2023/24 mid-season influenza and Omicron XBB.1.5 vaccine effectiveness estimates from the Canadian Sentinel Practitioner Surveillance Network (SPSN).

The Canadian Sentinel Practitioner Surveillance Network reports mid-season 2023/24 influenza vaccine effectiveness (VE) of 63% (95% CI: 51-72) against influenza A(H1N1)pdm09, lower for clade 5a.2a.1 (56%; 95% CI: 33-71) than clade 5a.2a (67%; 95% CI: 48-80), and lowest against influenza A(H3N2) (40%; 95% CI: 5-61). The Omicron XBB.1.5 vaccine protected comparably well, with VE of 47% (95% CI: 21-65) against medically attended COVID-19, higher among people reporting a prior confirmed SARS-CoV-2 infection at 67% (95% CI: 28-85).

Pediatric RSV-Associated Hospitalizations Before and During the COVID-19 Pandemic.

Importance: Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations. Objective: To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included. Main Outcomes and Measures: The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons. Results: Among 11 014 RSV-associated hospitalizations in children and adolescents (6035 hospitalizations among male patients [54.8%]; 5488 hospitalizations among patients aged <6 months [49.8%]), 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2% (95% CI, 3.1%-3.3%) before the pandemic to 4.5% (95% CI, 4.3%-4.6%) in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces (difference range, 2.5 percentage points; 95% CI, 1.4-3.6 percentage points for Quebec to 2.9 percentage points; 95% CI, 1.4-3.5 percentage points for Alberta; all corrected P < .001). Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May. Conclusions and Relevance: This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children.

National influenza mid-season report, 2022-2023: A rapid and early epidemic onset.

Canada's 2022-2023 national influenza epidemic was declared in epidemiological week 43 (week ending October 29, 2022), relatively early in comparison to historical seasons. This year marks the return to pre-pandemic-like influenza circulation, following the brief and delayed influenza epidemic declared in the spring of the 2021-2022 season. To date this season, 59,459 detections of influenza have been reported out of 456,536 tests; both values exceeding historical averages. This epidemic is being fundamentally driven by influenza A, with influenza A(H3N2) accounting for 94% of subtyped detections. This season to date has had a significant impact on adolescents and young children, with a high proportion of detections occurring in those aged 0-19 years (42%). Provinces and territories have reported higher than usual influenza-associated hospitalizations, intensive care unit admissions, and deaths in comparison with previous seasons; in particular, paediatric hospitalization incidence was persistently far above historical peak levels for several weeks. The return of seasonal influenza circulation highlights the importance of sustained vigilance with regard to influenza and employment of available mitigation measures, especially of annual seasonal influenza vaccination.

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.

National Influenza Annual Report, Canada, 2022-2023: Canada's first fall epidemic since the 2019-2020 season.

Coinciding with the beginning of the coronavirus disease 2019 (COVID-19) pandemic in March 2020, Canadian seasonal influenza circulation was suppressed, which was a trend reported globally. Canada saw a brief and delayed return of community influenza circulation during the spring of the 2021-2022 influenza season. Surveillance for Canada's 2022-2023 seasonal influenza epidemic began in epidemiological week 35 (week starting August 28, 2022) and ended in epidemiological week 34 (week ending August 26, 2023). The 2022-2023 season marked the return to pre-pandemic-like influenza circulation. The epidemic began in epidemiological week 43 (week ending October 29, 2022) and lasted 10 weeks. Driven by influenza A(H3N2), the epidemic was relatively early, extraordinary in intensity, and short in length. This season, a total of 74,344 laboratory-confirmed influenza detections were reported out of 1,188,962 total laboratory tests. A total of 93% of detections were influenza A (n=68,923). Influenza A(H3N2) accounted for 89% of the subtyped specimens (n=17,638/19,876). Late-season, Canada saw community circulation of influenza B for the first time since the 2019-2020 season. The 2022-2023 influenza season in Canada had an extraordinary impact on children and youth; nearly half (n=6,194/13,729, 45%) of reported influenza A(H3N2) detections were in the paediatric (younger than 19 years) population. Weekly paediatric influenza-associated hospital admissions were persistently above historical peak levels for several weeks. The total number of influenza-associated paediatric hospitalizations (n=1,792) far exceeded historical averages (n=1,091). With the return of seasonal influenza circulation and endemic co-circulation of multiple high burden respiratory viruses, sustained vigilance is warranted. Annual seasonal influenza vaccination is a key public health intervention available to protect Canadians.

Salivary testing for SARS-CoV-2 in the pediatric population: a diagnostic accuracy study.

BACKGROUND: Accurate and timely testing for SARS-CoV-2 in the pediatric population is crucial to control the COVID-19 pandemic; saliva testing has been proposed as a less invasive alternative to nasopharyngeal swabs. We sought to compare the detection of SARS-CoV-2 using saliva versus nasopharyngeal swab in the pediatric population, and to determine the optimum time of testing for SARS-CoV-2 using saliva. METHODS: We conducted a longitudinal diagnostic study in Ottawa, Canada, from Jan. 19 to Mar. 26, 2021. Children aged 3-17 years were eligible if they exhibited symptoms of COVID-19, had been identified as a high-risk or close contact to someone confirmed positive for SARS-CoV-2 or had travelled outside Canada in the previous 14 days. Participants provided both nasopharyngeal swab and saliva samples. Saliva was collected using a self-collection kit (DNA Genotek, OM-505) or a sponge-based kit (DNA Genotek, ORE-100) if they could not provide a saliva sample into a tube. RESULTS: Among 1580 paired nasopharyngeal and saliva tests, 60 paired samples were positive for SARS-CoV-2. Forty-four (73.3%) were concordant-positive results and 16 (26.6%) were discordant, among which 8 were positive only on nasopharyngeal swab and 8 were positive only on saliva testing. The sensitivity of saliva was 84.6% (95% confidence interval 71.9%-93.1%). INTERPRETATION: Salivary testing for SARS-CoV-2 in the pediatric population is less invasive and shows similar detection of SARS-CoV-2 to nasopharyngeal swabs. It may therefore provide a feasible alternative for diagnosis of SARS-CoV-2 infection in children.

Performance of an RNA-Based Next-Generation Sequencing Assay for Combined Detection of Clinically Actionable Fusions and Hotspot Mutations in NSCLC.

INTRODUCTION: With its expanding list of approved and emerging therapeutic indications, NSCLC is the exemplar tumor type requiring upfront assessment of several biomarkers to guide clinical management. Next-generation sequencing allows identification of different types of molecular alterations, each with specific analytical challenges. Library preparation using parallel DNA and RNA workflows can overcome most of them, but it increases complexity of laboratory operations, turnaround time, and costs. We describe the performance characteristics of a 15-gene RNA panel on the basis of anchored multiplex polymerase chain reaction for combined detection of clinically relevant oncogenic fusion transcripts and hotspot small variants. METHODS: Formalin-fixed, paraffin-embedded NSCLC clinical samples (N = 58) were used along cell lines and commercial controls to validate the assay's analytical performance, followed by an exploratory prospective cohort (N = 87). RESULTS: The raw assay sensitivity for hotspot mutations and fusions was 83% and 93%, respectively, reaching 100% after filtering for key assay metrics. Those include quantity and quality of input of nucleic acid and sequencing metric from primers on housekeeping genes included in the assay. In the prospective cohort, driver alterations were identified in most cases (≥58%). CONCLUSIONS: This ultrafocused RNA-next-generation sequencing assay offers an advantageous option with single unified workflow for simultaneous detection of clinically relevant hotspot mutations and fusions in NSCLC, focusing on actionable gene targets.

National FluWatch mid-season report, 2021-2022: Sporadic influenza activity returns.

Surveillance for Canada's 2021-2022 seasonal influenza epidemic began in epidemiological week 35 (the week starting August 29, 2021) during the ongoing coronavirus disease 2019 (COVID-19) global public health emergency. In the 2021-2022 surveillance season to date, there has been a return of persistent sporadic influenza activity, and the first influenza-associated hospitalizations since mid-2020 have been reported. However, as of week 52 (week ending 01/01/2022) activity has remained sporadic, and no influenza-confirmed outbreaks or epidemic activity have been detected. There has been a delay or absence in several traditional seasonal influenza milestones, including the declared start of the influenza season, marked by a threshold of 5% positivity, which historically has occurred on average in week 47. The 429 sporadic detections reported in Canada to date have occurred in 31 regions across seven provinces/territories. Nearly half (n=155/335, 46.3%) of reported cases have been in the paediatric (younger than 19 years) population. Three-quarters of the cases were influenza A detections (n=323/429, 75.3%). Of the subtyped influenza A detections, A(H3N2) predominated (n=83/86, 96.5%). Of the 12 viruses characterized by the National Microbiology Laboratory, 11 were seasonal strains. Among the seasonal strains characterized, only one was antigenically similar to the strains recommended for the 2021-2022 Northern Hemisphere vaccine, though all were sensitive to the antivirals, oseltamivir and zanamivir. Until very recently, seasonal influenza epidemics had not been reported since March 2020. Evidence on the re-emergence of seasonal influenza strains in Canada following the A(H1N1)pdm09 pandemic shows that influenza A(H3N2) and B epidemics ceased through the 2009-2010 season and second wave of A(H1N1)pdm09, but then re-emerged in subsequent seasons to predominate causing epidemics of higher intensity than in the pre-pandemic seasons. When and where seasonal influenza epidemic activity resumes cannot be predicted, but model-based estimates and historical post-pandemic patterns of intensified epidemics warrant continued vigilance through the usual season and for out-of-season re-emergence. In addition, ongoing population preparedness measures, such as annual influenza vaccination to mitigate the intensity and burden of future seasonal influenza epidemic waves, should continue.

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.

National Influenza Annual Report, Canada, 2021-2022: A brief, late influenza epidemic.

Canadian seasonal influenza circulation had been suppressed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This suppression was reported globally and generated concern that the return of community influenza circulation could be intense and that co-circulation of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was possible and potentially severe. Community circulation of influenza returned to Canada during the 2021-2022 influenza season. The influenza epidemic began in week 16 (mid-April 2022) and lasted only nine weeks. This epidemic was driven by influenza A(H3N2) and was exceptionally late in the season, low in intensity and short in length. Community co-circulation of influenza and SARS-CoV-2 was observed in Canada for the first time during the 2021-2022 seasonal influenza epidemic. The unusual characteristics of the 2021-2022 influenza epidemic suggest that a breadth of factors moderate transmission dynamics of the two viruses. Concerns of an intense seasonal influenza epidemic did not come to fruition during the 2021-2022 season; therefore, high influenza susceptibility remains, as does predisposition to larger influenza epidemics. Ongoing circulation of SARS-CoV-2 creates uncertainty about dynamics of future influenza epidemics, but influenza vaccination remains a key public health intervention available to protect Canadians. Public health authorities need to remain vigilant, maintain surveillance and continue to plan for both heightened seasonal influenza circulation and for the potential for endemic co-circulation of influenza and SARS-CoV-2.

Characterization of Swine Influenza A(H1N2) Variant, Alberta, Canada, 2020.

Influenza strains circulating among swine populations can cause outbreaks in humans. In October 2020, we detected a variant influenza A subtype H1N2 of swine origin in a person in Alberta, Canada. We initiated a public health, veterinary, and laboratory investigation to identify the source of the infection and determine whether it had spread. We identified the probable source as a local pig farm where a household contact of the index patient worked. Phylogenetic analysis revealed that the isolate closely resembled strains found at that farm in 2017. Retrospective and prospective surveillance using molecular testing did not identify any secondary cases among 1,532 persons tested in the surrounding area. Quick collaboration between human and veterinary public health practitioners in this case enabled a rapid response to a potential outbreak.

Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples.

BACKGROUND: Reverse-transcription polymerase chain reaction (RT-PCR) has become the primary method to diagnose viral diseases, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RT-PCR detects RNA, not infectious virus; thus, its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT), and infectivity in cell culture. METHODS: In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR-confirmed positive samples and determined their ability to infect Vero cell lines. RESULTS: Ninety RT-PCR SARS-CoV-2-positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median tissue culture infectious dose/mL was 1780 (interquartile range, 282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT, and Ct demonstrated an odds ratio (OR) for positive viral culture of 0.64 (95% confidence interval [CI], .49-.84; P < .001) for every 1-unit increase in Ct. Area under the receiver operating characteristic curve for Ct vs positive culture was OR, 0.91 (95% CI, .85-.97; P < .001), with 97% specificity obtained at a Ct of > 24. CONCLUSIONS: SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct < 24 and STT < 8 days. Infectivity of patients with Ct > 24 and duration of symptoms > 8 days may be low. This information can inform public health policy and guide clinical, infection control, and occupational health decisions. Further studies of larger size are needed.

Real-time PCR-based SARS-CoV-2 detection in Canadian laboratories.

With emergence of pandemic COVID-19, rapid and accurate diagnostic testing is essential. This study compared laboratory-developed tests (LDTs) used for the detection of SARS-CoV-2 in Canadian hospital and public health laboratories, and some commercially available real-time RT-PCR assays. Overall, analytical sensitivities were equivalent between LDTs and most commercially available methods.

Interim estimates of 2019/20 vaccine effectiveness during early-season co-circulation of influenza A and B viruses, Canada, February 2020.

Interim results from Canada's Sentinel Practitioner Surveillance Network show that during a season characterised by early co-circulation of influenza A and B viruses, the 2019/20 influenza vaccine has provided substantial protection against medically-attended influenza illness. Adjusted VE overall was 58% (95% confidence interval (CI): 47 to 66): 44% (95% CI: 26 to 58) for A(H1N1)pdm09, 62% (95% CI: 37 to 77) for A(H3N2) and 69% (95% CI: 57 to 77) for influenza B viruses, predominantly B/Victoria lineage.

National Influenza Mid-Season Report, 2019-2020.

Canada's national influenza season started in week 47 between November 17 to 23, 2019. Of the 3,762 laboratory-confirmed influenza detections reported from August 25 to December 14, 2019, 61% were influenza A, and of those subtyped, 68% were A(H3N2). Influenza B detections are above average for this time of year. Indicators of influenza activity are within the expected range for this time of year. The majority of hospitalizations reported by provinces and territories have been associated with influenza A(H3N2) (76%), and the greatest proportion have been among adults 65 years and older (40%). Among sentinel pediatric influenza hospitalizations, 55% were associated with influenza B and the majority have been under five years of age (63%). Antigenic and genetic characterization results to date suggest that the majority of circulating A(H3N2) and B viruses are not similar to the virus components recommended for use in the 2019-2020 seasonal influenza vaccines and that the majority of circulating A(H1N1) viruses are similar to the vaccine reference strains.

In Vitro Inactivation of SARS-CoV-2 Using Gamma Radiation.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is classified as a Risk Group 3 pathogen; propagative work with this live virus should be conducted in biosafety level-3 (BSL-3) laboratories. However, inactivated virus can be safely handled in BSL-2 laboratories. Gamma irradiation is one of the methods used to inactivate a variety of pathogens including viruses. Objective: To determine the radiation dose required to inactivate SARS-CoV-2 and its effect, if any, on subsequent polymerase chain reaction (PCR) assay. Methods: Aliquots of SARS-CoV-2 virus culture were subjected to increasing doses of gamma radiation to determine the proper dose required to inactivate the virus. Real-time quantitative polymerase chain reaction (RT-qPCR) data from irradiated samples was compared with that of the non-irradiated samples to assess the effect of gamma radiation on PCR assay. Results: A radiation dose of 1 Mrad was required to completely inactivate 106.5 TCID50/ml of SARS-CoV-2. The influence of gamma radiation on PCR sensitivity was inversely related and dose-dependent up to 0.5 Mrad with no further reduction thereafter. Conclusion: Gamma irradiation can be used as a reliable method to inactivate SARS-CoV-2 with minimal effect on subsequent PCR assay.

Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV).

IntroductionThe Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.AimTo explain a paradoxical signal of increased clade 3C.3a risk among 35-54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.MethodsWe assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.ResultsInfluenza A(H3N2) VE was 17% (95% CI: -13 to 39) overall: 27% (95% CI: -7 to 50) for 3C.2a1b and -32% (95% CI: -119 to 21) for 3C.3a. Among 20-64-year-olds, VE was -7% (95% CI: -56 to 26): 6% (95% CI: -49 to 41) for 3C.2a1b and -96% (95% CI: -277 to -2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35-54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.DiscussionImprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.

Impact of Specimen Characteristics on PD-L1 Testing in Non-Small Cell Lung Cancer: Validation of the IASLC PD-L1 Testing Recommendations.

INTRODUCTION: Molecules targeting programmed cell death 1 or its ligand programmed death ligand 1 (PD-L1) revolutionized the treatment of patients with NSCLC. The only approved biomarker for predicting treatment response is the PD-L1 tumor proportion score (TPS) determined by immunohistochemistry. According to International Association for the Study of Lung Cancer recommendations, specimens that include fewer than 100 tumor cells or are older than 3 years should not be used for PD-L1 testing and the reliability of cell blocks has yet to be validated. METHODS: This retrospective study included 1249 consecutive patients with NSCLC who were tested for PD-L1 (using the clone 22C3) between September 2016 and April 2017. The associations between the presence of suboptimal characteristics (specimens with <100 tumor cells, specimens older than 3 years, or cell blocks) and PD-L1 TPS were examined by using a multinomial logistic regression. RESULTS: Specimens from 35.5% of the patients had at least one suboptimal characteristic. For patients with a PD-L1 TPS of higher than 50%, there was a significantly higher probability that they had a specimen with more than 100 tumor cells (OR = 1.97, p = 0.008) and a more recent block (within 30 days versus after >3 years) (OR = 2.46, p = 0.023). There was no statistical difference in PD-L1 TPS between cell blocks and tissue specimens (biopsy OR = 0.99 [p = 0.996] and surgery OR = 0.73 [p = 0.302]). CONCLUSIONS: Our results suggest that specimens containing fewer than 100 tumor cells or older than 3 years may lead to an underestimation of PD-L1 status. Our findings also provide support for the use of cell blocks for PD-L1 testing, although further research is needed.

Children under 10 years of age were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic in Canada: possible cohort effect following the 2009 influenza pandemic.

IntroductionFindings from the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) suggest children were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic.AimTo compare the age distribution of A(H1N1)pdm09 cases in 2018/19 to prior seasonal influenza epidemics in Canada.MethodsThe age distribution of unvaccinated influenza A(H1N1)pdm09 cases and test-negative controls were compared across A(H1N1)pdm09-dominant epidemics in 2018/19, 2015/16 and 2013/14 and with the general population of SPSN provinces. Similar comparisons were undertaken for influenza A(H3N2)-dominant epidemics.ResultsIn 2018/19, more influenza A(H1N1)pdm09 cases were under 10 years old than controls (29% vs 16%; p < 0.001). In particular, children aged 5-9 years comprised 14% of cases, greater than their contribution to controls (4%) or the general population (5%) and at least twice their contribution in 2015/16 (7%; p < 0.001) or 2013/14 (5%; p < 0.001). Conversely, children aged 10-19 years (11% of the population) were under-represented among A(H1N1)pdm09 cases versus controls in 2018/19 (7% vs 12%; p < 0.001), 2015/16 (7% vs 13%; p < 0.001) and 2013/14 (9% vs 12%; p = 0.12).ConclusionChildren under 10 years old contributed more to outpatient A(H1N1)pdm09 medical visits in 2018/19 than prior seasonal epidemics in Canada. In 2018/19, all children under 10 years old were born after the 2009 A(H1N1)pdm09 pandemic and therefore lacked pandemic-induced immunity. In addition, more than half those born after 2009 now attend school (i.e. 5-9-year-olds), a socio-behavioural context that may enhance transmission and did not apply during prior A(H1N1)pdm09 epidemics.