Heat Inactivation of Clinical COVID-19 Samples on an Industrial Scale for Low Risk and Efficient High-throughput qRT-PCR Diagnostic Testing (preprint)

We report the development of a large scale process for heat inactivation of clinical COVID-19 samples prior to laboratory processing for detection of SARS-CoV-2 by RT-qPCR. With more than 120 million confirmed cases, over 3.8 million deaths already recorded at the time of writing, COVID-19 continues to spread in many parts of the world. Consequently, mass testing for SARS-CoV-2 will remain at the forefront of the COVID-19 response and prevention for the near future. Due to biosafety considerations the standard testing process requires a significant amount of manual handling of patient samples within calibrated microbiological safety cabinets. This makes the process expensive, effects operator ergonomics and restricts testing to higher containment level laboratories. We have successfully modified the process by using industrial catering ovens for bulk heat inactivation of oropharyngeal/nasopharyngeal swab samples within their secondary containment packaging before processing in the lab to enable all subsequent activities to be performed in the open laboratory. As part of a validation process, we tested greater than 1200 clinical COVID-19 samples and showed less than 1 Cq loss in RT-qPCR test sensitivity. We also demonstrate the bulk heat inactivation protocol inactivates a murine surrogate of human SARS-CoV-2. Using bulk heat inactivation, the assay is no longer reliant on containment level 2 facilities and practices, which reduces cost, improves operator safety and ergonomics and makes the process scalable. In addition, heating as the sole method of virus inactivation is ideally suited to streamlined and more rapid workflows such as ‘direct to PCR’ assays that do not involve RNA extraction or chemical neutralisation methods.

An iteratively optimised process for improving the efficiency and effectiveness of an industrial SARS-CoV-2 diagnostic facility (preprint)

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories.

Feasibility and efficacy of mass testing for SARS-CoV-2 in a UK university using swab pooling and PCR (preprint)

Transmission of SARS-CoV-2 without symptoms is well described, and may be mitigated by mass testing. Nonetheless, the optimal implementation and quantitative real-world impact of this approach remain unclear. During a period of rising SARS-CoV-2 prevalence, students at the University of Cambridge were enrolled in a voluntary programme of weekly PCR-based asymptomatic screening. Swab pooling by household reduced the total testing capacity required by five-fold, without affecting laboratory workflows or compromising test sensitivity. Participation remained >75% throughout the study period. 299/671 (45%) of students diagnosed with SARS-CoV-2 were either identified or pre-emptively quarantined because of the screening programme. After a negative screening test, the risk of developing COVID-19 over the following 7 days was decreased by 51%. Modelling transmission using parameters from our study suggests a reduction in R0 of up to 31% attributable to weekly screening. We therefore demonstrate the feasibility and efficacy of regular, voluntary mass testing for COVID-19.