AbstractBackgroundPoint-of-care (POC) tests for COVID-19 could relieve pressure on isolation resource, support infection prevention and control, and help commence more timely and appropriate treatment. We aimed to undertake a systematic review and pooled diagnostic test accuracy study of available individual patient data (IPD) to evaluate the diagnostic accuracy of a commercial POC test (FebriDx) in patients with suspected COVID-19.MethodsA literature search was performed on the 1st of October 2020 to identify studies reporting diagnostic accuracy statistics of the FebriDx POC test versus real time reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Studies were screened for risk of bias. IPD were sought from studies meeting the inclusion and exclusion criteria. Logistic regression was performed to investigate the study effect on the outcome of the RT-PCR test result in order to determine whether it was appropriate to pool results. Diagnostic accuracy statistics were calculated with 95% confidence intervals (CIs).Results15 studies were screened, and we included two published studies with 527 hospitalised patients. 523 patients had valid FebriDx results for Myxovirus resistance protein A (MxA), an antiviral host response protein. The FebriDx test produced a pooled sensitivity of 0.920 (95% CI: 0.875-0.950) and specificity of 0.862 (0.819-0.896) compared with RT-PCR, where there was an estimated true COVID-19 prevalence of 0.405 (0.364-0.448) and overall FebriDx test yield was 99.2%. Patients were tested at a median of 4 days [interquartile range: 2:9] after symptom onset. No differences were found in a sub-group analysis of time tested since the onset of symptoms.ConclusionsBased on a large sample of patients from two studies during the first wave of the SARS-CoV-2 pandemic, the FebriDx POC test had reasonable diagnostic accuracy in a hospital setting with high COVID-19 prevalence, out of influenza season. More research is required to determine how FebriDx would perform in other healthcare settings with higher or lower COVID-19 prevalence, different patient populations, or when other respiratory infections are in circulation.Trial registrationThis work was based on a pooled analysis of anonymised data from two previous studies; the CoV-19POC study, described by Clark et al. (9), the “Southampton study” [ISRCTN:14966673, date registered: 18/03/2020]; and a study described by Karim et al. (13) the “Kettering study”.Lay summaryTests to diagnose COVID-19 are crucial to help control the spread of the disease and to guide treatment. Over the last few months, tests have been developed that can detect the SARS-CoV-2 virus which causes COVID-19. These tests use complex machines in pathology laboratories accepting samples from large geographical areas. Sometimes it takes days for test results to come back. So, to reduce the wait for results, new portable tests are being developed. These point-of-care (POC) tests are designed to work close to where patients require assessment and care such as hospital emergency departments, GP surgeries or care homes. For these new POC tests to be useful, they should ideally be as good as standard laboratory tests so patients get their result quickly and can benefit from the best, safest care.In this study we looked at published research into a new test, FebriDx, which can detect the presence of any viral infection, including infections due to the SARS-CoV-2 virus, as well as bacterial infections which can have similar symptoms. The FebriDx result was compared with that obtained on the same patient’s throat and nose swab and using the standard COVID-19 viral laboratory test. We were able to analyse data from two studies with a total of 523 adult patients who were receiving emergency hospital care with symptoms of COVID-19 during the early stage of the UK pandemic. Almost half of the patients were diagnosed as positive for SARS-CoV-2 virus using standard laboratory COVID-19 viral tests.Our analysis demonstrated that the FebriDx POC test agreed 94 out of 100 times with the standard laboratory test results when FebriDx diagnosed the patient as free from COVID-19. However, FebriDx agreed only 82 out of 100 times with the standard laboratory test when FebriDx indicated that the patient had a COVID-19 infection. These differences have important implications for how these tests could be used. As there were far fewer FebriDx false results when the results of the FebriDx test were negative (6 out of 100) than when the results of the FebriDx test were positive (18 out of 100), we can have more confidence in a negative test result using FebriDx at the POC than a positive FebriDx result.Overall, we have shown that the FebriDx POC test performed quite well during the first wave of the COVID-19 pandemic when compared with laboratory tests, especially when the POC test returned a negative test. For the future, this means that the FebriDx POC test might be helpful in making a rapid clinical decision whether to isolate a patient with COVID-19-like symptoms arriving in a busy emergency department. However, our results indicate it would not completely replace the need to conduct a confirmatory laboratory test in certain cases.There are limitations to our findings. For example, we do not know if FebriDx will work in a similar way with patients in different settings such as in the community or care homes. Similarly, we do not know whether other viral and bacterial infections which cause similar COVID-19 symptoms, and are more common in the autumn and winter months, could influence the FebriDx test accuracy.
Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19)
