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Accuracy of rapid point-of-care antibody test in patients with suspected or confirmed COVID-19

2021; Elsevier BV; Volume: 84; Issue: 1 Linguagem: Inglês

10.1016/j.jinf.2021.07.006

1532-2742

Rama Vancheeswaran, Merlin Willcox, Beth Stuart, Matthew Knight, Hala Kandil, Andrew Barlow, Mayon Haresh Patel, Jade Stockham, Aisling O’Neill, Tristan Clark, Tom Wilkinson, Paul Little, Nick Francis, Gareth Griffiths, Michael Moore,

COVID-19 Clinical Research Studies

•The rapid test for antibodies to SARS-COV-2 was 90.1% sensitive and 100% specific.•This is comparable to reference antibody tests for prior infection with COVID-19.•It could support clinical decision-making for patients with >10 days of symptoms.•It would be useful in settings where vaccination is not widespread.•And where PCR tests are not widely available. We read with interest the article about use of lateral flow antigen detection tests to triage patients presenting to hospital to detect asymptomatic COVID-191Young B.C. Eyre D.W. Jeffery K. Use of lateral flow devices allows rapid triage of patients with SARS-CoV-2 on admission to hospital.J Infect. 2021; 82: 276-316Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar. In low-income countries, where most of the population is unvaccinated, and patients often present late, point-of-care rapid antibody tests could also contribute to diagnosis of COVID-19. Although a systematic review found that their overall sensitivity was low at 66% (95% CI 49.3–79.3)2Lisboa Bastos M. Tavaziva G. Abidi S.K. et al.Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.BMJ. 2020; 370: m2516Crossref PubMed Scopus (533) Google Scholar, most of the studies were small and under-powered. Most published data is based on stored blood samples from hospitalised patients, with no indication of the duration of illness prior to sampling 2Lisboa Bastos M. Tavaziva G. Abidi S.K. et al.Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.BMJ. 2020; 370: m2516Crossref PubMed Scopus (533) Google Scholar, 3Li Z. Yi Y. Luo X. et al.Development and Clinical Application of A rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis.J Med Virol. 2020; 92: 1518-1524Crossref PubMed Scopus (1182) Google Scholar, 4Bell J.Trouble in Testing Land. https://www.research.ox.ac.uk/Article/2020-04-05-trouble-in-testing-land (accessed 22/04/ 2020).Google Scholar. We report the real-world diagnostic accuracy of a rapid point-of-care antibody test compared to PCR and/or standard laboratory-based antibody tests, in patients with a history of symptoms consistent with COVID-195Vancheeswaran R., Willcox M.L., Stuart B., et al. Accuracy of rapid point-of-care antibody test in patients with suspected or confirmed COVID-19. medRxiv 2020:2020.11.17.20233296.Google Scholar. Adult participants were recruited at Watford General Hospital, in two groups: (1) patients who had confirmed COVID-19 on PCR (from 5th March to 18th June 2020) and (2) hospital staff with history of clinically suspected COVID-19 (based on reported symptoms) who had a standard venous antibody test (from 1st May to 22nd July 2020), at least 7 days after onset of symptoms. There was some overlap as many participants had both a PCR and a venous antibody test. The index test was the rapid point-of-care (POC) IgM / IgG colloidal gold lateral flow immunoassay (LFIA) manufactured by Livzon (Zhuhai, Guangdong, China) which detects antibodies directed against the spike protein of SARS-COV-2 from a drop of capillary blood. The test was read by two independent observers after 15 min. We used a composite reference and evaluated the components of this individually. The first component was SARS-COV-2 RT-PCR (using the available molecular technology during the study time: PHE laboratories, GeneXpert® system Xpert, Xpress SARS-CoV-2 and Source bioscience laboratory). The second reference test was the Elecsys Anti-SARS-CoV-2 assay, an ECLIA (Electro Chemi Luminescent Immuno Assay) manufactured by Roche Diagnostics GmbH which uses a recombinant protein representing the nucleocapsid (N) protein of SARS-CoV-2. We recruited 398 participants (173 in the first group and 225 in the second– see Fig. 1); 52.8% had never been seen in hospital, whereas the others had been assessed in A&E and 23.6% were admitted. Regarding the reference test, 130 participants had only a PCR test, 124 had only a reference antibody test, and 144 had both. The median interval between the positive PCR test in group 1 and the POC antibody test was 60 days (IQR 35–91). Of 268 participants who had a reference venous blood test for antibodies to SARS-COV-2, the test was positive in 190 (70.9%). The median interval between the POC test and the reference antibody test was 3 days (IQR −10 to 24 days). The median interval between onset of symptoms and the POC antibody test was 74 days (IQR 50–96, range 7–173 days). Only 11 participants had the POC test taken 7–14 days after onset of symptoms (of whom only 2 <10 days), 11 had it taken at 11–21 days, 19 at 22–34 days, and the remaining 312 at 35 days or more. Of the 218 participants with a positive PCR test for COVID-19, the POC test was positive in 197 cases (sensitivity = 90.4%, 95% CI: 85.7% to 93.9%). Compared to the reference venous antibody test, the POC test had a sensitivity of 92.0% (95% CI 87.2–95.5) and specificity of 98.7% (95% CI 93.1–100). Our sensitivity analysis, excluding cases where the interval between the POC test and the venous antibody test was greater than 28 days, resulted in a sensitivity of 137 / 148 = 92.6% (95%CI 87.1%–96.2%) and specificity of 58/59 = 98.3% (95% CI 90.9%–100.0%). Compared to the composite reference, the POC had an overall sensitivity of 90.1% (292/328, 95% CI 86.3–93.1) and specificity of 100% (68/68, 95% CI: 94.7% to 100% - see Table 1). In the subgroup of participants with presumed milder illness (who were never seen in hospital), the sensitivity was 84.4% (124/147, 95% CI 77.5% to 89.8%) whereas in patients admitted to hospital, the sensitivity was 97.8% (89/92, 95% CI 92.3% to 99.7%). In the subgroup where the POC test was conducted at least 20 days after onset of symptoms, sensitivity was 91.1% (288/316, 95% CI 87.4% to 94.0%). Numbers were too small to calculate diagnostic accuracy in the subgroups of patients in whom the POC test was taken at 7–14 days, 15–21 and 22–34 days after onset of symptoms.Table 1Accuracy of the POC antibody test compared to the composite reference standard (PCR and reference antibody, n = 396*POC result was inconclusive in 6 for the IgG, 10 for the IgM and 4 overall, excluded from this analysis.).Point-of-Care antibody test resultComposite referenceSensitivity (95% CI)Specificity (95% CI)ROCPPVNPVPosNegPOC IgGPositive2610261/322 = 81.1% (76.3% to 85.2%)68/68 = 100%(94.7% to 100%)0.91 (0.88 to 0.93)100% (98.6% to 100%)52.7%(43.7% to 61.6%)Negative6168POC IgMPositive2420242/318 = 76.1%(71% to 80.7%)68/68=100% (94.7% to 100%)0.88 (0.86 to 0.90)100% (98.5% to 100%)47.2%(38.9% to 55.7%)Negative7668POC IgG and IgM CombinedPositive2920292/324 = 90.1% (86.3% to 93.1%)68/68=100% (94.7% to 100%)0.95 (0.93 to 0.97)100% (98.7% to 100%)68%(57.9% to 77.0%)Negative3268 POC result was inconclusive in 6 for the IgG, 10 for the IgM and 4 overall, excluded from this analysis. Open table in a new tab As this was a "real-word" evaluation, some data were missing. In some cases there was a lengthy interval between symptoms and the point-of-care test, and between the point-of-care test and the reference venous antibody test. This was because the reference antibody test was only available from May 2020 and some participants first experienced symptoms in February and early March 2020. Another limitation is that the tests were only evaluated in one centre and from one batch. There have been reports of variation in sensitivity between batches of rapid antibody tests6Reuters. Denmark to send back inaccurate antibody tests from China's Livzon. https://www.reuters.com/article/us-health-coronavirus-denmark-kits-idUSKBN22W2TC (accessed 12 Oct 2020).Google Scholar so good quality control will be essential. In conclusion, the Livzon point-of-care antibody test had comparable sensitivity and specificity to the reference antibody test, so could be used to support decision-making about patients presenting with more than 10 days of symptoms of COVID-19. It may be more accurate than rapid antigen tests and PCR for patients with onset of symptoms at least 10 days previously, so it could be particularly useful in settings where access to PCR is limited, patients are unable to access a PCR within their first 10 days of illness, and most have not been vaccinated. The combination of PCR plus IgG and IgM testing in suitable patients has already been suggested to improve diagnostic accuracy7Xie J. Ding C. Li J. et al.Characteristics of patients with coronavirus disease (COVID-19) confirmed using an IgM-IgG antibody test.J Med Virol. 2020; 92: 2004-2010Crossref PubMed Scopus (117) Google Scholar. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf . Prof Wilkinson reports grants, personal fees and other from AstraZeneca, grants and personal fees from Synairgen, grants and personal fees from MyMHealth, grants from GSK, grants from Bergenbio and grants from UC, outside the submitted work. Prof Griffiths reports grants from Jannsenn-Cilag, grants from AZ, grants from Novartis, grants from Astex, grants from Roche, grants from Heartflow, personal fees from Celldex, grants from BMS, grants from BionTech, outside the submitted work. All other authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. We would like to thank Wendy O'Brien and Clare McDermott at the School of Primary Care and Catherine Simpson at Southampton Clinical Trials Unit at the University of Southampton who supported the trial management for this study. Rosie Bourke and Alex Newland Smith arranged follow up for the first group to have the POC tests. The POC tests were funded by The Medical Director's cardiology charity and by individuals donating to a "Just Giving" page. We received no commercial funding or free tests from the manufacturer. West Hertfordshire Hospitals NHS Trust supported clinical staff time. MLW's salary was funded by the National Institute of Health Research (NIHR), under grant CL-2016–26–005. Southampton CTU staff were supported by NIHR CTU Support Funding. The funders had no role in this research. This study was approved by the Faculty of Medicine Research Ethics Committee at the University of Southampton (reference 56480) and by the Wales Research Ethics Committee 4 (Wrexham, IRAS 283264, REC 20/WA/0148).