Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories

Therrien, Christian; Serhir, Bouchra; Bélanger-Collard, Mélina; Skrzypczak, Jana; Shank, D. K.; Renaud, Christian; Girouard, Julie; Loungnarath, Vilayvong; Carrier, Marc; Brochu, Gino; Tourangeau, Francine; Gilfix, Brian M.; Piché, Alain; Bazin, Renée; Guérin, Renée; Lavoie, Myriam; Martel-Laferrière, Valérie; Fortin, Claude; Benoît, Alexandre; Marcoux, Diane; Gauthier, Nicolas; Laumaea, Annemarie; Gasser, Romain; Finzi, Andrés; Roger, Michel

doi:10.1128/jcm.02511-20

Cited by 27 publications

(18 citation statements)

References 38 publications

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“…All serum aliquots were concomitantly thawed at the end of the study period, centrifuged and tested with six anti-SARS-CoV-2 immunoassays (Table 1), as well as with a manual enzyme linked immunoassay (ELISA) for quantification of serum SARS-CoV-2 spike concentration (COVID-19 Spike Protein ELISA Kit, Abcam, Cambridge, UK; measuring range: 2.7-2000 ng/mL, intra-assay imprecision: <10%). Previous evidence has been published that four of these six anti-SARS-CoV-2 immunoassays display good concordance with virus neutralization tests (Table 1) [8,9]. Molecular testing for detecting SARS-CoV-2 RNA (Seegene AllplexTM2019-nCoV Assay, Seegene, Seoul, South Korea) was also carried out on nasopharyngeal swabs 3 days before receiving the first vaccine dose, and then every ∼2 weeks afterwards, up till the end of the study.…”

Section: Methodsmentioning

confidence: 85%

Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Danese

Montagnana

Salvagno

et al. 2021

Preprint

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Background. Since universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. Methods. Three healthcare workers received 30 μg BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1. Results. All subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by ~30-, ~8- and ~8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing ~50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by ~24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points. Conclusions. BNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

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Section: Methodsmentioning

confidence: 85%

Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Danese

Montagnana

Salvagno

et al. 2021

Preprint

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“…Recent studies have confirmed that anti-S titres especially anti-RBD titres can serve as surrogates for virus neutralisation. 31 32 The Abbott SARS-CoV-2 IgG assay that targets antibodies to the N has a reported specificity and sensitivity of greater than 99% at 14 days or more following symptom onset and these measurements are not indicative or correlated to virus neutralisation titres. 33 In comparison, the MSH ELISA targets the full-length S protein including RBD, a major target for neutralising antibodies and has demonstrated excellent correlation to virus neutralisation.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal humoral antibody response to SARS-CoV-2 infection among healthcare workers in a New York City hospital

et al. 2021

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ObjectiveDynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs).DesignA prospective longitudinal study.SettingThis study was conducted in a New York City public hospital in the South Bronx, New York.ParticipantsHCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study.Primary outcome measureEvaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay.ResultsAnti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177–8812)) than in asymptomatic positive subjects (5803 (2825–11 920)). Marginally higher titres (2382 (1494–3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753–2755)) in phase 2. A positive correlation was noted between age (R=0.269, p<0.01), number (R=0.310, p<0.01) and duration of symptoms (R=0.434, p<0.01), and phase 1 anti-S antibody titre. A strong correlation (R=0.898, p<0.001) was observed between phase 1 titres and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever (R=0.428, p<0.001), gastrointestinal symptoms (R=0.340, p<0.05), and total number (R=0.357, p<0.01) and duration of COVID-19 symptoms (R=0.469, p<0.001).ConclusionsHigher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as a faster decay between the two time points.

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“…Low sensitivity early in infection could be a result of an assay detecting only IgG antibodies, but both the Ortho and Abbott IgG-specific assays had higher 0-14 day sensitivities which were similar to the total antibody assays. Other assay validation studies have reported similarly high sensitivities for samples collected after at least 14 days 6 , 7 , 8 , 9 , 10 . In the outbreak field study, where all samples were collected >14 days and within 2 months post-onset, >95% sensitivity was observed for all assays.…”

Section: Discussionmentioning

confidence: 63%

SARS-CoV-2 serology: Validation of high-throughput chemiluminescent immunoassay (CLIA) platforms and a field study in British Columbia

Sekirov¹,

Barakauskas²,

Simons³

et al. 2021

Journal of Clinical Virology

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Background SARS-CoV-2 antibody testing is required for estimating population seroprevalence and vaccine response studies. It may also increase case identification when as an adjunct to routine molecular testing. We performed a validation study and evaluated the use of automated high-throughput assays in a field study of COVID-19-affected care facilities. Methods Six automated assays were assessed: 1) DiaSorin LIAISON TM SARS-CoV-2 S1/S2 IgG; 2) Abbott ARCHITECT TM SARS-CoV-2 IgG; 3) Ortho VITROS TM Anti-SARS-CoV-2 Total; 4) VITROS TM Anti-SARS-CoV-2 IgG; 5) Siemens SARS-CoV-2 Total Assay; and 6) Roche Elecsys TM Anti-SARS-CoV-2. The validation study included 107 samples (42 known positive; 65 presumed negative). The field study included 296 samples (92 PCR positive; 204 PCR negative or not PCR tested). All samples were tested by the six assays. Results; All assays had sensitivities >90% in the field study, while in the validation study, 5/6 assays were >90% sensitive and DiaSorin was 79% sensitive. Specificities and negative predictive values were >95% for all assays. Field study estimated positive predictive values at 1%-10% disease prevalence were 100% for Siemens, Abbott and Roche, while DiaSorin and Ortho assays had lower PPVs at 1% prevalence, but PPVs increased at 5%-10% prevalence. In the field study, addition of serology increased diagnoses by 16% compared to PCR testing alone. Conclusions All assays evaluated in this study demonstrated high sensitivity and specificity for samples collected at least 14 days post-symptom onset, while sensitivity was variable 0-14 days after infection. The addition of serology to the outbreak investigations increased case detection by 16%.

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Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories

Cited by 27 publications

References 38 publications

Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

Longitudinal humoral antibody response to SARS-CoV-2 infection among healthcare workers in a New York City hospital

SARS-CoV-2 serology: Validation of high-throughput chemiluminescent immunoassay (CLIA) platforms and a field study in British Columbia

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