key: cord-0823479-g2uksn9o authors: Ducrest, P. J.; Freymond, A.; Segura, J.-M. title: Performance evaluation of the Simtomax CoronaCheck rapid diagnostic test date: 2020-11-01 journal: nan DOI: 10.1101/2020.10.28.20219667 sha: 0873ab724624dc1b17a04283ea9dd56aee1ef338 doc_id: 823479 cord_uid: g2uksn9o The aim of this study was to evaluate the diagnostic performance of Simtomax CoronaCheck, a serology rapid diagnostic test (RDT) for the detection of IgG and IgM against SARS-CoV-2. 48 plasma samples positive for SARS-CoV-2 based on RT-PCR and 98 negative control samples were studied. Diagnostic performance of the IgG/IgM RDT was assessed against RT-PCR and the electro-chemiluminescence immunoassay (ECLIA) Elecsys Anti-SARS-CoV-2 total Ig. Overall, the RDT sensitivity was 92% (95% confidence interval [95%CI]: 79-97), specificity 97% (95% CI: 91-99%), PPV 94% (95% CI: 81-98) and the NPV 96% (95% CI: 89-99). When considering only samples collected [≥] 15 days post-symptoms (DPS), the sensitivity increased to 98% (95%CI: 86-100) and the specificity was 97% (95% CI: 91-99%). Two samples with 180 DPS were still positive for IgG. Globally, this IgG/IgM RDT displayed a high diagnostic accuracy for SARS-CoV-2 IgG/IgM detection in plasma samples in high COVID-19 prevalence settings. It could be effectively used, in absence of facilities for routine diagnostic serology, for samples with a DPS between 15 and 180 days. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. . CC-BY-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. ; https://doi.org/10.1101/2020.10.28.20219667 doi: medRxiv preprint 4 The aim of this study was to evaluate the performance of this RDT in the case of plasma samples in a 80 high COVID-19 prevalence setting using as reference methods RT-PCR and an Electro-81 chemiluminescence immunoassay (ECLIA) Elecsys® Anti-SARS-CoV-2 total Ig (Roche, Switzerland). is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. ; https://doi.org/10.1101/2020.10.28.20219667 doi: medRxiv preprint The primary end point was to assess the accuracy of IgG/IgM detection in plasma using Augurix Interquartile range (IQR). Significance (p-values) were calculated using a Mann-Whitney U test. Statistical significance was defined as p < 0.05. The demographic characteristics of patients' samples was as follows: the 48 COVID-19-positive 132 samples were from patients older (median = 49 years old, IQR 33-58.75) compared to the healthy 133 patients (n=98) (median = 34.5 years old, IQR 18-44.75; p < 0.05). The proportion of females was 56% 134 (n=20) and 51% (n=50) in the COVID-19 positive and in the healthy control group, respectively. Among the COVID-19 samples, the median delay between symptom onset and sampling was 21 days 136 (IQR 16-32 days), but not less than 10 days. The longest DPS (one single sample) was 180 days. The diagnostic specificity of the IgG/IgM RDT was assessed on the COVID-19 negative control group 142 with a sampling date before 2018 (n=98). The results are shown in Table 1 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. As shown in Table 1 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. The accuracy of the IgG/IgM RDT was also assessed using an electro-chemiluminescence immunoassay The two false-negative results exhibited a DPS between 10 and 15. When using exclusively the results 180 in the ≥ 15 DPS group, there was a complete agreement between the results of the IgG/IgM RDT and 181 ECLIA. In this case, the IgG/IgM RDT sensitivity (SE) was therefore 100% (95% CI: 79-100), while 182 the PPV was 86% (95% CI: 64-96) and the NPV 100% (95% CI: 95-100). is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. It is interesting to notice that the two false-negative results obtained with Augurix RDT corresponded is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. The second notable finding of this study lies in the fact that IgG seropositivity is still present 180 days This study indicates also that a certain titer of SARS-CoV-2 IgG is present constantly with a 235 concentration sufficient to be detectable with RDT, from 15 days to at least 180 days post symptoms. . CC-BY-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. ; https://doi.org/10.1101/2020.10.28.20219667 doi: medRxiv preprint It would be interesting to quantitatively determine the level of IgG/IgM 180 days post symptoms onset 238 to confirm this finding obtained with a qualitative assay. In addition, the test provided clear results without indeterminate or invalid measurements. There are 240 however several limitations to this study. First, we present here the results of a method evaluation study 241 and not a seroprevalence study. Therefore, the PPV obtained here (based on a 32.9% proportion of cases 242 defined as laboratory confirmed SARS-CoV-2 by RT-PCR) will be lower in a low prevalence setting, 243 e.g. when testing the asymptomatic population. Another limitation of this validation study lies in the 244 limited sample size leading to broad 95% confidence intervals, requiring confirmation of these data at a 245 larger scale. Also, here we used plasma and the test was performed in a laboratory environment; we may 246 expect different results in real-life at patients' bed and using capillary blood. Finally, our present 247 conclusions only apply to the Augurix RDT, and must not be generalized to other currently available 248 RDTs. In conclusion, Augurix RDT is not meant to replace a SARS-CoV-2 RT-PCR diagnostic test in the first 250 week of the disease, but could be a reliable option for assessing the SARS-CoV-2 serology in moderate is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. ; https://doi.org/10.1101/2020.10.28.20219667 doi: medRxiv preprint . CC-BY-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted November 1, 2020. ; https://doi.org/10.1101/2020.10.28.20219667 doi: medRxiv preprint Diagnostic accuracy of Augurix COVID-19 IgG 283 serology rapid test CoV-2 serological tests with different antigen targets COVID-19 (Novel Coronavirus 2019) 288 -recent trends Laboratory diagnosis of coronavirus disease-291 2019 (COVID-19) Development and clinical application of a rapid IgM-IgG combined 293 antibody test for SARS-CoV-2 infection diagnosis Antibody responses to SARS-CoV-2 in patients with COVID-296 Clinical Characterization of Eleven Lateral Flow Assays for Detection of COVID-19 Antibodies 299 in a Population Longitudinal evaluation and decline of antibody 301 responses in SARS-CoV-2 infection Interpreting Diagnostic Tests for SARS-CoV-2 Temporal profiles of viral load in posterior oropharyngeal saliva samples and 306 serum antibody responses during infection by SARS-CoV-2: an observational cohort study Antibody Responses to SARS-CoV-2 in Patients with We thank Augurix SA (Monthey, Switzerland) for providing Simtomax CoronaCheck RDTs free-of- is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted November 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted November 1, 2020. ; https://doi.org/10.1101/2020.10.28.20219667 doi: medRxiv preprint