Combined RT-PCR and Host Response Point-of-Care Testing in Patients Hospitalised with Suspected COVID-19: A Prospective Diagnostic Accuracy Study.

INTRODUCTION: RT-PCR has suboptimal sensitivity for the diagnosis of COVID-19. A composite reference standard comprising RT-PCR plus radiological and clinical features has been recommended for diagnostic accuracy studies. The FebriDx finger prick point-of-care test detects an antiviral host response protein (MxA) in 10 min. We evaluated the diagnostic accuracy of FebriDx and RT-PCR compared to a composite reference standard. METHODS: Adults presenting to hospital with suspected COVID-19 were tested by FebriDx and RT-PCR. A composite reference standard was used to classify patients as having COVID-19 based on RT-PCR positivity, or RT-PCR negativity with COVID-19 radiological findings or other clinical criteria. Measures of accuracy were calculated for MxA alone, RT-PCR alone, and both combined. This study is registered with the ISRCTN (ISRCTN14966673) and has completed. RESULTS: A total of 478 patients were tested, with valid results in 475. Of these 475 patients, 222 (46.7%) were classified as having COVID-19; 192 (40.4%) were RT-PCR positive, and 30 (6.3%) were RT-PCR negative and diagnosed on radiological/clinical criteria. Sensitivity of FebriDx MxA vs the composite reference standard was 186/222 (83.8%, 95% CI 78.3-88.4) and was similar to the sensitivity of RT-PCR (192/222 (86.5%, 95% CI 81.3-90.7), (difference of 2.7%, 95% CI - 3.9 to 9.3, p = 0.42). The sensitivity of combined FebriDx and RT-PCR was 208/222 (93.7%) which was superior to both RT-PCR alone (difference of 9.9, 95% CI 4.1-15.9; p = 0.001) and FebriDx MxA alone (difference of 7.2, 95% CI 1.6-12.9; p = 0.011). CONCLUSION: Sensitivity of combined FebriDx and RT-PCR testing was superior to each alone for the detection of COVID-19 in hospital and may improve infection control and treatment decisions.

Routine molecular point-of-care testing for SARS-CoV-2 reduces hospital-acquired COVID-19.

OBJECTIVES: Risk of hospital-acquired COVID-19 (HA-COVID-19) infection is increased by cohorting infected and non-infected patients together in assessment areas, whist awaiting laboratory PCR results. Molecular point-of-care tests (mPOCT) reduce time to results and improve patient flow but the impact on HA-COVID-19 is unknown. METHODS: In this pre and post implementation study patients were evaluated across two time periods: March 1st to August 13th 2020, prior to the introduction of mPOCT in medical admissions areas, and 14th August 2020 to 1st April 2021, after mPOCT introduction. The primary outcome was proportion of HA-COVID-19 infection among all COVID-19 positive patients. Secondary outcome measures included time to SARS-CoV-2 results, length of time spent in the medical assessment area and comparison of local, regional and national proportions of HA-COVID-19. RESULTS: 1988 patients were admitted through the acute medicine admission cohorting area and tested for SARS-CoV-2 prior to introducing mPOCT and 4640 afterwards. Median (IQR) time to SARS-CoV-2 result was 6.5 (2.1-17.9) hours prior to introducing mPOCT and 1.0 (0.8-1.3) hours afterwards (p < 0.0001). Median (IQR) duration in the assessment cohort area was 12.0 (4.8-20.6) hours prior to introduction of POCT and 3.2 (2.0-5.6) hours afterwards (p < 0.0001). The proportion of hospital-acquired COVID-19 cases was 108 (16.5%) of 654 prior to introducing mPOCT compared with 168 (9.4%) of 1782 afterwards, (HR 0.55, 95%CI 0.43-0.70; p < 0.0001). In the period following the introduction of mPOCT up to 1st April 2021 the median proportion of HA-COVID-19 was 13.6% (95%CI 8.2-18.9%) locally, compared with 43.8% (95%CI 37.8-49.9%) for all acute NHS trusts regionally and 30.9% (95%CI 28.4-33.5%) for all NHS trusts nationally. CONCLUSIONS: Routine mPOCT for SARS-CoV-2 was associated with reduced time to results, time spent in admission cohort areas, and hospital-acquired COVID-19, compared to laboratory PCR.

SARS-CoV-2 viral load at presentation to hospital is independently associated with the risk of death.

Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.