Effectiveness of BNT162b2 Vaccine Against Omicron-SARS-CoV-2 Subvariants in Children 5-11 Years of Age in Quebec, Canada, January 2022 to January 2023.

BACKGROUND: In premarketing clinical trials conducted before Omicron emergence, BNT162b2 vaccine efficacy against COVID-19 was 90% in children. We conducted postmarketing evaluation of 1- and 2-dose vaccine effectiveness (VE) against Omicron BA.1, BA.2 and BA.4/5 subvariants in 5- to 11-year olds. METHODS: We estimated VE against SARS-CoV-2 infection using a test-negative design. Specimens collected between January 9, 2022, and January 7, 2023, from children 5-11 years old in Quebec, Canada, and tested by nucleic acid amplification test were eligible. We estimated VE by time since last vaccine dose, interval between doses and by period of Omicron subvariant predominance. RESULTS: A total of 48,826 NAATs were included in overall analysis. From 14-55 to 56-385 days postvaccination, 2-dose VE against symptomatic infection decreased from 68% (95% CI, 62-74) to 25% (95% CI, 11-36). Two-dose VE with restriction to specimens collected from acute care hospitals (emergency rooms or wards) did not decline but was stable at ~40%. VE against symptomatic infection remained comparable at any interval between doses but increased with longer interval among children tested in acute care settings, from 18% (95% CI, -17 to 44) with 21- to 55-day interval to 69% (95% CI, 43-86) with ≥84-day interval. Two-dose VE against symptomatic infection dropped from 70% (95% CI, 63-76) during BA.1, to 32% (95% CI, 13-47) with BA.2 and to nonprotective during BA.4/5 dominance. CONCLUSIONS: In children 5-11 years of age, VE against symptomatic infection was stable at any interval between doses but decreased with time since the last dose and against more divergent omicron subvariants.

School-based vaccination program against HPV and Hepatitis B: A longitudinal analysis of vaccine coverage between 2015 and 2021 in Quebec.

BACKGROUND: HPV vaccination prevents cancers, including 90% of cervical cancer. Since 2008, a school-based HPV vaccination program has been implemented in Quebec, but vaccine coverage is suboptimal. The COVID-19 pandemic disrupted school-based vaccination programs. This study aimed to assess variation in HPV vaccination coverage in the school-based program between 2015 and 2022 in Quebec and to identify sociodemographic characteristics associated with non-vaccination. METHODS: HPV vaccine coverage data were extracted from the Quebec Immunization Registry for students in Grade 4 and matched to the 2016 Canadian census sociodemographic data. Descriptive analysis was conducted to explore individual-level vaccine coverage according to sociodemographic data. A Generalized Estimating Equations model assessed the independent association between non-vaccination and students' sociodemographic characteristics. RESULTS: HPV vaccine coverage (at least one dose) was 84% in 2018-2019 and 85% in 2019-2020. A decrease was observed during the pandemic. In 2020-2021, the HPV vaccine coverage (at least one dose) was 52% (at the end of the school year) and rose to 84% with intense catch-up activities. In 2021-2022, the coverage was slightly lower than before the pandemic (81%). Factors in the dissemination area were statistically significantly associated with non-vaccination: material (p-value = 0.0001) and social deprivation index (p-value = 0.0048), the proportion of immigration (p-value < 0.0001), and the language spoken at home (English (p-value = 0.0318), other than French or English (p-value = 0.0001). CONCLUSION: School-based vaccination programs offer equitable access to vaccination, and our analysis showed that some groups have consistently lower vaccine acceptance and uptake. Strategies to improve HPV vaccine coverage should target children living in areas with a higher proportion of immigrants, non-French speakers, and people from underprivileged backgrounds. Although it is too early to assess the full impact of COVID-19 on school-based programs in Quebec, it remains important to ensure that catch-up strategies are implemented for missed doses.

"The problem is not lack of information": A qualitative study of parents and school nurses' perceptions of barriers and potential solutions for HPV vaccination in schools.

BACKGROUND: HPV vaccination has been offered in school programs for over a decade in Quebec, Canada, but the vaccine coverages are not reaching the target coverage in several regions. This qualitative study aimed to describe barriers and enabling conditions of HPV vaccination as perceived by parents and school nurses and identify potential solutions to improve HPV vaccine uptake rates and acceptance in school-based programs. METHODS: Three focus group discussions were conducted with parents of children in Grades 2 or 3 who were unsure or unwilling to vaccinate. Individual interviews were conducted with 24 school nurses. A thematic content analysis was performed using N'Vivo. RESULTS: The main parental questions and concerns regarding the HPV vaccination were the children's young age, the possible side effects, the rationale behind boys' vaccination and the possible interaction with COVID-19 vaccination. Except for interaction with COVID-19 vaccination, these concerns remain similar to those identified before the pandemic. Interviews highlighted that the information on HPV vaccination provided by the public was not well understood by parents. Parents suggested different tools to access information tailored to their concerns and situation. From the nurses' perspective, HPV vaccination promotion tools such as decision-aids and social media communication campaigns were needed and could reduce their work. CONCLUSION: COVID-19 may have disrupted the acceptance of the vaccines. While strategies to catch up on missed doses and reduce access barriers to vaccines are urgently needed, our findings highlight that a shift in attitudes toward routine vaccines may pose further challenges even if HPV vaccine coverage appears to have returned to pre-pandemic levels.

Effectiveness of previous infection-induced and vaccine-induced protection against hospitalisation due to omicron BA subvariants in older adults: a test-negative, case-control study in Quebec, Canada.

BACKGROUND: Older adults (aged ≥60 years) were prioritised for COVID-19 booster vaccination due to severe outcome risk, but the risk for this group is also affected by previous SARS-CoV-2 infection and vaccination. We estimated vaccine effectiveness against omicron-associated hospitalisation in older adults by previously documented infection, time since last immunological event, and age group. METHODS: This was a population-based test-negative case-control study done in Quebec, Canada, during BA.1 dominant (December, 2021, to March, 2022), BA.2 dominant (April to June, 2022), and BA.4/5 dominant (July to November, 2022) periods using provincial laboratory, immunisation, hospitalisation, and chronic disease surveillance databases. We included older adults (aged ≥60 years) with symptoms associated with COVID-19 who were tested for SARS-CoV-2 in acute-care hospitals. Cases were defined as patients who were hospitalised for COVID-19 within 14 days after testing positive; controls were patients who tested negative. Analyses spanned 3-14 months after last vaccine dose or previous infection. Logistic regression models compared COVID-19 hospitalisation risk by mRNA vaccine dose and previous infection versus unvaccinated and infection-naive participants. FINDINGS: Between Dec 26, 2021, and Nov 5, 2022, we included 174 819 specimens (82 870 [47·4%] from men and 91 949 [52·6%] from women; from 8455 cases and 166 364 controls), taken from 2951 cases and 48 724 controls in the BA.1 period; 1897 cases and 41 702 controls in the BA.2 period; and 3607 cases and 75 938 controls in the BA.4/5 period. In participants who were infection naive, vaccine effectiveness against hospitalisation improved with dose number, consistent with a shorter median time since last dose, but decreased with more recent omicron subvariants. Four-dose vaccine effectiveness was 96% (95% CI 93-98) during the BA.1 period, 84% (81-87) during the BA.2 period, and 68% (63-72) during the BA.4/5 period. Regardless of dose number (two to five doses) or timing since previous infection, hybrid protection was more than 90%, persisted for at least 6-8 months, and did not decline with age. INTERPRETATION: Older adults with both previous SARS-CoV-2 infection and two or more vaccine doses appear to be well protected for a prolonged period against hospitalisation due to omicron subvariants, including BA.4/5. Ensuring that older adults who are infection naive remain up to date with vaccination might reduce COVID-19 hospitalisations most efficiently. FUNDING: Ministère de la Santé et des Services Sociaux du Québec. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Self-reported Human Papillomavirus Vaccination and Vaccine Effectiveness Among Men Who Have Sex with Men: A Quantitative Bias Analysis.

BACKGROUND: Self-report of human papillomavirus (HPV) vaccination has ~80-90% sensitivity and ~75-85% specificity. We measured the effect of nondifferential exposure misclassification associated with self-reported vaccination on vaccine effectiveness (VE) estimates. METHODS: Between 2017-2019, we recruited sexually active gay, bisexual, and other men who have sex with men aged 16-30 years in Canada. VE was derived as 1-prevalence ratio × 100% for prevalent anal HPV infection comparing vaccinated (≥1 dose) to unvaccinated men using a multivariable modified Poisson regression. We conducted a multidimensional and probabilistic quantitative bias analysis to correct VE estimates. RESULTS: Bias-corrected VE estimates were relatively stable across sensitivity values but differed from the uncorrected estimate at lower values of specificity. The median adjusted VE was 27% (2.5-97.5th simulation interval = -5-49%) in the uncorrected analysis, increasing to 39% (2.5-97.5th simulation interval = 2-65%) in the bias-corrected analysis. CONCLUSION: A large proportion of participants erroneously reporting HPV vaccination would be required to meaningfully change VE estimates.

Vaccine Effectiveness Against 12-Month Incident and Persistent Anal Human Papillomavirus Infection Among Gay, Bisexual, and Other Men Who Have Sex With Men.

BACKGROUND: Real-world evidence of human papillomavirus (HPV) vaccine effectiveness (VE) against longitudinal outcomes is lacking among gay, bisexual, and other men who have sex with men (GBM). We compared 12-month incidence and persistence of anal HPV infection between vaccinated and unvaccinated GBM. METHODS: We recruited GBM aged 16-30 years in Montreal, Toronto, and Vancouver, Canada, from 2017 to 2019. Participants were followed over a median of 12 months (interquartile range, 12-13 months). Participants self-reported HPV vaccination and self-collected anal specimens for HPV DNA testing. We calculated prevalence ratios (PR) for 12-month cumulative incidence and persistence with ≥1 quadrivalent vaccine type (HPV 6/11/16/18) between vaccinated (≥1 dose at baseline) and unvaccinated participants using a propensity score-weighted, modified Poisson regression. RESULTS: Among 248 participants, 109 (44.0%) were vaccinated at baseline, of whom 62.6% received 3 doses. PRs for HPV 6/11/16/18 were 0.56 (95% confidence interval [CI], .24-1.31) for cumulative incidence and 0.53 (95% CI, .25-1.14) for persistence. PRs were 0.23 (95% CI, .05-1.03) and 0.08 (95% CI, .01-.59) for incidence and persistence, respectively, among participants who received their first dose at age ≤23 years and 0.15 (95% CI, .03-.68) and 0.12 (95% CI, .03-.54) among participants who were sexually active for ≤5 years before vaccination. CONCLUSIONS: Findings support national recommendations for HPV vaccination at younger ages or soon after sexual debut.

BNT162b2 Effectiveness Against Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2 in Adolescents Aged 12-17 Years, by Dosing Interval and Duration.

BACKGROUND: Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval. METHODS: Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12-17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36-17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose. RESULTS: The VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%-75% at 2-3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%-7% higher (absolute) when first and second doses were spaced ≥8 versus 3-4 weeks apart. CONCLUSIONS: In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.

Protection against omicron (B.1.1.529) BA.2 reinfection conferred by primary omicron BA.1 or pre-omicron SARS-CoV-2 infection among health-care workers with and without mRNA vaccination: a test-negative case-control study.

BACKGROUND: There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination. METHODS: We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection. FINDINGS: 258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47-63), two (69%, 64-73), or three (70%, 66-74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65-78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95-96), but was not improved with a third dose (96%, 95-97). INTERPRETATION: Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant. FUNDING: Ministère de la Santé et des Services Sociaux du Québec.

Estimated Protection of Prior SARS-CoV-2 Infection Against Reinfection With the Omicron Variant Among Messenger RNA-Vaccinated and Nonvaccinated Individuals in Quebec, Canada.

Importance: The Omicron variant 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 reinfection, with and without vaccination, requires quantification. Objective: To estimate the protection against Omicron reinfection and hospitalization conferred by prior heterologous non-Omicron SARS-CoV-2 infection and/or up to 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine. Design, Setting, and Participants: This test-negative, population-based case-control study was conducted between December 26, 2021, and March 12, 2022, and included community-dwelling individuals aged 12 years or older who were tested for SARS-CoV-2 infection in the province of Quebec, Canada. Exposures: Prior laboratory-confirmed SARS-CoV-2 infection with or without mRNA vaccination. Main Outcomes and Measures: The main outcome was laboratory-confirmed SARS-CoV-2 reinfection and associated hospitalization, presumed to be associated with the Omicron variant according to genomic surveillance. The odds of prior infection with or without vaccination were compared for case participants with Omicron infection and associated hospitalizations vs test-negative control participants. Estimated protection was derived as 1 - the odds ratio, adjusted for age, sex, testing indication, and epidemiologic week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results: This study included 696 439 individuals (224 007 case participants and 472 432 control participants); 62.2% and 63.9% were female and 87.4% and 75.5% were aged 18 to 69 years, respectively. Prior non-Omicron SARS-CoV-2 infection was detected for 9505 case participants (4.2%) and 29 712 control participants (6.3%). Among nonvaccinated individuals, prior non-Omicron infection was associated with a 44% reduction (95% CI, 38%-48%) in Omicron reinfection risk, which decreased from 66% (95% CI, 57%-73%) at 3 to 5 months to 35% (95% CI, 21%-47%) at 9 to 11 months postinfection and was below 30% thereafter. The more severe the prior infection, the greater the risk reduction. Estimated protection (95% CI) against Omicron infection was consistently significantly higher among vaccinated individuals with prior infection compared with vaccinated infection-naive individuals, with 65% (63%-67%) vs 20% (16%-24%) for 1 dose, 68% (67%-70%) vs 42% (41%-44%) for 2 doses, and 83% (81%-84%) vs 73% (72%-73%) for 3 doses. For individuals with prior infection, estimated protection (95% CI) against Omicron-associated hospitalization was 81% (66%-89%) and increased to 86% (77%-99%) with 1, 94% (91%-96%) with 2, and 97% (94%-99%) with 3 mRNA vaccine doses, without signs of waning. Conclusions and Relevance: The findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization. In the context of program goals to prevent severe outcomes and preserve health care system capacity, a third mRNA vaccine dose may add limited protection in twice-vaccinated individuals with prior SARS-CoV-2 infection.

Increases in human papillomavirus vaccine coverage over 12 months among a community-recruited cohort of gay, bisexual, and other men who have sex with men in Canada.

BACKGROUND: Starting in 2015/16, most Canadian provinces introduced publicly-funded human papillomavirus (HPV) vaccination programs for gay, bisexual, and other men who have sex with men (GBM) aged ≤ 26 years. We estimated 12-month changes in HPV vaccine coverage among community-recruited GBM from 2017 to 2021 and identified baseline factors associated with vaccine initiation (≥1 dose) or series completion (3 doses) among participants who were unvaccinated or partially vaccinated at baseline. METHODS: We recruited sexually-active GBM aged ≥ 16 years in Montreal, Toronto, and Vancouver, Canada, from 02/2017 to 08/2019 and followed them over a median of 12 months (interquartile range = 12-13 months). We calculated the proportion who initiated vaccination (≥1 dose) or completed the series (3 doses) by 12-month follow-up. Analyses were stratified by city and age-eligibility for the publicly-funded programs at baseline (≤26 years or > 26 years). We used multivariable logistic regression to identify baseline factors associated with self-reported incident vaccine initiation or series completion. RESULTS: Among 165 unvaccinated participants aged ≤ 26 years at baseline, incident vaccine initiation (≥1 dose) during follow-up was 24.1% in Montreal, 33.3% in Toronto, and 38.9% in Vancouver. Among 1,059 unvaccinated participants aged > 26 years, incident vaccine initiation was 3.4%, 8.9%, and 10.9%, respectively. Higher education and trying to access pre-exposure prophylaxis for HIV were associated with incident vaccination among those aged ≤ 26 years, while younger age, residing in Vancouver (vs. Montreal), being diagnosed with anogenital warts, having both government and private extended medical insurance, and being vaccinated against influenza were associated with incident vaccination among those aged > 26 years. CONCLUSIONS: We observed substantial gains in HPV vaccine coverage among young GBM within 5 + years of targeted program implementation, but gaps remain, particularly among older men who are ineligible for publicly-funded programs. Findings suggest the need for expanded public funding or insurance coverage for HPV vaccines.

Time trends in social contacts before and during the COVID-19 pandemic: the CONNECT study.

BACKGROUND: Since 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. METHODS: CONNECT 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 m 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 and by socio-demographic characteristics. RESULTS: A 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/in 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. CONCLUSION: Physical distancing measures in Quebec significantly decreased social contacts, which most likely mitigated the spread of COVID-19.

Time trends in social contacts of individuals according to comorbidity and vaccination status, before and during the COVID-19 pandemic.

BACKGROUND: As 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. METHODS: We 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 m 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. RESULTS: A 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) vs 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. CONCLUSIONS: It 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).

Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada.

BACKGROUND: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada's larger provinces. METHODS: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22-47) 2021. RESULTS: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7-8-week versus manufacturer-specified 3-4-week intervals between mRNA doses. CONCLUSIONS: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

Impact of the first vaccine dose on COVID-19 and its complications in long-term care facilities and private residences for seniors in Québec, Canada.

Background: Residents of long-term care facilities (LTCFs) and private residences for seniors (PRSs) were given priority for vaccination against coronavirus disease 2019 (COVID-19). Given the shortage of vaccine in the winter of 2021, the Comité sur l'immunisation du Québec recommended postponing the administration of second doses to ensure more rapid and widespread administration of first doses. The objective of this study was to measure the impact of first-dose vaccination on 1) the incidence of cases and complications in LTCFs and PRSs and 2) the frequency of outbreaks in LTCFs. Methods: In this ecological study, COVID-19 incidence and complications in residents of LTCFs and PRSs in Québec were compared with the general (community) population at a point in time when there was still only limited eligibility for vaccination. Results: After vaccination in LTCFs, the incidence rate of COVID-19 decreased by 92% compared with 49% in the community, and deaths decreased by 95%. By six weeks post-vaccination, almost no facility reported five or more cases per 100 beds per week. The incidence rate decreased by 91% in PRSs compared with 2% in the community. Hospitalizations and deaths in PRSs decreased by 94% and 90%, respectively. Conclusion: As a result of 1) vaccination of residents with one dose, 2) natural immunity already acquired in LTCFs and PRSs, 3) vaccination of healthcare workers and 4) other non-pharmaceutical prevention measures implemented, the circulation of the coronavirus in these settings was largely interrupted.

Single-Dose Messenger RNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Workers Extending 16 Weeks Postvaccination: A Test-Negative Design From Québec, Canada.

BACKGROUND: In Canada, first and second doses of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were uniquely spaced 16 weeks apart. We estimated 1- and 2-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Québec, Canada, including protection against varying outcome severity, variants of concern (VOCs), and the stability of single-dose protection up to 16 weeks postvaccination. METHODS: A 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 1 dose ≥14 days or 2 doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. RESULTS: Primary analysis included 5316 cases and 53 160 controls. Single-dose VE was 70% (95% confidence interval [CI], 68%-73%) against SARS-CoV-2 infection; 73% (95% CI, 71%-75%) against illness; and 97% (95% CI, 92%-99%) against hospitalization. Two-dose VE was 86% (95% CI, 81%-90%) and 93% (95% CI, 89%-95%), respectively, with no hospitalizations. VE was higher for non-VOCs than VOCs (73% Alpha) among single-dose recipients but not 2-dose recipients. Across 16 weeks, no decline in single-dose VE was observed, with appropriate stratification based upon prioritized vaccination determined by higher vs lower likelihood of direct patient contact. CONCLUSIONS: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least 4 months postvaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy.

Sexual behavior, clinical outcomes and attendance of cervical cancer screening by HPV vaccinated and unvaccinated sexually active women.

Concerns were raised about HPV vaccination possibly leading to riskier sexual behavior. We assessed sexual behaviors, risk of sexually transmitted infection, and attendance to cervical cancer screening by HPV vaccinated and unvaccinated young women. In this analysis, 1475 questionnaires completed by women aged 17-29 years were included. The majority of respondents (67.9%) were vaccinated against HPV. The proportion of those vaccinated decreased with age: from 93.2% in those aged 17-19 to 72.9% in those aged 20-22, and 21.8% in 23-29-year olds. A higher proportion of unvaccinated respondents had at least one sexual intercourse under the age of 15 when compared to those vaccinated (30% vs. 23%, p < .0001). The number of sexual partners during the last 12 months was similar between vaccinated and unvaccinated participants. Vaccinated participants reported more condom use (45% versus 38%; p = .0002), and less sexually transmitted infections (10% versus 28%; p < .0001), and less anogenital condylomas (2.2% vs. 11.6%; p < .0001). A screening test has been reported by 51% and 77% of vaccinated and unvaccinated participants, respectively (p < .0001). The association between vaccination status and cervical cancer screening disappeared when adjusting for participants' age. The study results consolidate the existing body of data regarding the absence of an impact of HPV vaccination on sexual behavior or use of contraceptives.

A systematic literature review of the recombinant subunit herpes zoster vaccine use in immunocompromised 18-49 year old patients.

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is indicated for prevention of herpes zoster (HZ) in adults aged ≥50 years. Questions regarding the use of RZV in immunocompromised patients < 50-year-old, who are at increased risk for HZ, were raised. OBJECTIVES: The objective of this systematic review was to consolidate existing evidences on safety, immunogenicity and efficacy of RZV in immunocompromised adults aged 18-49 years. METHODS: Four databases were searched. Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed. Screening and classification of search items was performed using the web-based platform DistillerSR. RESULTS: The search identified 1389 potentially relevant records. Six studies fulfilled inclusion criteria. The proportion of patients aged 18-49 varied between 23 and 62%. Pain at injection site (98.6%) and fatigue (75.3%) were the most common adverse events. The proportion of patients reporting serious adverse events (SAEs) ranged between 8.1 and 30.8% in RZV and between 4.1 and 36.5% in placebo groups. SAEs deemed related to vaccination were reported in < 1% of patients in both RZV and placebo groups. The proportion of patients that experienced clinically significant underlying disease-related events ranged between 0.0 and 20.0% in RZV and 0.0 and 26.7% in placebo groups. The humoral and cell-mediated immune response rate ranged between 65.4 and 96.2% and 50.0-93.0%, respectively. Vaccine efficacy in hematopoietic stem cell transplant patients was 72% (95%CI, 39-88%) in 18-49-year-olds and 67% (95%CI, 53-78%) in ≥ 50-year-olds (median follow-up 21 months). Vaccine efficacy in ≥ 18-year-old patients with hematologic malignancies was estimated at 87.2% (95%CI, 44.3-98.6%) up to 13 months post-vaccination. CONCLUSIONS: Results suggest that RZV has an acceptable safety profile and induces immunity in an important proportion of ≥ 18-year-old immunocompromised patients. Longer follow-up studies are warranted to assess the duration of RZV induced immunity in immunocompromised patients.

Participation in an action research project on vaccine services for children: relationship with vaccine delays.

Multicomponent interventions are effective in improving vaccine coverage. However, few studies have assessed their effect on timely vaccination. The aim of this study was to compare the proportion of children with vaccine delays at 2- and 12-month visits according to whether or not health centers have participated in an action research project on the organization of vaccination services for 0-5-year-olds. The action research project included a multicomponent intervention and was conducted between 2011 and 2015 in Quebec, Canada. An ecological before/after design was used for this analysis. A total of 264,579 DTaP-IPV-Hib (2-month visits) and 240,541 Men-C-C (12-month visits) vaccine doses were administered during 2011-2012 to 2014-2015 fiscal years, including 19% in 14 participating health centers and the remaining in 78 nonparticipating centers. Vaccine delays demonstrated a more pronounced decreasing trend in participating versus nonparticipating health centers (p < .0001 at 2 and 12 months). Between 2011-2012 and 2014-2015, participating centers managed to eliminate 35% of their vaccine delays at 2-month visits and 33% at 12-month visits, whereas nonparticipating centers eliminated 19% of delays at both visits. Our results are consistent with a positive impact of the multicomponent intervention, despite the fact that it had not specifically aimed at decreasing vaccine delays.

Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

Priming effect of bivalent and quadrivalent vaccine for HPV 31/33/45/52: an exploratory analysis from two clinical trials.

The main objective of this post hoc analysis is to compare the magnitude of the immune response to HPV31/33/45/52 and 58 after a dose of 9vHPV vaccine given to naïve (previously unvaccinated) subjects and subjects previously vaccinated with a dose of 2vHPV or 4vHPV vaccine. Results from two clinical trials conducted in the same region, in comparable populations and by the same research team were included in this analysis. In study A, a dose of 9vHPV was administered 6 months after a single dose of 2vHPV as well as to naïve subjects. In study B, a dose of 9vHPV was administered 36-96 months (mean 65 months) after a single dose of 4vHPV. Blood samples were collected just before and one month post-9vHPV vaccine administration. For both studies, antibody responses were measured using the same 9-plex virus-like particle based IgG ELISA (M9ELISA). One month after 9vHPV dose administration, all subjects were seropositive to HPV 31/33/45/52 and 58. Subjects who had previously received 2vHPV or 4vHPV had significantly higher (1.8-8.0-fold) GMTs than naive subjects for HPV31/33/45/52 types but not for HPV58. GMTs to HPV31/33/45/52 and 58 were not significantly different between subjects who received a 2vHPV or 4vHPV dose prior to 9vHPV. The strong anamnestic response to one dose of 9vHPV given as late as 3-8 years after a single dose of 2vHPV or 4vHPV vaccine indicates these vaccines induced priming to types only included in the 9vHPV vaccine.