Effectiveness and Duration of Protection of a Fourth Dose of COVID-19 mRNA Vaccine among Long-Term Care Residents in Ontario, Canada

BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine [≥]84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Seven months have passed since fourth doses were implemented, allowing for the examination of fourth dose protection over time. MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged [≥]60 years who were tested for SARS-CoV-2 between December 30, 2021 and August 3, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). ResultsWe included 21,275 Omicron cases and 273,466 test-negative controls. The marginal effectiveness of a fourth dose <84 days ago compared to a third dose received [≥]84 days ago was 23% (95% Confidence Interval [CI] 17-29%), 36% (95%CI 26-44%), and 37% (95%CI 24-48%) against SARS-CoV-2 infection, symptomatic infection, and severe outcomes, respectively. Additional protection provided by a fourth dose compared to a third dose was negligible against all outcomes [≥]168 days after vaccination. Compared to unvaccinated individuals, vaccine effectiveness (VE) of a fourth dose decreased from 49% (95%CI 44%-54%) to 18% (95%CI 5-28%) against infection, 69% (95%CI 62-75%) to 44% (95%CI 24-59%) against symptomatic infection, and 82% (95%CI 77-86%) to 74% (95%CI 62-82%) against severe outcomes <84 days versus [≥]168 days after vaccination. ConclusionsOur findings suggest that fourth doses of mRNA COVID-19 vaccines provide additional protection against Omicron-related outcomes in LTC residents, but the protection wanes over time, with more waning seen against infection than severe outcomes.

Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada

BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine [≥]84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged [≥]60 years who were tested for SARS-CoV-2 between December 30, 2021 and April 27, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). ResultsWe included 13,654 Omicron cases and 205,862 test-negative controls. The marginal effectiveness of a fourth dose (with 95% of fourth dose vaccine recipients receiving mRNA-1273) [≥]7 days after vaccination versus a third dose received [≥]84 days prior was 19% (95% Confidence Interval [CI], 12-26%) against infection, 31% (95%CI, 20-41%) against symptomatic infection, and 40% (95%CI, 24-52%) against severe outcomes. VE (compared to an unvaccinated group) increased with each additional dose, and for a fourth dose was 49% (95%CI, 43-54%), 69% (95%CI, 61-76%), and 86% (95%CI, 81-90%), against infection, symptomatic infection, and severe outcomes, respectively. ConclusionsOur findings suggest that compared to a third dose received [≥]84 days ago, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes caused by Omicron among long-term care residents. Compared to unvaccinated individuals, fourth doses provide strong protection against severe outcomes, but the duration of protection remains unknown.

Effectiveness of COVID-19 vaccines against hospitalization and death in Canada: A multiprovincial test-negative design study

BackgroundA major goal of COVID-19 vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against severe outcomes in four Canadian provinces between December 2020 and September 2021. MethodsWe conducted this multiprovincial retrospective test-negative study among community-dwelling adults aged [≥]18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random effects models. ResultsWe included 2,508,296 tested subjects, with 31,776 COVID-19 hospitalizations and 5,842 deaths. Vaccine effectiveness was 83% after a first dose, and 98% after a second dose, against both hospitalization and death (separately). Against severe outcomes (hospitalization or death), effectiveness was 87% (95%CI: 71%-94%) [≥]84 days after a first dose of mRNA vaccine, increasing to 98% (95%CI: 96%-99%) [≥]112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95%CI: 75%-94%) [≥]56 days after a first dose, increasing to 97% (95%CI: 91%-99%) [≥]56 days after a second dose. Lower one-dose effectiveness was observed for adults aged [≥]80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules, and against Alpha, Gamma, and Delta variants. ConclusionsTwo doses of mRNA or ChAdOx1 vaccines provide excellent protection against severe outcomes of hospitalization and death.

Vaccine effectiveness of BNT162b2 against Omicron and Delta outcomes in adolescents

IntroductionData on vaccine effectiveness (VE) against Omicron in adolescents are limited. We estimated 2-dose and 3-dose VE against Omicron and Delta in adolescents aged 12-17 years in Ontario, Canada. MethodsWe conducted a test-negative design study among SARS-CoV-2-tested adolescents aged 12-17 years between November 22, 2021 (date of first Omicron detection) and March 6, 2022; we assessed Delta outcomes prior to January 2, 2022. We used multivariable logistic regression to compare the odds of vaccination in cases to symptomatic test-negative controls and calculated VE as 1-adjusted odds ratio. ResultsVE was lower against symptomatic Omicron infection than against Delta and decreased more rapidly over time, from 51% (95%CI, 38-61%) in the 7-59 days following a second dose to 29% (95%CI, 17-38%) after 180 days, compared to 97% (95%CI, 94-99%) and 90% (95%CI, 79-95%) for the same intervals against symptomatic Delta infection. Overall, 2-dose VE against severe outcomes caused by Omicron was 85% (95%CI, 74-91%) [≥]7 days following a second dose and estimates were similar over time. VE against symptomatic Omicron infection was 62% (95%CI, 49-72%) [≥]7 days following a third dose. DiscussionTwo-dose VE against symptomatic Omicron infection wanes over time in adolescents. While lower than observed against Delta, protection against severe outcomes appears to be maintained over time. A third dose substantially improves protection against Omicron infection, but 3-dose VE is only moderate at approximately 60% in the early period following vaccination and the duration of this protection is unknown.

Vaccine Effectiveness Against Hospitalization Among Adolescent and Pediatric SARS-CoV-2 Cases in Ontario, Canada

BackgroundVaccines against SARS-CoV-2 have been shown to reduce risk of infection, as well as severe disease among those with breakthrough infection, in adults. The latter effect is particularly important as Immune evasion by Omicron variants appears to have made vaccines less effective for prevention of infection. There is currently little available information on the protection conferred by vaccination against severe illness due to SARS-CoV-2 in children. MethodsTo minimize confounding by changing vaccination practices and dominant circulating viral variants, we performed an age- and time-matched nested case-control design. Reported SARS-CoV-2 case records in Ontario children and adolescents aged 4 to 17 were linked to vaccination records. We used multivariable logistic regression to estimate the effectiveness of one and two vaccine doses against hospitalization. ResultsWe identified 130 hospitalized SARS-CoV-2 cases and 1,300 non-hospitalized, age- and time-matched controls, with disease onset between May 28, 2021 and January 9, 2022. One vaccine dose was shown to be 34% effective against hospitalization among SARS-CoV-2 cases (aOR = 0.66 [95% CI: 0.34, 1.21]). In contrast, two doses were 56% (aOR = 0.44 [95% CI: 0.23, 0.83]) effective at preventing hospitalization among SARS-CoV-2 cases. Exploratory instrumental variable analyses, and calculation of E-values, suggested that these effects are unlikely to be explained by unmeasured confounding. ConclusionsEven with immune evasion by SARS-CoV-2 variants, two vaccine doses continue to provide protection against hospitalization among adolescent and pediatric SARS-CoV-2 cases, even when the vaccines do not prevent infection.

Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review

BackgroundA correlate of protection (CoP) is an immunological marker associated with protection against infection. A CoP can be used to determine whether an individual is protected from infection, evaluate candidate vaccines, guide vaccination dosing intervals and policy, and understand population-level immunity against a pathogen. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined, leaving an evidence gap for informing public health policy and adapting it appropriately as new variants of concern emerge. The objective of this study was to systematically review and assess the evidence for a humoral SARS-CoV-2 CoP. Methods and FindingsWe searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus from inception to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) from inception to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment. Twenty-five studies were included in our systematic review. Several studies reported re-infection or breakthrough cases that occurred in the presence of robust antibody levels. Studies that compared aggregate antibody concentrations from individuals who experienced re-infection or breakthrough compared to those who remained protected did not always find differences that were statistically significant. However, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, and a correlation between antibody levels and vaccine efficacy (VE). Estimates of the contribution of antibody levels to VE varied from 48.5% to 94.2%, suggesting that both humoral immunity and other immune components contribute to protection. Only two studies estimated a quantitative CoP. For Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. As of our search date, no studies reported an Omicron-specific CoP. ConclusionsThe reviewed literature was limited by a wide variation in assay methodology and antibody targets. Few studies reported SARS-CoV-2 lineage. The studies included in our review suggest that if it exists, a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance

BackgroundBackground incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of nine adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. MethodsWe conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bells palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barre syndrome, and transverse myelitis during five pre-pandemic years (2015- 2019) and 2020. ResultsThe average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 43.9 for idiopathic thrombocytopenia, 27.8 for Bells palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.6 for pericarditis, 2.9 for myocarditis, 1.9 for Guillain-Barre syndrome, 1.7 for transverse myelitis, and 1.6 for Kawasaki disease. Females had higher rates of acute disseminated encephalomyelitis and transverse myelitis while males had higher rates of myocarditis, pericarditis, and Guillain-Barre syndrome. Bells palsy, acute disseminated encephalomyelitis, and Guillain-Barre syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12-59 years for myocarditis and [≥]12 years for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. ConclusionsOur estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Effectiveness of COVID-19 vaccines against Omicron or Delta infection

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.

Early estimates of SARS-CoV-2 Omicron variant severity based on a matched cohort study, Ontario, Canada

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.

Incidence of outbreak-associated COVID-19 cases by industry in Ontario, Canada, April 1, 2020- March 31, 2021

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.

Effectiveness of COVID-19 vaccines against variants of concern, Canada

SARS-CoV-2 variants of concern (VOC) are more transmissible and 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) VOCs in Ontario, Canada using a test-negative design study. Effectiveness against symptomatic infection [≥]7 days 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 days after one dose were lower. Effectiveness estimates against hospitalization or death were similar to, or higher than, against symptomatic infection. Effectiveness against symptomatic infection is generally lower for older adults ([≥]60 years) compared to younger adults (<60 years) for most of the VOC-vaccine combinations.

Inflection in prevalence of SARS-CoV-2 infections missing the N501Y mutation as a marker of rapid Delta (B.1.617.2) lineage expansion in Ontario, Canada

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.

Comparative Household Secondary Attack Rates associated with B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants

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.

Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada

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-BioNTechs BNT162b2 or Modernas 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.

Increased Interregional Travel to Shopping Malls and Restaurants in Response to Differential COVID-19 Restrictions in the Greater Toronto Area

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.

Impact of a nighttime curfew on overnight mobility

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, Canadas 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.

Increased household secondary attacks rates with Variant of Concern SARS-CoV-2 index cases

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) transmission OBJECTIVETo 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.

Pediatric household transmission of SARS-CoV-2 infection

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 <18 years. Logistic regression models were fit to estimate the association between age group of pediatric index cases (0-3, 4-8, 9-13, and 14-17 years) and odds of household transmission. 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 rates of all-cause mortality, hospitalizations, and emergency department visits among nursing home residents in Ontario, Canada to inform COVID-19 vaccine safety assessments

BackgroundNursing home (NH) residents are prioritized for COVID-19 vaccination. We report monthly mortality, hospitalizations, and emergency department (ED) visit incidence rates (IRs) during 2010-2020 to provide context for COVID-19 vaccine safety assessments. MethodsWe observed outcomes among NH residents using administrative databases. IRs were calculated by month, sex, and age group. Comparisons between months were assessed using one-sample t-tests; comparisons by age and sex were assessed using chi-squared tests. ResultsFrom 2010-2019, there were 83,453 (SD: 652.4) NH residents per 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. From March to December 2020, mortality IRs were increased, but hospitalization and ED visit IRs were reduced (p<0.05). ConclusionWe identified consistent monthly mortality, hospitalization, and ED visit IRs during 2010-2019. Marked differences in these rates were observed during 2020, coinciding with the COVID-19 pandemic.

Household secondary attack rate of COVID-19 by household size and index case characteristics

In this population-wide study in Ontario, Canada, we investigated the household secondary attack rate (SAR) to understand its relationship to household size and index case characteristics. We identified all patients with confirmed COVID-19 between July 1 and November 30, 2020. Cases within households were matched based on reported residential address; households were grouped based on the number of household contacts. The majority of households (68.2%) had a SAR of 0%, while 3,442 (11.7%) households had a SAR [≥]75%. Overall household SAR was 19.5% and was similar across household sizes, but varied across index case characteristics. Households where index cases had longer delays between symptom onset and test seeking, households with older index cases, households with symptomatic index cases, and larger households located in diverse neighborhoods, were associated with greater household SAR. Our findings present characteristics associated with greater household SARs and proposes immediate testing as a method to reduce household transmission and incidence of COVID-19.