key: cord-0748676-krnvtfzz
authors: Gunell, M.; Rantasarkka, K.; Arjonen, R.; Sanden, A.; Vuorinen, T.
title: Clinical evaluation of an automated, rapid mariPOC(R) antigen test in screening of symptomatics and asymptomatics for SARS-CoV-2 infections
date: 2022-04-27
journal: nan
DOI: 10.1101/2022.04.22.22273686
sha: 37cf05e5e0548816e55be3a070bcac4300a3b97c
doc_id: 748676
cord_uid: krnvtfzz

A novel automated mariPOC SARS-CoV-2 antigen test was evaluated in a Health care center laboratory among symptomatic and asymptomatic individuals seeking SARS-CoV-2 testing. According to the national testing strategy, RT-PCR was used as a reference method. A total of 962 subjects were included in this study, 4.8% (46/962) of their samples were SARS-CoV-2 RT-PCR positive, and 87% (40/46) of these were from symptomatics. Among the symptomatics, the overall sensitivity of the mariPOC SARS-CoV-2 test was 82.5% (33/40), though the sensitivity increased to 97.1% (33/34) in samples with a Ct value <30. The mariPOC SARS-CoV-2 test detected 2/6 PCR positive samples among the asymptomatics, four cases that remained antigen test negative had Ct values between 28 and 36. The specificity of the mariPOC SARS-CoV-2 test was 100% (916/916). The evaluation showed that the mariPOC SARS-CoV-2 rapid antigen test is very sensitive and specific for the detection of individuals who most probably are contagious.

The global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 25 has been a significant burden for both society and the carrying capacity of health care since late 2019 [1] 26 when this emerging virus was initially recognized in Wuhan, China. SARS-CoV-2 can mutate into the new 27 emerging variants escaping immunity, and it can in addition to symptomatic infections, manifest as both 28 asymptomatic and presymptomatic infections, and thus the virus has spread efficiently all over the world. 29

According to a simulation model made by US CDC, transmission from asymptomatic individuals, including 30 presymptomatic individuals and those who never develop symptoms, is estimated to account for more 31 than half of all SARS-CoV-2 infections [2] . To prevent the spread of infection there is a need for rapid and 32 accurate diagnostic tests, which detect contagious individuals irrespective of their presence or absence of 33 COVID-19 symptoms. 34 PCR-based methods, especially RT-PCR is up to date considered the cornerstone for fighting against the 35 pandemic [3,4]. However, large-scale RT-PCR testing, although with excellent sensitivity and analytical 36 specificity, also has some major disadvantages such as long turnaround time as well as the requirement for 37 sophisticated equipment and highly trained personnel. Furthermore, it has been proposed that a positive 38 PCR result may not correlate with infectivity [5] , as viral nucleic acids can be detected for a long time after 39 the acute infection, without the presence of infectious and actively replicating SARS-CoV-2 virus [6-12]. As 40 the COVID-19 continues to be a worldwide threat, there is a continuous demand for rapid testing of SARS-41

CoV-2. Several inexpensive and easy-to-use rapid antigen tests have been developed [13] . Rapid antigen 42 tests have been shown to correlate more accurately with SARS-CoV-2 viral culture than RT-PCR [ could not be collected in a reasonable time. Therefore, the protocol for sample collection and analysis was 79 altered. Thereafter, together with the strategy implemented in cohort 1, the primary screening of SARS-80

CoV-2 positive samples was performed with RT-PCR in the Clinical Microbiology laboratory. PCR positive 81 samples were stored at -20 °C and later analyzed by mariPOC ® antigen test in the Health care center 82 laboratory (cohort 2). Of the samples in cohort 2, two were omitted from the analysis due to improper 83 handling of the samples before being aliquotted for mariPOC ® testing and thus 23 consecutive SARS-CoV-2 84 positive samples of which six were taken from asymptomatic subjects, were included. For this cohort, NPS 85 specimens were suspended into 2 ml VTM (VACUETTE ® Virus Stabilization tube, 456162) for the primary 86 screening of SARS-CoV-2 by RT-PCR. In contrast to Bioer tube, VACUETTE VTM was found to be applicable 87 also in mariPOC ® antigen analysis. The mariPOC ® SARS-CoV-2 testing was performed in the on-site laboratory of Kaarina Health Care Center. 104 NPS specimens from cohort 1 were suspended into 1.3 ml mariPOC ® RTI sample buffer in sample tubes and 105 analyzed with the mariPOC ® test system according to the manufacturer`s instructions as soon as possible. 106

The samples in cohort 2 were collected in VACUETTE VTM and stored at -20 °C after the primary SARS-CoV-107 2 PCR test and were further diluted 1:1 (0.65 ml+ 0.65 ml) with mariPOC ® RTI sample buffer to gain the 108 required sample volume for mariPOC ® analysis. The VTM samples were diluted approximately 3-times more 109 than in the dry swab procedure recommended by the mariPOC ® manufacturer. 110

The mariPOC ® SARS-CoV-2 rapid antigen test sensitivity, including 95% confidence intervals (CI), was 112 determined using MedCalc Software [21] . 113

Demographic data of the population included in the mariPOC ® rapid antigen test evaluation is presented in 116 Table 1 . Of the whole study population, 6.7% (64) were asymptomatic and 93.3% (898) had symptoms 117 linked to COVID-19, such as sore throat, headache, fever, shortness of breath, and diarrhea. 118

. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 27, 2022. ; https://doi.org/10.1101/2022.04.22.22273686 doi: medRxiv preprint samples in cohort 2 were from asymptomatic subjects and 17 subjects had COVID-19-like symptoms. 124

The correlation of Ct values and mariPOC ® SARS-CoV-2 rapid antigen test results among asymptomatic and 126 symptomatic subjects are presented in Figure 1 Table 2 ). When only samples with Ct values <30 were considered, the mariPOC ® sensitivity in cohort 137 1 within symptomatic subjects was 100.0% (18/18). 138

In cohort 2, 17 of the 23 PCR positive samples were mariPOC ® SARS-CoV-2 test positive and six samples 139 remained negative (Table 2) . Four of the samples from cohort 2 were taken from patients whose second 140 NPS specimen was also included in cohort 1. Of the six PCR positive samples that remained negative in the 141 antigen detection, four were taken from asymptomatic patients and two have had only mild COVID-19 142 symptoms for one or two days. Ct values for 17 true positive samples in the antigen detection varied from 143

14.66 to 27.25 ( Figure 1 ) and the mean duration of symptoms was 2.5 days (range 0−7 days). Ct values for 144 . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) (Figure 1) , and the mean duration of symptoms was 0.5 days (range 0−2 days). The sensitivity of 146 the mariPOC ® antigen test for cohort 2 was 73.9% (17/23), but when only symptomatic subjects were 147 considered, the sensitivity was 88.2% (15/17, Table 2 The evaluation of the mariPOC ® SARS-CoV-2 rapid antigen test to be used in a health care laboratory was 162 performed in a medium-sized Finnish city representing adequate variation in social, ethnic, and age 163 distribution of the population seeking COVID-19 testing in Finland. The SARS-CoV-2 positivity rate among 164 the study population was 4.8%, determined by the RT-PCR method, which was well in correlation to the 165 SARS-CoV-2 prevalence in the hospital district of Southwest Finland during spring 2021. 166

The sensitivities of antigen tests in different published studies have varied considerably due to differences 167 in evaluated test products, study protocols, and patient cohorts [22, 23] . The overall sensitivity of the 168 mariPOC ® antigen test in our evaluation was 76.1% which is in correlation with a recent meta-analysis 169 . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. workplaces and, therefore, help to prevent the spread of the COVID-19 in the community [28, 30] . 205

We conclude that the mariPOC ® SARS-CoV-2 antigen test detected the majority of the samples with RT-PCR 207 cycle threshold below 30 among symptomatic and asymptomatic subjects justifying its use for rapid 208 detection of individuals who most probably are contagious. In addition, the mariPOC ® test system is 209 practicable in small and medium-size laboratories as well as health care centers to be used for rapid SARS-210

CoV-2 detection in symptomatics. 211 212

This study was approved by the Hospital District of Southwest Finland, research approval number 215 T12/009/21. Ethical aspects of the study were considered and approved by Turku Clinical Research Centre 216 (Turku CRC), no ethical committee review was required. Oral consent for sample collection was obtained 217 . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 27, 2022. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 27, 2022. ; https://doi.org/10.1101/2022.04.22.22273686 doi: medRxiv preprint

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