Feasibility and Acceptability of Community COVID-19 Testing Strategies (FACTS) in a University Setting (preprint)

Background: During the COVID-19 pandemic in 2020, the UK government began a mass SARS-CoV-2 testing programme. This study aimed to determine the feasibility and acceptability of organised regular self-testing for SARS-CoV-2.Methods: This was a mixed methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews.Findings: Across three main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks. 447 participants (81%) completed at least two, and 340 (62%) completed at least four tests. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. 2711 (99.4%) test results were negative, nine were positive and eight were inconclusive. Results from eighteen qualitative interviews with staff and students revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence.Interpretation: This is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment, adherence to, and acceptability of regular SARS-CoV-2 self-testing programmes for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.Funding: This work was funded by Oxford University Medical Science DivisionsDeclaration of Interests: LT works part-time for Sensyne Health as R&D Director and holds share options in the company. He also reports a research grant and personal fees from the company.Ethics Approval Statement: FACTS is a mixed methods cohort study conducted at the University of Oxford. It was approved by the University of Oxford Research Ethics Committee in October 2020 (CUREC ethics reference R72896/RE001).

Point of Care Testing using rapid automated Antigen Testing for SARS-COV-2 in Care Homes – an exploratory safety, usability and diagnostic agreement evaluation (preprint)

Introduction Successful adoption of POCTs (Point-of-Care tests) for COVID-19 in care homes requires the identification of ideal use cases and a full understanding of contextual and usability factors that affect test results and minimise biosafety risks. This paper presents findings from a scoping-usability and test performance study of a microfluidic immunofluorescence assay for COVID-19 in care homes. Methods A mixed-methods evaluation was conducted in four UK care homes to scope usability and to assess the agreement with qRT-PCR. A dry run with luminescent dye was carried out to explore biosafety issues. Results The agreement analysis was carried out on 227 asymptomatic participants (159 staff and 68 residents) and 14 symptomatic participants (5 staff and 9 residents). Asymptomatic specimens showed 50% (95% CI: 1.3%-98.7%) positive agreement and 96% (95% CI: 92.5%-98.1%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.911 (95% CI: 0.857-0.965). Symptomatic specimens showed 83.3% (95% CI: 35.9%-99.6%) positive agreement and 100% (95% CI: 63.1%-100%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.857 (95% CI: 0.549-1). The dry run showed four main sources of contamination that led to the modification of the standard operating procedures. Simulation after modification showed no further evidence of contamination. Conclusion Careful consideration of biosafety issues and contextual factors associated with care home are mandatory for safe use the POCT. Whilst POCT may have some utility for ruling out COVID-19, further diagnostic accuracy evaluations are needed to promote effective adoption.

Perceptions on undertaking regular asymptomatic self-testing for COVID-19 using lateral flow tests: A qualitative study of university students and staff (preprint)

Background There has been an increased interest from governments in implementing mass testing for COVID-19 of asymptomatic individuals using Lateral Flow Tests (LFTs). Successful implementation of such programmes depends on several factors, including feasibility, acceptability and how people act on test results. There is a paucity of studies examining these issues. Objective We aimed to examine experiences of university students and staff with experience of regular asymptomatic self-testing using LFTs, and their subsequent behaviours. Methods We invited people who were participating in a weekly testing feasibility study. We conducted semi-structured remote interviews between December 2020 and January 2021. Additional qualitative data from a survey were also analysed. Data were analysed thematically. Results We interviewed 18 and surveyed 214 participants. Participants were motivated to regularly self-test as they wanted to know whether or not they were infected with SARS-CoV-2. Most reported that a negative test result did not change their behaviour but it did provide them with reassurance to engage with permitted activities. In contrast, some participants reported making decisions about visiting other people when they would not have done so otherwise, because they felt reassured by a negative test result. Participants valued the test training but some participants still doubted their ability to carry out the test. Participants were concerned about safety of attending test sites with lots of people and reported home testing was most convenient. Conclusions If governments want to increase uptake of LFT use, clear messages highlighting the benefits of regular testing for family, friends and society in identifying asymptomatic cases are needed. This should be coupled with transparent communication about accuracy of LFTs and how to act on either a positive or negative result. Concerns about safety, convenience of testing, and ability to do tests need to be addressed to ensure successful scaling up asymptomatic testing.

Changes in cardiovascular disease monitoring in English primary care during the COVID-19 pandemic: an observational cohort study (preprint)

ObjectiveTo quantify the impact and recovery in cardiovascular disease monitoring in primary care associated with the first COVID-19 lockdown. DesignRetrospective nationwide primary care cohort study, utilising data from 1st January 2018 to 27th September 2020. SettingWe extracted primary care electronic health records data from 514 primary care practices in England contributing to the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID). These practices were representative of English primary care across urban and non-urban practices. ParticipantsThe ORCHID database included 6,157,327 active patients during the study period, and 13,938,390 patient years of observation (final date of follow-up 27th September 2020). The mean (SD) age was 38{+/-}24 years, 49.4% were male and the majority were of white ethnicity (65% [21.9% had unknown ethnicity]) ExposureThe primary exposure was the first national lockdown in the UK, starting on 23rd March 2020. Main outcome measuresRecords of cholesterol, blood pressure, HbA1c and International Normalised Ratio (INR) measurement derived from coded entries in the primary care electronic health record. ResultsRates of cholesterol, blood pressure, HbA1c and INR recording dropped by 23-87% in the week following the first UK national lockdown, compared with the previous week. The largest decline was seen in cholesterol (IRR 0.13, 95% CI 0.11 to 0.15) and smallest for INR (IRR 0.77, 95% CI 0.72 to 0.81). Following the immediate drop, rates of recorded tests increased on average by 5-9% per week until 27th September 2020. However, the number of recorded measures remained below that expected for the time of year, reaching 51.8% (95% CI 51.8 to 51.9%) for blood pressure, 63.7%, (95% CI 63.7% to 63.8%) for cholesterol measurement and 70.3% (95% CI 70.2% to 70.4%) for HbA1c. Rates of INR recording declined throughout the previous two years, a trend that continued after lockdown. There were no differences in the times series trends based on sex, age, ethnicity or deprivation. ConclusionsCardiovascular disease monitoring in English primary care declined substantially from the time of the first UK lockdown. Despite a consistent recovery in activity, there is still a substantial shortfall in the numbers of recorded measurements to those expected. Strategies are required to ensure cardiovascular disease monitoring is maintained during the COVID-19 pandemic.

Is Point-of-Care testing feasible and safe in care homes in England? An exploratory usability and accuracy evaluation of Point-of-Care Polymerase Chain Reaction test for SARS-COV-2 (preprint)

IntroductionReliable rapid testing on COVID-19 is needed in care homes to reduce the risk of outbreaks and enable timely care. Point-of-care testing (POCT) in care homes could provide rapid actionable results. This study aimed to examine the usability and test performance of point of care polymerase chain reaction (PCR) for COVID-19 in care homes. MethodsPoint-of-care PCR for detection of SARS-COV2 was evaluated in a purposeful sample of four UK care homes. Test agreement with laboratory real-time PCR and usability and use errors were assessed. ResultsPoint of care and laboratory polymerase chain reaction (PCR) tests were performed on 278 participants. The point of care and laboratory tests returned uncertain results or errors for 17 and 5 specimens respectively. Agreement analysis was conducted on 256 specimens. 175 were from staff: 162 asymptomatic; 13 symptomatic. 69 were from residents: 59 asymptomatic; 10 symptomatic. Asymptomatic specimens showed 83.3% (95% CI: 35.9%-99.6%) positive agreement and 98.7% negative agreement (95% CI: 96.2%-99.7%), with overall prevalence and bias-adjusted kappa (PABAK) of 0.965 (95% CI: 0.932 - 0.999). Symptomatic specimens showed 100% (95% CI: 2.5%-100%) positive agreement and 100% negative agreement (95% CI: 85.8%-100%), with overall PABAK of 1. No usability-related hazards emerged from this exploratory study. ConclusionApplications of point-of-care PCR testing in care homes can be considered with appropriate preparatory steps and safeguards. Agreement between POCT and laboratory PCR was good. Further diagnostic accuracy evaluations and in-service evaluation studies should be conducted, if the test is to be implemented more widely, to build greater certainty on this initial exploratory analysis. Key pointsO_LIPoint of care tests (POCT) in care homes are feasible and could increase testing capacity for the control of COVID-19 infection. C_LIO_LIThe test of agreement between POCT and laboratory PCR for care home residents and the staff was good. C_LIO_LIAdoption of POCT in care homes can be considered with appropriate preparatory steps and safeguards in place. C_LIO_LIRepetitive errors and test malfunctioning can be mitigated with bespoke training for care home staff. C_LIO_LIIntegrated care pathways should be investigated to test the high variability of the context of use. C_LI

OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. (preprint)

Background Establishing who is at risk from a novel rapidly arising cause of death, and why, requires a new approach to epidemiological research with very large datasets and timely data. Working on behalf of NHS England we therefore set out to deliver a secure and pseudonymised analytics platform inside the data centre of a major primary care electronic health records vendor establishing coverage across detailed primary care records for a substantial proportion of all patients in England. The following results are preliminary. Data sources Primary care electronic health records managed by the electronic health record vendor TPP, pseudonymously linked to patient-level data from the COVID-19 Patient Notification System (CPNS) for death of hospital inpatients with confirmed COVID-19, using the new OpenSAFELY platform. Population 17,425,445 adults. Time period 1st Feb 2020 to 25th April 2020. Primary outcome Death in hospital among people with confirmed COVID-19. Methods Cohort study analysed by Cox-regression to generate hazard ratios: age and sex adjusted, and multiply adjusted for co-variates selected prospectively on the basis of clinical interest and prior findings. Results There were 5683 deaths attributed to COVID-19. In summary after full adjustment, death from COVID-19 was strongly associated with: being male (hazard ratio 1.99, 95%CI 1.88-2.10); older age and deprivation (both with a strong gradient); uncontrolled diabetes (HR 2.36 95% CI 2.18-2.56); severe asthma (HR 1.25 CI 1.08-1.44); and various other prior medical conditions. Compared to people with ethnicity recorded as white, black people were at higher risk of death, with only partial attenuation in hazard ratios from the fully adjusted model (age-sex adjusted HR 2.17 95% CI 1.84-2.57; fully adjusted HR 1.71 95% CI 1.44-2.02); with similar findings for Asian people (age-sex adjusted HR 1.95 95% CI 1.73-2.18; fully adjusted HR 1.62 95% CI 1.43-1.82). Conclusions We have quantified a range of clinical risk factors for death from COVID-19, some of which were not previously well characterised, in the largest cohort study conducted by any country to date. People from Asian and black groups are at markedly increased risk of in-hospital death from COVID-19, and contrary to some prior speculation this is only partially attributable to pre-existing clinical risk factors or deprivation; further research into the drivers of this association is therefore urgently required. Deprivation is also a major risk factor with, again, little of the excess risk explained by co-morbidity or other risk factors. The findings for clinical risk factors are concordant with policies in the UK for protecting those at highest risk. Our OpenSAFELY platform is rapidly adding further NHS patients' records; we will update and extend these results regularly. Keywords COVID-19, risk factors, ethnicity, deprivation, death, informatics.