Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Maternal varicella antibodies in children aged less than one year: Assessment of antibody decay.

OBJECTIVES: To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. STUDY DESIGN: In this study, we included specimens from infants <12 months of age, born at ≥37 weeks gestational age, who had sera collected at The Hospital for Sick Children (Toronto, Canada) between 2014-2016. We tested sera using a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). We measured varicella susceptibility (antibody concentration <150mIU/mL) and mean varicella antibody concentration, and assessed the probability of susceptibility and concentration between one and 11 months of age using multivariable logistic regression and Poisson regression. RESULTS: We found that 32% of 196 included specimens represented infants susceptible to varicella at one month of age, increasing to nearly 80% at three months of age. At six months of age, all infants were susceptible to varicella and the predicted mean varicella antibody concentration declined to 62 mIU/mL (95% confidence interval 40, 84), well below the threshold of protection. CONCLUSIONS: We found that varicella maternal antibody levels wane rapidly in infants, leaving most infants susceptible by four months of age. Our findings have implications for the timing of first dose of varicella-containing vaccine, infection control measures, and infant post-exposure prophylaxis recommendations.

Effectiveness of maternal influenza vaccination during pregnancy against laboratory-confirmed seasonal influenza among infants under 6 months of age in Ontario, Canada.

BACKGROUND: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. METHODS: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010-2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. RESULTS: Among 23,806 infants tested for influenza, 1,783 (7.5%) were positive and 1,708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI]: 50%-74%). VE was similar by trimester of vaccination (1st/2nd: 66%, 40%-80%; 3rd: 63%, 46%-74%), infant age at testing (0-<2 months: 63%, 46%-75%; 2-<6 months: 64%, 36%-79%), and gestational age at birth (≥37 weeks: 64%, 50%-75%; < 37 weeks: 61%, 4%-86%). VE against influenza hospitalization was 67% (95%CI: 50%-78%). CONCLUSIONS: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.

Association Between Cycle Threshold Value and Vaccination Status Among Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Cases in Ontario, Canada, in December 2021.

Background: Increased immune evasion by emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and occurrence of breakthrough infections raise questions about whether coronavirus disease 2019 vaccination status affects SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the onset of the Omicron wave onset in Ontario, Canada. Methods: Using linked provincial databases, we compared median Ct values across vaccination status among polymerase chain reaction-confirmed Omicron variant SARS-CoV-2 cases (sublineages B.1.1.529, BA.1, and BA.1.1) between 6 and 30 December 2021. Cases were presumed to be Omicron based on S-gene target failure. We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex, and symptom status. Results: Of the 27 029 presumed Omicron cases in Ontario, the majority were in individuals who had received a complete vaccine series (87.7%), followed by unvaccinated individuals (8.1%), and those who had received a booster dose (4.2%). The median Ct value for post-booster dose individuals (18.3 [interquartile range, 15.4-22.3]) was significantly higher than that for unvaccinated (17.9 [15.2-21.6]; P = .02) and post-vaccine series individuals (17.8 [15.3-21.5]; P = .005). Post-booster dose cases remained associated with a significantly higher median Ct value than cases in unvaccinated individuals (P ≤ .001), after adjustment for covariates. Compared with values in persons aged 18-29 years, Ct values were significantly lower among most age groups >50 years. Conclusions: While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared with post-booster dose cases, further research is required to determine whether a significant difference in secondary transmission exists between these groups.

Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes.

We estimated the effectiveness of booster doses of monovalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults in Ontario, Canada. We used a test-negative design to estimate vaccine effectiveness (VE) against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years from January 2 to October 1, 2022, stratified by age and time since vaccination. We also compared VE during BA.1/BA.2 and BA.4/BA.5 sublineage predominance. We included 11,160 cases and 62,880 tests for test-negative controls. Depending on the age group, compared to unvaccinated adults, VE was 91-98% 7-59 days after a third dose, waned to 76-87% after ≥240 days, was restored to 92-97% 7-59 days after a fourth dose, and waned to 86-89% after ≥120 days. VE was lower and declined faster during BA.4/BA.5 versus BA.1/BA.2 predominance, particularly after ≥120 days. Here we show that booster doses of monovalent mRNA COVID-19 vaccines restored strong protection against severe outcomes for at least 3 months after vaccination. Across the entire study period, protection declined slightly over time, but waned more during BA.4/BA.5 predominance.

Geographic clustering of travel-acquired infections in Ontario, Canada, 2008-2020.

As the frequency of international travel increases, more individuals are at risk of travel-acquired infections (TAIs). In this ecological study of over 170,000 unique tests from Public Health Ontario's laboratory, we reviewed all laboratory-reported cases of malaria, dengue, chikungunya, and enteric fever in Ontario, Canada between 2008-2020 to identify high-resolution geographical clusters for potential targeted pre-travel prevention. Smoothed standardized incidence ratios (SIRs) and 95% posterior credible intervals (CIs) were estimated using a spatial Bayesian hierarchical model. High- and low-incidence areas were described using data from the 2016 Census based on the home forward sortation area of patients testing positive. A second model was used to estimate the association between drivetime to the nearest travel clinic and incidence of TAI within high-incidence areas. There were 6,114 microbiologically confirmed TAIs across Ontario over the study period. There was spatial clustering of TAIs (Moran's I = 0.59, p<0.0001). Compared to low-incidence areas, high-incidence areas had higher proportions of immigrants (p<0.0001), were lower income (p = 0.0027), had higher levels of university education (p<0.0001), and less knowledge of English/French languages (p<0.0001). In the high-incidence Greater Toronto Area (GTA), each minute increase in drive time to the closest travel clinic was associated with a 3% reduction in TAI incidence (95% CI 1-6%). While urban neighbourhoods in the GTA had the highest burden of TAIs, geographic proximity to a travel clinic in the GTA was not associated with an area-level incidence reduction in TAI. This suggests other barriers to seeking and adhering to pre-travel advice.

Genotyping SARS-CoV-2 Variants Using Ratiometric Nucleic Acid Barcode Panels.

Designing diagnostic assays to genotype rapidly mutating viruses remains a challenge despite the overall improvements in nucleic acid detection technologies. RT-PCR and next-generation sequencing are unsuitable for genotyping during outbreaks or in point-of-care detection due to their infrastructure requirements and longer turnaround times. We developed a quantum dot barcode multiplexing system to genotype mutated viruses. We designed multiple quantum dot barcodes to target conserved, wildtype, and mutated regions of SARS-CoV-2. We calculated ratios of the signal output from different barcodes that enabled SARS-CoV-2 detection and identified SARS-CoV-2 variant strains from a sample. We detected different sequence types, including conserved genes, nucleotide deletions, and single nucleotide substitutions. Our system detected SARS-CoV-2 patient specimens with 98% sensitivity and 94% specificity across 91 patient samples. Further, we leveraged our barcoding and ratio system to track the emergence of the N501Y SARS-CoV-2 mutation from December 2020 to May 2021 and demonstrated that the more transmissible N501Y mutation started to dominate infections by April 2021. Our barcoding and signal ratio approach can genotype viruses and track the emergence of viral mutations in a single diagnostic test. This technology can be extended to tracking other viruses. Combined with smartphone detection technologies, this assay can be adapted for point-of-care tracking of viral mutations in real time.

Evaluating the Impact of Statin Use on Influenza Vaccine Effectiveness and Influenza Infection in Older Adults.

BACKGROUND: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. METHODS: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. RESULTS: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for ß-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated ß-blocker users. CONCLUSIONS: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves.

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics. In this study, we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data. The impact of the choice of tree-priors, informative epidemiological priors, and evolutionary parameters on the transmission potential estimation is evaluated. North American Influenza A(H1N1)pdm09 hemagglutinin (HA) gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number (R 0 ). Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models. Path-sampling marginal likelihood estimation is conducted to assess model fit. A bibliographic search to gather surveillance-based R 0 values were consistently lower (mean ≤ 1.2) when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness (mean ≥ 1.3 to ≤2.88 days). The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates. While there was no certain impact of clock rate and tree height on the R 0 estimation, an opposite relationship was observed between coalescent and birth-death tree priors. There was no significant difference (p = 0.46) between the birth-death model and surveillance R 0 estimates. This study concludes that tree-prior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters. The study also reports a consensus between the sequence-based R 0 estimation and surveillance-based R 0 estimates. Altogether, these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.

Maternal mRNA covid-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study.

OBJECTIVE: To estimate the effectiveness of maternal mRNA covid-19 vaccination during pregnancy against delta and omicron severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and hospital admission in infants. DESIGN: Test negative design study. SETTING: Community and hospital testing in Ontario, Canada. PARTICIPANTS: Infants younger than six months of age, born between 7 May 2021 and 31 March 2022, who were tested for SARS-CoV-2 between 7 May 2021 and 5 September 2022. INTERVENTION: Maternal mRNA covid-19 vaccination during pregnancy. MAIN OUTCOME MEASURES: Laboratory confirmed delta or omicron infection or hospital admission of the infant. Multivariable logistic regression estimated vaccine effectiveness, with adjustments for clinical and sociodemographic characteristics associated with vaccination and infection. RESULTS: 8809 infants met eligibility criteria, including 99 delta cases (4365 controls) and 1501 omicron cases (4847 controls). Infant vaccine effectiveness from two maternal doses was 95% (95% confidence interval 88% to 98%) against delta infection and 97% (73% to 100%) against infant hospital admission due to delta and 45% (37% to 53%) against omicron infection and 53% (39% to 64%) against hospital admission due to omicron. Vaccine effectiveness for three doses was 73% (61% to 80%) against omicron infection and 80% (64% to 89%) against hospital admission due to omicron. Vaccine effectiveness for two doses against infant omicron infection was highest with the second dose in the third trimester (53% (42% to 62%)) compared with the first (47% (31% to 59%)) or second (37% (24% to 47%)) trimesters. Vaccine effectiveness for two doses against infant omicron infection decreased from 57% (44% to 66%) between birth and eight weeks to 40% (21% to 54%) after 16 weeks of age. CONCLUSIONS: Maternal covid-19 vaccination with a second dose during pregnancy was highly effective against delta and moderately effective against omicron infection and hospital admission in infants during the first six months of life. A third vaccine dose bolstered protection against omicron. Effectiveness for two doses was highest with maternal vaccination in the third trimester, and effectiveness decreased in infants beyond eight weeks of age.

Vaccine effectiveness estimates from an early-season influenza A(H3N2) epidemic, including unique genetic diversity with reassortment, Canada, 2022/23.

The Canadian Sentinel Practitioner Surveillance Network estimated vaccine effectiveness (VE) during the unusually early 2022/23 influenza A(H3N2) epidemic. Like vaccine, circulating viruses were clade 3C.2a1b.2a.2, but with genetic diversity affecting haemagglutinin positions 135 and 156, and reassortment such that H156 viruses acquired neuraminidase from clade 3C.2a1b.1a. Vaccine provided substantial protection with A(H3N2) VE of 54% (95% CI: 38 to 66) overall. VE was similar against H156 and vaccine-like S156 viruses, but with potential variation based on diversity at position 135.

Three on Three: Universal and High-Affinity Molecular Recognition of the Symmetric Homotrimeric Spike Protein of SARS-CoV-2 with a Symmetric Homotrimeric Aptamer.

Our previously discovered monomeric aptamer for SARS-CoV-2 (MSA52) possesses a universal affinity for COVID-19 spike protein variants but is ultimately limited by its ability to bind only one subunit of the spike protein. The symmetrical shape of the homotrimeric SARS-CoV-2 spike protein presents the opportunity to create a matching homotrimeric molecular recognition element that is perfectly complementary to its structural scaffold, causing enhanced binding affinity. Here, we describe a branched homotrimeric aptamer with three-fold rotational symmetry, named TMSA52, that not only possesses excellent binding affinity but is also capable of binding several SARS-CoV-2 spike protein variants with picomolar affinity, as well as pseudotyped lentiviruses expressing SARS-CoV-2 spike protein variants with femtomolar affinity. Using Pd-Ir nanocubes as nanozymes in an enzyme-linked aptamer binding assay (ELABA), TMSA52 was capable of sensitively detecting diverse pseudotyped lentiviruses in pooled human saliva with a limit of detection as low as 6.3 × 103 copies/mL. The ELABA was also used to test 50 SARS-CoV-2-positive and 60 SARS-CoV-2-negative patient saliva samples, providing sensitivity and specificity values of 84.0 and 98.3%, respectively, thus highlighting the potential of TMSA52 for the development of future rapid tests.

Monkeypox Virus Detection in Different Clinical Specimen Types.

A global monkeypox outbreak began in May 2022. Limited data exist on specimen type performance in associated molecular diagnostics. Consequently, a diverse range of specimen sources were collected in the initial weeks of the outbreak in Ontario, Canada. Our clinical evaluation identified skin lesions as the optimal diagnostic specimen source.

A Prolonged Outbreak of Human Adenovirus A31 (HAdV-A31) Infection on a Pediatric Hematopoietic Stem Cell Transplantation Ward with Whole Genome Sequencing Evidence of International Linkages.

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.

Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes.

Importance: The incidence of SARS-CoV-2 infection, including among individuals who have received 2 doses of COVID-19 vaccine, increased substantially following the emergence of the Omicron variant in Ontario, Canada. Understanding the estimated effectiveness of 2 or 3 doses of COVID-19 vaccine against outcomes associated with Omicron and Delta infections may aid decision-making at the individual and population levels. Objective: To estimate vaccine effectiveness (VE) against symptomatic infections due to the Omicron and Delta variants and severe outcomes (hospitalization or death) associated with these infections. Design, Setting, and Participants: This test-negative case-control study used linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination, and health administration in Ontario, Canada. Participants were individuals aged 18 years or older who had COVID-19 symptoms or severe outcomes (hospitalization or death) and were tested for SARS-CoV-2 between December 6 and 26, 2021. Exposures: Receipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose. Main Outcomes and Measures: The main outcomes were symptomatic Omicron or Delta infection and severe outcomes (hospitalization or death) associated with infection. Multivariable logistic regression was used to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose compared with no vaccination. Estimated VE was calculated using the formula VE = (1 - [adjusted odds ratio]) × 100%. Results: Of 134 435 total participants, 16 087 were Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), 4261 were Delta-positive cases (mean [SD] age, 44.2 [16.8] years; 2199 [51.6%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 67 884 [59.5%] female). Estimated VE against symptomatic Delta infection decreased from 89% (95% CI, 86%-92%) 7 to 59 days after a second dose to 80% (95% CI, 74%-84%) after 240 or more days but increased to 97% (95% CI, 96%-98%) 7 or more days after a third dose. Estimated VE against symptomatic Omicron infection was 36% (95% CI, 24%-45%) 7 to 59 days after a second dose and 1% (95% CI, -8% to 10%) after 180 days or longer, but 7 or more days after a third dose, it increased to 61% (95% CI, 56%-65%). Estimated VE against severe outcomes was high 7 or more days after a third dose for both Delta (99%; 95% CI, 98%-99%) and Omicron (95%; 95% CI, 87%-98%). Conclusions and Relevance: In this study, in contrast to high estimated VE against symptomatic Delta infection and severe outcomes after 2 doses of COVID-19 vaccine, estimated VE was modest and short term against symptomatic Omicron infection but better maintained against severe outcomes. A third dose was associated with improved estimated VE against symptomatic infection and with high estimated VE against severe outcomes for both variants. Preventing infection due to Omicron and potential future variants may require tools beyond the currently available vaccines.

Effectiveness of COVID-19 Vaccines Over Time Prior to Omicron Emergence in Ontario, Canada: Test-Negative Design Study.

Background: Waning protection from 2 doses of coronavirus disease 2019 (COVID-19) vaccines led to third dose availability in multiple countries even before the emergence of the Omicron variant. Methods: We used the test-negative study design to estimate vaccine effectiveness (VE) against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, any symptomatic infection, and severe outcomes (COVID-19-related hospitalizations or death) by time since second dose of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between January 11, and November 21, 2021, for subgroups based on patient and vaccine characteristics. Results: We included 261 360 test-positive cases (of any SARS-CoV-2 lineage) and 2 783 699 individuals as test-negative controls. VE of 2 mRNA vaccine doses decreased from 90% (95% CI, 90%-90%) 7-59 days after the second dose to 75% (95% CI, 72%-78%) after ≥240 days against infection, decreased from 94% (95% CI, 84%-95%) to 87% (95% CI, 85%-89%) against symptomatic infection, and remained stable (98% [95% CI, 97%-98%] to 98% [95% CI, 96%-99%]) against severe outcomes. Similar trends were seen with heterologous ChAdOx1 and mRNA vaccine schedules. VE estimates for dosing intervals <35 days were lower than for longer intervals (eg, VE of 2 mRNA vaccines against symptomatic infection at 120-179 days was 86% [95% CI, 85%-88%] for dosing intervals <35 days, 92% [95% CI, 91%-93%] for 35-55 days, and 91% [95% CI, 90%-92%] for ≥56 days), but when stratified by age group and subperiod, there were no differences between dosing intervals. Conclusions: Before the emergence of Omicron, VE of any 2-dose primary series, including heterologous schedules and varying dosing intervals, decreased over time against any infection and symptomatic infection but remained high against severe outcomes.

Influenza vaccine effectiveness against A(H3N2) during the delayed 2021/22 epidemic in Canada.

Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95% CI: -38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization's decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.