Correlates of Breakthrough SARS-CoV-2 Infections in People with HIV: Results from the CIHR CTN 328 Study.

COVID-19 breakthrough infection (BTI) can occur despite vaccination. Using a multi-centre, prospective, observational Canadian cohort of people with HIV (PWH) receiving ≥2 COVID-19 vaccines, we compared the SARS-CoV-2 spike (S) and receptor-binding domain (RBD)-specific IgG levels 3 and 6 months post second dose, as well as 1 month post third dose, in PWH with and without BTI. BTI was defined as positivity based on self-report measures (data up to last study visit) or IgG data (up to 1 month post dose 3). The self-report measures were based on their symptoms and either a positive PCR or rapid antigen test. The analysis was restricted to persons without previous COVID-19 infection. Persons without BTI remained COVID-19-naïve until ≥3 months following the third dose. Of 289 participants, 92 developed BTI (31.5 infections per 100 person-years). The median days between last vaccination and BTI was 128 (IQR 67, 176), with the most cases occurring between the third and fourth dose (n = 59), corresponding to the Omicron wave. In analyses adjusted for age, sex, race, multimorbidity, hypertension, chronic kidney disease, diabetes and obesity, a lower IgG S/RBD (log10 BAU/mL) at 1 month post dose 3 was significantly associated with BTI, suggesting that a lower IgG level at this time point may predict BTI in this cohort of PWH.

COVID-19 vaccine effectiveness by HIV status and history of injection drug use: a test-negative analysis.

INTRODUCTION: People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS-CoV-2 infection. METHODS: A validated algorithm was applied to population-based, linked administrative datasets in the British Columbia COVID-19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV-negative individuals. The study population was limited to individuals who received an RT-PCR laboratory test for SARS-CoV-2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test-negative study design (modified case-control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU. RESULTS: Our analysis included 2700 PLWH and a matched population of 375,043 HIV-negative individuals, among whom there were 351 and 103,049 SARS-CoV-2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV-negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5-79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7-89.6), and VE was particularly low at 4-6 months (42.4%, 95% CI = -17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7-84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2-89.0) in the matched HIV-negative population with no history of IDU and remained relatively high at 4-6 months after second dose (84.6%, 95% CI = 83.8-85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations. CONCLUSIONS: PLWH with a history of IDU may experience lower VE against COVID-19 infection, although findings were limited by a small sample size. The lower VE at 4-6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co-occurring comorbidities may partly explain these findings.

Antibody neutralization capacity after coronavirus disease 2019 vaccination in people with HIV in Canada.

OBJECTIVES: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Here, we compare coronavirus disease 2019 (COVID-19) vaccine-induced antibody neutralization capacity in PWH vs. HIV-negative individuals following two vaccine doses. DESIGN: In Canadian prospective observational cohorts, including a multicentre study of PWH receiving at least two COVID-19 vaccinations (mRNA or ChAdOx1-S), and a parallel study of HIV-negative controls (Stop the Spread Ottawa Cohort), we measured vaccine-induced neutralization capacity 3 months post dose 2 (±1 month). METHODS: COVID-19 neutralization efficiency was measured by calculating the half maximal inhibitory dilution (ID50) using a high-throughput protein-based neutralization assay for Ancestral (Wuhan), Delta and Omicron (BA.1) spike variants. Univariable and multivariable quantile regression were used to compare COVID-19-specific antibody neutralization capacity by HIV status. RESULTS: Neutralization assays were performed on 256 PWH and 256 controls based on specimen availability at the timepoint of interest, having received two vaccines and known date of vaccination. There was a significant interaction between HIV status and previous COVID-19 infection status in median ID50. There were no differences in median ID50 for HIV+ vs. HIV-negative persons without past COVID-19 infection. For participants with past COVID-19 infection, median ICD50 was significantly higher in controls than in PWH for ancestral SARS-CoV-2 and Omicron variants, with a trend for the Delta variant in the same direction. CONCLUSION: Vaccine-induced SARS-CoV-2 neutralization capacity was similar between PWH vs. HIV-negative persons without past COVID-19 infection, demonstrating favourable humoral-mediated immunogenicity. Both HIV+ and HIV-negative persons demonstrated hybrid immunity. TRIAL REGISTRATION: clinicaltrials.gov NCT04894448.

Risk of COVID-19 hospitalization in people living with HIV and HIV-negative individuals and the role of COVID-19 vaccination: A retrospective cohort study.

OBJECTIVE: To examine the risk of hospitalization within 14 days of COVID-19 diagnosis among people living with HIV (PLWH) and HIV-negative individuals who had laboratory-confirmed SARS-CoV-2 infection. METHODS: We used Cox proportional hazard models to compare the relative risk of hospitalization in PLWH and HIV-negative individuals. Then, we used propensity score weighting to examine the influence of sociodemographic factors and comorbid conditions on risk of hospitalization. These models were further stratified by vaccination status and pandemic period (pre-Omicron: December 15, 2020, to November 21, 2021; Omicron: November 22, 2021, to October 31, 2022). RESULTS: The crude hazard ratio (HR) for risk of hospitalization in PLWH was 2.44 (95% confidence interval [CI]: 2.04-2.94). In propensity score-weighted models that included all covariates, the relative risk of hospitalization was substantially attenuated in the overall analyses (adjusted HR [aHR]: 1.03; 95% CI: 0.85-1.25), in vaccinated (aHR 1.00; 95% CI: 0.69-1.45), inadequately vaccinated (aHR: 1.04; 95% CI: 0.76-1.41) and unvaccinated individuals (aHR: 1.15; 95% CI: 0.84-1.56). CONCLUSION: PLWH had about two times the risk of COVID-19 hospitalization than HIV-negative individuals in crude analyses which attenuated in propensity score-weighted models. This suggests that the risk differential can be explained by sociodemographic factors and history of comorbidity, underscoring the need to address social and comorbid vulnerabilities (e.g., injecting drugs) that were more prominent among PLWH.

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.

Understanding COVID-19 Vaccine Confidence in People Living with HIV: A pan-Canadian Survey.

Understanding the roots of Covid-19 vaccine hesitancy in at-risk groups, such as persons living with HIV (PLWH), is of utmost importance. We developed a modified Vaccine Hesitancy Scale (VHS) questionnaire using items from the National Advisory Committee on Immunization Acceptability Matrix. To examine factors associated with receiving COVID-19 vaccine and the link between vaccine attitudes and beliefs with vaccine behavior, PLWH were recruited via social media and community-based organizations (February-May 2022). Descriptive statistics were used to summarize results. Total VHS score was generated by adding Likert scale scores and linear regression models used to compare results between participants who received or did not receive COVID-19 vaccines. Logistic regression models were used to identify factors associated with vaccine uptake. A total of 246 PLWH indicated whether they received a COVID-19 vaccine. 89% received ≥ 1 dose. Mean total VHS(SD) for persons having received ≥ 1 COVID-19 vaccine was 17.8(6.2) vs. 35.4(9.4) for participants not having received any COVID-19 vaccine. Persons who received ≥ 1 dose were significantly older than those who had not received any (48.4 ± 13.8 vs. 34.0 ± 7.7 years, p < 0.0001). The majority of participants considered COVID-19 vaccination important for their health(81.3%) and the health of others(84.4%). Multivariate logistic regression revealed the odds of taking ≥ 1dose were increased 2.4-fold [95% CI 1.6, 3.5] with each increase in age of 10 years (p < 0.0001). Sex and ethnicity were not different between groups. In conclusion, PLWH accept COVID-19 vaccines for both altruistic and individual reasons. With evolving recommendations and increasing numbers of booster vaccines, we must re-examine the needs of PLWH regularly.

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.

Effectiveness of COVID-19 vaccines in people living with HIV in British Columbia and comparisons with a matched HIV-negative cohort: a test-negative design.

OBJECTIVES: We estimated the effectiveness of COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among people living with HIV (PLWH) and compared the estimates with a matched HIV-negative cohort. METHODS: We used the British Columbia COVID-19 Cohort, a population-based data platform, which integrates COVID-19 data on SARS-CoV-2 tests, laboratory-confirmed cases, and immunizations with provincial health services data. The vaccine effectiveness (VE) was estimated with a test-negative design using the multivariable logistic regression. RESULTS: The adjusted VE against SARS-CoV-2 infection was 71.1% (39.7, 86.1%) 7-59 days after two doses, rising to 89.3% (72.2, 95.9%) between 60 and 89 days. VE was preserved 4-6 months after the receipt of two doses, after which noticeable waning was observed (51.3% [4.8, 75.0%]). In the matched HIV-negative cohort (n = 375,043), VE peaked at 91.4% (90.9, 91.8%) 7-59 days after two doses and was sustained for up to 4 months, after which evidence of waning was observed, dropping to 84.2% (83.4, 85.0%) between 4 and 6 months. CONCLUSION: The receipt of two COVID-19 vaccine doses was effective against SARS-CoV-2 infection among PLWH pre-Omicron. VE estimates appeared to peak later in PLWH than in the matched HIV-negative cohort and the degree of waning was relatively quicker in PLWH; however, peak estimates were comparable in both populations.

COVID-19 vaccine immunogenicity in people with HIV.

OBJECTIVES: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Our objective was to compare COVID-19 vaccine immunogenicity in PWH to HIV-negative individuals. DESIGN: In a Canadian multi-center prospective, observational cohort of PWH receiving at least two COVID-19 vaccinations, we measured vaccine-induced immunity at 3 and 6 months post 2nd and 1-month post 3rd doses. METHODS: The primary outcome was the percentage of PWH mounting vaccine-induced immunity [co-positivity for anti-IgG against SARS-CoV2 Spike(S) and receptor-binding domain proteins] 6 months post 2nd dose. Univariable and multivariable logistic regressions were used to compare COVID-19-specific immune responses between groups and within subgroups. RESULTS: Data from 294 PWH and 267 controls were analyzed. Immunogenicity was achieved in over 90% at each time point in both groups. The proportions of participants achieving comparable anti-receptor-binding domain levels were similar between the group at each time point. Anti-S IgG levels were similar by group at month 3 post 2nd dose and 1-month post 3rd dose. A lower proportion of PWH vs. controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose [92% vs. 99%; odds ratio: 0.14 (95% confidence interval: 0.03, 0.80; P = 0.027)]. In multivariable analyses, neither age, immune non-response, multimorbidity, sex, vaccine type, or timing between doses were associated with reduced IgG response. CONCLUSION: Vaccine-induced IgG was elicited in the vast majority of PWH and was overall similar between groups. A slightly lower proportion of PWH vs. controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose demonstrating the importance of timely boosting in this population.

Coronavirus disease 2019 vaccine effectiveness among a population-based cohort of people living with HIV.

OBJECTIVE: People with HIV were underrepresented in coronavirus disease 2019 (COVID-19) vaccine clinical trials. We estimated vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for the BNT162b2, mRNA-1273, and ChAdOx1 vaccines among a population-based cohort of people with HIV in Ontario, Canada. DESIGN: Test-negative design. METHODS: We identified people with HIV aged ≥19 years who were tested for SARS-CoV-2 by RT-PCR between December 14, 2020 (first availability of COVID-19 vaccines) and November 21, 2021 (pre-Omicron circulation). Outcomes included any infection, symptomatic infection, and COVID-19-related hospitalization/death. We compared the odds of vaccination between test-positive cases and test-negative controls using multivariable logistic regression with adjustment for age, sex, region, calendar time, SARS-CoV-2 test histories, influenza vaccination, comorbidities, and neighborhood-level socio-economic status. VE was derived as (1 - adjusted odds ratio) × 100%. RESULTS: Among 21 023 adults living with HIV, there were 801 (8.3%) test-positive cases and 8,879 (91.7%) test-negative controls. 20.1% cases and 47.8% of controls received ≥1 COVID-19 vaccine dose; among two-dose recipients, 93.4% received ≥1 mRNA dose. Two-dose VE ≥7 days before specimen collection was 82% (95% confidence interval [CI] = 74-87%) against any infection, 94% (95% CI = 82-98%) against symptomatic infection, and 97% (95% CI = 85-100%) against hospitalization/death. Against any infection, VE declined from 86% (95% CI = 77-92%) within 7-59 days after the second dose to 66% (95% CI = -15-90%) after ≥180 days; we did not observe evidence of waning protection for other outcomes. CONCLUSION: Two doses of COVID-19 vaccine offered substantial protection against symptomatic illness and hospitalization/death in people with HIV prior to the emergence of the Omicron variant. Our findings do not support a broad conclusion that COVID-19 VE is lower among people with HIV in populations that, for the most part, are attending HIV care, taking antiretroviral medication, and are virally suppressed.

Low human papillomavirus vaccine uptake among women engaged in HIV care in Ontario, Canada.

Women living with HIV are at higher risk for human papillomavirus (HPV)-related dysplasia and cancers and thus are prioritized for HPV vaccination. We measured HPV vaccine uptake among women engaged in HIV care in Ontario, Canada, and identified socio-demographic, behavioural, and clinical characteristics associated with HPV vaccination. During annual interviews from 2017 to 2020, women participating in a multi-site, clinical HIV cohort responded to a cross-sectional survey on HPV vaccine knowledge and receipt. We used logistic regression to derive age-adjusted odds ratios and 95% confidence intervals (CI) for factors associated with self-reported vaccine initiation (≥1 dose) or series completion (3 doses). Among 591 women (median age = 48 years; interquartile range = 40-56 years), 13.2% (95%CI = 10.5-15.9%) had received ≥1 dose. Of those vaccinated, 64.6% had received 3 doses. Vaccine initiation (≥1 dose) was significantly higher among women aged 20-29 years at 31.0% but fell to 13.9% in those aged 30-49 years and < 10% in those aged ≥50 years. After age adjustment, vaccine initiation was significantly associated with being employed (vs. unemployed but seeking work), income $40,000-$59,999 (vs. <$20,000), being married/common-law (vs. single), living with children, immigrating to Canada >5 years ago (vs. immigrating ≤5 years ago), never smoking (vs. currently smoking), and being in HIV care longer (per 10 years). Similar factors were identified for series completion (3 doses). HPV vaccine uptake remains low among women living with HIV in our cohort despite regular engagement in care. Recommendations for improving uptake include education of healthcare providers, targeted community outreach, and public funding of HPV vaccination.

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.

Influenza Vaccine Effectiveness by A(H3N2) Phylogenetic Subcluster and Prior Vaccination History: 2016-2017 and 2017-2018 Epidemics in Canada.

BACKGROUND: The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015-2016 to 3C.2a for 2016-2017 and 2017-2018. Circulating 3C.2a viruses showed considerable hemagglutinin glycoprotein diversification and the egg-adapted vaccine also bore mutations. METHODS: Vaccine effectiveness (VE) in 2016-2017 and 2017-2018 was assessed by test-negative design, explored by A(H3N2) phylogenetic subcluster and prior season's vaccination history. RESULTS: In 2016-2017, A(H3N2) VE was 36% (95% confidence interval [CI], 18%-50%), comparable with (43%; 95% CI, 24%-58%) or without (33%; 95% CI, -21% to 62%) prior season's vaccination. In 2017-2018, VE was 14% (95% CI, -8% to 31%), lower with (9%; 95% CI, -18% to 30%) versus without (45%; 95% CI, -7% to 71%) prior season's vaccination. In 2016-2017, VE against predominant clade 3C.2a1 viruses was 33% (95% CI, 11%-50%): 18% (95% CI, -40% to 52%) for 3C.2a1a defined by a pivotal T135K loss of glycosylation; 60% (95% CI, 19%-81%) for 3C.2a1b (without T135K); and 31% (95% CI, 2%-51%) for other 3C.2a1 variants (with/without T135K). VE against 3C.2a2 viruses was 45% (95% CI, 2%-70%) in 2016-2017 but 15% (95% CI, -7% to 33%) in 2017-2018 when 3C.2a2 predominated. VE against 3C.2a1b in 2017-2018 was 37% (95% CI, -57% to 75%), lower at 12% (95% CI, -129% to 67%) for a new 3C.2a1b subcluster (n = 28) also bearing T135K. CONCLUSIONS: Exploring VE by phylogenetic subcluster and prior vaccination history reveals informative heterogeneity. Pivotal mutations affecting glycosylation sites, and repeat vaccination using unchanged antigen, may reduce VE.

Anal Human Papillomavirus Prevalence Among Vaccinated and Unvaccinated Gay, Bisexual, and Other Men Who Have Sex With Men in Canada.

BACKGROUND: Starting in 2015, human papillomavirus (HPV) vaccine has been publicly funded for gay, bisexual, and other men who have sex with men (GBM) 26 years or younger in Canada. METHODS: Self-identified GBM who reported having sex with another man within the past 6 months were enrolled using respondent-driven sampling (RDS) between February 2017 and August 2019 in Montreal, Toronto, and Vancouver, Canada. Men aged 16 to 30 years self-collected anal specimens for HPV-DNA testing. Prevalence was estimated using RDS-II weights. We compared the prevalence of quadrivalent (HPV-6/11/16/18) and 9-valent (HPV-6/11/16/18/31/33/45/52/58) vaccine types between GBM who self-reported HPV vaccination (≥1 dose) and those reporting no vaccination using a modified Poisson regression for binary outcomes. RESULTS: Among 645 GBM who provided a valid anal specimen (median age, 26 years; 5.9% HIV positive), 40.3% reported receiving ≥1 dose of HPV vaccine, of whom 61.8% received 3 doses. One-quarter were infected with ≥1 quadrivalent type (crude, 25.7%; RDS weighted, 24.4%). After adjustment for potential confounders, vaccinated GBM had a 27% lower anal prevalence of quadrivalent types compared with unvaccinated GBM (adjusted prevalence ratio [aPR], 0.73; 95% confidence interval [CI], 0.54-1.00). Lower prevalence ratios were found among vaccinated participants who were vaccinated >2 years before enrollment (aPR, 0.47; 95% CI, 0.25-0.86) or received their first vaccine dose at age ≤23 years (aPR, 0.64; 95% CI, 0.42-0.99). Point estimates were similar for ≥2 or 3 doses and 9-valent types. CONCLUSIONS: Human papillomavirus vaccination was associated with a lower anal prevalence of vaccine-preventable HPV types among young, sexually active GBM. Findings will help inform shared decision making around HPV vaccination for GBM and their healthcare providers.

Using observational epidemiology to evaluate COVID-19 vaccines: integrating traditional methods with new data sources and tools.

Although clinical trials are necessary for vaccine approval, observational epidemiology will be required to evaluate the long-term effectiveness, safety, and population impacts of newly approved COVID-19 vaccines under real-world field conditions. In this commentary, I argue that a hybrid approach that combines new data sources and tools, including COVID-19 vaccine registries, with traditional epidemiological methods will be needed to evaluate COVID-19 vaccines using observational epidemiology. Wherever possible, primary data collection, active surveillance, and linkage with existing population-based cohorts should be leveraged to supplement secondary data sources and passive surveillance systems. Evidence-informed public health decision making around provincial COVID-19 immunization programs will need to account for potential biases, incomplete or conflicting information, and heterogeneity across subpopulations.

RéSUMé: Des essais cliniques sont nécessaires à l'approbation des vaccins, mais il faudra recourir à l'épidémiologie d'observation pour évaluer en conditions réelles de terrain l'efficacité à long terme, l'innocuité et les effets sur les populations des vaccins contre la COVID-19 nouvellement approuvés. Dans ce commentaire, je fais valoir qu'il faudra adopter une démarche hybride combinant de nouvelles sources de données et de nouveaux outils, dont les registres de vaccins anti-COVID-19, et des méthodes épidémiologiques classiques pour évaluer les vaccins anti-COVID-19 à l'aide de l'épidémiologie d'observation. Dans la mesure du possible, il faudra utiliser la collecte de données primaires, la surveillance active et les maillages avec les cohortes populationnelles existantes pour compléter les sources de données secondaires et les systèmes de surveillance passive. Les décisions de santé publique éclairées par les données probantes sur les programmes d'immunisation provinciaux contre la COVID-19 devront tenir compte des biais possibles, des informations incomplètes ou contradictoires et de l'hétérogénéité des sous-populations.

Influenza Vaccine Does Not Increase the Risk of Coronavirus or Other Noninfluenza Respiratory Viruses: Retrospective Analysis From Canada, 2010-2011 to 2016-2017.

Influenza vaccine effectiveness against influenza and noninfluenza respiratory viruses (NIRVs) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network, spanning 2010-2011 to 2016-2017. Vaccine significantly reduced the risk of influenza illness by >40% with no effect on coronaviruses or other NIRV risk.

Influenza Classification Suite: An automated Galaxy workflow for rapid influenza sequence analysis.

Influenza viruses continually evolve to evade population immunity, and the different lineages are assigned into clades based on shared mutations. We have developed a publicly available computational workflow, the Influenza Classification Suite, for rapid clade mapping of sequenced influenza viruses. This suite provides a user-friendly workflow implemented in Galaxy to automate clade calling and antigenic site extraction. Workflow input includes clade definition and amino acid index array files, which can be customized to identify any clades of interest. The Influenza Classification Suite provides rapid, high-resolution understanding of circulating influenza strain evolution to inform influenza vaccine effectiveness and the need for potential vaccine reformulation.

Vaccine Effectiveness Against Lineage-matched and -mismatched Influenza B Viruses Across 8 Seasons in Canada, 2010-2011 to 2017-2018.

Vaccine effectiveness (VE) against influenza B was derived separately for Victoria and Yamagata lineages across 8 seasons (2010-2011 to 2017-2018) in Canada when trivalent influenza vaccine was predominantly used. VE was ≥50% regardless of lineage match to circulating viruses, except when the vaccine strain was unchanged from the prior season.

Should Sex Be Considered an Effect Modifier in the Evaluation of Influenza Vaccine Effectiveness?

We investigated sex as a potential modifier of influenza vaccine effectiveness (VE) between 2010-2011 and 2016-2017 in Canada. Overall VE was 49% (95% confidence interval [CI], 43% to 55%) for females and 38% (95% CI, 28% to 46%) for males (absolute difference [AD], 11%; P = .03). Sex differences were greatest for influenza A(H3N2) (AD, 17%; P = .07) and B(Victoria) (AD, 20%; P = .08) compared with A(H1N1)pdm09 (AD, 10%; P = .19) or B(Yamagata) (AD, -3%; P = .68). They were also more pronounced in older adults ≥50 years (AD, 19%; P = .03) compared with those <20 years (AD, 4%; P = .74) or 20-49 years (AD, -1%; P = .90) but with variation by subtype/lineage. More definitive investigations of VE by sex and age are warranted to elucidate these potential interactions.

Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness, Canada, January 2018.

Using a test-negative design, we assessed interim vaccine effectiveness (VE) for the 2017/18 epidemic of co-circulating influenza A(H3N2) and B(Yamagata) viruses. Adjusted VE for influenza A(H3N2), driven by a predominant subgroup of clade 3C.2a viruses with T131K + R142K + R261Q substitutions, was low at 17% (95% confidence interval (CI): -14 to 40). Adjusted VE for influenza B was higher at 55% (95% CI: 38 to 68) despite prominent use of trivalent vaccine containing lineage-mismatched influenza B(Victoria) antigen, suggesting cross-lineage protection.