Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19).

BACKGROUND AND OBJECTIVE: Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care. METHODS: Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups. RESULTS: Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms. CONCLUSIONS: Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile's minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced. REGISTRATION: ISRCTN142269.

Development of a modified Cambridge Multimorbidity Score for use with SNOMED CT: an observational English primary care sentinel network study.

BACKGROUND: People with multiple health conditions are more likely to have poorer health outcomes and greater care and service needs; a reliable measure of multimorbidity would inform management strategies and resource allocation. AIM: To develop and validate a modified version of the Cambridge Multimorbidity Score in an extended age range, using clinical terms that are routinely used in electronic health records across the world (Systematized Nomenclature of Medicine - Clinical Terms, SNOMED CT). DESIGN AND SETTING: Observational study using diagnosis and prescriptions data from an English primary care sentinel surveillance network between 2014 and 2019. METHOD: In this study new variables describing 37 health conditions were curated and the associations modelled between these and 1-year mortality risk using the Cox proportional hazard model in a development dataset (n = 300 000). Two simplified models were then developed - a 20-condition model as per the original Cambridge Multimorbidity Score and a variable reduction model using backward elimination with Akaike information criterion as the stopping criterion. The results were compared and validated for 1-year mortality in a synchronous validation dataset (n = 150 000), and for 1-year and 5-year mortality in an asynchronous validation dataset (n = 150 000). RESULTS: The final variable reduction model retained 21 conditions, and the conditions mostly overlapped with those in the 20-condition model. The model performed similarly to the 37- and 20-condition models, showing high discrimination and good calibration following recalibration. CONCLUSION: This modified version of the Cambridge Multimorbidity Score allows reliable estimation using clinical terms that can be applied internationally across multiple healthcare settings.

Representativeness, Vaccination Uptake, and COVID-19 Clinical Outcomes 2020-2021 in the UK Oxford-Royal College of General Practitioners Research and Surveillance Network: Cohort Profile Summary.

BACKGROUND: The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. OBJECTIVE: The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice. METHODS: The RSC's pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC's cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)-collecting virological and serological specimens-and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort's sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19-related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death. RESULTS: As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively. CONCLUSIONS: The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.