CITF-funded findings on methodologic approaches to improve seroprevalence estimates

Assessing seroprevalence is the main methodology used in Canada and around the world to determine the extent and trends in SARS-CoV-2 immunity, whether from infection, vaccination, or both. Here, we summarize results from the four presentations given during the breakout session “Methodologic approaches to improving seroprevalence estimates” at the CITF Scientific Meeting in Vancouver, March 8-10, 2023. The study teams presented data, advantages, and limitations of new serological tests; ways to effectively manage high-throughput testing facilities during a pandemic; and the importance of biobanks and lessons learned from them.

1. Presenter and CITF PI Dr. Upton Allen: Disproportionate rates of COVID-19 among Black Canadian communities: lessons from the first year of the pandemic

This study’s objective was to determine the seroprevalence of SARS-CoV-2 among Black Canadians compared to other populations in Canada and to characterize the relationship between seropositivity and the presence of neutralizing antibodies.

• Ontarians in COVID-19 hot zones were over three times more likely to have infection-acquired antibodies to SARS-CoV-2 in year one (August to December 2020).
• The percentage of SARS-CoV-2 seropositive Black individuals was greater in frontline workers (13.0%) than in non-frontline workers (3.2%).
• Black participants residing in the Greater Toronto Area and the North West/Peel regions were 10 times more likely to have had a SARS-CoV-2 infection than those residing in Oakville/London.
• Overall SARS-CoV-2 positivity rates in Black Canadians increased from August 2020 to December 2022. Specific populations, including those living in the Greater Toronto Area North West, frontline workers, and students/teachers, experienced a surge in cases during the period January to June 2022.

2. Presenter Dr. Alton Russell and CITF PI Dr. Chantale Pambrun: Neighbourhood characteristics in blood donor-based COVID-19 serosurveillance

This study’s objective was to assess how representative blood donors are of the general population for the purpose of SARS-Co-V-2 serologic research surveillance.

• In terms of geographical representation, blood donor samples are taken from healthy adults residing in most forward sortation areas (FSA) in Canada (first three digits of the postal code), although blood donors are more likely to be from urban areas. They do not include members of the military, incarcerated populations, or First Nations reserve residents.
• In terms of socioeconomic representation, blood donors tend to be from less materially deprived neighbourhoods (i.e., they are from wealthier neighbourhoods) and less socially deprived neighbourhoods (socially deprived: fewer social ties like living alone, being divorced, or being a single parent).
• High material deprivation and low social deprivation were associated with SARS-CoV-2 seropositivity in donors.

3. Presenters CITF PI Dr. Rahul Arora and Ms. Harriet Ware: Serology assays used in SARS-CoV-2 seroprevalence surveys worldwide: A systematic review and meta-analysis of assay features, testing algorithms, and performance

This study’s objective was to describe the features and use of serological assays, comparing assay performance across manufacturers, third-party reference labs, and independent evaluations. In addition, researchers also quantitatively assessed assay performance for seroprevalence estimates.

• According to manufacturer data, 29.7% of all commercial assays met the World Health Organization criteria for emergency use. This requires 90% sensitivity (ability of a test to correctly identify patients with SARS-CoV-2 antibodies) and 97% specificity (ability of a test to correctly identify patients without SARS-CoV-2 antibodies).
• Third parties indicated that manufacturers overstated the serological assay sensitivity by 1% and specificity by 0.9%.
• Independent group evaluations indicated that manufacturers overstated their serological assay sensitivity by 3.3% and specificity by 0.2%.
• There is substantial heterogeneity in assays and assay evaluation techniques, which could bias seroprevalence estimates by up to ± 9.5%.

4. Presenter and CITF PI Dr. Marc Germain: Evaluation of anti-nucleocapsid level variation in frequent plasma donors to assess SARS-CoV-2 seroprevalence in a vaccinated population

This study’s objective was to describe SARS-CoV-2 serosurveillance in blood donors from the Plasma Donor Biobank (PLASCOV) at Héma-Québec, using a SARS-CoV-2 anti-nucleocapsid ELISA on blood samples to estimate the impact of the Omicron wave.

• SARS-CoV-2 serosurveillance studies among blood donors have been very useful to public health authorities as a method to assess the progression of the COVID-19 pandemic in the general population.
• Cross-sectional seroprevalence studies can no longer present an accurate picture of the cumulative incidence of infection, as infection-acquired antibodies (anti-nucleocapsid) wane over time. In addition, the anti-N response may be blunted by previous vaccination.
• The ratio-based approach (comparing post-infection samples with pre-infection samples) has a sensitivity of 95.2%, which is greater than the conventional approach (testing only post-infection samples) at detecting SARS-CoV-2 seropositivity.
• By November 2022, the Omicron wave had struck about 85% of the Quebec population.