Introduction

Ethnic communities, which are vulnerable in terms of socioeconomic status and health inequality, faced heightened risk of COVID-19 infection related hospitalizations and mortality worldwide [1]. A recent population-based cohort study of 17 million adults from the United Kingdom found that South Asians, defined as people who originate from the Indian subcontinent, were at increased risk of testing positive for SARS-CoV-2 and of COVID-19-related hospitalizations, ICU admissions, and deaths [2].

South Asians are the largest non-white and fastest growing ethnic group in Canada. During the COVID-19 pandemic, indirect as well as direct assessment indicated that South Asians in the Greater Toronto Area of Ontario, Canada experienced a higher rate of COVID-19 compared to other ethnic groups [3].

Vaccines are effective in reducing the risk of COVID-19 infection and associated hospitalizations and deaths, as shown by Phase 3 randomized clinical trials. [4–7]. However, there is significant disparity in vaccine uptake among ethnic groups, especially South Asians [8–10]. Approximately 25% of people living in the Indian subcontinent are vaccine hesitant due to cultural or religious reasons, concomitant comorbidities, low health literacy, receipt of misinformation on social media, and due to the influence of their peers [11]. Furthermore, in COVID-19 vaccine trials, “Asian” participants in which South Asians would be included, were substantially underrepresented (<5%) [7, 12], and therefore, there are sparse data on effectiveness of COVID-19 vaccines among South Asians. These factors as well as timing and reason for immigration to Canada may limit vaccine confidence and therefore uptake amongst the South Asian population in Canada.

To address these concerns, we conducted a series of studies [13, 14], including this population-based study using health administrative databases among South Asians living in Ontario, Canada. The specific objectives of this analysis were to: 1) evaluate the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians, and 2) compare the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians. Finally, we explored potential explanatory factors for differences in COVID-19 infection rates including co-morbid conditions, socioeconomic status, immigrant status, reason for and duration of immigration to Canada.

Methods

This study is reported in accordance with the Reporting of studies Conducted using Observational Routinely collected health Data (RECORD) guidelines [15]. The Ontario Personal Health Information Protection Act states that the use of data in this project is authorized under section 45 and does not require to be reviewed by a research ethics committee or institutional board.

Results

A total of 883,155 individuals who had a PCR test for SARS-CoV-2 between 14 December 2020 and November 15, 2021, were identified. Among them, 126,016 were cases and 757,139 were controls (S1 Fig). S2 Table depicts the cohort creation process. Of 344,411 participants who were excluded, 342,409 (99.4%) were <18 years of age. The cohort creation, baseline characteristics and comorbidities of the cases and controls are shown in S3–S5 Tables. The important SARS-CoV-2 variants during our study period were Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron (B.1.1.529).

The overall cohort was divided into 4 subgroups as shown in Table 1. South Asians were younger, more frequently male, and less likely to live in rural communities compared to the non-South Asian group. More than half (54.8%) of South Asians resided in local health integrated networks 5 and 6, which included the cities of Mississauga and Brampton. Notably, South Asians had an overall lower prevalence of comorbid conditions compared to non-South Asians, except for diabetes mellitus (S2 Table). 54.7% of South Asians were immigrants compared to 17.6% of non-South Asians.

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Table 1. Baseline characteristics of the overall cohort stratified by ethnicity and vaccination status.

https://doi.org/10.1371/journal.pgph.0003490.t001

Vaccine effectiveness

Among South Asians, 2 doses of COVID-19 vaccine were 93.8% (95% CI 93.2, 94.4) and 97.5% (95% CI 95.2, 98.6) effective in preventing SARS Co-V-2 infection and related hospitalizations or deaths, respectively. Among non-South Asians, vaccine effectiveness was lower at 86.6% (CI 86.3, 86.9) and 93.1% (CI 92.2, 93.8) for SARS Co-V-2 infection and related hospitalizations or deaths, respectively. (Table 2).

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Table 2. Vaccine effectiveness among South Asians and non-South Asians.

https://doi.org/10.1371/journal.pgph.0003490.t002

Results were similar when COVID-19 related hospitalizations and death were analysed separately (S6 Table). Vaccines had similar effectiveness among South Asians (95.5%, 95% CI 81.5, 98.9) to prevent COVID-19 associated deaths compared to non-South Asians (89.8%, 95% CI 87.2, 91.9). Vaccines effectiveness remained similar after excluding participants with pre-existing respiratory conditions (S7 Table).

COVID-19 infection and related hospitalizations/deaths among non-vaccinated individuals

South Asian non-vaccinated individuals had two-fold higher odds of symptomatic COVID-19 infection (aOR 2.35, 95% CI 2.3, 2.4) compared to the non-South Asian non-vaccinated cohort (referent cohort), after adjustment for multiple potential covariates. Similarly, the risk of COVID-19-related hospitalizations and deaths was 2-fold higher among non-vaccinated South Asians compared to non-vaccinated non-South Asians (aOR 2.03, 95% CI 1.9, 2.2). (Table 3).

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Table 3. Adjusted logistic regression models for various outcomes in non-vaccinated South Asians, stratified by immigration status and reason for immigration (Referent cohort: Non-South Asian non-vaccinated).

https://doi.org/10.1371/journal.pgph.0003490.t003

Discussion

In this large population-based study including close to 900,000 individuals, we show that in the 2^nd to 4^th waves of the COVID pandemic in Canada, COVID-19 vaccines were effective in preventing symptomatic SARS CoV-2 infections, hospitalizations and/or deaths among both South Asians and non-South Asians. We also demonstrate that, among non-vaccinated individuals, South Asians had higher odds of COVID-19 infection, and an increased risk of COVID-19 hospitalizations and deaths compared to non-South Asians which was not explained by difference in comorbid, socioeconomic, or immigration-related factors.

The social determinants of health are important to understand the higher impact of COVID-19 among South Asians. Some South Asian communities in Canada are vulnerable groups as they are more likely to live in multigenerational households, earn lower income compared to their education level, and are frequently employed as front-line workers, such as in transit, grocery stores, warehouses, health care, and construction [13]. Due to these reasons, it is imperative to ensure adequate COVID-19 vaccine coverage among South Asians. Data from outside of Canada indicate a substantial amount of misinformation regarding the importance and effectiveness of COVID-19 vaccine in South Asian communities [8–10]. Among South Asians in Canada, the top three sources of information regarding COVID-19 came from health care providers and Public Health officials, national news, and traditional media sources, as well as social media [14]. In addition, outside of Canada, issues such as language barriers, messaging not being tailored for the South Asian community, and lack of access to technology, were observed to be associated with lower rates of vaccine uptake and access [11]. However, in Canada, South Asian advocacy groups and specialized knowledge translation strategies bridged this gap [21]. Finally, ethnic communities including South Asians, were significantly underrepresented in COVID-19 vaccine trials, leading to sparse data on the effectiveness for this ethnic group [22], which may have affected vaccine confidence and rates of vaccination.

The disproportionate impact of COVID-19 among racialized groups has been confirmed by a number of studies conducted worldwide, [2, 23–27] including recent meta-analyses [26, 28]. In one study which was published prior to the introduction of the COVID-19 vaccines, 18,728,893 patients were included. Black individuals (adjusted RR 2.02, 95% CI 1.67–2.44) and Asians (defined broadly, and differentiation between Chinese and South Asians was not provided) were at a higher risk of COVID-19 infections after adjusting for age, sex, and comorbid conditions (adjusted RR 1.50, 95% CI 1.24–1.83). Moreover, Asians were at higher risk of ICU admission (RR 1.97, 95% CI 1.34–2.89) compared to those of white European descent [28].

Studies evaluating the association between ethnic populations and COVID-19 in Canada are limited due to non-uniform collection of ethnicity data [29]. For that reason, proxy measures of ethnicity are used [1, 3, 4]. In this study, we used a validated last name-based algorithm to identify South Asians living in Ontario. Our findings show that non-vaccinated South Asians have a higher risk of COVID-19 related adverse clinical outcomes. Interestingly, among South Asians, we did not find any differences in the frequency COVID-19 infection among the immigrant and non-immigrant sub-populations. These findings show that there may be several complex sociocultural factors that are in play within the South Asian community which are responsible for their increased risk of COVID-19 related adverse outcomes. It is also plausible that unique biologic pathways such a genetic variation and immune response, among South Asians account for their higher odds of COVID-19 infection. For example, the Angiotensin-Converting Enzyme-2 (ACE2) receptor gene and gene expression affect entry of SARS COV-2 into cells and varies between ethnic groups and may be implicated in differential susceptibility and severity to SARS CoV-2 among South Asians [30, 31]. Additionally, the potential impact of HLA and genetic factors on COVID-19 risk among different ancestral groups is also an important area for further research [32–34], and more such studies are needed among South Asians to understand their increased COVID-19 susceptibility and severity.

To our knowledge, this is the first study to evaluate the effectiveness of COVID-19 vaccines among South Asians using a test-negative design at a population level. This study design mitigates potential bias arising from differences in access to healthcare by restricting to those individuals who presented for SARS-CoV-2 testing. Despite our study’s strengths, there are some limitations that deserve mention. First, our results are generalizable only to those healthcare systems with universal healthcare coverage like Ontario. Second, there is a possibility those individuals with no information on symptoms recorded in the databases might have had symptoms at the time of testing, and those recorded as asymptomatic might have subsequently developed symptoms. Third, the last name-based algorithm only allows us to identify South Asian and Chinese ethnic groups but not other ethnic communities, thus the non-South Asian group was heterogeneous by ethnicity. Fourth, we did not have data on employment, education, gender, and other social factors to further understand the increased risk of adverse outcomes among non-vaccinated South Asians. Finally, due to administrative nature of our databases, there is a potential for residual confounding and measurement error for a few variables.

Conclusions

This study shows that COVID-19 vaccines are effective in reducing COVID-19 infections, hospitalizations and death among South Asians living in Ontario, Canada. These results should provide reassurance and foster confidence among the South Asian community regarding vaccination. Non-vaccinated South Asians have a higher odds of COVID-19 related adverse outcomes compared to non-South Asians. Future studies are needed to explain the higher risk of COVID-19 infection and worse outcomes among non-vaccinated South Asians.

Supporting information

Acknowledgments

We acknowledge the support and guidance we received from the entire ICES team. Parts of this material are based on data and information compiled and provided by MOHLTC and CIHI. This work was also supported by the Ontario Health Data Platform (OHDP), a Province of Ontario initiative to support Ontario’s ongoing response to COVID-19 and its related impacts. This document used data adapted from the Statistics Canada Postal Code^OM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from Canada Post Corporation and Statistics Canada. Parts of this material are based on data and information compiled and provided by the MOH, the Canadian Institute for Health Information (CIHI), and Immigration Refugees and Citizenship Canada. The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. No endorsement by the OHDP, its partners, or the Province of Ontario is intended or should be inferred. The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred.