Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults' primary care records through OpenSAFELY (preprint)

Background The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to describe this impact on primary care activity and monitor its recovery. Objectives To develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods With the approval of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. We developed SNOMED-CT codelists for key measures of primary care clinical activity selected by a expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.

OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care activity across six clinical areas during the COVID-19 pandemic (preprint)

Background The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. Aims Using routinely collected data, our aim was to describe changes in the volume and variation of coded clinical activity in general practice in: (i) cardiovascular disease, (ii) diabetes, (iii) mental health, (iv) female and reproductive health, (v) screening, and (vi) processes related to medication. Design and setting With the approval of NHS England, we conducted a cohort study of 23.8 million patient records in general practice, in-situ using OpenSAFELY. Methods We selected common primary care activity using CTV3 codes and keyword searches from January 2019 - December 2020, presenting median and deciles of code usage across practices per month. Results We identified substantial and widespread changes in clinical activity in primary care since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health, e.g. "Depression interim review" (median across practices in December 2020 -41.6% compared to December 2019). Conclusions Granular NHS GP data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for key measures identified here as well as further studies, using primary care data to monitor and mitigate the indirect health impacts of Covid-19 on the NHS.

RT-LAMP has high accuracy for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs from asymptomatic and symptomatic individuals (preprint)

Previous studies have described RT-LAMP methodology for the rapid detection of SARS-CoV-2 in nasopharyngeal/oropharyngeal swab and saliva samples. Here we describe the validation of an improved simple sample preparation method for Direct SARS-CoV-2 RT-LAMP, removing the need for RNA extraction, using 559 swabs and 86,760 saliva samples from asymptomatic and symptomatic individuals across multiple healthcare settings. Using this improved method we report a diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs and 84.62% (79.50-88.88%) on saliva, with diagnostic specificity (DSp) 100% (98.98-100.00%) on swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR. Analysing samples with RT-qPCR ORF1ab CT values of <25 and <33 (high and medium-high viral loads, respectively), we found DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs, and 99.01% (94.61-99.97%) and 87.32% (80.71-92.31%) for saliva. We also describe RNA RT-LAMP (on extracted RNA) performed on 12,619 swabs and 12,521 saliva samples to provide updated performance data with DSe and DSp of 95.98% (92.74-98.06%) and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, respectively. We also report on daily samples collected from one individual from symptom onset where both Direct and RNA RT-LAMP detected SARS-CoV-2 in saliva collected on all six days where symptoms were recorded, with RNA RT-LAMP detecting SARS-CoV-2 for an additional further day. The findings from these studies demonstrate that RT-LAMP testing of swabs and saliva is potentially applicable to a variety of use-cases, including frequent, interval-based testing of saliva from asymptomatic individuals via Direct RT-LAMP that may be missed using symptomatic testing alone.

Preliminary optimisation of a simplified sample preparation method to permit direct detection of SARS-CoV-2 within saliva samples using reverse-transcription loop-mediated isothermal amplification (RT-LAMP) (preprint)

We describe the optimization of a simplified sample preparation method which permits rapid and direct detection of SARS-CoV-2 RNA within saliva using reverse-transcription loop-mediated isothermal amplification (RT-LAMP). Treatment of saliva samples prior to RT-LAMP by dilution 1:1 in MucolyseTM, followed by dilution (within the range of 1 in 5 to 1 in 40) in 10% (w/v) Chelex 100 Resin and a 98oC heat step for 2 minutes enabled detection of SARS-CoV-2 RNA in all positive saliva samples tested, with no amplification detected in pooled negative saliva. The time to positivity for which SARS-CoV-2 RNA was detected in these positive saliva samples was proportional to the real-time reverse-transcriptase PCR cycle threshold (CT), with SARS-CoV-2 RNA detected in as little as 05:43 (CT 21.08), 07:59 (CT 24.47) and 08:35 (CT 25.27) minutes, respectively. The highest CT where direct RT-LAMP detected SARS-CoV-2 RNA was 31.39 corresponding to a 1 in 40 dilution of a positive saliva sample (1:1 in MucolyseTM) with a starting CT of 25.27. When RT-LAMP was performed on pools of SARS-CoV-2 negative saliva samples spiked with whole inactivated SARS-CoV-2 virus, RNA was detected at dilutions spanning 1 in 5 to 1 in 160 representing CTs spanning 22.49-26.43. Here we describe a simple but critical rapid sample preparation method which can be used up front of RT-LAMP to permit direct detection of SARS-CoV-2 within saliva samples. Saliva is a sample which can be collected non-invasively without the use of highly skilled staff and critically can be obtained from both healthcare and home settings. Critically, this approach overcomes both the requirement and validation of different swabs and the global bottleneck in obtaining RNA extraction robots and reagents to enable molecular testing by PCR. Such testing opens the possibility of public health approaches for effective intervention to control the COVID-19 pandemic through regular SARS-CoV-2 testing at a population scale, combined with isolation and contact tracing for positive cases.