Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study

Michael Crone; Paul Randell; Zoey Herm; Arthi Anand; Saghar Missaghian-Cully; Loren Perelman; Panagiotis Pantelidis; Paul Freemont

doi:10.12688/wellcomeopenres.17226.1

Rapid design and implementation of an adaptive pooling workflow for SARS-CoV-2 testing in an NHS diagnostic laboratory: a proof-of-concept study

Wellcome Open Res. 2021 Oct 13:6:268. doi: 10.12688/wellcomeopenres.17226.1. eCollection 2021.

Authors

Michael Crone^{1

2

3}, Paul Randell^{4

5}, Zoey Herm⁶, Arthi Anand^{7

8}, Saghar Missaghian-Cully^{5

9}, Loren Perelman⁶, Panagiotis Pantelidis^{4

5}, Paul Freemont^{1

2

3}

Affiliations

¹ London Biofoundry, Imperial College Translation and Innovation Hub, White City Campus, 84 Wood Lane, London, W12 0BZ, UK.
² Section of Structural and Synthetic Biology, Department of Infectious Disease, Imperial College London, London, SW7 2AZ, UK.
³ UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London and the University of Surrey, London, Guildford, UK.
⁴ Department of Infection and Immunity, North West London Pathology, London, UK.
⁵ Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK.
⁶ Riffyn, Inc., 484 9th Street, Oakland, California, 94607, USA.
⁷ Histocompatibility and Immunogenetics Laboratories, Department of Infection and Immunity, North West London Pathology, London, UK.
⁸ Imperial College Healthcare NHS Trust, Hammersmith Hospitals Trust, Du Cane Road, London, W12 0HS, UK.
⁹ North West London Pathology, London, UK.

Abstract

Background: Diagnostic laboratories are currently required to provide routine testing of asymptomatic staff and patients as a part of their clinical screening for SARS-CoV-2 infection. However, these cohorts display very different disease prevalence from symptomatic individuals and testing capacity for asymptomatic screening is often limited. Group testing is frequently proposed as a possible solution to address this; however, proposals neglect the technical and operational feasibility of implementation in a front-line diagnostic laboratory. Methods: Between October and December 2020, as a seven-week proof of concept, we took into account scientific, technical and operational feasibility to design and implement an adaptive pooling strategy in an NHS diagnostic laboratory in London (UK). We assessed the impact of pooling on analytical sensitivity and modelled the impact of prevalence on pooling strategy. We then considered the operational constraints to model the potential gains in capacity and the requirements for additional staff and infrastructure. Finally, we developed a LIMS-agnostic laboratory automation workflow and software solution and tested the technical feasibility of our adaptive pooling workflow. Results: First, we determined the analytical sensitivity of the implemented SARS-CoV-2 assay to be 250 copies/mL. We then determined that, in a setting with limited analyser capacity, the testing capacity could be increased by two-fold with pooling, however, in a setting with limited reagents, this could rise to a five-fold increase. These capacity increases could be realized with modest additional resource and staffing requirements whilst utilizing up to 76% fewer plastic consumables and 90% fewer reagents. Finally, we successfully implemented a plate-based pooling workflow and tested 920 patient samples using the reagents that would usually be required to process just 222 samples. Conclusions: Adaptive pooled testing is a scientifically, technically and operationally feasible solution to increase testing capacity in frontline NHS diagnostic laboratories.

Keywords: SARS-CoV-2; diagnostics; laboratory automation.

Grants and funding

WT_/Wellcome Trust/United Kingdom