What factors converged to create a COVID-19 hot-spot? Lessons from the South Asian community in Ontario.

BackgroundSouth Asians represent the largest non-white ethnic group in Canada. The Greater Toronto Area (GTA), home to a high proportion of South Asians, emerged as a COVID-19 hot spot. Early in the pandemic, the South Asian community was identified as having risk factors for exposure and specific barriers to accessing testing and reliable health information, rendering them uniquely vulnerable to SARS-CoV-2 infection. ObjectivesTo investigate the burden of SARS-CoV-2 infection among South Asians in the GTA, and to determine which demographic characteristics were most closely aligned with seropositivity, in this cross-sectional analysis of a prospective cohort study. MethodsParticipants from the GTA were enrolled between April and July 2021. Seropositivity for anti-spike and anti-nucleocapsid antibodies was determined from dried blood spots, and age and sex standardized to the Ontario South Asian population. Demographics, risk perceptions, and sources of COVID-19 information were collected via questionnaire in a subset. ResultsAmong the 916 South Asians enrolled, mean age 41 years, the age and sex standardized seropositivity was 23.6% (95% CI: 20.8%-26.4%). Approximately one-third identified as essential workers, and 19% reported living in a multi-generational household. Over half perceived high COVID-19 risk due to their geographic location, and 36% due to their type of employment. The top three most trusted sources of COVID-related information included healthcare providers/public health, traditional media sources, and social media. ConclusionBy the third wave of the COVID-19 pandemic, approximately one-quarter of a sample of South Asians in Ontario had serologic evidence of prior SARS-CoV-2 infection. Insight into factors that render certain populations at risk can help future pandemic planning and disease control efforts.

A "Made-in-Canada" serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination

OBJECTIVESAntibody 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. METHODSWe 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 neutralization (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. RESULTSOur 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. CONCLUSIONSMeasuring antibodies to three viral antigens and identify neutralizing 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 standardized serological assays, permitting inter-laboratory data comparison and aggregation.

Real-world serologic responses to Extended-interval and Heterologous COVID-19 mRNA vaccination in Frail Elderly - Interim report from a prospective observational cohort study

BackgroundThe Coronavirus disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted accelerated vaccines development. Their use was prioritized to protect the most vulnerable, notably, the elderly. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been employed. The effectiveness of these strategies in the frail elderly are unknown. MethodsIn this real-world vaccination study, under a government-decreed rationing strategy, elderly adults residing in long-term care facilities, with or without previously-documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. Clinical data and blood were serially collected during and after this interval period. Sera were tested for SARS-CoV-2-specific IgG antibodies (to trimeric S; RBD; nucleocapsid) by automated chemiluminescent ELISA. FindingsAfter a significant increase 4 weeks post-prime dose, there was a significant decline in anti-RBD and anti-S IgG levels until the boost dose, followed by an increase 4 weeks later. Previously uninfected individuals exhibited lower antibody responses up to 16 weeks post-prime dose, but achieved comparable levels to previously infected counterparts by 4 weeks post-second dose. Individuals primed with BNT162b2 exhibited larger decrease in anti-RBD and anti-S IgG levels with 16-week interval between doses, compared to those who received mRNA-1273. No differences in antibody levels 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. InterpretationsThese interim results of this ongoing longitudinal study show that, among frail elderly, neither age, sex, nor comorbidity affect antigenicity of mRNA-based COVID vaccines, but previous SARS-CoV-2 infection and type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. Homologous/heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following second dose, supporting their interchangeability. FundingThis project was supported by funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference group and the COVID-19 Immunity Task Force (CITF).