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Delta Variant (B.1.617.2) of SARS-CoV-2

Rapid antigen tests (RATs) for COVID-19 based on lateral flow immunoassays are useful for rapid diagnosis in a variety of settings. Although many kinds of RATs are available, their respective sensitivity has not been compared. 

  • SARS-CoV-2
  • COVID-19
  • rapid antigen test

1. Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The WHO reported that more than 230 million cases of COVID-19, including approximately 4.8 million deaths, have occurred as of 29 September 2021 (https://covid19.who.int/). To reduce the burden by SARS-CoV-2, nonpharmaceutical interventions, vaccination, and patient treatment are required. For mitigation of infectious diseases, early and accurate patient diagnosis is essential.
For COVID-19 diagnosis, reverse transcription-quantitative PCR (RT-qPCR) using upper respiratory swabs or saliva has become the gold standard [1] because it possesses high sensitivity and specificity against the target agent. RT-qPCR is usually not available in local clinics where patients who suspect they have COVID-19 go first. Therefore, the collected specimens are transported to sites with RT-qPCR capability, resulting in delayed test results. To obtain results at local clinics, rapid antigen tests (RATs) for COVID-19 have become popular because RATs require just 15–30 min to give results. RATs are also helpful as screening tests for asymptomatic individuals since model analyses showed that population screening tests should prioritize frequency and turnaround time over sensitivity [2][3]. Therefore, RATs might be useful to reduce COVID-19 clusters and spread if frequent self-testing using RATs was performed before mass gatherings, domestic travel, or dining at restaurants. Although the sensitivity of RATs is lower than that of RT-qPCR [4][5][6][7][8][9][10][11], it is essential to utilize RATs with superior sensitivity for better detection.

2. Comparison of Rapid Antigen Tests (RATs)

We evaluated 27 RATs that were available in Japan in September 2021 (Table 1). Of these 27 RATs (#1–17), 17 are approved for clinical diagnosis in Japan, whereas the other 10 RATs (#18–27) are not approved for such purpose in Japan. The 27 RATs are divided into three formats: the test strip format, the pen format, and the well format. In the test strip format, a test strip is soaked in lysis buffer containing the specimen or is dipped in the specimen and then soaked in the lysis buffer; the reaction occurs on the strip. In the pen format, the test strip is dipped into the specimen and the reaction occurs on the strip. This format allows saliva specimens to be loaded by holding the cartridge directly in the mouth. For the well format, lysis buffer containing the specimen is dropped into the well, and the reaction occurs inside a covered plastic body. The well format can be further subdivided into two groups based on how the result is evaluated; for tests #15, #16, and #17, a specific analyzer is required to evaluate the results, whereas the other well-format RATs are assessed by the human eye. Most RATs can process upper respiratory swabs including nasopharyngeal (NP), pharyngeal (P), oropharyngeal (O), or nasal (N) swabs, whereas saliva is the recommended sample for seven RATs (#19, #22, #23, #24, #25, #26, and #27) (Table 1). Tests #18, #20, and #21 can be used for both upper respiratory swabs and saliva. Since it is easy for individuals to collect nasal swabs and saliva, the RATs available for such specimens are suitable for self-testing.
Table 1. Characteristics of the rapid antigen tests for COVID-19 evaluated in this study.
No Rapid Antigen Test Manufacturer Country of Origin Clinical Use in Japan Format a Recommended Test Sample b
1 ESPLINE SARS-CoV-2 Fujirebio Japan Yes Well NP or N swab
2 ImmunoAce SARS-CoV-2 TAUNS Laboratories Japan Yes Well NP or N swab
3 PanbioTM COVID-19 Ag Rapid Test Device Abbott Diagnostics Medical USA Yes Well N swab
4 PRORAST SARS-CoV-2 Ag ADTEC/LSI Medience Japan Yes Well NP or N swab
5 SARS-CoV-2 Rapid Antigen Test Roche Diagnostics Switzerland Yes Well NP or N swab
6 Fuji Dry-Chem IMMUNO AG Handy COVID-19 Ag Fujifilm Japan Yes Well NP or N swab
7 ALSONIC COVID-19 Ag Alfresa Pharma Japan Yes Well NP or N swab
8 COVID-19 and Influenza A+B Antigen Combo Rapid Test Nichirei Bioscience/Hangzhou AllTest Biotech Japan/China Yes Well NP or N swab
9 ImmunoArrow SARS-CoV-2 Toyobo Japan Yes Well NP or N swab
10 Check MR-COV19 Rohto Pharmaceutical Japan Yes Well NP or N swab
11 RapidTesta SARS-CoV-2 Sekisui Medical Japan Yes Well NP or N swab
12 QuickNavi-Flu+COVID19 Ag Denka Japan Yes Well NP or N swab
13 QuickNavi -COVID19 Ag Denka Japan Yes Well NP or N swab
14 KBM LineCheck nCoV Kohjin Bio Japan Yes Test strip NP swab
15 BD Veritor System for Rapid Detection of SARS-CoV-2 Becton Dickinson USA Yes Well + Analyzer N swab
16 Sofia SARS Antigen FIA Quidel USA Yes Well + Analyzer NP or N swab
17 Fuji Dri-chem immuno AG cartridge COVID-19 Ag Fujifilm/Mizuho Medy Japan Yes Well + Analyzer NP or N swab
18 COVID-19 NP rapid test kit Shanghai Cagenbio Science China No Well Saliva or P or O swab
19 SARS-CoV-2 Antigen Rapid Test Zhuhai Encode Medical Engineering China No Well Saliva
20 2019-nCoV Ag rapid detection kit Guangdong Longsee Biomedical China No Well Saliva or O or NP swab
21 Novel Coronavirus (SARS-CoV-2) Antigen Rapid Test Kit Beijing Jinwofu Bioengineering Technology China No Well Saliva or O or NP swab
22 Saliva SARS-CoV-2(2019-nCoV) Antigen Test Kit Jiaxing Wisetest Bio-tech China No Pen Saliva
23 Corona Virus (COVID-19) Antigen Rapid Test Hoyotek Biomedical China No Well Saliva
24 SARS-CoV-2 Antigen Rapid Test Kit JOYSBIO (Tianjin) Biotechnology China No Well Saliva
25 Novel coronavirus (2019-nCoV) antigen testing kit Nanjing Norman Biological Technology China No Well Saliva
26 COVID19 antigen rapid test device Toa Industry Japan No Test strip Saliva
27 Rabliss SARS-CoV-2 antigen detection kit COVID19 AG Undisclosed China No Well Saliva
a RATs were divided into three types based on their format: (i) well format, in which the lysed sample is dropped into the well and the reaction occurs inside a covered plastic body; (ii) test strip format, in which a test strip is soaked in lysis buffer containing the specimen or dipped in the specimen and then soaked in the lysis buffer, and the reaction occurs on the strip; or (iii) pen format, in which a test strip is dipped into the specimen and the reaction occurs on the strip. “+ Analyzer” means that these RATs need an analyzer to evaluate the result. b NP, nasopharyngeal; N, nasal; P, pharyngeal; O, oropharyngeal.
All of the RATs we tested are immunochromatographic tests, meaning that their sensitivity is dependent on the binding kinetics and epitopes of the monoclonal antibodies used in each RAT, the composition of the lysis buffer, the volume of specimen used for analysis, and the method to visualize the result. We cannot directly compare the performance of monoclonal antibodies because the manufacturers do not disclose the properties or amino acid sequence of monoclonal antibodies; however, most RATs likely use monoclonal antibodies against the nucleoprotein of SARS-CoV-2. Because the amino acid sequences of nucleoprotein are similar among human betacoronaviruses, especially the subgenera sarbecovirus, cross-detection is likely to occur against SARS-CoV or SARS-CoV-2-related viruses such as RaTG13 and bat SARS-like coronaviruses. Most of the RATs claim cross-detection of SARS-CoV, with three exceptions: the manufacturers of tests #11 and #15 state that their tests show no cross-reactivity against SARS-CoV, and test #6 cross-detects a high concentration of human coronavirus HKU1 as well as SARS-CoV. Therefore, RATs that show cross-reactivity against SARS-CoV are not able to differentiate patients infected with SARS-CoV-2 and other sarbecoviruses under conditions where these viruses are co-circulating.
The amount of specimen used for each test varied between the RATs (Table 2). The input ratio for three RATs with the pen and test strip formats (#14, #22, and #26) was 100% because of the mechanism. Among the well-format tests, the lowest input ratio was for test #20 at 2%, and the highest was for test #24 at 45.7%. According to the detection limits stated in the manufacturers’ product information, the RATs could detect SARS-CoV-2 at 35–800 TCID50/mL or target virus protein at 10–25 pg/mL (Table 2). The results are assessed 5–30 min after adding the analyte (Table 2).
Table 2. Rapid antigen tests for COVID-19.
No. Rapid Antigen Test Input Rate (%) a Detection Limit b Time to Result (min) c
1 ESPLINE SARS-CoV-2 8.0 25 pg/mL 10–30
2 ImmunoAce SARS-CoV-2 13.3 35.6 TCID50/test 15
3 PanbioTM COVID-19 Ag Rapid Test Device 14.3 157.7 TCID50/mL 15–20
4 PRORAST SARS-CoV-2 Ag 18.2 42 Pfu/mL 15
5 SARS-CoV-2 Rapid Antigen Test 14.3 490 TCID50/mL 15–30
6 Fuji Dry-Chem IMMUNO AG Handy COVID-19 Ag 6.0 110 TCID50/mL 10
7 ALSONIC COVID-19 Ag 10.9 800 TCID50/mL 5
8 COVID-19 and Influenza A+B Antigen Combo Rapid Test 28.6 100 pg/mL 15
9 ImmunoArrow SARS-CoV-2 22.2 25 pg/mL 15
10 Check MR-COV19 21.9 100 TCID50/mL 15
11 RapidTesta SARS-CoV-2 21.8 110 TCID50/mL 10
12 QuickNavi-Flu+COVID19 Ag 12.5 53 TCID50/mL 10
13 QuickNavi -COVID19 Ag 12.5 53 TCID50/mL 10
14 KBM LineCheck nCoV 100 625 TCID50/mL 10
15 BD Veritor System for Rapid Detection of SARS-CoV-2 26.7 140 TCID50/mL 15
16 Sofia SARS Antigen FIA 34.3 113 TCID50/mL 15
17 Fuji Dri-chem immuno AG cartridge COVID-19 Ag 23.1 10 pg/mL 15
18 COVID-19 NP rapid test kit 22.2 N.A. d 15
19 SARS-CoV-2 Antigen Rapid Test 8.6 N.A. 20
20 2019-nCoV Ag rapid detection kit 2.0 N.A. 15
21 Novel Coronavirus (SARS-CoV-2) Antigen Rapid Test Kit 11.1 100 TCID50/mL 15
22 Saliva SARS-CoV-2(2019-nCoV) Antigen Test Kit 100 N.A. 15
23 Corona Virus (COVID-19) Antigen Rapid Test 25 N.A. 15
24 SARS-COV-2 Antigen Rapid Test Kit 45.7 160 TCID50/mL 15–20
25 Novel coronavirus (2019-nCoV) antigen testing kit 22.9 121 TCID50/mL 15–20
26 COVID19 antigen rapid test device 100 N.A. 15
27 Rabliss SARS-CoV-2 antigen detection kit COVID19 AG 10.9 N.A. 8

3. Sensitivity of RATs for SARS-CoV-2 Delta Variant Detection

To compare the sensitivity of the 27 RATs, a delta variant (lineage B.1.617.2) of SARS-CoV-2 was diluted to the indicated PFU and then examined by RT-qPCR to determine the Cq value of each sample. The Cq values were 17.1, 20.9, 24.5, 27.6, and 31.0 at 75,000, 7500, 750, 75, and 7.5 PFU (Table 3). Test #22 detected 75 PFU of delta variant in one out of the two tests but failed to detect 7.5 PFU of virus (Table 3). Tests #1, #8, #9, and #17 detected 750 PFU of delta variant in both two tests, whereas tests #7, #20, and #27 detected 750 PFU of delta variant in one out of the two tests. Tests #2, #4, #1, and #14 detected 75,000 PFU of delta variant in both two tests but failed to detect 7500 PFU. The other RATs detected 7500 PFU of delta variant. Taken together with the RT-qPCR data, our findings show that the sensitivity for delta variants of tests #1, #7, #8, #9, #17, #20, #22, and #27 is relatively high but lower than that of RT-qPCR.
Table 3. Sensitivity of rapid antigen tests for the delta variant.
No. Rapid Antigen Test Virus Titer Tested (PFU/Test)
75,000 7500 750 75 7.5
- RT-qPCR 17.1 a 20.9 24.5 27.6 31.0
1 ESPLINE SARS-CoV-2 + b + + n.d.
2 ImmunoAce SARS-CoV-2 + n.d. n.d.
3 PanbioTM COVID-19 Ag Rapid Test Device + + n.d. n.d.
4 PRORAST SARS-CoV-2 Ag + n.d. n.d.
5 SARS-CoV-2 Rapid Antigen Test n.d. c + n.d.
6 Fuji Dry-Chem IMMUNO AG Handy COVID-19 Ag n.d. + n.d.
7 ALSONIC COVID-19 Ag n.d. + ± n.d.
8 COVID-19 and Influenza A+B Antigen Combo Rapid Test n.d. + + n.d.
9 ImmunoArrow SARS-CoV-2 n.d. + + n.d.
10 Check MR-COV19 + n.d. n.d.
11 RapidTesta SARS-CoV-2 + + n.d. n.d.
12 QuickNavi-Flu+COVID19 Ag + + n.d. n.d.
13 QuickNavi -COVID19 Ag + + n.d.
14 KBM LineCheck nCoV + n.d.
15 BD Veritor System for Rapid Detection of SARS-CoV-2 + + n.d.
16 Sofia SARS Antigen FIA + + n.d.
17 Fuji Dri-chem immuno AG cartridge COVID-19 Ag n.d. + + n.d.
18 COVID-19 NP rapid test kit + + n.d.
19 SARS-CoV-2 Antigen Rapid Test + + n.d.
20 2019-nCoV Ag rapid detection kit + + ± n.d.
21 Novel Coronavirus (SARS-CoV-2) Antigen Rapid Test Kit + + n.d.
22 Saliva SARS-CoV-2(2019-nCoV) Antigen Test Kit n.d. + + ±
23 Corona Virus (COVID-19) Antigen Rapid Test + ± n.d.
24 SARS-CoV-2 Antigen Rapid Test Kit + + n.d.
25 Novel coronavirus (2019-nCoV) antigen testing kit + + n.d.
26 COVID19 antigen rapid test device + + n.d.
27 Rabliss SARS-CoV-2 antigen detection kit COVID19 AG n.d. + ±

References

  1. Sethuraman, N.; Jeremiah, S.S.; Ryo, A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA 2020, 323, 2249–2251.
  2. Larremore, D.B.; Wilder, B.; Lester, E.; Shehata, S.; Burke, J.M.; Hay, J.A.; Tambe, M.; Mina, M.J.; Parker, R. Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening. Sci. Adv. 2021, 7, eabd5393.
  3. Paltiel, A.D.; Zheng, A.; Walensky, R.P. Assessment of SARS-CoV-2 Screening Strategies to Permit the Safe Reopening of College Campuses in the United States. JAMA Netw. Open 2020, 3, e2016818.
  4. Nagura-Ikeda, M.; Imai, K.; Tabata, S.; Miyoshi, K.; Murahara, N.; Mizuno, T.; Horiuchi, M.; Kato, K.; Imoto, Y.; Iwata, M.; et al. Clinical Evaluation of Self-Collected Saliva by Quan-titative Reverse Transcription-PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription-Loop-Mediated Isothermal Amplification, and a Rapid Antigen Test To Diagnose COVID-19. J. Clin. Microbiol. 2020, 58, e01438-20.
  5. Mak, G.C.; Cheng, P.K.; Lau, S.S.; Wong, K.K.; Lau, C.S.; Lam, E.T.; Chan, R.C.; Tsang, D.N. Evaluation of rapid antigen test for detection of SARS-CoV-2 virus. J. Clin. Virol. 2020, 129, 104500.
  6. Lambert-Niclot, S.; Cuffel, A.; Le Pape, S.; Vauloup-Fellous, C.; Morand-Joubert, L.; Roque-Afonso, A.M.; Le Goff, J.; Delaugerre, C. Evaluation of a Rapid Diagnostic Assay for Detection of SARS-CoV-2 Antigen in Nasopharyngeal Swabs. J. Clin. Microbiol. 2020, 58.
  7. Porte, L.; Legarraga, P.; Vollrath, V.; Aguilera, X.; Munita, J.M.; Araos, R.; Pizarro, G.; Vial, P.; Iruretagoyena, M.; Dittrich, S.; et al. Evaluation of a novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples. Int. J. Infect. Dis. 2020, 99, 328–333.
  8. Scohy, A.; Anantharajah, A.; Bodéus, M.; Kabamba-Mukadi, B.; Verroken, A.; Rodriguez-Villalobos, H. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J. Clin. Virol. 2020, 129, 104455.
  9. Mertens, P.; De Vos, N.; Martiny, D.; Jassoy, C.; Mirazimi, A.; Cuypers, L.; Wijngaert, S.V.D.; Monteil, V.; Melin, P.; Stoffels, K.; et al. Development and Potential Usefulness of the COVID-19 Ag Respi-Strip Diagnostic Assay in a Pandemic Context. Front. Med. 2020, 7, 225.
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Subjects: Virology
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Update Time: 09 Nov 2021
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    Yamayoshi, S. Delta Variant (B.1.617.2) of SARS-CoV-2. Encyclopedia. Available online: https://encyclopedia.pub/entry/15814 (accessed on 29 June 2022).
    Yamayoshi S. Delta Variant (B.1.617.2) of SARS-CoV-2. Encyclopedia. Available at: https://encyclopedia.pub/entry/15814. Accessed June 29, 2022.
    Yamayoshi, Seiya. "Delta Variant (B.1.617.2) of SARS-CoV-2," Encyclopedia, https://encyclopedia.pub/entry/15814 (accessed June 29, 2022).
    Yamayoshi, S. (2021, November 09). Delta Variant (B.1.617.2) of SARS-CoV-2. In Encyclopedia. https://encyclopedia.pub/entry/15814
    Yamayoshi, Seiya. ''Delta Variant (B.1.617.2) of SARS-CoV-2.'' Encyclopedia. Web. 09 November, 2021.
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