2Aitken J Ambrose K Barrell S et al.Scalable and robust SARS-CoV-2 testing in an academic center.Nat Biotechnol. 2020; 38: 927-931Crossref PubMed Scopus (22) Google Scholar serving as a lifeboat laboratory and delivering testing for the NHS in advance of the planned national programme. The CCTP was designed to protect both staff and patients with testing; we show important heterogeneity in the uptake of testing by hospitals. Health-care workers are susceptible to the occupational acquisition of SARS-CoV-2 despite infection control practices.8Houlihan CF Vora N Byrne T et al.Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers.Lancet. 2020; 396: e6-e7Summary Full Text Full Text PDF PubMed Scopus (148) Google Scholar, 9Meredith LW Hamilton WL Warne B et al.Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.Lancet Infect Dis. 2020; 20: 1263-1271Summary Full Text Full Text PDF PubMed Scopus (259) Google Scholar Estimates of true asymptomatic infections vary, but up to 40% of all COVID-19 infections might be asymptomatic.10Ma Q Liu J Liu Q et al.Global percentage of asymptomatic SARS-CoV-2 infections among the tested population and individuals with confirmed COVID-19 diagnosis: a systematic review and meta-analysis.JAMA Netw Open. 2021; 4e2137257Crossref Scopus (251) Google Scholar Although our study is restricted by its observational design, our data suggest that asymptomatic testing strategies captured a considerable number of additional infections, particularly in the early phase of the pandemic, and supports NHS England Infection Prevention and Control advice on the use of asymptomatic testing with non-pharmaceutical interventions to maintain green sites to provide care for clinically susceptible patients.11UK Health Security AgencyNational infection prevention and control manual (NIPCM) for England.https://www.england.nhs.uk/national-infection-prevention-and-control-manual-nipcm-for-england/Date: 2021Date accessed: November 3, 2021Google Scholar Our data also provide a unique insight into workplace exposure risk and screening strategies outside of hospital settings, with most studies focusing on higher risk settings such as homeless shelters, prisons, schools, and cruise ships. UK Government recommendations on non-clinical workplace safety during COVID-19 centred on ventilation, social distancing, encouraging vaccination, and self isolation. The Francis Crick Institute's enforced testing policy supported a safe workplace, potentially minimising infection peaks during the delta wave in summer 2021. In the absence of data from similar organisations, our study suggests that asymptomatic screening with non-pharmaceutical interventions are an important addition to guidelines on workplace safety. Overall, this study provides a blueprint for future NHS–academic partnerships to follow. With active planning underway on national preparedness for the next potential pandemic, our work highlights the importance of prioritising testing—including regular asymptomatic testing of key workers including NHS and care home staff—during the first phase of the pandemic response. Sequencing data for all positive samples are publicly available through COG-UK resources. CB, TS, HT, JGo, RGi, JN, DLVB, and ECW accessed and verified the data. CB, ECW, DLVB, SGan, and CSw were responsible for the decision to submit the Correspondence for publication. CB and TS were responsible for formal analysis, investigation, methodology, visualisation, writing the original draft, and conceptualisation. HT was involved in the investigation, methodology, visualisation, manuscript review and editing, and conceptualisation. JGo was responsible for software, methodology, formal analysis, and data curation. JRMB performed formal analysis and validation. JGan was responsible for the methodology, resources, data curation, and project administration. GY performed formal analysis. RGo was responsible for software, resources, and data curation. ASF, SW, DJJ, LC, VD, OO'N, MC, DS, MF, AE, JP-L, AR, JA, NO'R, SC, MYW, PAW, and CSa were involved with the methodology, resources, data curation, and project administration. EJC was involved with software and project administration. SH, JF, and KA helped with supervision, software, and methodology. MHo performed project administration and supervision. AJ was responsible for methodology, resources, data curation, and project administration. CH, EN, MHu, RM, DH, PP, TC, RGi, JM, NVA, ST, RB, ML, and SB managed resources, data curation, and project administration. BW and SGam handled funding acquisition and project administration with SGam also providing supervision. JN was involved with project administration, supervision, and methodology. SGan performed supervision, funding acquisition, methodology, project administration, writing, review, and editing. DLVB was responsible for supervision, methodology, formal analysis, visualisation, conceptualisation, and writing the original draft. ECW performed supervision, investigation, data curation, conceptualisation, writing, review, and editing. CSw was responsible for supervision, funding acquisition, conceptualisation, project administration, writing, review, and editing. This research was funded in whole, or in part, by the Wellcome Trust (FC011104, FC011233, FC001030, FC001159, FC001827, FC001078, FC001099, and FC001169). TS is supported by a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust grant 210918/Z/18/Z. Unrelated to this Correspondence, CSw reports grants from BMS, Ono-Pharmaceuticals, Boehringer Ingelheim, Roche-Ventana, Pfizer, and Archer Dx; personal fees from Genentech, Sarah Canon Research Institute, Medicxi, Metabomed, Bicycle Therapeutics, GRAIL, Amgen, AstraZeneca, BMS, Illumina, GlaxoSmithKline, MSD, and Roche-Ventana; and stock options from Apogen Biotech, Epic Biosciences, GRAIL, Achilles Therapeutics, and Bicycle Therapeutics. We thank Sir Paul Nurse, Jules Marczack, Bobbi Clayton, Gita Mistry, and all the research staff who volunteered to work on the COVID-19 testing pipeline at the Francis Crick Institute. We also thank the staff of the National Institute for Health and Care Research Clinical Research Facility at University College London Hospitals NHS Foundation Trust including Dr Mike Brown, Martin Bruce, Kirsty Adams, Miguel Alvarez, Marivic Ricamara, and Dr Mike Gandy at the Health Services Laboratory. Download .pdf (2.92 MB) Help with pdf files Supplementary appendix COVID-19: the case for health-care worker screening to prevent hospital transmissionThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed unprecedented strain on health-care services worldwide, leading to more than 100 000 deaths worldwide, as of April 15, 2020.1 Full-Text PDF

In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March-6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth's (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes. (C) 2020 Elsevier Inc. All rights reserved.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARSCoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARS-CoV-2 detection by RT-LAMP that is robust, reliable, repeatable, specific, and inexpensive.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARS-CoV-2 detection by RT-LAMP that is robust, reliable, repeatable, specific, and inexpensive.

An initiative to screen asymptomatic health-care workers for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was timely and logical,1Black JRM Bailey C Przewrocka J Dijkstra KK Swanton C COVID-19: the case for health-care worker screening to prevent hospital transmission.Lancet. 2020; 395: 1418-1420Summary Full Text Full Text PDF PubMed Scopus (302) Google Scholar and contrasted markedly with the UK Government's testing strategy of National Health Service (NHS) staff during the epidemic. The NHS staff testing policy was only to test symptomatic staff, precisely to reduce absenteeism by encouraging staff with negative results back to work, thus intentionally reducing their time in self-isolation. The Secretary of State for Health and Social Care, Matt Hancock, himself stated that "we want to get [NHS staff absences] down, and the way to do that is to get the amount of testing up".2Booth R Number of NHS doctors off sick 'may be nearly triple the official estimate'.https://www.theguardian.com/world/2020/apr/05/number-nhs-doctors-off-sick-may-be-three-times-more-than-thoughtDate: April 5, 2020Date accessed: April 19, 2020Google Scholar This testing approach was then also applied to other groups of public sector workers.3The GuardianUK Covid-19 testing expanded to police, fire service and judiciary.https://www.theguardian.com/world/2020/apr/17/uk-covid-19-testing-expanded-to-police-fire-service-and-judiciaryDate: April 17, 2020Date accessed: April 19, 2020Google Scholar The UK Government's approach of using SARS-CoV-2 testing as a strategy to reduce absenteeism rather than to increase the detection of otherwise asymptomatic spreaders was surely symptomatic of flawed analysis and misunderstanding of the utility of the SARS-CoV-2 pharyngeal swab RT-PCR test. WHO expressly advises against using this test as a rule-out in the event of negative results.4WHOLaboratory testing for coronavirus disease (COVID-19) in suspected human cases.https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117Date: March 19, 2020Date accessed: April 19, 2020Google Scholar Sensitivity of the test might be as low as 83%,5Long C Xu H Shen Q et al.Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT?.Eur J Radiol. 2020; 126108961Summary Full Text Full Text PDF PubMed Scopus (663) Google Scholar and in our practice many colleagues believe it to be lower still. Overzealous redirection of self-isolating staff back to work before they had completed sufficient self-isolation to exclude infectivity was therefore likely to increase spread of the virus to other staff and to patients or care-receivers in a substantial number of cases, especially given the high prevalence and likelihood of SARS-CoV-2 infection among exposed health-care workers during the epidemic. Surely the only defensible policy would have been national opportunistic and frequent testing of NHS and social care sector staff regardless of symptomology, and the test should be used exclusively as a rule-in and not a rule-out test as per existing WHO guidance.4WHOLaboratory testing for coronavirus disease (COVID-19) in suspected human cases.https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117Date: March 19, 2020Date accessed: April 19, 2020Google Scholar I declare no competing interests. COVID-19: the case for health-care worker screening to prevent hospital transmissionThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed unprecedented strain on health-care services worldwide, leading to more than 100 000 deaths worldwide, as of April 15, 2020.1 Full-Text PDF Misuse of SARS-CoV-2 testing in symptomatic health-care staff in the UK – Authors' replyWe thank Bernard Freudenthal for his response to our previous Correspondence.1 We agree that use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing among health-care workers (HCWs) solely to reduce absenteeism is inappropriate. Freudenthal correctly outlines the risks, posed by false-negative results, of advising potentially infectious HCWs to return to work. Moreover, staffing levels are currently far less problematic within UK health-care settings than during the peak of the pandemic. Full-Text PDF

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 40,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated standard operating procedure (SOP) for high-throughput SARS- CoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.