Assessment of SARS-CoV-2 Seropositivity During the First and Second Viral Waves in 2020 and 2021 Among Canadian Adults

Tang, Xuyang; Sharma, Abha; Brown, Patrick; Colwill, Karen; Gelband, Hellen; Birnboim, H. Chaim; Nagelkerke, Nico; Bogoch, Isaac I.; Bansal, Aditya; Newcombe, Leslie; Slater, Justin; Rodriguez, Peter S; Huang, Guowen; Fu, Sze Hang; Meh, Catherine; Wu, Daphne; Kaul, Rupert; Langlois, Marc‐André; Morawski, Ed; Hollander, Andy; Eliopoulos, Demetre; Aloi, Benjamin; Lam, Teresa; Abe, Kento T.; Rathod, Bhavisha; Fazel‐Zarandi, Mahya; Wang, Jenny; Iskilova, Mariam; Pasculescu, Adrian; Caldwell, Lauren; Barrios‐Rodiles, Miriam; Mohammed‐Ali, Zahraa; Vas, Nandita; Santhanam, Divya Raman; Cho, Eo Rin; Qu, Kathleen; Jha, Shreya; Jha, Vedika; Suraweera, Wilson; Malhotra, Varsha; Mastali, Kathy; Wen, Richard; Sinha, Samir K.; Reid, Angus; Gingras, Anne‐Claude; Chakraborty, Pranesh; Slutsky, Arthur S.; Jha, Prabhat

doi:10.1001/jamanetworkopen.2021.46798

Cited by 25 publications

(30 citation statements)

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“… To the Editor: The incidence of the omicron BA.1/1.1 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which rapidly spread worldwide even among vaccinated persons, is incompletely defined. 1 We quantified the incidence of SARS-CoV-2 infection during the initial omicron BA.1/1.1 variant wave among Canadian adults 2 and the contribution of previous infection and concurrent vaccination to age-specific active immunity (Fig. S1 in the Supplementary Appendix , available with the full text of this letter at NEJM.org).…”

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confidence: 99%

“…Dried-blood-spot samples that had been obtained by the participants were tested with highly sensitive and specific chemiluminescence-based enzyme-linked immunosorbent assays targeting the spike protein, receptor-binding domain, and nucleocapsid (N) protein. 2 , 4 Vaccines that have been used in Canada contain only spike protein and thus should not elicit N protein positivity. 5 Approval for the study was obtained from the institutional review board at Unity Health Toronto.…”

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confidence: 99%

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Omicron BA.1/1.1 SARS-CoV-2 Infection among Vaccinated Canadian Adults

Brown¹,

Fu²,

Bansal³

et al. 2022

N Engl J Med

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Omicron BA.1/1.1 SARS-CoV-2 Infection among Vaccinated Canadian Adults

Brown¹,

Fu²,

Bansal³

et al. 2022

N Engl J Med

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“…The validated automated ELISA assays described here are currently being used in multiple Canadian studies (with > 150 000 unique samples profiled to date). These include large serosurveys that monitor the global (and regional) humoral response (from both infection and vaccination) in the Canadian population, including the Canadian COVID‐19 Antibody and Health Survey from Statistics Canada, 2 seroprevalence studies with Canadian Blood Services, 33 , 34 the Action to Beat Coronavirus study, 35 and the Canadian Partnership for Tomorrow’s Health study. 36 Additionally, these assays are used in > 30 studies focused on infection and/or vaccine responses across different cohorts, e.g.…”

Section: Discussionmentioning

confidence: 99%

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

et al. 2022

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Objectives Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been instrumental in detecting previous exposures and analyzing vaccine‐elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS‐CoV‐2 antibodies, discriminate between natural infection‐ and vaccination‐induced responses, and assess antibody‐mediated inhibition of the spike‐angiotensin converting enzyme 2 (ACE2) interaction. Methods We developed methods and reagents to detect SARS‐CoV‐2 antibodies by enzyme‐linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2‐spike or ‐RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. Results Our single‐point IgG‐based ELISAs accurately distinguished non‐infected and infected individuals. For seroprevalence assessment (in a non‐vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti‐spike and ‐RBD (but not ‐N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability. Conclusions Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike‐ACE2 interactions in high‐throughput enables large‐scale analyses of humoral immune responses to SARS‐CoV‐2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter‐laboratory data comparison and aggregation.

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“…The validated automated ELISA assays described here are currently being used in multiple Canadian studies (with >150,000 unique samples profiled to date). These include large serosurveys that monitor the global (and regional) humoral response (from both infection and vaccination) in the Canadian population, including the Canadian COVID-19 Antibody and Health Survey from Statistics Canada 2 , seroprevalence studies with Canadian Blood Services 33,34 , the Action to Beat Coronavirus study 35 , and the Canadian Partnership for Tomorrow's Health study 36 . Additionally, these assays are used in > 30 studies focused on infection and/or vaccine responses across different cohorts, e.g.…”

Section: Discussionmentioning

confidence: 99%

A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination

Colwill

Galipeau

Stuible

et al. 2021

Preprint

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BACKGROUND: Testing for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable "Made-in-Canada" solution that can detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction. METHODS: We developed a set of methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD), and the nucleocapsid (N) protein. These antigens are complemented by a detection antibody (human anti-IgG fused to horseradish peroxidase (HRP)) and a positive control reference antibody (recombinant IgG against the RBD), permitting intra- and inter-laboratory comparisons. Using this toolkit and commercial reagents, we optimized automated ELISAs on two different high throughput platforms to measure antibody responses to SARS-CoV-2 antigens. The assays were calibrated to a reference standard from the World Health Organization. We also automated a surrogate neutralization (sn)ELISA that measures inhibition of ACE2-Spike or -RBD interactions by antibodies using biotinylated ACE2. RESULTS: Our individual IgG-based ELISAs measure antibody levels in single-point measurements in reference to a standard antibody curve to accurately distinguish non-infected and infected individuals (area under the curve > 0.96 for each assay). Positivity thresholds can be established in individual assays using precision-recall analysis (e.g., by fixing the false positive rate), or more stringently, by scoring against the distribution of the means of negative samples across multiple assays performed over several months. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for at least 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. Here, we present detailed protocols to perform these assays using either serum/plasma or dried blood spots both manually and on two automated platforms, and to express the results in international units to facilitate data harmonization and inter-study comparisons. We also demonstrate that the snELISA can be performed automatically at single points, increasing the scalability of this functional assay for large seroprevalence studies. INTERPRETATION: The ability to measure antibodies to three viral antigens and identify neutralizing antibodies capable of disrupting spike-ACE2 interactions in high-throughput assays enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The "Made-in-Canada" set of protein reagents, produced at the National Research Council of Canada are publicly available to enable the up-scaling of standardized serological assays, permitting nationwide data comparison and aggregation.

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Assessment of SARS-CoV-2 Seropositivity During the First and Second Viral Waves in 2020 and 2021 Among Canadian Adults

Cited by 25 publications

References 36 publications

Omicron BA.1/1.1 SARS-CoV-2 Infection among Vaccinated Canadian Adults

Omicron BA.1/1.1 SARS-CoV-2 Infection among Vaccinated Canadian Adults

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination

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