SARS-CoV-2 Serology: Utility and Limits of Different Antigen-Based Tests through the Evaluation and the Comparison of Four Commercial Tests
Abstract
:1. Introduction
2. Methods
2.1. Patients and Commercial Serology Tests
2.2. Evaluation and Comparison
2.3. Statistical Analysis
3. Results
3.1. Evaluation of the Analytical Performances
3.2. Improvement of the Analytical Performances
3.3. Antibody Ratio Distribution over Time
3.4. Comparison of the Tests
3.5. Combinations between Tests
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Certifications | Detection Principle | Antibodies Isotypes | Targeted Antigen | Sample Volume | Cut-Off | Result Interpretation | Reported Sensitivity | Reported Specificity | |
---|---|---|---|---|---|---|---|---|---|
Vidas® | CE-IVD, FDA-EUA | ELFA, qualitative | IgM IgG | S1 RBD | 100 μL including the dead volume | 1 for both | Index <cut-off; Negative Index > or = cut-off; Positive | IgM 100% CI 95% (63.1–100.0) after 8 days IgG 100% CI 95% (80.5–100.0) after 15 days | IgG 99.9% CI 95% (99.4–100.0) IgM 99.4% CI 95% (97.7–99.9) |
Mindray® | CE-IVD | CLIA, qualitative | IgM IgG | S and N protein | 10 μL with a minimum of 100 μL of dead volume | 1 for IgM10 for IgG | Index < cut-off; Negative Index > or = cut-off; Positive | IgM 82.22% after 15 days IgG 100% after 15 days | 87.60% 94.9% |
Cobas® | CE-IVD, FDA-EUA, WHO-EUL | ECLIA, qualitative | Total antibodies: IgG+++, IgM and IgA | N protein | 10 μL with a minimum of 100 μL of dead volume | 1 | Index <cut-off; Negative Index > or = cut-off; Positive | 100% CI 95% (88.1–100) after 14 days | 99.8% CI 95% (99.7–99.9) |
Access® | CE-IVD, FDA-EUA | CLIA, qualitative | IgG | S1 RBD | 10 μL with a minimum of 100 μL of dead volume | 1 | Index < cut-off; Negative Index > or = cut-off; Positive | 100% CI 95% (93.8–100) after 18 days | 99.8% CI 95% (99.4–99.9) |
Experimental Data | Data Based on Proposed Cut-Offs | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Sensitivity ≥ 14 Days % CI 95% | Sensitivity % CI 95% | Specificity % CI 95% | AUC CI 95% | PPV % CI 95% | NPV % CI 95% | Proposed Cut-Off | Sensitivity% CI 95% | Sensitivity ≥ 14 days% CI 95% | Specificity% CI 95% | AUC CI 95% | |
Vidas® IgM | 39.6 (25.7–54.7) | 51.4 (39.3–63.3) | 94.1 (88.2–97.6) | 0.728 (0.659–0.789) | 31.5 (17.8–49.4) | 97.4 (96.6–97.9) | >0.87, p = 0.01 | 59.7 (47.5–71.1) | 52 (37.2–66.7) | 94.1 (88.3–97.6) | 0.767 (0.703–0.827) |
Vidas® IgG | 83.3 (69.8–92.5) | 76.4 (64.9–85.6) | 100 (96.9–100) | 0.882 (0.828–0.924) | 100 | 98.7 (98.1–99.2) | >0.55, p = 0.05 | 84.7 (74.3–92.1) | 91.2 (80–97.7) | 98.3 (94.1–99.8) | 0.922 (0.875–0.956) |
Cobas® | 85.4 (72.2–93.9) | 79.2 (68–87.8) | 100 (96.9–100) | 0.896 (0.844–0.935) | 100 | 98.9 (98.3–99.3) | >0.725, p = 0.36 | 81.94 (71.1–90) | 85.4 (72.2–93.9) | 99.2 (95.4–100) | 0.906 (0.855–0.943) |
Access® | 41.7 (27.6–56.8) | 55.5 (43.4–67.3) | 100 (96.9–100) | 0.778 (0.712–0.835) | 100 | 97.7 (97–98.2) | >0.14, p < 10−4 | 83.3 (72.7–91.1) | 83.3 (69.8–92.5) | 100 (96.9–100) | 0.917 (0.868–0.952) |
Mindray® IgM | 66.7 (51.6–79.6) | 44.4 (32.7–56.6) | 97.5 (92.8–99.5) | 0.710 (0.640–0.773) | 48.1 (22.7–74.5) | 97 (96.4–97.6) | >0.83, p = 0.63 | 47.2 (35.3–59.3) | 37.5 (23.9–52.6) | 95.8 (90.5–98.6) | 0.715 (0.645–0.778) |
Mindray® IgG | 83.3 (69.7–92.5) | 79.2 (68–87.8) | 95.8 (90.5–98.6) | 0.875 (0.819–0.918) | 49.8 (29.4–70.2) | 98.8 (98.2–99.3) | >7.94, p = 0.34 | 81.9 (72.7–91.9) | 87.5 (74.7–95.2) | 94.1 (88.3–97.6) | 0.887 (0.834–0.928) |
Group | VIDAS® IgG and/or IgM | Cobas® | Access ® | Mindray ® IgG and/or IgM | n | n days after COVID-19 Infection Med(Min-Max) | |
---|---|---|---|---|---|---|---|
Concordant results between tests (43 out of 72, 59.7%) | All tests positive | + | + | + | + | 35 | 25 (4–140) |
All tests negative | - | - | - | - | 8 | 14 (0–60) | |
Discordance results between tests (29 out of 72, 40.3%) | Pattern 1: 3 positive tests over 4 n = 17 | + | + | - | + | 13 | 21 (6–90) |
+ | - | + | + | 4 | 20 (8–39) | ||
- | + | + | + | 0 | NA | ||
Pattern 2: 2 positive tests over 4 n = 11 | + | + | - | - | 3 | 39, 90, 162 | |
+ | - | + | - | 1 | 17 | ||
+ | - | - | + | 1 | 9 | ||
- | + | + | - | 0 | NA | ||
- | + | - | + | 6 | 23 (15–86) | ||
- | - | + | + | 0 | NA | ||
Pattern 3: 1 positive test over 4 n = 01 | + | - | - | - | 1 | 7 | |
- | + | - | - | 0 | NA | ||
- | - | + | - | 0 | NA | ||
- | - | - | + | 0 | NA |
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Gdoura, M.; Halouani, H.; Sahli, D.; Mrad, M.; Chamsa, W.; Mabrouk, M.; Hogga, N.; Ben-Salem, K.; Triki, H. SARS-CoV-2 Serology: Utility and Limits of Different Antigen-Based Tests through the Evaluation and the Comparison of Four Commercial Tests. Biomedicines 2022, 10, 3106. https://doi.org/10.3390/biomedicines10123106
Gdoura M, Halouani H, Sahli D, Mrad M, Chamsa W, Mabrouk M, Hogga N, Ben-Salem K, Triki H. SARS-CoV-2 Serology: Utility and Limits of Different Antigen-Based Tests through the Evaluation and the Comparison of Four Commercial Tests. Biomedicines. 2022; 10(12):3106. https://doi.org/10.3390/biomedicines10123106
Chicago/Turabian StyleGdoura, Mariem, Habib Halouani, Donia Sahli, Mehdi Mrad, Wafa Chamsa, Manel Mabrouk, Nahed Hogga, Kamel Ben-Salem, and Henda Triki. 2022. "SARS-CoV-2 Serology: Utility and Limits of Different Antigen-Based Tests through the Evaluation and the Comparison of Four Commercial Tests" Biomedicines 10, no. 12: 3106. https://doi.org/10.3390/biomedicines10123106