Dramatic impact of rapid point of care nucleic acid testing for SARS-CoV-2 in hospitalised patients: a clinical validation trial and implementation study

Abstract

Objective To compare a point of care (POC) nucleic acid amplification based platform for rapid diagnosis of COVID-19 against the standard laboratory RT-PCR test and perform an implementation study. Design: prospective clinical trial (COVIDx) and observational study Setting: a large UK teaching hospital Participants: patients presenting to hospital with possible COVID-19 disease and tested on a combined nasal/throat swab using the SAMBA II SARS-CoV-2 rapid POC test and in parallel a combined nasal/throat swab for standard lab RT-PCR testing. Implementation phase participants underwent SARS-CoV-2 POC testing for a range of indications over a ten day period pre and post SAMBA II platform implementation. Main outcome measures: concordance and sensitivity and specificity of POC using the lab test as the reference standard, test turnaround time in trial and implementation periods; time to definitive patient triage from ED, time spent on COVID-19 holding wards, bay closures avoided, proportions of patients in isolation rooms following test, proportions of patients able to be moved to COVID negative areas following test. Results 149 participants were included in the COVIDx trial. 32 (21.5%) tested positive and 117 (78.5%) tested negative by standard lab RT-PCR. Median age was 62.7 (IQR 37 to 79) years and 47% were male. Cohen's kappa correlation between the index and reference tests was 0.96, 95% CI (0.91, 1.00). Sensitivity and specificity of SAMBA against the RT-PCR lab test were 96.9% (95% CI 0.838-0.999) and 99.1% (0.953-0.999) respectively. Median time to result was 2.6 hours (IQR 2.3 to 4.8) for SAMBA II and 26.4 hours (IQR 21.4 to 31.4) for the standard lab RT-PCR test (p<0.001). In the first 10 days of the SAMBA II SARS-CoV-2 test implementation for all hospital COVID-19 testing, analysis of the first 992 tests showed 59.8% of tests were used for ED patients, and the remainder were done for pre-operative screening (11.3%), discharges to nursing homes (10%), in-hospital screening of new symptoms (9.7%), screening in asymptomatic patients requiring hospital admission screening (3.8%) and access to interventions such as dialysis and chemotherapy for high risk patients (1.2%). Use of single occupancy rooms amongst those tested fell from 30.8% before to 21.2% after testing (p=0.03). 11 bay closures were avoided by use of SAMBA over ten days. The post implementation group was then compared with 599 individuals who had a standard lab RT-PCR test in the 10 days prior to SAMBA introduction. Median time to result during implementation fell from 39.4 hours (IQR 24.7-51.3) to 3.6 hours (IQR 2.6-5.8), p<0.0001 and the median time to definitive ward move from ED was significantly reduced from 24.1 hours (9.2-48.6) to 18.5 hours (10.2-28.8), p=0.002. Mean length of stay on a COVID-19 holding ward decreased from 58.5 hours to 29.9 hours (p<0.001) compared to the 10 days prior to implementation. Conclusions SAMBA II SARS-CoV-2 rapid POC test performed as well as standard lab RT-PCR and demonstrated shorter time to result both in trial and real-world settings. It was also associated with faster time to triage from the ED, release of isolation rooms, avoidance of hospital bay closures and movement of patients to COVID negative open green category wards, allowed discharge to care homes and expediting access to hospital investigations and procedures. POC testing will be instrumental in mitigating the impact of COVID-19 on hospital systems by allowing rapid triage and patient movement to safe and appropriate isolation wards in the hospital. This is also likely to reduce delays in patients accessing appropriate investigation and treatment, thereby improving clinical outcomes.

Performance Evaluation of the SAMBA II SARS-CoV-2 Test for Point-of-Care Detection of SARS-CoV-2

“…These data include 3 positive samples detected by SAMBA that were original negative by centralised testing indicating good sensitivity. In a separate study SAMBA II was shown to have a sensitivity of 96.9% (95% CI 84.2-99.9) and specificity of 100% (95% CI 96.9-100) in A&E settings compared to the centralised reference method [20]. Clinical evaluation by Zhen et al [25] comparing the performance of Xpert® Xpress SARS-CoV-2 (Cepheid), ePlex® SARS-CoV-2 (GenMark) and ID NOW™ COVID-19 (Abbott) showed limit of detection of 100 cp/mL, 1,000 cp/mL and 10,000 cp/mL and clinical agreement with the reference standard of 98.3%, 91.4% and 87.7% respectively.…”

“…POC molecular tests for SARS-CoV-2, such as SAMBA II, are required to quickly triage patients as centralised testing can take 2-5 days for results [20,21]. In addition, POC tests would be extremely useful for non-laboratory residential settings such as prisons, immigration centres, nursing homes and rehabilitative centres.…”

Specificity and positive predictive value of SARS-CoV-2 nucleic acid amplification testing in a low-prevalence setting

“…Samples from patients with a preceding positive SARS-CoV-2 NAAT were reported positive without confirmation, reflecting the higher prior probability of true positive results, and the lower probability of significant adverse impact from false positives. Only preceding positive results from samples tested by our laboratory, or our local hospital’s point-of-care laboratory [ 12 ], were considered here. Although data on previous tests in other laboratories were sought, we conducted confirmatory testing without awaiting this information.…”

Reducing nosocomial transmission of COVID-19: implementation of a COVID-19 triage system

“…9,[13][14][15][16] However, in our Trust, median turnaround time between taking samples and obtaining results was 2 days (range 0-11 days) during March and April 2020. Rapid PCR tests for COVID-19, such as the SAMBA II (DRW, Cambridge, UK) and the Xpert Xpress (Cepheid, CA, USA) have the potential to identify patients with COVID-19 within 30-90 minutes at the point of care, 17 facilitating early isolation and minimising exposure to susceptible patients. Within our Trust, patients with a low clinical likelihood of COVID-19 are prioritised for testing using SAMBA II (DRW, Cambridge, UK).…”