Detecting SARS-CoV-2 at point of care: preliminary data comparing loop-mediated isothermal amplification (LAMP) to polymerase chain reaction (PCR)

Marc F Österdahl,Rachel Horsfall,Stuart Wilson,Karla A Lee,Simon D Goldenberg,Claire J Steves,Mary Ni Lochlainn,Sam Douthwaite,Tim D Spector,Christopher J Stanley,Alyce Sheedy

doi:10.1186/s12879-020-05484-8

Abstract

BackgroundA cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting.MethodsThis prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines.ResultsThe novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19.ConclusionsRT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.

Highlights

Current diagnosis of COVID-19 relies on centralised laboratory-based reverse transcription polymerase chain reaction (RT-PCR) (Reverse Transcription Polymerase Chain Reaction) testing
Older residents are at higher risk of mortality from COVID-19 [9], and care homes have reported significant outbreaks both in the United Kingdom (UK) and internationally [10]
A single RT-Loop-mediated isothermal amplification (LAMP) test had a sensitivity of 80% and a specificity of 73% on single test compared to a “better than gold standard” of two consecutive RT-PCR swabs

Summary

Introduction

Current diagnosis of COVID-19 relies on centralised laboratory-based RT-PCR (Reverse Transcription Polymerase Chain Reaction) testing. It is abundantly clear that urgent research is needed to enable health services globally to plan resources and this research must both move rapidly from bench to bedside and be scalable and rapidly available In light of this urgency, we present a preliminary evaluation of a novel, quick test for COVID-19 that can be implemented at the point of need. Point-of-care (PoC) testing may be critical to enable rapid detection of disease when an outbreak is suspected This is important in community settings like care homes, where multiple vulnerable patients reside together, and COVID-19 can spread quickly if not identified early [8]. Older residents are at higher risk of mortality from COVID-19 [9], and care homes have reported significant outbreaks both in the United Kingdom (UK) and internationally [10] They have limited access to laboratory diagnostic services. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting

Methods

Results

Conclusion