Abstract
Background
Accurate anti-SARS-CoV-2 assays are needed to inform diagnostic, therapeutic, and public health decisions. The first manufacturer-independent head-to-head comparison of two rapid high-throughput automated electrochemiluminescence double-antigen sandwich immunoassays targeting total anti-SARS-CoV-2 antibodies against two different viral proteins, Elecsys Anti-SARS-CoV-2 (Elecsys-N) and Elecsys Anti-SARS-CoV-2 S (Elecsys-S) (Roche Diagnostics), was performed in a routine setting during the exponential growth phase of the epidemic’s second wave.
Methods
The diagnostic specificity of Elecsys-N and Elecsys-S was initially evaluated on a panel of 572 pre−COVID-19 samples, showing 100 % specificity of both assays. Elecsys-N/Elecsys-S head-to-head comparison used 3,416 consecutive blood samples from individuals that were tested for the presence of anti-SARS-CoV-2 within commercial out-of-pocket serologic testing.
Results
Elecsys-N/Elecsys-S head-to-head comparison showed overall agreement of 98.68 % (3,371/3,416; 95 % CI, 98.23–99.03 %), positive agreement of 95.16 % (884/929; 95 % CI, 93.52–96.41 %), and a high kappa value of 0.996 (95 % CI, 0.956–0.976). Previous SARS-CoV-2 PCR positivity was identified in 14/24 (58.3 %) Elecsys-N negative/Elecsys-S positive individuals and in 4/21 (19.0 %) Elecsys-N positive/Elecsys-S negative individuals.
Conclusion
The first Elecsys-N/Elecsys-S head-to-head comparison showed excellent agreement of two highly specific and rapid high-throughput automated anti-SARS-CoV-2 assays. An important question is whether laboratories offering two different antibody assays could benefit from combining the assays; if so, should use be concomitant or sequential—and, in the latter case, in which order? Based on our results, we favor concomitant over sequential Elecsys-N/Elecsys-S use when testing individuals for anti-SARS-CoV-2 antibodies in high-incidence settings; for example, during the exponential or stationary growth phase of the COVID-19 epidemic.
Keywords: SARS-CoV-2, COVID-19, Antibody, Electrochemiluminescence, Immunoassay
1. Introduction
The availability of assays to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) created excitement and hope among the laboratory community, government leaders, and the public [1]. Unfortunately, early in the pandemic, the global market was flooded with antibody assays of unproven performance and various governments purchased large quantities of ineffective tests [2,3]. The situation improved with implementation of verification/authorization procedures and recommendations for antibody test utilization and result interpretation [[1], [2], [3], [4]].
Antibody tests are a useful diagnostic aid, primarily for patients that present later in the disease course and are negative for SARS-CoV-2 RNA, when a lower-respiratory-tract sample cannot be collected, for diagnosing multisystem inflammatory syndrome in children, and to screen potential donors for convalescent-phase plasma therapy [5,6]. Serologic testing may prove useful in determining immunity, stratifying individuals for vaccine receipt, and documenting vaccine response, which could inform return-to-work and travel decisions and other public health measures [5,6]. Finally, they play an important role in understanding the epidemiology, including seroprevalence at the local, national, and global levels [[5], [6], [7]].
Although several commercial anti-SARS-CoV-2 assays have received U.S. Food and Drug Administration (FDA) emergency-use authorization (EUA), most approved assays lack manufacturer-independent performance evaluations in peer-reviewed literature.
Here we present a manufacturer-independent head-to-head comparison of two rapid (18-minute) high-throughput automated electrochemiluminescence double-antigen sandwich immunoassays targeting total anti-SARS-CoV-2 antibodies against two different viral proteins: Elecsys Anti-SARS-CoV-2 (Elecsys-N) and Elecsys Anti-SARS-CoV-2 S (Elecsys-S) (Roche Diagnostics, Mannheim, Germany).
Elecsys-N is an assay for qualitative detection of total anti-SARS-CoV-2 antibodies against nucleoprotein (N) that received FDA EUA on May 3, 2020, and Conformitè Europëenne (CE) mark on April 28, 2020. The assay has been extensively evaluated by the manufacturer, showing 99.80 % (95 % confidence interval (CI), 99.69‑99.88 %) clinical specificity on 10,453 samples and 99.5 % (95 % CI, 97.0‑100 %) sensitivity on 185 samples obtained 14 days or later after SARS-CoV-2 PCR-confirmation. Elecsys-N has also been evaluated in several manufacturer-independent studies, with diagnostic specificity and sensitivity values spanning claims made by the manufacturer in most studies [1,5,[7], [8], [9], [10], [11], [12], [13], [14], [15], [16]], and it is consequently considered one of the most appropriate assays for seroprevalence surveys, especially in low-prevalence settings [6,17].
Elecsys-S is an assay for quantitative detection (linear range 0.4–250 U/mL) of total anti-SARS-CoV-2 antibodies against the spike (S) protein receptor binding domain (RBD), launched in Europe in September 2020. It received FDA EUA on November 25, 2020, and CE mark on September 17, 2020. The assay has been extensively evaluated by the manufacturer, showing 99.98 % (95 % CI, 99.91–100 %) specificity on 5,991 samples and 98.8 % (95 % CI, 98.1–99.3 %) sensitivity on 1,423 samples obtained 14 days or later after SARS-CoV-2 PCR-confirmation. As far as we know, no Elecsys-S evaluation data have been published in peer-reviewed literature yet.
This study evaluated Elecsys-N and Elecsys-S head-to-head in a routine setting during the exponential growth phase of the epidemic’s second wave. During the 84-day study period, the cumulative number of PCR-confirmed COVID-19 cases in Slovenia increased 18.4-fold, from 6,105 to 112,048 (https://www.nijz.si/sl/dnevno-spremljanje-okuzb-s-sars-cov-2-covid-19), providing a challenging but informative environment for evaluating two highly specific anti-SARS-CoV-2 assays directed against different SARS-CoV-2 antigens.
2. Material and methods
Before head-to-head comparison, the diagnostic specificity of Elecsys-N and Elecsys-S was internally evaluated in May and September 2020, respectively, on a panel of 572 samples collected prior to the emergence of COVID-19 (Table 1 ).
Table 1.
Internal assessment of clinical specificity of Elecsys-N and Elecsys-S assays using 572 pre−COVID-19 serum samples.
| Elecsys-N |
Elecsys-S |
||||
|---|---|---|---|---|---|
| Panel/Cohort | n | Positive | Specificity | Positive | Specificity |
| Laboratory-confirmed acute human cytomegalovirus (CMV) (n = 6) or Epstein–Barr virus (EBV) (n = 16) infection | 22 | 0 | 100 % | 0 | 100 % |
| Pneumonia caused by Mycoplasma pneumoniae | 15 | 0 | 100 % | 0 | 100 % |
| Laboratory-confirmed pertussis | 7 | 0 | 100 % | 0 | 100 % |
| PCR-confirmed viral non-SARS-CoV-2 respiratory infections with coronavirus HKU1 (n = 1), NL63 (n = 5), 229E (n = 3), or OC43 (n = 1), influenza virus A (n = 3), influenza virus B (n = 4), respiratory syncytial virus (n = 4), or rhinoviruses (n = 7) | 28 | 0 | 100 % | 0 | 100 % |
| Serum samples collected for different medical reasons (testing for HIV (n = 210) and serological markers of viral hepatitis (n = 290)) before June 2019 | 500 | 0 | 100 % | 0 | 100 % |
| Total number of samples | 572 | 0 | 100 % | 0 | 100 % |
For head-to-head comparison, 3,416 consecutive blood samples received between October 1, 2020, and December 23, 2020 were tested in parallel using Elecsys-N and Elecsys-S on a cobas e411 analyzer following the manufacturer’s instructions, using cut-off values for positive results of ≥1.0 and ≥0.8 U/mL, respectively. Blood samples were obtained from the same number of individuals that attended out-of-pocket anti-SARS-CoV-2 testing with a commercial test provider. In contrast to SARS-CoV-2 RNA testing [18], which is fully covered by national health insurance, SARS-CoV-2 antibody testing in Slovenia is not reimbursed. Thus, the study population consisted of individuals that requested out-of-pocket anti-SARS-CoV-2 testing for several reasons: travel purposes; to check serological response after PCR-confirmed COVID-19 or clinically compatible but virologically non-confirmed COVID-19; recent contact with a person with COVID-19, but not eligible for PCR-testing; or pure curiosity.
Due to the inability of obtaining follow-up sample(s) from individuals with Elecsys-N/Elecsys-S discordant results, the national SARS-CoV-2 PCR notification database was consulted and all discrepant samples were additionally tested by two anti-SARS-CoV-2 antibody assays with excellent analytical performance proven in manufacturer-independent evaluations: SARS-CoV-2 Ab Elisa Kit (Wantai; Wantai Biological Pharmacy Enterprise Co, Beijing, China) detecting total antibodies against the S protein RBD [[19], [20], [21], [22]] and Architect SARS-CoV-2 IgG (Abbott; Abbott Diagnostics, IL, USA) detecting IgG antibodies against N protein [5,8,10,13,14]. Furthermore, 10 % and 5% randomly selected samples with Elecsys-N/Elecsys-S concordantly positive and concordantly negative results, respectively, were additionally tested by Wantai and Abbott.
A contingency table was constructed to assess overall and positive agreements with 95 % CIs. The level of agreement between both tests was assessed using kappa statistics. All statistical analyses were performed using Excel (Microsoft, Redmond, WA, USA) and R software version 3.2.5 (Free Software Foundation, Boston, MA, USA).
3. Results
Internal evaluation on the panel of 572 pre−COVID-19 samples showed 100 % specificity of both assays (Table 1). As shown in Table 2 , head-to-head Elecsys-N/Elecsys-S comparison showed overall agreement of 98.68 % (3,371/3,416; 95 % CI, 98.23–99.03 %), positive agreement of 95.16 % (884/929; 95 % CI, 93.52–96.41 %) and a high kappa value of 0.996 (95 % CI, 0.956–0.976). A total of 45/3,416 discordant results were observed (Table 2, Table 3).
Table 2.
Results of head-to-head comparison of Elecsys-N (detecting total anti-SARS-CoV-2 antibodies against nucleoprotein) and Elecsys-S (detecting total anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain) on 3,416 consecutive blood samples received between October 1, 2020 and December 23, 2020 using cut-off values for positive results of ≥ 1.0 and ≥ 0.8 U/mL, respectively.
23/24 tested positive using supplemental Wantai test (detecting total anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain) and 24/24 tested negative using supplemental Abbott test (detecting anti-SARS-CoV-2 IgG antibodies against nucleoprotein).
17/21 tested positive using supplemental Abbott test and 20/21 tested negative using supplemental Wantai test.
Table 3.
Overview of anti-SARS-CoV-2 Elecsys-N and Elecsys-S testing results, available SARS-CoV-2 RNA PCR testing results and results of supplemental testing using Abbott and Wantai assays in 45 individuals with Elecsys-N/Elecsys-S discordant results. For SARS-CoV-2 RNA–positive individuals the date of the first recorded PCR positive result is presented, and for SARS-CoV-2 RNA–negative individuals the date of the last recorded PCR negative result is presented. N/A = no record in the national SARS-CoV-2 PCR notification database.
| Sample ID | Testing date (M/D/Y) | Elecsys-N |
Elecsys-S |
SARS-CoV-2 RNA PCR |
Abbott | Wantai | |||
|---|---|---|---|---|---|---|---|---|---|
| Value (pos ≥ 1.0) | Result | Value (pos ≥ 0.80 U/mL) | Result | Nasopharyngeal swab collection date (M/D/Y) | PCR result | Result | Result | ||
| 1 | 10/28/2020 | 0.104 | NEG | 1.16 | POS | 10/16/2020 | POS | NEG | POS |
| 2 | 10/29/2020 | 0.149 | NEG | 1.48 | POS | 11/02/2020 | POS | NEG | POS |
| 3 | 10/20/2020 | 0.089 | NEG | 1.61 | POS | 04/22/2020 | NEG | NEG | NEG |
| 4 | 11/01/2020 | 0.462 | NEG | 2.25 | POS | 04/30/2020 | NEG | NEG | POS |
| 5 | 12/04/2020 | 0.227 | NEG | 2.45 | POS | 04/24/2020 | POS | NEG | POS |
| 6 | 12/04/2020 | 0.090 | NEG | 2.63 | POS | 03/23/2020 | NEG | NEG | POS |
| 7 | 11/19/2020 | 0.421 | NEG | 3.27 | POS | 11/06/2020 | POS | NEG | POS |
| 8 | 10/29/2020 | 0.093 | NEG | 3.79 | POS | 04/12/2020 | NEG | NEG | POS |
| 9 | 10/24/2020 | 0.750 | NEG | 6.65 | POS | 09/10/2020 | POS | NEG | POS |
| 10 | 11/20/2020 | 0.568 | NEG | 7.30 | POS | N/A | N/A | NEG | POS |
| 11 | 11/20/2020 | 0.384 | NEG | 10.19 | POS | 10/14/2020 | POS | NEG | POS |
| 12 | 10/23/2020 | 0.259 | NEG | 11.62 | POS | 04/28/2020 | POS | NEG | POS |
| 13 | 10/30/2020 | 0.731 | NEG | 14.89 | POS | 10/16/2020 | POS | NEG | POS |
| 14 | 11/13/2020 | 0.862 | NEG | 28.14 | POS | 09/14/2020 | POS | NEG | POS |
| 15 | 10/29/2020 | 0.848 | NEG | 33.06 | POS | 09/01/2020 | POS | NEG | POS |
| 16 | 11/30/2020 | 0.655 | NEG | 9.75 | POS | 10/20/2020 | POS | NEG | POS |
| 17 | 11/30/2020 | 0.095 | NEG | 1.63 | POS | 10/17/2020 | POS | NEG | POS |
| 18 | 12/01/2020 | 0.597 | NEG | 6.89 | POS | 11/16/2020 | POS | NEG | POS |
| 19 | 12/08/2020 | 0.091 | NEG | 15.11 | POS | N/A | N/A | NEG | POS |
| 20 | 12/09/2020 | 0.143 | NEG | 2.06 | POS | N/A | N/A | NEG | POS |
| 21 | 12/10/2020 | 0.376 | NEG | 2.13 | POS | N/A | N/A | NEG | POS |
| 22 | 12/10/2020 | 0.355 | NEG | 4.08 | POS | N/A | N/A | NEG | POS |
| 23 | 12/14/2020 | 0.501 | NEG | 28.26 | POS | N/A | N/A | NEG | POS |
| 24 | 12/17/2020 | 0.775 | NEG | 6.42 | POS | 11/20/2020 | POS | NEG | POS |
| 25 | 11/05/2020 | 1.38 | POS | < 0.400 | NEG | N/A | N/A | POS | NEG |
| 26 | 11/17/2020 | 1.44 | POS | < 0.400 | NEG | N/A | N/A | POS | NEG |
| 27 | 10/22/2020 | 1.44 | POS | < 0.400 | NEG | 08/21/2020 | NEG | POS | NEG |
| 28 | 11/09/2020 | 1.59 | POS | 0.446 | NEG | 10/24/2020 | POS | POS | NEG |
| 29 | 11/09/2020 | 1.65 | POS | < 0.400 | NEG | N/A | N/A | POS | NEG |
| 30 | 11/01/2020 | 1.65 | POS | < 0.400 | NEG | 10/20/2020 | POS | POS | NEG |
| 31 | 10/25/2020 | 1.67 | POS | < 0.400 | NEG | 04/21/2020 | NEG | NEG | NEG |
| 32 | 11/06/2020 | 1.87 | POS | < 0.400 | NEG | N/A | N/A | POS | NEG |
| 33 | 11/06/2020 | 2.35 | POS | < 0.400 | NEG | N/A | N/A | NEG | NEG |
| 34 | 10/26/2020 | 2.41 | POS | < 0.400 | NEG | 04/25/2020 | NEG | POS | NEG |
| 35 | 10/07/2020 | 2.45 | POS | < 0.400 | NEG | N/A | N/A | POS | NEG |
| 36 | 11/04/2020 | 4.15 | POS | 0.462 | NEG | N/A | N/A | POS | NEG |
| 37 | 10/18/2020 | 4.75 | POS | < 0.400 | NEG | 03/21/2020 | NEG | NEG | NEG |
| 38 | 10/21/2020 | 4.84 | POS | < 0.400 | NEG | 05/25/2020 | NEG | NEG | NEG |
| 39 | 11/02/2020 | 5.97 | POS | < 0.400 | NEG | 05/24/2020 | NEG | POS | NEG |
| 40 | 11/12/2020 | 7.47 | POS | 0.413 | NEG | 10/12/2020 | NEG | POS | POS |
| 41 | 11/18/2020 | 7.63 | POS | < 0.400 | NEG | 08/04/2020 | NEG | POS | NEG |
| 42 | 11/20/2020 | 8.12 | POS | 0.626 | NEG | 11/20/2020 | POS | POS | NEG |
| 43 | 11/02/2020 | 10.56 | POS | < 0.400 | NEG | 10/30/2020 | NEG | POS | NEG |
| 44 | 11/09/2020 | 10.86 | POS | < 0.400 | NEG | 07/16/2020 | NEG | POS | NEG |
| 45 | 10/27/2020 | 25.73 | POS | 0.505 | NEG | 10/15/2020 | POS | POS | NEG |
Of 24 Elecsys-N negative / Elecsys-S positive samples, 23 (95.8 %) tested Wantai positive and all Abbott negative. Previous SARS-CoV-2 PCR positivity was identified in 14/24 (58.3 %) of Elecsys-N negative / Elecsys-S positive individuals (Table 3 ).
Of 21 Elecsys-N positive / Elecsys-S negative samples, 17 (80.9 %) tested Abbott positive and all but one tested Wantai negative. Previous SARS-CoV-2 PCR positivity was identified in 4/21 (19.0 %) of Elecsys-N positive/Elecsys-S negative individuals (Table 3).
All 124 Elecsys-N/Elecsys-S concordantly negative samples tested also negative using both Wantai and Abbott. Out of 87 Elecsys-N/Elecsys-S concordantly positive samples, 87 (100 %) and 85 (97.7 %) tested positive using Wantai and Abbott, respectively.
4. Conclusions
Accurate anti-SARS-CoV-2 assays are needed to inform diagnostic, therapeutic, and public health decisions [5,23]. When selecting antibody assays, virologists must consider not only sensitivity and specificity, but also prevalence in the tested population, the intended use of results, sample throughput, test complexity, reagent and instrument availability, and cost per reportable result [5]. Especially assays’ throughput and specificity are crucial parameters if large-scale antibody testing is desirable in a low-prevalence pre-vaccination environment [9,23].
This comparison showed high overall and positive agreement of two highly specific and rapid high-throughput automated assays. Equal distribution of Elecsys-N/Elecsys-S discordant results was observed. Such distribution of discordant results was confirmed by additional testing using two supplementary assays: Wantai detecting the equivalent total anti-S RBD antibodies as Elecsys-S and Abbott detecting IgG fraction of the total anti-N antibodies targeted by Elecsys-N. The recorded slight Elecsys-N/Abbott discordance is most probably a result of the presence of anti-N antibodies other than IgG detected by Elecsys-N and missed by Abbott. Thus, although we were unable to obtain follow-up sample(s) from individuals with discordant results, we strongly believe that not more than 5% of discordant results are due to false positivity of one of the Elecsys assays. This is supported by: (i) extremely high specificity of both Elecsys assays recorded in the manufacturer’s and manufacturer-independent evaluations [1,5,[7], [8], [9], [10], [11], [12], [13], [14], [15]], including this study; (ii) confirmation of the presence of targeted antibodies using supplementary serological assays in 40/45 samples with Elecsys-N/Elecsys-S discordant results; (iii) confirmation of previous COVID-19 in 18/45 individuals with discordant results through the national SARS-CoV-2 PCR notification database; (iv) distribution of Elecsys-N and Elecsys-S testing values in samples with discordant results not concentrated near the cut-off; and (v) high-incidence study settings in which anti-S-only and anti-N-only responders are not unusual in the early convalescent phase [[24], [25], [26]].
An important open question is whether laboratories offering different antibody assays could benefit from combining the assays; if so, should use be concomitant or sequential—and, in the latter case, in which order? Previous studies showed that a two-assay algorithm improves the positive predictive value compared with an individual assay alone while maintaining the negative predictive value [5,17,27]. Thus, the two-assay approach was recently recommended for identifying potential convalescent-phase plasma donors and assessing candidacy for experimental COVID-19 therapeutics in PCR-negative patients with respiratory symptoms [5]. As far as we know, the Elecsys-N and Elecsys-S manufacturer issued no recommendation for combination use, but the manufacturer’s unpublished data showed that concomitant use of both assays could increase overall sensitivity (some convalescent patients were anti-S-only and some anti-N-only responders) and that sequential use (initially Elecsys-N followed by Elecsys-S for N-positives) could improve positive predictive value to 100 % in low-prevalence settings. Based on our results, we favor concomitant over sequential Elecsys-N/Elecsys-S use when testing in high-incidence settings (e.g., during the exponential or stationary growth phase of the COVID-19 epidemic), which in February 2021 is still unfortunate reality in most of the world.
Funding
This study was funded by the Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana and the Slovenian Research Agency (grants P3-0083 and V3-2034). The assays used in the comparative evaluation were not provided by the manufacturer, and the manufacturer had no role in the study design, data collection, analysis, interpretation of the results, writing of the article, or decision to submit the work for publication.
CRediT authorship contribution statement
Mario Poljak: Conceptualization, Methodology, Validation, Investigation, Writing - original draft, Writing - review & editing, Supervision. Anja Oštrbenk Valenčak: Methodology, Validation, Investigation, Data curation, Formal analysis, Writing - review & editing. Tina Štamol: Methodology, Validation, Investigation, Data curation, Writing - review & editing. Katja Seme: Conceptualization, Writing - original draft, Writing - review & editing, Supervision.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
We thank Robert Krošelj and Maja Accetto Kos for their excellent laboratory assistance.
References
- 1.Theel E.S., Couturier M.R., Filkins L., Palavecino E., Mitchell S., Campbell S., et al. Application, verification, and implementation of SARS-CoV-2 serologic assays with emergency use authorization. J. Clin. Microbiol. 2020;59:e02148–20. doi: 10.1128/JCM.02148-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Duong Y.T., Wright C.G., Justman J. Antibody testing for coronavirus disease 2019: not ready for prime time. BMJ. 2020;370 doi: 10.1136/bmj.m2655. m2655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Houlihan C.F., Beale R. The complexities of SARS-CoV-2 serology. Lancet Infect. Dis. 2020;20:1350–1351. doi: 10.1016/S1473-3099(20)30699-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Hanson K.E., Caliendo A.M., Arias C.A., Englund J.A., Hayden M.K., Lee M.J., et al. Infectious Diseases Society of America guidelines on the diagnosis of COVID-19: serologic testing. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa1343. Online ahead of print. ciaa134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Turbett S.E., Anahtar M., Dighe A.S., Garcia Beltran W., Miller T., Scott H., et al. Evaluation of three commercial SARS-CoV-2 serologic assays and their performance in two-test algorithms. J. Clin. Microbiol. 2020;59:e01892–20. doi: 10.1128/JCM.01892-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Mekonnen D., Mengist H.M., Derbie A., Nibret E., Munshea A., He H., et al. Diagnostic accuracy of serological tests and kinetics of severe acute respiratory syndrome coronavirus 2 antibody: a systematic review and meta-analysis. Rev. Med. Virol. 2020 doi: 10.1002/rmv.2181. Online ahead of print. [DOI] [PubMed] [Google Scholar]
- 7.Coste A.T., Jaton K., Papadimitriou-Olivgeris M., Greub G., Croxatto A. Comparison of SARS-CoV-2 serological tests with different antigen targets. J. Clin. Virol. 2020;134:104690. doi: 10.1016/j.jcv.2020.104690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Harley K., Gunsolus I.L. Comparison of the clinical performances of the abbott alinity IgG, abbott architect IgM, and Roche elecsys total SARS-CoV-2 antibody assays. J. Clin. Microbiol. 2020;59:e02104–02120. doi: 10.1128/JCM.02104-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Manthei D.M., Whalen J.F., Schroeder L.F., Sinay A.M., Li S.H., Valdez R., et al. Differences in performance characteristics among four high-throughput assays for the detection of antibodies against SARS-CoV-2 using a common set of patient samples. Am. J. Clin. Pathol. 2020 doi: 10.1093/ajcp/aqaa200. aqaa200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.National SARS-CoV-2 Serology Assay Evaluation Group Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison. Lancet Infect. Dis. 2020;20:1390–1400. doi: 10.1016/S1473-3099(20)30634-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Wolff F., Dahma H., Duterme C., Van den Wijngaert S., Vandenberg O., Cotton F., et al. Monitoring antibody response following SARS-CoV-2 infection: diagnostic efficiency of 4 automated immunoassays. Diagn. Microbiol. Infect. Dis. 2020;98:115140. doi: 10.1016/j.diagmicrobio.2020.115140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Tan S.S., Saw S., Chew K.L., Wang C., Pajarillaga A., Khoo C., et al. Comparative clinical evaluation of the Roche Elecsys and Abbott Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) serology assays for Coronavirus Disease 2019 (COVID-19) Arch. Pathol. Lab. Med. 2021;145:32–38. doi: 10.5858/arpa.2020-0499-SA. [DOI] [PubMed] [Google Scholar]
- 13.Tan S.S., Saw S., Chew K.L., Huak C.Y., Khoo C., Pajarillaga A., et al. Head-to-head evaluation on diagnostic accuracies of six SARS-CoV-2 serological assays. Pathology. 2020;52:770–777. doi: 10.1016/j.pathol.2020.09.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Van Elslande J., Decru B., Jonckheere S., an Wijngaerden E., Houben E., Vandecandelaere P., et al. Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs. Clin. Microbiol. Infect. 2020;26:1557.e1–1557.e7. doi: 10.1016/j.cmi.2020.07.038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Zilla M., Wheeler B.J., Keetch C., Mitchell G., McBreen J., Wells A., et al. Variable performance in 6 commercial SARS-CoV-2 antibody assays may affect convalescent plasma and seroprevalence screening, in press Am. J. Clin. Pathol. 2020 doi: 10.1093/ajcp/aqaa228. aqaa228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Muecksch F., Wise H., Batchelor B., Squires M., Semple E., Richardson C., et al. Longitudinal serological analysis and neutralizing antibody levels in coronavirus disease 2019 convalescent patients. J. Infect. Dis. 2021;223:389–398. doi: 10.1093/infdis/jiaa659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Lisboa Bastos M., Tavaziva G., Abidi S.K., Campbell J.R., Haraoui L.P., Johnston J.C., et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ. 2020;370 doi: 10.1136/bmj.m2516. m2516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Poljak M., Korva M., Knap Gašper N., Fujs Komloš K., Sagadin M., Uršič T., et al. Clinical evaluation of the cobas SARS-CoV-2 Test and a diagnostic platform switch during 48 hours in the midst of the COVID-19 Pandemic. J. Clin. Microbiol. 2020;58 doi: 10.1128/JCM.00599-20. e00599 20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Gudbjartsson D.F., Norddahl G.L., Melsted P., Gunnarsdottir K., Holm H., Eythorsson E., et al. Humoral immune response to SARS-CoV-2 in Iceland. N. Engl. J. Med. 2020;383:1724–1734. doi: 10.1056/NEJMoa2026116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.GeurtsvanKessel C.H., Okba N.M.A., Igloi Z., Bogers S., Embregts C.W.E., Laksono B.M., et al. An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nat. Commun. 2020;11:3436. doi: 10.1038/s41467-020-17317-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Jespersen S., Mikkelsen S., Greve T., Kaspersen K.A., Tolstrup M., Boldsen J.K., et al. SARS-CoV-2 seroprevalence survey among 17,971 healthcare and administrative personnel at hospitals, pre-hospital services, and specialist practitioners in the Central Denmark Region. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa1471. Online ahead of print. ciaa1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Harritshøj L.H., Gybel-Brask M., Afzal S., Kamstrup P.R., Jørgensen C.S., Thomsen M.K., et al. Comparison of sixteen serological SARS-CoV-2 immunoassays in sixteen clinical laboratories. J. Clin. Microbiol. 2021 doi: 10.1128/JCM.02596-20. Online ahead of print JCM.02596-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Watson J., Richter A., Deeks J. Testing for SARS-CoV-2 antibodies. BMJ. 2020;370 doi: 10.1136/bmj.m3325. m3325. [DOI] [PubMed] [Google Scholar]
- 24.Lumley S.F., O’Donnell D., Stoesser N.E., Matthews P.C., Howarth A., Hatch S.B., et al. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N. Engl. J. Med. 2021;384:533–540. doi: 10.1056/NEJMoa2034545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Lumley S.F., Wei J., O’Donnell D., Stoesser N.E., Matthews P.C., Howarth A., et al. The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers. Clin. Infect. Dis. 2021 doi: 10.1093/cid/ciab004. Online ahead of print ciab004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.L’Huillier A.G., Meyer B., Andrey D.O., Arm-Vernez I., Baggio S., Didierlaurent A., et al. Antibody persistence in the first six months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study. Clin. Microbiol. Infect. 2021 doi: 10.1016/j.cmi.2021.01.005. Online ahead of print S1198-743X(21)00031-00038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Hicks S.M., Pohl K., Neeman T., McNamara H.A., Parsons K.M., He J.S., et al. A dual antigen ELISA allows the assessment of SARS-CoV-2 antibody seroprevalence in a low transmission setting. J. Infect. Dis. 2021;223:10–14. doi: 10.1093/infdis/jiaa623. [DOI] [PMC free article] [PubMed] [Google Scholar]