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Combined RT-PCR and host response point-of-care testing in patients hospitalised with suspected COVID-19: a prospective diagnostic accuracy study

Combined RT-PCR and host response point-of-care testing in patients hospitalised with suspected COVID-19: a prospective diagnostic accuracy study
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.
COVID-19, Composite clinical reference standard, Diagnostic accuracy, FebriDx, MxA, Point-of-care test, RT-PCR
2193-6382
1267–1280
Brendish, Nathan
a8a4189e-01eb-4ab3-933e-a24cd188a4d7
Tanner, Alex
cac6d816-602b-4dcf-961e-22f2cbdc501d
Poole, Stephen
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Beard, Kate
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Naidu, Vasanth
df9bd215-344a-43b6-b568-60c783353fa9
Mansbridge, Christopher
a33c33a8-f813-46d2-92a0-ecde2233514a
Norton, Nicholas
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Wheeler, Helen
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Presland, Laura
f9595a32-b871-4d73-8444-dd0fffc08592
Clark, Tristan
712ec18e-613c-45df-a013-c8a22834e14f
Brendish, Nathan
a8a4189e-01eb-4ab3-933e-a24cd188a4d7
Tanner, Alex
cac6d816-602b-4dcf-961e-22f2cbdc501d
Poole, Stephen
440d7904-ab72-469c-892b-c910cd1cb19b
Beard, Kate
85604fec-3541-48cb-9abf-a76c2a32c3f1
Naidu, Vasanth
df9bd215-344a-43b6-b568-60c783353fa9
Mansbridge, Christopher
a33c33a8-f813-46d2-92a0-ecde2233514a
Norton, Nicholas
14bdade9-e59d-4b4a-a87f-ddb74d86d725
Wheeler, Helen
9ec21ee3-2e24-40c7-b342-64a2c371ef7a
Presland, Laura
f9595a32-b871-4d73-8444-dd0fffc08592
Clark, Tristan
712ec18e-613c-45df-a013-c8a22834e14f

Brendish, Nathan, Tanner, Alex, Poole, Stephen, Beard, Kate, Naidu, Vasanth, Mansbridge, Christopher, Norton, Nicholas, Wheeler, Helen, Presland, Laura and Clark, Tristan (2022) Combined RT-PCR and host response point-of-care testing in patients hospitalised with suspected COVID-19: a prospective diagnostic accuracy study. Infectious Diseases and Therapy, 11 (3), 1267–1280. (doi:10.1007/s40121-022-00646-4).

Record type: Article

Abstract

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.

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Accepted/In Press date: 20 April 2022
Published date: June 2022
Additional Information: Funding Information: Dr Tristan W Clark reports non-financial support from QIAGEN in the form of discounted equipment and consumables for this work. He also reports personal fees from BioMerieux and BioFire LLC, non-financial support from BioMerieux and BioFire LLC, personal fees from Synairgen Research Ltd, Roche, Cidara therapeutics, Janssen, Planet Innovation and Randox Diagnostics, and grants from NIHR, all outside this work. Dr Kate R Beard has received honoraria from Randox Laboratories Ltd, outside this work. Dr Nathan J Brendish, Dr Alex R Tanner, Dr Stephen Poole, Dr Vasanth V Naidu, Dr Christopher T Mansbridge, Dr Nicholas J Norton, Mrs Helen Wheeler, and Mrs Laura Presland have nothing to disclose. Funding Information: We acknowledge and thank to all the patients who kindly participated in this study and all the clinical staff at University Hospital Southampton NHS Foundation Trust who cared for them. This report is independent research supported by the National Institute for Health Research (NIHR Post Doctoral Fellowship, Dr Tristan Clark, PDF 2016-09-061). Dr Nathan Brendish is supported by a NIHR Clinical Lecturer post. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. This study was funded by University Hospital Southampton NHS Foundation Trust and supported by the NIHR Southampton Biomedical Research Centre. Statistical analysis was supported by Cancer Research UK core funding and NIHR CTU support funding at the Southampton Clinical Trials Unit. The FebriDx kits were purchased independently from a UK distributer and the manufacturer (Lumos Diagnostics, Sarasota, Florida, USA) had no role in the study conception, design, data analysis or manuscript preparation. The parent study was supported by QIAGEN in the form of discounted equipment and consumables. The senior author had full access to all data and the final responsibility to submit for publication. The Journal’s Rapid Service Fee was funded by the authors. Dr Tristan W Clark reviewed the medical literature, conceived of and designed the study, oversaw the conduct of the study, did the analysis and interpretation of results, and drafted the manuscript. Dr Nathan J Brendish assisted with the design of the study, screened and recruited patients, collected data and drafted the manuscript. Dr Alex R Tanner collected data and drafted the manuscript. Dr Stephen Poole screened and recruited patients, collected data, and curated data. Dr Kate R Beard, Dr Vasanth V Naidu, Dr Christopher T Mansbridge, Dr Nicholas J Norton, Mrs Helen Wheeler and Mrs Laura Presland screened and recruited patients and/or collected data. All authors reviewed and contributed to the manuscript during its development. Dr Tristan W Clark, Dr Stephen Poole, and Dr Nathan J Brendish have verified the underlying data. Dr Tristan W Clark reports non-financial support from QIAGEN in the form of discounted equipment and consumables for this work. He also reports personal fees from BioMerieux and BioFire LLC, non-financial support from BioMerieux and BioFire LLC, personal fees from Synairgen Research Ltd, Roche, Cidara therapeutics, Janssen, Planet Innovation and Randox Diagnostics, and grants from NIHR, all outside this work. Dr Kate R Beard has received honoraria from Randox Laboratories Ltd, outside this work. Dr Nathan J Brendish, Dr Alex R Tanner, Dr Stephen Poole, Dr Vasanth V Naidu, Dr Christopher T Mansbridge, Dr Nicholas J Norton, Mrs Helen Wheeler, and Mrs Laura Presland have nothing to disclose. The study was approved by the South Central—Hampshire A Research Ethics Committee: reference 20/SC/0138, on 16 March 2020. The study was conducted in accordance with the Helsinki Declaration of 1964 and its later amendments. This study was prospectively registered with the ISRCTN (ISRCTN14966673) on 18 March 2020. Access to de-identified study participant data may be available on reasonable request to the senior author after this publication. Funding Information: We acknowledge and thank to all the patients who kindly participated in this study and all the clinical staff at University Hospital Southampton NHS Foundation Trust who cared for them. This report is independent research supported by the National Institute for Health Research (NIHR Post Doctoral Fellowship, Dr Tristan Clark, PDF 2016-09-061). Dr Nathan Brendish is supported by a NIHR Clinical Lecturer post. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. Funding Information: This study was funded by University Hospital Southampton NHS Foundation Trust and supported by the NIHR Southampton Biomedical Research Centre. Statistical analysis was supported by Cancer Research UK core funding and NIHR CTU support funding at the Southampton Clinical Trials Unit. The FebriDx kits were purchased independently from a UK distributer and the manufacturer (Lumos Diagnostics, Sarasota, Florida, USA) had no role in the study conception, design, data analysis or manuscript preparation. The parent study was supported by QIAGEN in the form of discounted equipment and consumables. The senior author had full access to all data and the final responsibility to submit for publication. The Journal’s Rapid Service Fee was funded by the authors. Publisher Copyright: © 2022, The Author(s).
Keywords: COVID-19, Composite clinical reference standard, Diagnostic accuracy, FebriDx, MxA, Point-of-care test, RT-PCR

Identifiers

Local EPrints ID: 457371
URI: http://eprints.soton.ac.uk/id/eprint/457371
ISSN: 2193-6382
PURE UUID: f7aa5b72-146f-4754-976e-64593c0840df
ORCID for Nathan Brendish: ORCID iD orcid.org/0000-0002-9589-4937
ORCID for Tristan Clark: ORCID iD orcid.org/0000-0001-6026-5295

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Date deposited: 06 Jun 2022 16:36
Last modified: 31 Jan 2023 03:01

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Contributors

Author: Nathan Brendish ORCID iD
Author: Alex Tanner
Author: Stephen Poole
Author: Kate Beard
Author: Vasanth Naidu
Author: Christopher Mansbridge
Author: Nicholas Norton
Author: Helen Wheeler
Author: Laura Presland
Author: Tristan Clark ORCID iD

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