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Background and ObjectivesTwo- and three-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccine effectiveness (VE) against SARS-CoV-2 infection, including Delta and Omicron variants, was assessed among adolescents in two Canadian provinces where first and second doses were spaced longer than the manufacturer-specified 3-week interval. MethodsTest-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection among 12-17-year-olds in Quebec and British Columbia, Canada between September 5, 2021 (epi-week 36), and April 30, 2022 (epi-week 17). Delta-dominant and Omicron-dominant periods spanned epi-weeks 36-47 and 51-17, respectively. VE was assessed from 14 days and explored by interval between first and second doses, time since second dose, and with administration of a third dose. ResultsMedian first-second dosing-interval was [~]8 weeks and second-third dosing-interval was [~]29-31 weeks. Median follow-up post-second dose was [~]10-11 weeks for Delta-dominant and [~]21-22 weeks for Omicron-dominant periods, and [~]2-7 weeks post-third dose. VE against Delta was [≥]90% to at least the 5th month post-second dose. VE against Omicron declined from [~]65-75% at 2-3 weeks to [≤]50% by the 3rd month post-vaccination, restored to [~]65% shortly following a third dose. VE exceeded 90% against Delta regardless of dosing-interval but appeared improved against Omicron with [≥]8 weeks between first and second doses. ConclusionIn adolescents, two BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly-waning VE against Omicron. Longer interval between first and second doses and a third dose improved Omicron protection. Updated vaccine antigens, increased doses and/or dosing-intervals may be needed to improve adolescent VE against immunological-escape variants.
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BackgroundWe estimated the protection against the Omicron BA.2 variant associated with prior primary infection (PI) due to pre-Omicron or Omicron BA.1 virus, with and without mRNA vaccination. MethodsA test-negative case-control study was conducted among healthcare workers (HCWs) tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 predominated and was presumptively diagnosed. Logistic regression models compared the likelihood of BA.2 reinfection (second positive test [≥]30 days after PI) among HCWs with history of PI and none to three doses of mRNA vaccine versus infection-naive, unvaccinated HCWs. FindingsAmong 37,732 presumed BA.2 cases, 2,521 (6.7%) and 659 (1.7%) were reinfections following pre-Omicron or BA.1 PI, respectively. Among 73,507 controls, 7,360 (10.0%) and 12,315 (16.8%) had a pre-Omicron or BA.1 PI, respectively. Pre-Omicron PI was associated with 38% (95%CI:19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those also vaccinated with one (56%), two (69%) or three (70%) vaccine doses. Omicron BA.1 PI was associated with greater protection against BA.2 (72%; 95%CI:65-78), higher among two-dose vaccinated at 96% (95%CI:95-96) but not improved with a third dose (96%; 95%CI:95-97). Hybrid Omicron BA.1 PI plus two or three dose vaccine-induced protection persisted for five months post-infection. InterpretationTwice-vaccinated individuals who experienced BA.1 infection were subsequently well-protected for a prolonged period against BA.2 reinfection and derived no meaningful added benefit against BA.2 from a third dose of mRNA vaccine.
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ImportanceOmicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification. ObjectiveTo estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine. DesignTest-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022. SettingPopulation-based, province of Quebec, Canada ParticipantsCommunity-dwelling [≥]12-year-olds tested for SARS-CoV-2. ExposuresPrior laboratory-confirmed infection with/without mRNA vaccination. OutcomesLaboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test-negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing-indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. ResultsWithout vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses. Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively). Conclusions and relevancePrior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.
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BackgroundAs we are confronted with more transmissible/severe variants with immune escape and the waning of vaccine efficacy, it is particularly relevant to understand how the social contacts of individuals at greater risk of COVID-19 complications evolved over time. We described time trends in social contacts of individuals according to comorbidity and vaccination status before and during the first three waves of the COVID-19 pandemic in Quebec, Canada. MethodsWe used data from CONNECT, a repeated cross-sectional population-based survey of social contacts conducted before (2018/2019) and during the pandemic (April 2020 to July 2021). We recruited non-institutionalized adults from Quebec, Canada, by random digit dialling. We used a self-administered web-based questionnaire to measure the number of social contacts of participants (two-way conversation at a distance [≤]2 meters or a physical contact, irrespective of masking). We compared the mean number of contacts/day according to the comorbidity status of participants (pre-existing medical conditions with symptoms/medication in the past 12 months) and 1-dose vaccination status during the third wave. All analyses were performed using weighted generalized linear models with a Poisson distribution and robust variance. ResultsA total of 1441 and 5185 participants with and without comorbidities, respectively, were included in the analyses. Contacts significantly decreased from a mean of 6.1 (95%CI 4.9-7.3) before the pandemic to 3.2 (95%CI 2.5-3.9) during the first wave among individuals with comorbidities, and from 8.1 (95%CI 7.3-9.0) to 2.7 (95%CI 2.2-3.2) among individuals without comorbidities. Individuals with comorbidities maintained fewer contacts than those without comorbidities in the second wave, with a significant difference before the Christmas 2020/2021 holidays (2.9 (95%CI 2.5-3.2) v 3.9 (95%CI 3.5-4.3); P<0.001). During the third wave, contacts were similar for individuals with (4.1, 95%CI 3.4- 4.7) and without comorbidities (4.5, 95%CI 4.1-4.9; P=0.27). This could be partly explained by individuals with comorbidities vaccinated with their first dose who increased their contacts to the level of those without comorbidities. ConclusionsIt will be important to closely monitor COVID-19-related outcomes and social contacts by comorbidity and vaccination status to inform targeted or population-based interventions (e.g., booster doses of the vaccine).
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BackgroundThe Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canadas larger provinces. MethodsTwo-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults [≥]18-years-old in British Columbia (BC) and Quebec, Canada. FindingsIn both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with [~]95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at [~]70% when both doses were ChAdOx1. Estimates were similar by age group (including adults [≥]70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained [≥]80%. InterpretationTwo doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.
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BackgroundSince the beginning of the COVID-19 pandemic, many countries, including Canada, have adopted unprecedented physical distancing measures such as closure of schools and non-essential businesses, and restrictions on gatherings and household visits. We described time trends in social contacts for the pre-pandemic and pandemic periods in Quebec, Canada. MethodsCONNECT is a population-based study of social contacts conducted shortly before (2018/2019) and during the COVID-19 pandemic (April 2020 - February 2021), using the same methodology for both periods. We recruited participants by random-digit-dialing and collected data by self-administered web-based questionnaires. Questionnaires documented socio-demographic characteristics and social contacts for two assigned days. A contact was defined as a two-way conversation at a distance [≤]2 meters or as a physical contact, irrespective of masking. We used weighted generalized linear models with a Poisson distribution and robust variance (taking possible overdispersion into account) to compare the mean number of social contacts over time by characteristics. ResultsA total of 1291 and 5516 Quebecers completed the study before and during the pandemic, respectively. Contacts significantly decreased from a mean of 8 contacts/day prior to the pandemic to 3 contacts/day during the spring 2020 lockdown. Contacts remained lower than the pre-COVID period thereafter (lowest=3 contacts/day during the Christmas 2020/2021 holidays, highest=5 in September 2020). Contacts at work, during leisure activities/other locations, and at home with visitors showed the greatest decreases since the beginning of the pandemic. All sociodemographic subgroups showed significant decreases of contacts since the beginning of the pandemic. The mixing matrices illustrated the impact of public health measures (e.g. school closure, gathering restrictions) with fewer contacts between children/teenagers and fewer contacts outside of the three main diagonals of contacts between same-age partners/siblings and between children and their parents. ConclusionPhysical distancing measures in Quebec significantly decreased social contacts, which most likely mitigated the spread of COVID-19.
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IntroductionIn Canada, first and second doses of mRNA vaccines against SARS-CoV-2 were uniquely spaced 16 weeks apart, but the duration of single-dose protection remains uncertain. We estimated one- and two-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Quebec, Canada including protection against varying outcome severity, variants of concern (VOC), and the stability of single-dose protection out to 16 weeks post-vaccination. MethodsA test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly-matched (10:1), randomly-sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by one dose [≥]14 days or two doses [≥]7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. ResultsPrimary analysis included 5,316 cases and 53,160 controls. Single-dose VE was 70% (95%CI: 68-73) against SARS-CoV-2 infection, 73% (95%CI: 71-75) against COVID-19 illness and 97% (95%CI: 92-99) against associated hospitalization. Two-dose VE was 86% (95%CI: 81-90) and 93% (95%CI: 89-95), respectively, with no associated hospitalizations. VE was higher for non-VOC than VOC (73% Alpha) among single-dose (77%, 95%CI: 73-81 versus 63%, 95%CI: 57-67) but not two-dose recipients (87%, 95%CI: 57-96 versus 94%, 95%CI: 89-96). Across 16 weeks, no decline in single-dose VE was observed with appropriate stratification based upon prioritized vaccination determined by higher versus lower likelihood of direct patient contact. ConclusionOne mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least four months post-vaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy to consider.
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BACKGROUND: In June 2009, the World Health Organization declared an A(H1N1) influenza pandemic. In October 2009, the largest vaccination campaign in Canadian history began. The aim of this study was to document paediatricians' knowledge, attitudes and practices (KAP) regarding A(H1N1) pandemic influenza and its prevention by vaccination just after the beginning of the A(H1N1) vaccination campaign and to compare the results with those obtained before campaign initiation. METHODS: A self-administered mail-based questionnaire was sent to all Canadian paediatricians. Questionnaires were analyzed in two subsets: those received before and after the beginning of the vaccination campaign. RESULTS: Overall the response rate was 50%. Respondents' characteristics were comparable between the two subsets. Before the beginning of the campaign, 63% of paediatricians perceived A(H1N1) pandemic infection as a serious disease, that would occur frequently without vaccination compared to more than 75% after. Before the vaccination campaign, half of respondents or less thought that the A(H1N1) vaccine was safe (50%) and effective (35%) compared to 77% and 72% after. The proportion of paediatricians who reported they had received sufficient information on A(H1N1) vaccine increased from 31% before to 73% after the beginning of the vaccination campaign. The majority of respondents intended to get vaccinated against A(H1N1) influenza themselves (84% before and 92% after). Respondents' intention to recommend the A(H1N1) vaccine to their patients increased from 80% before the beginning of the campaign to 92% after. In multivariate analysis, the main determinants of paediatricians' intention to recommend the A(H1N1) vaccine were their intention to get vaccinated against A(H1N1) influenza themselves and a belief that A(H1N1) vaccine would be well accepted by health professionals who administer vaccines to the public. CONCLUSION: Results of this study show important increases in physicians' level of confidence about A(H1N1) vaccine's safety and immunogenicity and their willingness to recommend this vaccine to their patients. These changes could be explained, at least partially, by the important effort done by public health authorities to disseminate information regarding A(H1N1) vaccination.