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Depuis le 22 janvier 2020, la « maladie causée par un nouveau coronavirus » est devenue une maladie à déclaration obligatoire d’importance pour la santé publique en Ontario. Les bureaux de santé publique ont reçu des directives sur la saisie des patients testés pour le coronavirus responsable du syndrome respiratoire aigu sévère (SRAS-CoV-2), le virus causant la maladie à coronavirus 2019 (COVID-19), dans le système provincial d’information sur la santé publique. Entre le 22 janvier et le 22 février 2020, 359 personnes ont reçu un résultat négatif de test et trois cas de COVID-19 ont été confirmés. Parmi les personnes dont le résultat était négatif, 51 % étaient des femmes et 71 % avaient moins de 50 ans. Les symptômes les plus fréquemment signalés étaient la toux (55 %), la fièvre (37 %) et le mal de gorge (35 %). La majorité des personnes ont été testées dans les trois jours suivant l’apparition des symptômes, mais plus d’un quart d’entre elles l’ont été plus de sept jours après. Durant le premier mois de déclaration, les antécédents de voyage déclarés ont passé de la Chine à une proportion croissante de voyages ailleurs qu’en Chine.

Setting Syndemics occur when two or more health conditions interact to increase morbidity and mortality and are exacerbated by social, economic, environmental, and political factors. Routine provincial surveillance in Ontario assesses and reports on the epidemiology of single infectious diseases separately. Therefore, we aimed to develop a method that allows disease overlaps to be examined routinely as a path to better understanding and addressing syndemics in Ontario. Intervention We extracted data for individuals with a record of chlamydia, gonorrhea, infectious syphilis, hepatitis B and C, HIV/AIDS, invasive group A streptococcal disease (iGAS), or tuberculosis in Ontario’s reportable disease database from 1990 to 2018. We transformed the data into a person-based integrated surveillance dataset retaining individuals (clients) with at least one record between 2006 and 2018. Outcomes The resulting dataset had 659,136 unique disease records among 470,673 unique clients. Of those clients, 23.1% had multiple disease records with 50 being the most for one client. We described the frequency of disease overlaps; for example, 34.7% of clients with a syphilis record had a gonorrhea record. We quantified known overlaps, finding 1274 clients had gonorrhea, infectious syphilis, and HIV/AIDS records, and potentially emerging overlaps, finding 59 clients had HIV/AIDS, hepatitis C, and iGAS records. Implications Our novel person-based integrated surveillance dataset represents a platform for ongoing in-depth assessment of disease overlaps such as the relative timing of disease records. It enables a more client-focused approach, is a step towards improved characterization of syndemics in Ontario, and could inform other jurisdictions interested in adopting similar approaches.

BackgroundThe incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, increased substantially following the emergence of Omicron in Ontario, Canada.MethodsApplying the test-negative study design to linked provincial databases, we estimated vaccine effectiveness (VE) against symptomatic infection and severe outcomes (hospitalization or death) caused by Omicron or Delta between December 6 and 26, 2021. We used multivariable logistic regression to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose, compared to unvaccinated individuals.ResultsWe included 16,087 Omicron-positive cases, 4,261 Delta-positive cases, and 114,087 test-negative controls. VE against symptomatic Delta infection declined from 89% (95%CI, 86-92%) 7-59 days after a second dose to 80% (95%CI, 74-84%) after ≥240 days, but increased to 97% (95%CI, 96-98%) ≥7 days after a third dose. VE against symptomatic Omicron infection was only 36% (95%CI, 24-45%) 7-59 days after a second dose and provided no protection after ≥180 days, but increased to 61% (95%CI, 56-65%) ≥7 days after a third dose. VE against severe outcomes was very high following a third dose for both Delta and Omicron (99% [95%CI, 98-99%] and 95% [95%CI, 87-98%], respectively).ConclusionsIn contrast to high levels of protection against both symptomatic infection and severe outcomes caused by Delta, our results suggest that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for both variants.

Background Pregnant women are recommended to receive coronavirus disease 2019 (COVID-19) vaccines; however, relative effectiveness of vaccination by pregnancy status is unclear. Methods We compared the relative effectiveness of messenger RNA (mRNA) COVID-19 vaccines according to whether women received both doses while pregnant (n = 7412), 1 dose while pregnant (n = 3538), both doses while postpartum (n = 1856), or both doses while neither pregnant nor postpartum (n = 6687). We estimated risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection starting 14 days after the second dose using Cox regression, reporting hazard ratios (HRs) and 95% confidence intervals (CIs). Second, we examined relative effectiveness of a third (booster) dose while pregnant compared to outside pregnancy. The major circulating variant during the study period was the Delta variant. Results Fifty-four percent of women received 2 doses of the BNT162b2 vaccine, 16% received 2 doses of the mRNA-1273 vaccine, while 30% received 1 dose of both vaccines. Compared to women who received both doses while neither pregnant nor postpartum, the adjusted HR for a positive SARS-CoV-2 polymerase chain reaction test was similar if the woman received both doses while pregnant (1.04 [95% CI, .94–1.17]), 1 dose while pregnant and 1 dose before or after pregnancy (1.03 [95% CI, .93–1.14]), or both doses while postpartum (0.99 [95% CI, .92–1.07]). The findings were similar for BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax), and during Delta- and Omicron-dominant periods. We observed no differences in the relative effectiveness of the booster dose according to pregnancy status. Conclusions We observed similar effectiveness of mRNA vaccines against SARS-CoV-2 infection among women regardless of pregnancy status at the time of vaccination.

While it is now evident that Omicron is rapidly replacing Delta, largely due to immune escape, it is less clear how the severity of Omicron compares to Delta. In Ontario, we sought to examine hospitalization and death associated with Omicron, as compared to cases infected with Delta. We conducted a matched cohort study, considering time to hospitalization or death as the outcome. Cases were matched on gender, age, vaccination status, health region and onset date. We identified 29,594 Omicron cases that met eligibility criteria, of which 11,622 could be matched with at least one Delta case (N=14,181). There were 59 (0.51%) hospitalizations and 3 (0.03%) deaths among matched Omicron cases, compared to 221 (1.6%) hospitalizations and 17 (0.12%) deaths among matched Delta cases. The risk of hospitalization or death was 65% lower (hazard ratio, HR=0.35, 95%CI: 0.26, 0.46) among Omicron cases compared to Delta cases, while risk of intensive care unit admission or death was 83% lower (HR=0.17, 95%CI: 0.08, 0.37). While severity is likely to be reduced, the absolute number of hospitalizations and impact on the healthcare system may nevertheless be significant due to the increased transmissibility of Omicron.

Background Serosurveys for SARS-CoV-2 aim to estimate the proportion of the population that has been infected. Aim This observational study assesses the seroprevalence of SARS-CoV-2 antibodies in Ontario, Canada during the first pandemic wave. Methods Using an orthogonal approach, we tested 8,902 residual specimens from the Public Health Ontario laboratory over three time periods during March–June 2020 and stratified results by age group, sex and region. We adjusted for antibody test sensitivity/specificity and compared with reported PCR-confirmed COVID-19 cases. Results Adjusted seroprevalence was 0.5% (95% confidence interval (CI): 0.1–1.5) from 27 March–30 April, 1.5% (95% CI: 0.7–2.2) from 26–31 May, and 1.1% (95% CI: 0.8–1.3) from 5–30 June 2020. Adjusted estimates were highest in individuals aged ≥ 60 years in March–April (1.3%; 95% CI: 0.2–4.6), in those aged 20–59 years in May (2.1%; 95% CI: 0.8–3.4) and in those aged ≥ 60 years in June (1.6%; 95% CI: 1.1–2.1). Regional seroprevalence varied, and was highest for Toronto in March–April (0.9%; 95% CI: 0.1–3.1), for Toronto in May (3.2%; 95% CI: 1.0–5.3) and for Toronto (1.5%; 95% CI: 0.9–2.1) and Central East in June (1.5%; 95% CI: 1.0–2.0). We estimate that COVID-19 cases detected by PCR in Ontario underestimated SARS-CoV-2 infections by a factor of 4.9. Conclusions Our results indicate low population seroprevalence in Ontario, suggesting that public health measures were effective at limiting the spread of SARS-CoV-2 during the first pandemic wave.

ImportanceIncreased rates of myocarditis/pericarditis following COVID-19 mRNA vaccines have been observed. However, little data are available related to product-specific differences, which have important programmatic impacts.ObjectiveThe objective of this study was to estimate reporting rates of myocarditis/pericarditis following COVID-19 mRNA vaccine by product, age, sex, and dose number, as well inter-dose interval.DesignWe conducted a population-based cohort study using passive vaccine safety surveillance data. All individuals in Ontario, Canada who received at least one dose of COVID-19 mRNA vaccine between December 14, 2020 and September 4, 2021 were included.SettingThis study was conducted in Ontario, Canada (population: 14.7 million) using the provincial COVID-19 vaccine registry and provincial adverse events following immunization database.ParticipantsWe included all individuals with a reported episode of myocarditis/pericarditis following COVID-19 vaccine in the study period. We obtained information on all doses administered in the province to calculate reporting rates.ExposureReceipt of COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).Main Outcome(s) and Measure(s)Reported rate of myocarditis/pericarditis meeting level 1-3 of the Brighton Collaboration case definitions.ResultsThere were 19,740,741 doses of mRNA vaccines administered and 297 reports of myocarditis/pericarditis meeting our inclusion criteria. Among these, 69.7% occurred following the second dose of COVID-19 mRNA vaccine and 76.8% occurred in males. The median age of individuals with a reported event was 24 years. The highest reporting rate of myocarditis/pericarditis was observed in males aged 18-24 years following mRNA-1273 as the second dose; the rate in this age group was 5.1 (95% CI 1.9-15.5) times higher than the rate following BNT162b2 as the second dose. Overall reporting rates were higher when the inter-dose interval was shorter (i.e., ≤30 days) for both vaccine products. Among individuals who received mRNA-1273 for the second dose, rates were higher for those who had a heterologous as opposed to homologous vaccine schedule.Conclusions and RelevanceOur results suggest that vaccine product, inter-dose interval and vaccine schedule combinations may play a role in the risk of myocarditis/pericarditis, in addition to age and sex. Certain programmatic strategies could reduce the risk of myocarditis/pericarditis following mRNA vaccines.

Epidemic curves are used by decision makers and the public to infer the trajectory of the COVID-19 pandemic and to understand the appropriateness of current response measures. Symptom onset date is commonly used to date cases on the epidemic curve in public health reports and dashboards. However, third-party trackers often plot cases on the epidemic curve by the date they were publicly reported by the public health authority. These two curves create very different impressions of epidemic progression. On April 1, the epidemic curve for Ontario, Canada based on public reporting date showed an accelerating epidemic, whereas the curve based on a proxy variable for symptom onset date showed a rapidly declining epidemic. This illusory downward trend (the "ghost trend") is a feature of epidemic curves anchored using date variables earlier in time than the date a case was publicly reported, such as symptom onset date or sample collection date. This is because newly discovered cases are backdated, creating a perpetual downward trend in incidence due to incomplete data in the most recent days. Public reporting date is not subject to backdating bias and can be used to visualize real-time epidemic curves meant to inform the public and policy makers.

We identify amino acid variants within dominant SARS-CoV-2 T-cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T-cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T-cell responsiveness was seen due to Q213K in the A*01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215, due to P13L, P13S and P13T in the B*27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17, and due to T362I and P365S in the A*03:01/A*11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T-cell lines unable to recognise variant epitopes have diverse T-cell receptor repertoires. These data demonstrate the potential for T-cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T-cell as well as humoral immunity., Graphical Abstract

SARS-CoV-2 variants of concern (VOC) are more transmissible and may have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax) and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC in Ontario, Canada, using a test-negative design study. We identified 682,071 symptomatic community-dwelling individuals who were tested for SARS-CoV-2, and 15,269 individuals with a COVID-19 hospitalization or death. Effectiveness against symptomatic infection ≥7 d after two doses was 89-92% against Alpha, 87% against Beta, 88% against Gamma, 82-89% against Beta/Gamma and 87-95% against Delta across vaccine products. The corresponding estimates ≥14 d after one dose were lower. Effectiveness estimates against hospitalization or death were similar to or higher than against symptomatic infection. Effectiveness against symptomatic infection was generally lower for older adults (≥60 years) than for younger adults (60 years) for most of the VOC-vaccine combinations. Our findings suggest that jurisdictions facing vaccine supply constraints may benefit from delaying the second dose in younger individuals to more rapidly achieve greater overall population protection; however, older adults would likely benefit most from minimizing the delay in receiving the second dose to achieve adequate protection against VOC.

Objective To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). Design Test negative design study. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. Interventions BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Main outcome measures Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. Results Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. Conclusions Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

This cohort study examines whether the implementation of differentially timed restrictions in a highly interconnected metropolitan area was associated with increased interregional travel.

ObjectiveTo assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy.DesignPopulation based retrospective cohort study.SettingOntario, Canada, 1 May to 31 December 2021.ParticipantsAll liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g.Main outcome measuresUsing Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (ResultsAmong 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy—42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinatedv6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7%v4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59%v0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1%v9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25%v0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy.ConclusionThe findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth.

ObjectivesThe objective of our study was to estimate the rate of workplace outbreak-associated cases of COVID-19 by industry in labour market participants aged 15-69 years who reported working the majority of hours outside the home in Ontario, Canada.MethodsWe conducted a population based cross-sectional study of COVID-19 workplace outbreaks and associated-cases reported in Ontario between April 1, 2020 and March 31, 2021. All outbreaks were manually classified into two digit North American Industry Classification System (NAICS) codes. We obtained denominator data from the Statistics Canada Labour Force Survey in order to estimate the incidence of outbreak-associated cases per 100,000,000 hours amongst individuals who reported the majority of hours were worked outside the home. We performed this analysis across industries and in three distinct time periods.ResultsOverall, 12% of cases were attributed to workplace outbreaks among working age adults across our study period. While incidence varied across the time periods, the five industries with the highest incidence rates across our study period were agriculture; healthcare and social assistance; food manufacturing; educational services; and, transportation and warehousing.ConclusionsCertain industries have consistently increased incidence of COVID-19 over the course of the pandemic. These results may assist in ongoing efforts to reduce transmission of COVID-19, by prioritizing resources, as well as industry-specific guidance, vaccination, and public health messaging.

Background SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We sought to estimate the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (AstraZeneca) vaccines against symptomatic SARS-CoV-2 infection and severe outcomes (COVID-19 hospitalization or death) caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs during December 2020 to May 2021. Methods We conducted a test-negative design study using linked population-wide vaccination, laboratory testing, and health administrative databases in Ontario, Canada. Findings Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination (≥14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination (≥7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Protection against symptomatic infection caused by Beta/Gamma was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Vaccine effectiveness against hospitalization or death caused by all VOCs was generally higher than for symptomatic infection after partial vaccination for all three vaccines. Interpretation Our findings suggest that even a single dose of these 3 vaccines provide substantial protection against these 4 VOCs, and 2 doses likely provide higher protection. Jurisdictions facing vaccine supply constraints might consider delaying second doses to more rapidly achieve greater overall population protection.

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta lineage (B.1.617.2) was implicated in the SARS-CoV-2 surge in India. We sought to describe the rapid expansion of the Delta lineage in Ontario, Canada (population 15 million) using mutation profile information and confirmatory whole genome sequencing.MethodsAll laboratory-confirmed SARS-CoV-2 cases reported to Public Health Ontario between April 1st and June 12th 2021, with cycle threshold values ≤35, were eligible for screening for the N501Y and the E484K mutations. We classified cases via mutation screening as: (1) N501Y-/E484K- (wild-type/Delta), (2) Alpha (N501Y+/E484K-), (3) Beta/Gamma (N501Y+/E484K+), or (4) N501Y-/E484K+ (predominantly B.1.525, and B.1.1.318).ResultsThe N501Y-/E484K- mutation profile went from having a 29% transmission deficit relative to Alpha (relative Re = 0.71, 95%CI: 0.64, 0.77) on April 1st to having a 50% transmission advantage on June 12th (relative Re = 1.50, 95%CI: 1.31, 1.71). Whole genome sequencing of N501Y-/E484K-cases (N=583) confirmed that the pattern of increasing relative reproduction number coincided with the replacement of wild-type with Delta variant (from 2.2% in early April, to 83% in late May).DiscussionDelta is rapidly overtaking other SARS-CoV-2 variants in Ontario, and has a substantial transmission advantage. An inflection in the proportion of cases missing the N501Y mutation from rapidly decreasing to rapidly increasing,3 may be an early warning signal for Delta lineage expansion.

Background Many countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries. Methods As members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18–50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010–11 through 2015–16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site. Results More than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39–58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination. Conclusions Though increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.

BackgroundThe emergence of SARS-CoV-2 variants associated with increased transmissibility are driving a 3rd global surge in COVID-19 incidence. There are currently few reliable estimates for the P.1 and B.1.351 lineages. We sought to compare the secondary attack rates of SARS-COV-2 mutations and variants in Canadas largest province of Ontario, using a previously validated household-based approach. MethodsWe identified individuals with confirmed SARS-CoV-2 infection in Ontarios provincial reportable disease surveillance system. Cases were grouped into households based on reported residential address. Index cases had the earliest of symptom onset in the household. Household secondary attack rate was defined as the percentage of household contacts identified as secondary cases within 1-14 days after the index case. ResultsWe identified 26,888 index household cases during the study period. Among these, 7,555 (28%) were wild-type, 17,058 (63%) were B.1.1.7, 1674 (6%) were B.1.351 or P.1, and 601 (2%) were non-VOC mutants (Table 1). The secondary attack rates, according to index case variant were as follows: 20.2% (wild-type), 25.1% (B.1.1.7), 27.2% (B.1.351 or P.1), and 23.3% (non-VOC mutants). In adjusted analyses, we found that B.1.1.7, B.1.351, and P.1 index cases had the highest transmissibility (presumptive B.1.1.7 ORadjusted=1.49, 95%CI 1.36, 1.64; presumptive B.1.351 or P.1 ORadjusted=1.60, 95%CI 1.37, 1.87). O_TBL View this table: org.highwire.dtl.DTLVardef@1f1a4e9org.highwire.dtl.DTLVardef@181f042org.highwire.dtl.DTLVardef@1c483fborg.highwire.dtl.DTLVardef@b4fba0org.highwire.dtl.DTLVardef@1f3d626_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONSecondary attack rates of persons infected with SARS-CoV-2, March 1 to April 17. C_TABLECAPTION C_TBL DiscussionSubstantially higher transmissibility associated with variants will make control of SARS-CoV-2 more difficult, reinforcing the urgent need to increase vaccination rates globally.

We compared secondary attack rates in households with B.1.1.7 variant of concern (VOC) versus non-VOC index cases in a matched cohort in Ontario, Canada. The secondary attack rate for VOC index cases was 1.31 times higher than non-VOC index cases. This increase was particularly accentuated for asymptomatic or presymptomatic index cases.

ObjectivesTo estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes.DesignWe applied a test-negative design study to linked laboratory, vaccination, and health administrative databases, and used multivariable logistic regression adjusting for demographic and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness (VE) against symptomatic infection and severe outcomes.SettingOntario, Canada between 14 December 2020 and 19 April 2021.ParticipantsCommunity-dwelling adults aged ≥16 years who had COVID-19 symptoms and were tested for SARS-CoV-2.InterventionsPfizer-BioNTech’s BNT162b2 or Moderna’s mRNA-1273 vaccine.Main outcome measuresLaboratory-confirmed SARS-CoV-2 by RT-PCR; hospitalization/death associated with SARS-CoV-2 infection.ResultsAmong 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received ≥1 vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. VE against symptomatic infection ≥14 days after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14–20 days after the first dose to 71% (95%CI, 63 to 78%) at 35–41 days. VE ≥7 days after 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, VE ≥14 days after 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14–20 days to 91% (95%CI, 73 to 97%) at ≥35 days, whereas VE ≥7 days after 2 doses was 98% (95%CI, 88 to 100%). For adults aged ≥70 years, VE estimates were lower for intervals shortly after receiving 1 dose, but were comparable to younger adults for all intervals after 28 days. After 2 doses, we observed high VE against E484K-positive variants.ConclusionsTwo doses of mRNA COVID-19 vaccines are highly effective against symptomatic infection and severe outcomes. Single-dose effectiveness is lower, particularly for older adults shortly after the first dose.

Supplemental Digital Content is available in the text, Objective: To analyze workplace outbreaks by industry sector in the first wave of the pandemic, and associated household cases. Methods: Number, size, and duration of outbreaks were described by sector, and outbreak cases were compared to sporadic cases in the same time frame. Address matching identified household cases with onset ≥2 days before, ≥2 days after, or within 1 day of the workplace outbreak case. Results: There were 199 outbreaks with 1245 cases, and 68% of outbreaks and 80% of cases belonged to (1) Manufacturing, (2) Agriculture, Forestry, Fishing, Hunting, (3) Transportation and Warehousing. There were 608 household cases associated with 339 (31%) outbreak cases, increasing the burden of illness by 56%. Conclusions: Workplace outbreaks primarily occurred in three sectors. Prevention measures should target industry sectors at risk to prevent spread in and out of the workplace.

PURPOSE Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer. PATIENTS AND METHODS We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time. RESULTS We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, –5% to 19%) for patients with hematologic malignancies ( P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer. CONCLUSION Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Background Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD. Methods We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010–11 to 2015–16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza. Results Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%–27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%–52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables. Conclusions During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies.

Background Linking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE. Methods We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies. Results We included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010–11 to 2015–16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27–44%) in 2010–11 and 5% (95%CI, –2, 11%) in 2014–15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies. Conclusions Routinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults.

ObjectivesTo estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant.DesignTest negative design.SettingLong term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022.ParticipantsAfter exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included.Main outcome measuresLaboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously.Results13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes.ConclusionsThe findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown.

Increased rates of myocarditis or pericarditis following receipt of COVID-19 mRNA vaccines have been observed. However, few available data are associated with differences in rates of myocarditis or pericarditis specific to vaccine products, which may have important implications for vaccination programs.To estimate rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccine by product, age, sex, dose number, and interdose interval.This population-based cohort study was conducted in Ontario, Canada (population: 14.7 million) from December 2020 to September 2021 and used data from Ontario's COVID-19 vaccine registry and passive vaccine-safety surveillance system. All individuals in Ontario, Canada, who received at least 1 dose of COVID-19 mRNA vaccine between December 14, 2020, and September 4, 2021, and had a reported episode of myocarditis or pericarditis following receipt of the COVID-19 vaccine during this period were included. We obtained information on all vaccine doses administered in the province to calculate reported rates of myocarditis or pericarditis.Receipt of a COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).All reports of myocarditis or pericarditis meeting levels 1 to 3 of the Brighton Collaboration case definitions were included. Rates and 95% CIs of reported cases of myocarditis or pericarditis per 1 000 000 mRNA vaccine doses administered were calculated by age, sex, dose number, vaccine product, and interdose interval.Among 19 740 741 doses of mRNA vaccines administered, there were 297 reports of myocarditis or pericarditis meeting the inclusion criteria; 228 (76.8%) occurred in male individuals, and the median age of individuals with a reported event was 24 years (range, 12-81 years). Of the reported cases, 207 (69.7%) occurred following the second dose of the COVID-19 mRNA vaccine. When restricted to individuals who received their second dose during the period of enhanced passive surveillance (on or after June 1, 2021), the highest rate of myocarditis or pericarditis was observed in male individuals aged 18 to 24 years following mRNA-1273 as the second dose (299.5 cases per 1 000 000 doses; 95% CI, 171.2-486.4 cases per 1 000 000 doses); the rate following BNT162b2 as the second dose was 59.2 cases per 1 000 000 doses (95% CI, 19.2-138.1 cases per 1 000 000 doses). Overall rates for both vaccine products were significantly higher when the interdose interval was 30 or fewer days (BNT162b2: 52.1 cases per 1 000 000 doses [95% CI, 31.8-80.5 cases per 1 000 000 doses]; mRNA-1273: 83.9 cases per 1 000 000 doses [95% CI, 47.0-138.4 cases per 1 000 000 doses]) compared with 56 or more days (BNT162b2: 9.6 cases per 1 000 000 doses [95% CI, 6.5-13.6 cases per 1 000 000 doses]; mRNA-1273: 16.2 cases per 1 000 000 doses [95% CI, 10.2-24.6 cases per 1 000 000 doses]).The findings of this population-based cohort study of Ontario adolescents and adults with myocarditis or pericarditis following mRNA COVID-19 vaccination suggest that vaccine products and interdose intervals, in addition to age and sex, may be associated with the risk of myocarditis or pericarditis after receipt of these vaccines. Vaccination program strategies, such as age-based product considerations and longer interdose intervals, may reduce the risk of myocarditis or pericarditis following receipt of mRNA vaccines.

BackgroundIn the fall of 2020, the government of Ontario, Canada adopted a 5-tier, regional framework of public health measures for the COVID-19 pandemic. During the second wave of COVID-19 in Ontario, the urban core of the Greater Toronto Area (Toronto and Peel) were the first regions in the province to enter the highest restriction tier (“lockdown”) on November 23, 2020, which closed restaurants to in-person dining and limited non-essential businesses, including shopping malls, to curbside pickup. The peripheral regions of the Greater Toronto Area (York, Durham, Halton) would not enter lockdown until later the following month. In this analysis, we examine whether the implementation of differentially timed restrictions in a highly interconnected metropolitan area led to increased interregional travel, potentially driving further transmission of SARS-CoV-2.MethodsWe used anonymized smartphone data to estimate the number of visits by residents of regions in the urban core to shopping malls and restaurants in peripheral regions in the week before compared to the week after the November 23 lockdown.ResultsResidents of Toronto and Peel took fewer trips to shopping malls and restaurants in the week following lockdown. This was entirely driven by reductions in visits within the locked down regions themselves, as there was a significant increase in trips to shopping malls in peripheral regions by these residents in the same period (Toronto: +40.7%, Peel: +65.5%). Visits to restaurants in peripheral regions also increased slightly (Toronto: +6.3%, Peel: +11.8%).DiscussionHeterogeneous restrictions may undermine lockdowns in the urban core as well as driving residents from zones of higher transmission to zones of lower transmission. These concerns are likely generalizable to other major metropolitan areas, which often comprise interconnected but administratively independent regions.

BackgroundAmong non-pharmaceutical interventions, individual movement restrictions have been among the most impactful methods for controlling COVID-19 case growth. While nighttime curfews to control COVID-19 case growth have been implemented in certain regions and cities, few studies have examined their impacts on mobility or COVID-19 incidence. In the second wave of COVID-19, Canada’s two largest and adjacent provinces implemented lockdown restrictions with (Quebec) and without (Ontario) a nighttime curfew, providing a natural experiment to study the association between curfews and mobility.MethodsThis study spanned from December 1, 2020 to January 23, 2021 and included the populations of Ontario (including Toronto) and Quebec (including Montreal). The intervention of interest was a nighttime curfew implemented across Quebec on January 9, 2021. Unadjusted and adjusted difference-in-differences models (DID) were used to measure the incremental impact of the curfew on nighttime mobility in Quebec as compared to Ontario.ResultsThe implementation of the curfew was associated with an immediate reduction in nighttime mobility. The adjusted DID analysis indicated that Quebec experienced a 31% relative reduction in nighttime mobility (95%CI: -36% to -25%) compared to Ontario, and that Montreal experienced a 39% relative reduction compared to Toronto (95%CI: -43, -34).DiscussionHowever, this natural experiment among two neighbouring provinces provides useful evidence that curfews lead to an immediate and substantial decrease nighttime mobility, particularly in these provinces’ largest urban areas hardest hit by COVID-19.

IMPORTANCEHigher secondary attack rates related to variant of concern (VOC) index cases have been reported, but have not been explored within households, which continue to be an important source of coronavirus disease 2019 (COVID-19) transmissionOBJECTIVETo compare secondary attack rates in households with VOC versus non-VOC index cases.DESIGNA retrospective cohort study of household index cases reported from February 7 – 27, 2021. A propensity-score matched cohort was derived to calculate adjusted estimates.SETTINGOntario, Canada.PARTICIPANTSA population-based cohort of all private households with index cases. We excluded cases in congregate settings, as well as households with one individual or with >1 case with the same earliest symptom onset date.EXPOSUREVOC status, defined as either individuals confirmed as B.1.1.7 using whole genome sequencing or those that screened positive for the N501Y mutation using real-time PCR.MAIN OUTCOME AND MEASUREHousehold secondary attack rate, defined as the number of household secondary cases that occurred 1-14 days after the index case divided by the total number of household secondary contacts.RESULTSWe included 1,259 index VOC and non-VOC cases in the propensity score-matched analysis. The secondary attack rate for VOC index cases in this matched cohort was 1.31 times higher than non-VOC index cases (RR=1.31, 95%CI 1.14-1.49), similar to the unadjusted estimate. In stratified analyses, the higher secondary attack rate for VOC compared to non-VOC index cases was accentuated for asymptomatic index cases (RR=1.91, 95% CI 0.96-3.80) and presymptomatic cases (RR=3.41, 95%CI 1.13-10.26)CONCLUSIONS AND RELEVANCEThis study provides strong evidence of increased transmissibility in households due to VOCs and suggests that asymptomatic and pre-symptomatic transmission may be of particular importance for VOCs. Our study suggests that more aggressive public health measures will be needed to control VOCs and that ongoing research is needed to understand mechanisms of VOC transmissibility to curb their associated morbidity and mortality.

BACKGROUNDAs a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic. This study sought to determine whether there are differences in the odds of household transmission for younger children compared to older children.METHODSWe assembled a cohort of all individuals in Ontario, Canada with laboratory-confirmed SARS-CoV-2 infection between June 1 and December 31, 2020. The cohort was restricted to individuals residing in private households (N=132,232 cases in 89,191 households), identified through an address matching algorithm. Analysis focused on households in which the index case was aged RESULTSA total of 6,280 households had pediatric index cases, and 1,717 (27.3%) experienced secondary transmission. Children aged 0-3 years had the highest odds of household transmission compared to children aged 14-17 years (model adjusted for gender, month of disease onset, testing delay, and average family size: 1.43, 95% CI: 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2-14 days or 4-14 days after the index case, and stratified analyses by presence of symptoms, association with a school/childcare outbreak, or school/childcare reopening. Children aged 4-8 years and 9-13 years also had increased odds of transmission (4-8: 1.40, 95% CI: 1.18-1.67; 9-13: 1.13, 95% CI: 0.97-1.32).CONCLUSIONSThis study suggests that younger children are more likely to transmit SARS-CoV-2 infection compared to older children, and the highest odds of transmission was observed for children aged 0-3 years. Differential infectivity of pediatric age groups has implications for infection prevention controls within households, as well as schools/childcare, to minimize risk of household secondary transmission.

Background. Nursing home (NH) residents have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic and are prioritized for vaccination. NH residents are generally at increased risk of poor outcomes due to advanced age, frailty, and complex health conditions. We report monthly incidence rates of deaths, hospitalizations, and emergency department (ED) visits during ten pre-pandemic years (2010-2019) and 2020 to provide context for assessments of COVID-19 vaccine safety in NH residents. Methods. We observed deaths, hospitalizations, and ED visits among all Ontarians living in NHs using health administrative databases. Monthly incidence rates were calculated by month, by sex, and by age group. Direct comparisons between months were assessed using one-sample t-tests; direct comparisons by age and sex were assessed using chi-squared tests. Results. From January 1, 2010 through December 31, 2019, there were, on average, 83,453 (SD: 652.4) Ontarians living in NHs in any given month, with an average of 2.3 (SD: 0.28) deaths, 3.1 (SD: 0.16) hospitalizations, and 3.6 (SD: 0.17) ED visits per 100 residents per month. Mortality rates were higher for men (p

BackgroundMinimizing delays in disease identification and reporting improves the timeliness of surveillance data, and can reduce transmission of COVID-19. Our study investigates factors associated with timely testing and reporting of COVID-19 during the first pandemic wave in one province of Canada.MethodsWe identified all persons with confirmed SARS-CoV-2 infection residing in private households across the largest province of Canada, Ontario from the date of the first confirmed case in Ontario (January 25) to July 19, 2020. Our primary outcomes consisted of: (1) specimen collection within 1 day of symptom onset (test seeking), (2) test result reported to local public health within 1 day of specimen collection (test turnaround), and (3) entry of case data into the provincial database within 1 day of reporting test results (reporting). We examined 14 covariates including eight case characteristics, and six neighborhood characteristics. In addition to descriptive measures, logistic regression models were fitted. Unadjusted models included the covariate alone, while adjusted models included age, gender, month, and region.FindingsAmong 27,198 COVID-19 cases from January 25 2020 to July 19 2020, 28·7% had timely test seeking, 40·2% had timely test turnaround, and 75·5% had timely reporting. Male gender had lower odds of timely test seeking (adjusted odds ratio [aOR] 0·79 [95% CI: 0·74-0·85]) compared to females. Healthcare worker status (aOR 2·77 [95% CI: 2·52-3·05] compared to non-healthcare workers), and age ≥80 years (aOR 1·59 [95% CI: 1·33-1·91] compared to 40-59 year olds) were associated with timely test seeking. Specimen collection on Fridays and Saturdays (aOR 0·88 [95% CI: 0·79-0·98], aOR 0·83 [95% CI: 0·74-0·92] respectively, compared to Wednesdays) had lower odds of timely test turnaround. Urban areas (aOR 1·55 [95% CI: 1·41-1·70] compared to rural areas) were associated with timely test turnaround. Urban areas (aOR 0·79 [95% CI: 0·70-0·89] compared to rural areas) were less likely to have timely reporting.InterpretationIndividual, neighborhood, and administrative factors are associated with timely testing and reporting of SARS-CoV-2 infections. These findings present considerations for developing targeted strategies to minimize delays and improve timely testing and reporting of SARS-CoV-2 infections.FundingThis study was funded by Public Health Ontario.Research in ContextEvidence before this studyWe searched PubMed and medRxiv up to November 30 2020 to identify studies examining the impact of delays in the disease reporting process on the public health response to COVID-19. We used the search terms (“2019-nCoV” OR “COVID-19” OR “SARS-CoV-2”) AND (“delays” OR “timely” OR “reporting” OR “test” OR “turnaround”), and reviewed reference lists of any relevant articles in the original search. Numerous modeling studies have highlighted the importance of timely testing and reporting to effectively control the spread of COVID-19. Additional studies have also identified delays of only 1 day in testing were associated with increased risk of secondary transmission within households. However no study has described the multiple delays in the disease reporting process of COVID-19 and examined factors associated with timely disease reporting using a large population cohort.Added value of this studyOur study described timely test seeking, test turnaround, and reporting for laboratory-confirmed COVID-19 cases in Ontario, Canada and identified associated individual, neighbourhood, and administrative factors. To the best of our knowledge, this study is the first to describe detailed delays in the disease reporting process of COVID-19 and identified associated factors using a large population cohort.Implications of all the available evidenceNumerous individual, neighborhood, and administrative characteristics are associated with timely testing and reporting of COVID-19. These identified factors may be used to develop strategies such as broadened test access, prioritization of vulnerable populations, and increased testing capacity to reduce delays in testing and reporting and improve the effectiveness of public health response to COVID-19.

A novel variant of SARS-CoV-2, B.1.1.7, originally discovered in the United Kingdom (UK), is rapidly overtaking other strains around the globe. In certain assays, absence of detection of the S-gene target, also known as S-gene target failure (SGTF) can be a sensitive surrogate of B.1.1.7. We analyzed daily counts of SGTF among samples from Dynacare Laboratory Ontario (which draws samples from the Greater Toronto Area) and resulted between December 16, 2020 and February 3, 2021. We identified 11,485 positive COVID-19 tests, of which 448 had SGTF (3.9%). The estimated prevalence of SGTF rose from 2.0% on December 16 to 15.2% on February 3 (1.8-fold weekly increase, 95%CI: 1.5, 2.2). The estimated reproduction number for SGTF cases was 1.17 (95%CI: 0.94 to 1.46), while the reproduction number for non-SGTF cases was 0.82 (95%CI: 0.65 to 1.01); the relative reproduction number was 1.44 (95%CI: 1.03, 1.99). 59 samples were sent for confirmatory testing, of which 53 (90%) were identified as B.1.1.7 using whole genome sequencing or found to have the N501Y mutation. In order to pre-emptively plan and implement public health measures to control COVID-19 now and through the spring, accurate and up-to-date early warning systems for new variants, including B.1.1.7, are essential across North America and the globe.

BackgroundNon-pharmaceutical interventions remain a primary means of suppressing COVID-19 until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures in seven Canadian provinces to quantify the mobility level needed to suppress COVID-19 (mobility threshold), and the difference relative to current mobility levels (mobility gap).MethodsWe conducted a longitudinal study of weekly COVID-19 incidence from March 15, 2020 to January 16, 2021, among provinces with 20 COVID-19 cases in at least 10 weeks. The outcome was weekly growth rate defined as the ratio of current cases compared to the previous week. We examined the effects of average time spent outside the home (non-residential mobility) in the prior three weeks using a lognormal regression model accounting for province, season, and mean temperature. We calculated the COVID-19 mobility threshold and gap.ResultsAcross the 44-week study period, a total of 704,294 persons were infected with COVID-19. Non-residential mobility dropped rapidly in the spring and reached a median of 36% (IQR: 31,40) in April 2020. After adjustment, each 5% increase in non-residential mobility was associated with a 9% increase in the COVID-19 weekly growth rate (ratio=1.09, 95%CI: 1.07,1.12). The mobility gap increased through the fall months, which was associated with increasing case growth.InterpretationMobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control COVID-19 through winter 2021. Mobility measures from anonymized smartphone data can be used to guide the provincial and regional implementation and loosening of physical distancing measures.

BackgroundRacialized and low income communities face disproportionally high rates of coronavirus 2019 (COVID-19) infection and death. However, data on inequities in COVID-19 across granular categories of socio-demographic characteristics is more sparse.MethodsNeighbourhood-level counts of COVID-19 cases and deaths in Ontario, Canada recorded as of July 28th, 2020 were extracted from provincial and local reportable infectious disease surveillance systems. Associations between COVID-19 incidence and mortality and 18 neighbourhood-level measures of immigration, race, housing and socio-economic characteristics were estimated with Poisson generalized linear mixed models. Housing characteristic variables were subsequently added to models to explore if housing may have a confounding influence on the relationships between immigration, race, and socio-economic status and COVID-19 incidence.ResultsThere were large inequities in COVID-19 incidence and mortality across the socio-demographic variables examined. Neighbourhoods having a higher proportion immigrants, racialized populations, large households and low socio-economic status were associated with COVID-19 risk. Adjusting for housing characteristics, especially unsuitably crowded housing, attenuated COVID-19 risks. However persistent risk remained for neighbourhoods having high proportions of immigrants, racialized populations, and proportion of Black, Latin American, and South Asian residents.ConclusionsSocio-demographic factors account for some of the neighbourhood-level differences in COVID-19 across Ontario. Housing characteristics account for a portion, but not all, of the excess burden of COVID-19 experienced by immigrant, racialized, low income and low education populations.

Older adults are at increased risk of herpes zoster (HZ) and post-herpetic neuralgia (PHN) and HZ vaccines are available to help prevent infection. The objective of our study was to provide updated data on incidence of HZ and PHN related to clinical and demographic factors in older adults to inform immunization practices. We conducted a population-based, retrospective cohort study and included all cases of HZ seen in outpatient, emergency department, and hospital settings for adults aged 65 years and over between April 1, 2002 to August 31, 2016 in Ontario, Canada. We calculated the incidence of HZ and PHN, and estimated the proportion within each subgroup that developed PHN. We also assessed incidence by neighbourhood-level income quintile before and after the availability of vaccine for private purchase. The average annual incidence of HZ in any setting was 59.0 per 10,000 older adults, with higher incidence in outpatient as opposed to hospital settings. Incidence was higher in the oldest age groups, females, and those classified as immunocompromised or frail. Relative to the pre-vaccine era, the disparities in incidence of HZ by neighbourhood-level income increased, with higher rates of HZ and PHN seen in those residing in lower income quintiles. Additional prevention efforts should be targeted toward adults who are immunocompromised, frail, and those living in lower socioeconomic quintiles. Future work should assess the impact of the zoster vaccine program with a particular focus on equity in the publicly-funded era.

Background: Co-infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We assess the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%), this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.

This paper examines the role of participatory codesign in the creation of parent, teacher, and administrator dashboards for a game-based adaptive instructional system designed to teach math to young children. Taking a learning engineering approach, our team of researchers, curriculum specialists, and UX designers engaged in an iterative design process with six primary school teachers and 4 school administrators with the goal of understanding the appropriateness and effectiveness of the dashboards for different role types. Using ongoing interviews and a participatory codesign workshop, we engaged with teachers and administrators over several months and worked with them to understand how the dashboards could serve and be used by role types at varying levels (parent, teacher, principal, administrator, superintendent). We found that the effectiveness and appropriateness of the dashboard stemmed from its ability to communicate information across systems, like allowing teachers to communicate with parents on how to help their child, allowing principals to check-in on teachers on student progress, and allowing superintendents to review school-wide learning goals with principals. In sum, the participatory codesign process was highly successful, leading to a rich understanding of how the dashboards can be better designed to connect information across systems to better serve different role types.

Background: We estimated the effectiveness of BNT162b2 and mRNA-1273 vaccines among residents of Ontario, Canada, where a policy to use an up to 16-week interval between doses was adopted in March 2021. Methods: We conducted a test-negative design study using linked province-wide laboratory, vaccination, and health administrative datasets. We included symptomatic individuals tested for SARS-CoV-2 by RT-PCR between 14 December 2020 and 19 April 2021. Study outcomes included symptomatic infection and associated severe outcomes (hospitalization or death). We estimated adjusted vaccine effectiveness (aVE) using multivariable logistic regression. Findings: Among 324,033 symptomatic tested individuals, 53,270 (16·4%) were positive for SARS-CoV-2 and 21,272 (6·6%) had received ≥1 dose of mRNA vaccine. Among test-positive cases, 2,479 (4·7%) had a severe outcome. aVE against symptomatic infection ≥14 days after receiving only 1 dose was 60% (95%CI, 57–64%), increasing from 48% (95%CI, 41–54%) at 14–20 days after the first dose to 71% (95%CI, 63–78%) at 35–41 days. aVE ≥7 days after receiving 2 doses was 91% (95%CI, 89–93%). Against severe outcomes, aVE ≥14 days after receiving 1 dose was 70% (95%CI, 60–77%) and aVE ≥7 days after receiving 2 doses was 98% (95%CI, 88–100%). We observed lower aVE against both outcomes after receiving 1 dose for adults aged ≥70 years, but aVE estimates for older adults were comparable to younger adults after 28 days. After 2 doses, we observed high aVE against E484K-positive variants. Interpretation: Our findings suggest that 2 doses of BNT162b2 and mRNA-1273 vaccines are highly effective against both symptomatic infection and associated severe outcomes for all circulating variants, with effectiveness lower after only a single dose, particularly for older adults shortly after the first dose. Funding Information: Canadian Institutes of Health Research, Public Health Agency of Canada, Ontario Ministries of Health and Long-Term Care. Declaration of Interests: KW is CEO of CANImmunize and serves on the data safety board for the Medicago COVID-19 vaccine trial. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer, and Roche-Assurex for unrelated studies. SMM has received fees as an advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. CHR has received an unrestricted research grant from Pfizer for an unrelated study. The other authors declare no conflicts of interest. Ethics Approval Statement: ICES is a prescribed entity under Ontario’s Personal Health Information Protection Act (PHIPA). Section 45 of PHIPA authorizes ICES to collect personal health information, without consent, for the purpose of analysis or compiling statistical information with respect to the management of, evaluation or monitoring of, the allocation of resources to or planning for all or part of the health system. Projects that use data collected by ICES under section 45 of PHIPA, and use no other data, are exempt from REB review. The use of the data in this project is authorized under section 45 and approved by ICES’ Privacy and Legal Office.

Background: Co-infections of SARS-CoV-2 with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We assess the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single respiratory virus infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other respiratory viruses may assist with patient management.

IntroductionWorkplaces requiring in-person attendance of employees for ongoing operations may be susceptible to SARS-CoV-2 outbreaks that impact workers as well as their close contacts. To understand industry sectors impacted by workplace outbreaks in the first wave of the pandemic, and the additional burden of illness through household transmission, we analyzed public health declared workplace outbreaks between January 21 to June 30, 2020, and their associated cases from January 21 to July 28.MethodsNumber, size and duration of outbreaks were described by sector, and outbreak cases were compared to sporadic cases in the same time frame. Address matching identified household cases with onset ≥2 days before, ≥2 days after, or within 1 day of the workplace outbreak case.ResultsThere were 199 outbreaks with 1245 cases, and 68% of outbreaks and 80% of cases belonged to i) Manufacturing, ii) Agriculture, Forestry, Fishing, Hunting, iii) Transportation and Warehousing. Median size of outbreaks was 3 cases (range: 1-140), and lasted median 7days (range: 0-119). Outbreak cases were significantly more likely to be male, younger, healthier, and have better outcomes. There were 608 household cases associated with 339 (31%) outbreak cases with valid addresses, increasing the burden of illness by 56%. The majority of household cases (368, 60%) occurred after the outbreak case.ConclusionsWorkplace outbreaks primarily occurred in three sectors. COVID-19 prevention measures should target industry sectors at risk by preventing introduction from exposed employees, spread in the workplace, and spread outside of the workplace.What is already known about this topic?COVID-19 outbreaks occur within workplaces and can spread to the communityWhat is added by this report?From January 21 – June 30, 2020, there were 199 workplace outbreaks in Ontario, Canada; 68% of outbreaks and 80% of outbreak-associated COVID-19 case were in three industry sectors: Manufacturing, Agriculture/Forestry/Fishing/Hunting, and Transportation/Warehousing. Household transmission occurred among 31% of outbreak cases, resulting in a 56% increase in workplace outbreak-associated cases when burden of household transmission is considered.What are the implications for public health practice?Workplace outbreak prevention measures should be targeted to industry sectors at risk by preventing introduction from exposed employees, spread in the workplace, and transmission to the greater community.

Introduction - Worldwide, nursing home residents have experienced disproportionately high COVID-19 mortality due to the intersection of congregate living, multimorbidity, and advanced age. Among 12 OECD countries, Canada has had the highest proportion of COVID-19 deaths in nursing home residents (78%), raising concerns about a skewed pandemic response that averted much transmission and mortality in community-dwelling residents, but did not adequately protect those in nursing homes. To investigate this, we measured temporal variations in hospitalizations among community and nursing home-dwelling decedents with COVID-19 during the first and second waves of the pandemic.Methods - We conducted a population-based cohort study of residents of Ontario, Canada with COVID-19 who died between March 11, 2020 (first COVID-19 death in Ontario) and October 28, 2020. We examined hospitalization prior to death as a function of 4 factors: community (defined as all non-nursing home residents) vs. nursing home residence, age in years (Results - A total of 3,114 people with confirmed COVID-19 died in Ontario from March to October, 2020 (Table 1), of whom 1,354 (43.5%) were hospitalized prior to death (median: 9 days before death, interquartile range: 4-19). Among nursing home decedents (N=2000), 22.4% were admitted to hospital prior to death, but this varied substantially from a low of 15.5% in March-April (peak of wave 1) to a high of 41.2% in June-July (nadir of wave 1). Among community-dwelling decedents (N=1,114), admission to acute care was higher (81.4%) and remained relatively stable throughout the first and second waves. Similar temporal trends for nursing home versus community decedents were apparent in age-stratified analyses (Figure 1). Women who died were less likely to have been hospitalized compared to men in both community (80% women vs 84% men) and nursing home (21% women vs 24% men) settings.Discussion - Only a minority of Ontario nursing home residents who died of COVID-19 were hospitalized prior to death, and that there were substantial temporal variations, with hospitalizations reaching their lowest point when overall COVID-19 incidence peaked in mid-April, 2020. While many nursing home residents had pre-pandemic advance directives precluding hospitalization, the low admission rate observed in March-April 2020 (15.5%) was inconsistent with both higher admission rates in subsequent months (>30%), and comparatively stable rates among community-dwelling adults. Our findings substantiate reports suggesting that hospitalizations for nursing home residents with COVID-19 were low during the peak of the pandemic’s first wave in Canada, which may have contributed to the particularly high concentration of COVID-19 mortality in Ontario’s nursing homes.

BACKGROUNDWithin-household transmission of SARS-CoV-2 infection has been identified as one of the main sources of spread of COVID-19 after lockdown restrictions and self-isolation guidelines are implemented. Secondary attack rates among household contacts are estimated to be five to ten times higher than among non-household contacts, but it is unclear which individuals are more prone to transmit infection within their households.METHODSUsing address matching, a cohort was assembled of all laboratory-confirmed cases of COVID-19 residing in private households in Ontario, Canada. Descriptive analyses were performed to compare characteristics of cases in households that experienced secondary transmission versus those that did not. Logistic regression models were fit to determine index case characteristics and neighbourhood characteristics associated with transmission.FINDINGSBetween January and July, 2020, there were 26,152 cases of COVID-19 residing in 21,226 households. Longer testing delays (≥5 days versus 0 days OR=3·02, 95% CI: 2·53 - 3·60) and male sex (OR=1·28, 95% CI: 1·18 - 1·38) were associated with greater odds of household secondary transmission, while being a healthcare worker (OR=0·56, 95% CI: 0·50 - 0·62) was associated with lower odds of transmission. Neighbourhoods with larger average economic family size and a higher proportion of households with multiple persons per room were also associated with greater odds of transmission.INTERPRETATIONIt is important for individuals to get tested for SARS-CoV-2 infection as soon as symptoms appear, and to isolate away from household contacts; this is particularly important in neighbourhoods with large family sizes and/or crowded households.FUNDINGThis study was supported by Public Health Ontario.Research in ContextEVIDENCE BEFORE THIS STUDYWe searched PubMed and Google Scholar up to September 3, 2020 to identify individual-level cohort studies or meta-analyses on household transmission of COVID-19. We used the search terms (“COVID” OR “SARS-CoV-2”) AND (“household” [Title]), and also reviewed the reference lists of any studies found during the search to identify additional studies. We considered studies that reported secondary attack rates and/or other measures of association (i.e., relative risk, odds ratio, or hazard ratio) for household transmission. We did not consider any modelling studies, studies that focused specifically on children, or small case studies that included less than three households. The search returned 53 studies, of which 51 were included in three meta-analyses. Pooled household secondary attack rates from the three meta-analyses were 19%, 27%, and 30%; secondary attack rates in households were estimated to be five to ten times as high as in non-household settings. Most studies were conducted in Asia and identified households from contact tracing, with individual studies reporting on fewer than 6000 households. Most studies did not consider households with no secondary transmission, and focused on a limited set of secondary case characteristics.ADDED VALUE OF THIS STUDYWe applied an address matching algorithm, which identified 21,226 private households of laboratory-confirmed cases of COVID-19 in Ontario, Canada. Ontario has the advantage of a universal healthcare system and population-wide data for the entire province. To our knowledge, this study contains the largest number of private households with at least one confirmed case of COVID-19. We compared a variety of individual- and neighbourhood-level characteristics of households with and without secondary transmission. We also applied logistic regression models to determine index case characteristics associated with transmission, which gave important insights into factors that may help reduce secondary transmission in households.IMPLICATIONS OF ALL THE AVAILABLE EVIDENCEFindings from this study and existing evidence suggest that testing delays and household crowding play important roles in whether household secondary transmission occurs. Odds of household transmission may be reduced by cases seeking testing as soon as symptoms appear, and self-isolating outside the home or in a room alone if possible. These strategies may be considered by public health officials to reduce household transmission and mitigate local spread of COVID-19. Future research should further investigate the role of children and youth in household transmission.

ImportanceProtecting healthcare workers (HCWs) from COVID-19 is a priority to maintain a safe and functioning healthcare system. The risk of transmitting COVID-19 to family members is a source of stress for many.ObjectiveTo describe and compare HCW and non-HCW COVID-19 cases in Ontario, Canada, as well as the frequency of COVID-19 among HCWs’ household members.Design, Setting, and ParticipantsUsing reportable disease data at Public Health Ontario which captures all COVID-19 cases in Ontario, Canada, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with COVID-19 as of 14 May 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address.Exposures and OutcomesWe contrasted age, gender, comorbidities, clinical presentation (including asymptomatic and presymptomatic), exposure histories including nosocomial transmission, and clinical outcomes between HCWs and non-HCWs with confirmed COVID-19.ResultsThere were 4,230 (17.5%) HCW COVID-19 cases in Ontario, of whom 20.2% were nurses, 2.3% were physicians, and the remaining 77.4% other specialties. HCWs were more likely to be between 30-60 years of age and female. HCWs were more likely to present asymptomatically (8.1% versus 7.0%, p=0.010) or with atypical symptoms (17.8% versus 10.5%, pConclusions and RelevanceHCWs represent a disproportionate number of COVID-19 cases in Ontario but with low confirmed numbers of nosocomial transmission. The data support substantial testing bias and under-ascertainment of general population cases. Protecting HCWs through appropriate personal protective equipment and physical distancing from colleagues is paramount.Key PointsQuestionWhat are the differences between healthcare workers and non-healthcare workers with COVID-19?FindingsIn this population-based cross-sectional study there were 4,230 healthcare workers comprising 17.5% of COVID-19 cases. Healthcare workers were diagnosed with COVID-19 at a rate 5.5 times higher than the general population with 0.8% of all healthcare workers, compared to 0.1% of non-healthcare workers.MeaningHigh healthcare worker COVID-19 burden highlights the importance of physical distancing from colleagues, appropriate personal protective equipment, as well as likely substantial testing bias and under-ascertainment of COVID-19 in the general population.

Introduction: Invasive pneumococcal disease (IPD) is a disease of public health significance in Ontario, Canada, where publicly funded pneumococcal vaccination programs target children, older adults, and people at high risk of disease. Since the implementation of pneumococcal conjugate vaccines (PCV), serotype replacement has been documented, where non-PCV serotypes replace the niche created by the reduction in vaccine-preventable serotypes. Our objective was to determine whether there has been serotype replacement or a change in IPD severity in Ontario since implementation of the childhood 13-valent (PCV13) program by assessing IPD burden over a 12-year period (2007-2018). Methods: We included all confirmed IPD cases reported in Ontario’s integrated Public Health Information System (iPHIS) and defined the pre-PCV13 era (January 2007-December 2010) and post-PCV13 era (January 2011-December 2018). We grouped IPD serotypes according to associated vaccine type: PCV13; 23-valent polysaccharide vaccine (unique PPV23); and non-vaccine-preventable (NVP). We used population data to calculate incidence and hospitalization rates (per 100,000 population) by age group, vaccine type, and era. Results: In the post-PCV13 era, PCV13-specific incidence and hospitalization rates decreased, while the incidence and hospitalizations due to unique PPV23 and NVP serotypes increased; this was consistent across all age groups. The greatest decrease in incidence (RR=0.4) and hospitalizations (RR=0.4) was observed in children

Introduction Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive. Aim We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults. Methods We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history. Results We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1–3 (26%; 95%CI: 13 to 37%), 4–6 (24%; 95%CI: 15 to 33%), 7–8 (13%; 95%CI: 2 to 22%), or 9–10 (7%; 95%CI: −4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously. Conclusions Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.