ORIGINAL RESEARCH published: 03 January 2022 doi: 10.3389/fpubh.2021.780801 The Rapid Antigen Detection Test for SARS-CoV-2 Underestimates the Identification of COVID-19 Positive Cases and Compromises the Diagnosis of the SARS-CoV-2 (K417N/T, E484K, and N501Y) Variants Edited by: Carlos Barrera-Avalos 1 , Roberto Luraschi 1 , Eva Vallejos-Vidal 1,2 , Andrea Mella-Torres 1 , Carla Sofia e Sá Farinha, New University of Lisbon, Portugal Felipe Hernández 1 , Maximiliano Figueroa 1 , Claudia Rioseco 1 , Daniel Valdés 1,3 , Mónica Imarai 1,3 , Claudio Acuña-Castillo 1,3 , Felipe E. Reyes-López 1,4,5* and Reviewed by: Ana María Sandino 1,3* Anabela Coelho, Instituto Politécnico de 1 Centro de Biotecnología Acuícola, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile, Lisboa, Portugal 2 Centro de Nanociencia y Nanotecnología CEDENNA, Universidad de Santiago de Chile, Santiago, Chile, 3 Department of Estefania Nova-Lamperti, Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile, 4 Department of Cell Biology, University of Concepcion, Chile Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain, 5 Facultad de Medicina Veterinaria y *Correspondence: Agronomía, Universidad de Las Américas, Santiago, Chile Felipe E. Reyes-López felipe.reyes.l@usach.cl Ana María Sandino Timely detection of severe acute respiratory syndrome due to coronavirus 2 ana.sandino@usach.cl (SARS-CoV-2) by reverse transcription quantitative polymerase chain reaction (RT-qPCR) has been the gold- strategy for identifying positive cases during the current pandemic. Specialty section: This article was submitted to However, faster and less expensive methodologies are also applied for the massive Public Health Policy, diagnosis of COVID-19. In this way, the rapid antigen test (RAT) is widely used. However, a section of the journal it is necessary to evaluate its detection efficiency considering the current pandemic Frontiers in Public Health context with the circulation of new viral variants. In this study, we evaluated the sensitivity Received: 21 September 2021 Accepted: 23 November 2021 and specificity of RAT (SD BIOSENSOR, South Korea), widely used for testing and Published: 03 January 2022 SARS-CoV-2 diagnosis in Santiago of Chile. The RAT showed a 90% (amplification range Citation: of 20≤Cq<25) and 10% (amplification range of 25≤Cq<30) of positive SARS-CoV-2 Barrera-Avalos C, Luraschi R, Vallejos-Vidal E, Mella-Torres A, cases identified previously by RT-qPCR. Importantly, a 0% detection was obtained for Hernández F, Figueroa M, Rioseco C, samples within a Cq value>30. In SARS-CoV-2 variant detection, RAT had a 42.8% Valdés D, Imarai M, Acuña-Castillo C, detection sensitivity in samples with RT-qPCR amplification range 20≤Cq<25 containing Reyes-López FE and Sandino AM (2022) The Rapid Antigen Detection the single nucleotide polymorphisms (SNP) K417N/T, N501Y and E484K, associated Test for SARS-CoV-2 Underestimates with beta or gamma SARS-CoV-2 variants. This study alerts for the special attention that the Identification of COVID-19 Positive Cases and Compromises the must be paid for the use of RAT at a massive diagnosis level, especially in the current Diagnosis of the SARS-CoV-2 scenario of appearance of several new SARS-CoV-2 variants which could generate false (K417N/T, E484K, and N501Y) negatives and the compromise of possible viral outbreaks. Variants. Front. Public Health 9:780801. Keywords: rapid antigen test, SARS-CoV-2 detection, COVID-19 diagnosis, COVID-19 false negative rapid test for doi: 10.3389/fpubh.2021.780801 COVID-19 diagnosis, pandemic control strategies Frontiers in Public Health | www.frontiersin.org 1 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis INTRODUCTION SARS-CoV-2 Identification by Rapid Antigen Test (RAT), RT-qPCR, and The 2019 coronavirus disease (COVID-19) is a current pandemic respiratory disease caused by the severe acute respiratory Detection of Variants syndrome coronavirus 2 (SARS-CoV-2) (1). In Chile, more than The SARS-CoV-2 identification by rapid antigen test (SD 1.6 million infections and 37 thousand deaths have been reported BIOSENSOR, South Korea; Cat no: 99COV30D-ML02; from this disease (2). Currently, the most effective way to prevent Lot: QCO391081I) was made following the manufacturer’s and control its spread is the timely detection and isolation instructions. The viral SARS-CoV-2 genome sequence was of infected people. The reverse transcription quantitative PCR carried out using the ORF1ab probe (TaqManTM 2019nCoV (RT-qPCR) is the recommended and widely used technique for Assay Kit v1; Thermo Fisher Scientific, Cat. No. A47532) diagnosis due to its high sensitivity and precision (3). However, following a one-step strategy. Positive internal control probes new and faster methodologies for detecting and diagnosing for ORF1ab and RNase P (TaqManTM 2019-nCoV Control have recently been implemented, including the rapid antigen Kit v1; Thermo Fisher Scientific, Cat. No. A47533) were test (RAT) for SARS-CoV-2. The technique’s principle consists included and assessed individually in the 96-well PCR plate. of a rapid chromatographic immunoassay for the qualitative The polymerase from TaqManTM Fast Virus 1-Step Master Mix detection of specific SARS-CoV-2 antigens from nasopharyngeal (Applied BiosystemsTM , Cat. No. 44-444-36) was included in swab samples (NPSs) (4). This strategy has begun to be used each reaction. Each reaction contained 5 µl of TaqManTM Fast in several countries, and its effectiveness compared to the Virus 1-Step Master Mix 4X, 1 µl of ORF1ab assay 20X (FAM standard RT-qPCR method has been the target of study and detector channel), 1 µl of RNase P assay 20X (HEX detector analysis (5). In Chile, it was implemented in Health centers channel), 11 µl of nuclease-free water, and 2 µl of extracted RNA by the Ministry of Health in March 2021 as an alternative sample. The thermal amplification conditions include the reverse to RT-qPCR. More than 20 million RT-qPCR tests and more transcription at 50 ◦ C for 5 min, predenaturation at 95 ◦ C for than 750 thousand RATs have been carried out in Chile. 20 s, followed by 40 cycles at 95 ◦ C for 3 seconds and 60 ◦ C for Although its effectiveness has been verified in various studies 30 seconds. All the RT-qPCR reactions were performed on the showing differences between manufacturers, currently, there are Agilent AriaMx Real-Time PCR System (Agilent Technologies, no studies on the effectiveness of the antigenic tests used in Part. No. G8830A). Data and graphics were extracted using the Chile, nor on their performance for detecting the outbreak Agilent AriaMx software. The detection of different variants of new SARS-CoV-2 variants. In this study, we compare the was made by the AccuPower R SARS-CoV-2 Variants ID Real- efficacy of the results of 55 NPSs obtained by the rapid Time RT-PCR kit (Bioneer Cat. No. SMVR-2112) according antigen test for SARS-CoV-2 (SD Biosensor, South Korea), a to manufacturer instructions. The Exicycler 96 V4 Real-Time chromatographic assay using a monoclonal antibody against the thermal cycler (Bioneer) was used for detecting fluorescence nucleocapsid (N) protein of the SARS-CoV-2 virus, and the on the TET, TexasRed, FAM, TAMRA, and Cyanine5 channels. standard RT-qPCR detection method. We observed differences in The data obtained were exported in an Excel spreadsheet, and the detection of positive COVID-19 cases for the different ranges the Cq value and relative fluorescence intensity were analyzed of amplification assessed. Interestingly, we determined that this for the internal positive control, IPC (TAMRA), and each of the antigen test loses sensitivity for detecting SARS-CoV-2 variants assessed variants. carrying the K417N/T, E484K and N501Y single nucleotide polymorphisms (SNPs). Ethics Statement The experimental procedures included in this study were authorized by the Ethical Committee of the University of MATERIALS AND METHODS Santiago of Chile (No. 226/2021) and the Scientific Ethical Committee of the Central Metropolitan Health Service, Ministry Samples of Health, Government of Chile (No. 370/2021), and following Nasopharyngeal swab samples (NPSs) of clinical patients the Chilean law in force. Verbal consent for using of the included in this study were collected by the Primary Care Centers sample for SARS-CoV-2 diagnostic purposes was given to the and the Hospitals that belong to the Central Metropolitan healthcare professional at CESFAM. Results were communicated Health Service (Santiago of Chile) (SSMC, acronym in Spanish). to the patient in the Family Health Center they attended The swab samples were taken, preserved, and transported (CESFAM, acronym in Spanish; Central Metropolitan Health using the CITOSWAB R transport kit (Cat. No. 2118-0015; Service, Ministry of Health, Government of Chile). Citotest Labware Manufacturing Co., Ltd, Jiangsu, China). All the samples arrived at the laboratory before the first 24 h after the sampling collection. These samples were processed in the RESULTS laboratory of Virology (University of Santiago of Chile, USACH). Total RNA was extracted using the AccuPrep R Universal RNA To determine the detection sensitivity of the rapid antigen test Extraction Kit (Bionner, Daejeon, South Korea. Code product: (RAT), we evaluated 55 samples in different ranges of the cycle K-3140) following the manufacturer’s instructions. The extracted of quantification (Cq) for ORF1ab, in a similar way to studies RNA was used immediately for RT-qPCR assays. previously reported (6, 7). The sensitivity of RAT was performed Frontiers in Public Health | www.frontiersin.org 2 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis FIGURE 1 | Sensitivity evaluation of the rapid antigen test (RAT; SD BIOSENSOR, South Korea) at different ranges of Cq values for ancestral strain of SARS-CoV-2 positive samples diagnosed by RT-qPCR. SARS-CoV-2 detection by RAT from RT-qPCR positive samples with Cq value between 20≤Cq<25, 25≤Cq<30, 30≤Cq<35, and Cq≥35, respectively. All samples were positive by RT-qPCR. Table shows: the RFU (relative fluorescence units) and Cq value for the viral ORF1ab probe (n = 10 samples per Cq range). Frontiers in Public Health | www.frontiersin.org 3 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis only for those samples containing the ancestral strain SARS-CoV- RT-qPCR. For example, Chaimayo et al. compared the sensitivity 2 from Wuhan. Using NPSs, we determined that the detection and specificity of the Standard Q COVID-19 Ag rapid test (SD sensitivity of RAT for the RT-qPCR Cq range 20≤Cq<25 was Biosensor) against Allplex TM 2019-nCoV Assay RT-qPCR assay 90% (Figure 1), while a 10% sensitivity was observed for samples (Seegene) in the diagnosis of COVID-19 in a Thailand population comprised within the range of 25≤Cq<30 (Figure 1). On the (9). They showed a 98% of comparable sensitivity with the real- other hand, at higher Cq values, which include lower viral time RT-PCR assay. Other rapid detection kits have shown, loads, the detection sensitivity was 0% for both Cq value ranges, for example, a sensitivity of 85% (Shenzhen Bioeasy Biotech- 30≤Cq<35 and Cq≥35 (Figure 1). We made semi-quantitative 2019-nCoV Ag) (10) or 72% (Abbott-Panbio COVID-19 Ag) analysis of the RAT band intensity, where the SARS-CoV-2 (11), while the minimum sensitivity accepted in the rapid test positive samples for the Cq range 20≤Cq<25 and 25≤Cq<30 by the World Health Organization is 80% for its diagnostic showed a high band intensity (Table 1). Negative NPSs samples use (12). Dinnes et al. (5), after an analysis of 58 rapid tests, were also determined. Altogether, data showed a significantly concluded that sensitivity of antigen assays significantly decrease lower sensitivity of RAT for the detection of SARS-CoV-2 in in asymptomatic patients or after the second week of infection comparison to RT-qPCR technique. and, indicated that the sensitivity of these tests increases with the On the other hand, we determined the ability of RAT Cq≤25. For example, Linares et al. (13) reported that patients to detect variants of the SARS-CoV-2 virus. We select NPSs with less than seven days of symptoms showed a high viral from patients diagnosed as SARS-CoV-2 positive by RT- load and a sensitivity of 86.5%, while the sensitivity dropped to qPCR, containing variants according to the RT-qPCR SNP 53.8% in asymptomatic patients or lower viral loads using the detection. When we evaluated these NPSs containing SARS-CoV- Panbio COVID-19 Ag Rapid Test Device (Abbot). The same 2 variants, we observed that the sensitivity of RAT decreased effect was observed using the SD Biosensor-STANDARD Q in the variants that carry K417N/T and E484K amino acid COVID-19 test, where a sensitivity of 65.3% was observed in substitutions, even in samples with the lowest ranges of Cq symptomatic patients and 44% in asymptomatic patients (14). (20≤Cq<25). As a result, detection sensitivity decreases to Krüttgen et al. (6) using the rapid SARS-CoV-2 antigen test 42% detection, obtaining 58% false-negative samples when the from the Roche manufacturer, indicated that the sensitivity of virus presents these mutations (Figure 2). Interestingly, from the assay in 75 NPSs is 100% (Cq≤25), 95% (Cq≤30), 44.8% the three SARS-CoV-2 (K417N/T, E484K, and N501Y) positive (Cq≤35), and 22.2% (Cq>35) compared to RT-qPCR. Such samples for RAT, two of them presented a band of low intensity sensitivity is directly related to the patient’s viral load. In the (Table 2) compared to SARS-CoV-2 samples with no mutations same line, Schildgen et al. (15) reported a sensitivity of 100% in identified, which present a high-intensity band in the range symptomatic patients and 84.6% in asymptomatic patients using 20≥Cq<25 (Table 1). Furthermore, for Cq over 25 no SARS- the rapid test from Roche. CoV-2 variant (K417N/T, E484K, and N501Y) sample was In this study, we observed that the rapid antigen test detected by RAT. A flow chart of the results obtained are (SD Biosensor) has a detection efficiency depending on the described on Figure 3. Cq values, being 90, 10, 0, and 0% within the ranges of Taking together, these data suggest that RAT loses its full 20≤Cq<25; 25≤Cq<30; 30≤Cq<35, and Cq≥35, respectively. ability to detect SARS-CoV-2 against these variants. In this regard, the manufacturer and distributor indicate that 95.5% of effectiveness at Cq<30. Although our study shows lower sensitivity as previously described, it is also important to mention DISCUSSION that we used a smaller number of samples in each Cq range compared to previous evidence (16). Furthermore, we observed RT-qPCR test is the gold standard technique for COVID-19 that RAT sensitivity for detecting ancestral strain of SARS-CoV- diagnosis (3). However, despite its high sensitivity, the extent 2 decreased from 90 to 42.8% with the SARS-CoV-2 variants that of analysis and the associated costs have encouraged the use carry K417N/T, E484K and N501Y amino acid substitutions, even of faster and low-cost SARS-CoV-2 detection assays for better in the lower Cq range of 20≤Cq<25. The low intensity of bands control of the pandemic (8). Previous studies have documented showed for two of the three SARS-CoV-2 variants identified the efficiency of different brands of rapid antigen tests for SARS- by RAT suggests a decreased specificity for samples with the CoV-2 detection as a diagnostic alternative compared to standard K417N/T, E484K, and N501Y mutations. By contrast, the virus with no mutations showed a high intensity band of detection by TABLE 1 | Qualitative analysis of SARS-CoV-2 samples tested by Rapid Antigen RAT in the 90% of the samples evaluated. Because the amino Test (RAT). acid substitutions E484K and N501Y are present in the beta (B.1.351) and gamma (P.1) variants, and the substitution K417N Band intensity in RAT is found in the beta variant and K417T in the gamma variant Cq ranges None Low High (17), we hypothesized that RAT might not detect both or at least one of these two virus variants. In this line, Frediani et al. (7) 20≤Cq<25 1 0 9 reported that the Abbott BinaxNOW COVID-19 Ag Card rapid 25≤Cq<30 9 0 1 test detects the P.1 variant, even between the Cq ranges of 20-22. 30≤Cq<35 10 0 0 However, this data corresponds only to one sample analyzed (7). Cq≥35 10 0 0 Other variant studies using rapid antigen tests, including analysis Frontiers in Public Health | www.frontiersin.org 4 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis FIGURE 2 | SARS-CoV-2 Variant detection by RAT. RAT detection of SARS-CoV-2 variants which contain K417N/T, E484K, and N501Y mutations, from RT-qPCR positive samples with Cq value between 20≥Cq<25, 25≥Cq<30, 30≥Cq<35. All samples were positive by RT-qPCR. Table shows: the RFU (relative fluorescence units) and Cq value for the viral ORF1ab probe (n = 16). TABLE 2 | Qualitative analysis of SARS-CoV-2 variant (K417N/T/, E484K, and The rapid antigen test analyzed in this study detects the N501Y) samples tested by Rapid Antigen Test (RAT). nucleocapsid (N) of the original SARS-CoV-2 virus using a Band intensity in RAT monoclonal antibody. This kind of detection can explain the low capacity of RAT to detect the variants, which has the substitutions Cq Ranges None Low High P80R and R203K in the N protein. These data further suggest 20≤Cq<25 4 2 1 that this rapid antigen test could also fail to detect other variants, 25≤Cq<30 5 0 0 such as delta (B.1.617.2), because, in addition of Spike protein 30≤Cq<35 3 0 0 mutations (19), the delta variant also has mutations in the N protein (different to R203K). This data suggests a lack of specificity of RAT to detect specific variants, which agrees with of the alpha (B.1.1.7) and beta (B.1.351) variants (18), showed no the fact that RAT initially manufactured to detect the ancestral detection at Cq values between 29–35 (7) like this study. strain of SARS-CoV-2. In addition, this takes on real relevance Frontiers in Public Health | www.frontiersin.org 5 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis FIGURE 3 | Summary of the results obtained for the analysis of the 55 nasopharyngeal swab samples (NPSs) evaluated by Rapid Antigen Test (RAT). The 55 NPSs were diagnosed as positive for SARS-CoV-2 using the ORF1ab probe following a one-step strategy. From them, 40 NPSs showed no mutations for SARS-CoV-2 (black arrow) (Group 1). By contrast, in the other 15 positive samples we identified the SARS-CoV-2 variants K417N/T, E484K, and N501Y (gray arrows) (Group 2). Each one of these groups were used to evaluate the sensitivity of the Rapid Antigen Test (RAT) according to the Cq ranges previously obtained by RT-qPCR. The group 1 showed a 90% of positive diagnosis using the RAT. However, the group 2 showed only a 42.8% of positive diagnosis. Importantly, all of them were grouped in the 20≤Cq<25 interval. when the RAT is used as an active search or mass testing in load, who will probably be asymptomatic, should be done only by public places in infected patients with a high Cq (low viral load). the RT-qPCR assay, one of the safest ways to be massively tested According to the results shown in our work, the diagnosis by in the population to control the pandemic. Further studies are RAT will be negative, and the patient will be able to infect needed for evaluating by RAT a higher number of samples and their contacts and, consequently, may generate important local SARS-CoV-2 variants. Although we found significant differences outbreaks. Therefore, detecting positive patients with low viral in each condition (ancestral strain of SARS-CoV-2; SARS-CoV-2 Frontiers in Public Health | www.frontiersin.org 6 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis variants), it is still necessary to increase the number of samples AUTHOR CONTRIBUTIONS to obtain more accurate detection percentages of SARS-CoV-2 in each range of Cq analyzed. We suggest restricting the use of RAT CB-A, RL, MI, CA-C, FER-L, and AMS: conceptualization. only to confirm COVID-19 symptomatic positive cases but not CB-A, RL, and FER-L: data curation. CB-A, RL, FER-L, and as a massive strategy for traceability and identification of cases in AMS: formal analysis. MI, CA-C, FER-L, and AMS: funding the population. acquisition. CB-A, AM-T, FH, MF, and CR: investigation. CB-A, EV-V, FER-L, and AMS: methodology. DV, FER-L, and AMS: supervision. DV, MI, CA-C, FER-L, and AMS: validation. CB-A, CONCLUSIONS RL, CA-C, and FER-L: writing—original draft. CB-A, RL, EV-V, The sensitivity of the rapid antigen test (SD Biosensor, South CA-C, MI, FER-L, and AMS: writing—review and editing. All Korea) is determined by the viral load of the sample. While authors have read and agreed to the published version of high viral loads (20≤Cq<25) present 90% sensitivity, 25≤Cq<30 the manuscript. and >30 present 10 and 0% respectively. On the other hand, the rapid test reduces its detection sensitivity compared to FUNDING samples positive for SARS-CoV-2, but that present the mutations K417N/T, E484K, and N501Y observing a detection capacity of The Laboratory of Virology supported the COVID-19 42% in ranges of 20≤Cq<25. diagnosis in the University laboratories network (Ministry of Sciences, Ministry of Health, Government of Chile) DATA AVAILABILITY STATEMENT for diagnosis tasks. The funders had no role in study design, data collection and analysis, decision to publish, or The original contributions presented in the study are included manuscript preparation. in the article/supplementary material, further inquiries can be directed to the corresponding author/s. ACKNOWLEDGMENTS ETHICS STATEMENT The authors thank the Rapid Assignment of Resources for Research Projects on the Coronavirus (COVID-19) (project The studies involving human participants were reviewed and number COVID1038; ANID, Government of Chile) (MI, CA-C, approved by Ethical Committee of the University of Santiago FER-L, and AMS), Fondecyt regular project numbers 1201664 of Chile (No. 226/2021), and Scientific Ethical Committee of (MI) and 1211841 (FER-L) (ANID, Government of Chile), and the Central Metropolitan Health Service, Ministry of Health, DICYT-USACH project number 021943AC (CA-C) grants. EV-V Government of Chile (No. 370/2021). Written informed consent was partially funded by FONDEQUIP grant project number for participation was not required for this study in accordance EQM200016, and Basal project CEDENNA AFB-180001 (ANID; with the national legislation and the institutional requirements. Government of Chile). REFERENCES 8. Santaella-Tenorio J. Sars-cov-2 diagnostic testing alternatives for latin america. Colomb Med. (2020) 51:1–7. doi: 10.25100/cm.v51i2.4272 1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus 9. Chaimayo C, Kaewnaphan B, Tanlieng N, Athipanyasilp N, Sirijatuphat from patients with pneumonia in China, 2019. N Engl J Med. (2020) 382:727– R, Chayakulkeeree M, et al. Rapid SARS-CoV-2 antigen detection assay 33. doi: 10.1056/NEJMoa2001017 in comparison with real-time RT-PCR assay for laboratory diagnosis of 2. Ministry of science and interior G of C. Cifras Oficiales COVID-19. (2021). COVID-19 in Thailand. Virol J. (2020) 17:1–7. doi: 10.1186/s12985-020- Available online at: https://www.gob.cl/coronavirus/cifrasoficiales/ (accessed 01452-5 September 16, 2021). 10. Porte L, Legarraga P, Vollrath V, Aguilera X. Evaluation of a novel 3. Barreto HG, de Pádua Milagres FA, de Araújo GC, Daúde MM, antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in Benedito VA. Diagnosing the novel SARS-CoV-2 by quantitative respiratory samples. Int J Infect Dis. (2020) 99:328–33. doi: 10.1016/j.ijid.2020. RT-PCR: variations and opportunities. J Mol Med. (2020) 05.098 98:1727–36. doi: 10.1007/s00109-020-01992-x 11. Gremmels H, Winkel BMF, Schuurman R, Rosingh A, Rigter NAM, 4. Centers for disease control and prevention. Interim Guidance for Antigen Rodriguez O, et al. Real-life validation of the PanbioTM COVID- Testing for SARS-CoV-2. (2021). Available online at: https://www.cdc. 19 antigen rapid test (Abbott) in community-dwelling subjects with gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html symptoms of potential SARS-CoV-2 infection. EClinicalMedicine. (2021) (accessed September 16, 2021). 31:100677. doi: 10.1016/j.eclinm.2020.100677 5. Dinnes J, Deeks JJ, Berhane S, Taylor M, Adriano A, Davenport C, 12. World Health Organization. COVID-19 Target product profiles for priority et al. Rapid, point-of-care antigen and molecular-based tests for diagnosis diagnostics to support response to the COVID-19 pandemic v.1.0. (2020). p. of SARS-CoV-2 infection. Cochrane Database Syst Rev. (2021) 2021:1– 1–38. Available online at: https://www.jstor.org/stable/resrep28228 (accessed 409. doi: 10.1002/14651858.CD013705.pub2 September 16, 2021). 6. Krüttgen A, Cornelissen CG, Dreher M, Hornef MW, Kleines M. Comparison 13. Linares M, Pérez-Tanoira R, Carrero A, Romanyk J, Pérez-García F, Gómez- of the SARS-CoV-2 rapid antigen test to the real star Sars-CoV-2 RT PCR kit. Herruz P, et al. Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 J Virol Methods. (2021) 288:e114024. doi: 10.1016/j.jviromet.2020.114024 infection in the first 7 days after the onset of symptoms. J Clin Virol. (2020) 7. Frediani JK, Levy JM, Rao A, Bassit L, Figueroa J, Vos MB, et al. 133:104659. doi: 10.1016/j.jcv.2020.104659 Multidisciplinary assessment of the Abbott BinaxNOW SARS-CoV-2 point- 14. Jegerlehner S, Suter-riniker F, Jent P. Diagnostic accuracy of a SARS-CoV- of-care antigen test in the context of emerging viral variants and self- 2 rapid antigen test in real-life clinical settings. Int J Infect Dis. (2020) administration. Sci Rep. (2021) 11:1–9. doi: 10.1038/s41598-021-94055-1 109:118–22. doi: 10.1016/j.ijid.2021.07.010 Frontiers in Public Health | www.frontiersin.org 7 January 2022 | Volume 9 | Article 780801 Barrera-Avalos et al. Rapid Test for COVID-19 Diagnosis 15. Schildgen V, Demuth S, Lüsebrink J, Schildgen O. Limits and opportunities of Conflict of Interest: The authors declare that the research was conducted in the sars-cov-2 antigen rapid tests: an experienced-based perspective. Pathogens. absence of any commercial or financial relationships that could be construed as a (2021) 10:1–7. doi: 10.3390/pathogens10010038 potential conflict of interest. 16. Peña M, Ampuero M, Garcés C, Gaggero A, García P, Velasquez MS, et al. Performance of SARS-CoV-2 rapid antigen test compared with real-time Publisher’s Note: All claims expressed in this article are solely those of the authors RT-PCR in asymptomatic individuals. Int J Infect Dis. (2021) 107:201– and do not necessarily represent those of their affiliated organizations, or those of 4. doi: 10.1016/j.ijid.2021.04.087 the publisher, the editors and the reviewers. Any product that may be evaluated in 17. Gobeil SMC, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, this article, or claim that may be made by its manufacturer, is not guaranteed or et al. Effect of natural mutations of SARS-CoV-2 on spike structure, endorsed by the publisher. conformation, and antigenicity. Science. (2021) 80:373: doi: 10.1126/science. abi6226 18. Jungnick S, Hobmaier B, Mautner L, Hoyos M, Haase M, Copyright © 2022 Barrera-Avalos, Luraschi, Vallejos-Vidal, Mella-Torres, Baiker A, et al. Detection of the new SARS-CoV-2 variants of Hernández, Figueroa, Rioseco, Valdés, Imarai, Acuña-Castillo, Reyes-López and concern B.1.1.7 and B.1.351 in five SARS-CoV-2 rapid antigen Sandino. This is an open-access article distributed under the terms of the Creative tests (RATs), Germany, March 2021. Eurosurveillance. (2021) Commons Attribution License (CC BY). The use, distribution or reproduction in 26:1–6. doi: 10.2807/1560-7917.ES.2021.26.16.2100413 other forums is permitted, provided the original author(s) and the copyright owner(s) 19. University S. CORONAVIRUS ANTIVIRAL & RESISTANCE DATABASE. are credited and that the original publication in this journal is cited, in accordance (2021). Available online at: https://covdb.stanford.edu/page/mutation- with accepted academic practice. No use, distribution or reproduction is permitted viewer/#delta (accessed September 16, 2021). which does not comply with these terms. Frontiers in Public Health | www.frontiersin.org 8 January 2022 | Volume 9 | Article 780801