Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults (preprint)

Introduction: We assessed protection conferred by COVID-19 vaccines and/or prior SARS-CoV-2 infection against Omicron-associated severe outcomes during successive sublineage-predominant periods. Methods: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, PCR-tested adults aged >50 years in Ontario, Canada between January 2, 2022 and June 30, 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection. Results: We included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance, but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95%CI 63%-72%; fourth-dose, 6-month: 80%, 95%CI 77%-83%), but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95%CI 48%-67%; 12-month: 49%, 95%CI 41%-56%; fourth-dose, 6-month: 62%, 95%CI 56%-68%, 12-months: 51%, 95%CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance, but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95%CI 36%-75%; fourth-dose, 6-month: 63%, 95%CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95%CI 79%-96%). Prior infection alone did not confer lasting protection. Conclusion: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

Effectiveness of mRNA COVID-19 monovalent and bivalent vaccine booster doses against Omicron severe outcomes among adults aged >=50 years in Ontario, Canada (preprint)

Objective: We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged [≥]50 years in Ontario, Canada. Methods: We used a test-negative design to estimate vaccine effectiveness (VE), with unvaccinated adults as the comparator, against hospitalization or death among SARS-CoV-2-tested adults aged [≥]50 years between June 19, 2022 and January 28, 2023 stratified by time since vaccination. We explored VE by vaccine product (Moderna Spikevax (R) monovalent; Pfizer-BioNTech Comirnaty(R) monovalent; Moderna Spikevax(R) BA.1 bivalent; Pfizer-BioNTech Comirnaty(R) BA.4/BA.5 bivalent). Results: We included 3,755 Omicron cases and 14,338 test-negative controls. For the Moderna and Pfizer-BioNTech monovalent vaccines, VE 7-29 days after vaccination was 85% (95% confidence interval [CI], 72-92%) and 88% (95%CI, 82-92%), respectively, and was 82% (95%CI, 76-87%) and 82% (95%CI, 77-86%) 90-119 days after vaccination. For the Moderna BA.1 bivalent vaccine, VE was 86% (95%CI, 82-90%) 7-29 days after vaccination and was 76% (95%CI, 66-83%) 90-119 days after vaccination. For the Pfizer-BioNTech BA.4/BA.5 bivalent vaccine, VE 7-29 days after vaccination was 83% (95%CI, 77-88%) and was 81% (95%CI 72-87%) 60-89 days after vaccination. Conclusions: Booster doses of monovalent and bivalent mRNA COVID-19 vaccines provided similar, strong initial protection against severe outcomes in community-dwelling adults aged [≥]50 years in Ontario. Nonetheless, uncertainty remains around waning protection of these vaccines.

Characterizing responsiveness to the COVID-19 pandemic in the United States and Canada using mobility data (preprint)

Background: Mobile phone-derived human mobility data are a proxy for disease transmission risk and have proven useful during the COVID-19 pandemic for forecasting cases and evaluating interventions. We propose a novel metric using mobility data to characterize responsiveness to rising case rates. Methods: We examined weekly reported COVID-19 incidence and retail and recreation mobility from Google Community Mobility Reports for 50 U.S. states and nine Canadian provinces from December 2020 to November 2021. For each jurisdiction, we calculated the responsiveness of mobility to COVID-19 incidence when cases were rising. Responsiveness across countries was summarized using subgroup meta-analysis. We also calculated the correlation between the responsiveness metric and the reported COVID-19 death rate during the study period. Findings: Responsiveness in Canadian provinces ({beta} = -1.45; 95% CI: -2.45, -0.44) was approximately five times greater than in U.S. states ({beta} = -0.30; 95% CI: -0.38, -0.21). Greater responsiveness was moderately correlated with a lower reported COVID-19 death rate during the study period (Spearman's {rho} = 0.51), whereas average mobility was only weakly correlated the COVID-19 death rate (Spearman's {rho} = 0.20). Interpretation: Our study used a novel mobility-derived metric to reveal a near-universal phenomenon of reductions in mobility subsequent to rising COVID-19 incidence across 59 states and provinces of the U.S. and Canada, while also highlighting the different public health approaches taken by the two countries. Funding: This study received no funding.

Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada (preprint)

Background: Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. Interpretation: Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.

Effectiveness of COVID-19 vaccines against Omicron or Delta infection (preprint)

Background The incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, has increased substantially since Omicron was first identified in the province of Ontario, Canada. Methods Applying the test-negative design to linked provincial data, we estimated vaccine effectiveness against infection (irrespective of symptoms or severity) caused by Omicron or Delta between November 22 and December 19, 2021. We included individuals who had received at least 2 COVID-19 vaccine doses (with at least 1 mRNA vaccine dose for the primary series) and used multivariable logistic regression to estimate the effectiveness of two or three doses by time since the latest dose. Results We included 3,442 Omicron-positive cases, 9,201 Delta-positive cases, and 471,545 test-negative controls. After 2 doses of COVID-19 vaccine, vaccine effectiveness against Delta infection declined steadily over time but recovered to 93% (95%CI, 92-94%) [≥]7 days after receiving an mRNA vaccine for the third dose. In contrast, receipt of 2 doses of COVID-19 vaccines was not protective against Omicron. Vaccine effectiveness against Omicron was 37% (95%CI, 19-50%) [≥]7 days after receiving an mRNA vaccine for the third dose. Conclusions Two doses of COVID-19 vaccines are unlikely to protect against infection by Omicron. A third dose provides some protection in the immediate term, but substantially less than against Delta. Our results may be confounded by behaviours that we were unable to account for in our analyses. Further research is needed to examine protection against severe outcomes.

Effectiveness of COVID-19 vaccines against variants of concern, Canada (preprint)

Objectives: 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) variants of concern (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. Results: Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination ([≥]14 days after dose 1) was higher for mRNA-1273 than BNT162b2 and ChAdOx1. Full vaccination ([≥]7 days after dose 2) increased vaccine effectiveness for BNT162b2 and mRNA-1273 against Alpha. Protection against symptomatic infection caused by Beta/Gamma was lower with partial vaccination for ChAdOx1 than mRNA-1273. Against Delta, vaccine effectiveness after partial vaccination tended to be lower than against Alpha for BNT162b2 and mRNA-1273, but was similar to Alpha for ChAdOx1. Full vaccination with BNT162b2 increased protection against Delta to levels comparable to Alpha and Beta/Gamma. Vaccine effectiveness against hospitalization or death caused by all studied VOCs was generally higher than for symptomatic infection after partial vaccination with all three vaccines. Conclusions: Our findings suggest that even a single dose of these 3 vaccine products provide good to excellent protection against symptomatic infection and severe outcomes caused by the 4 currently circulating variants of concern, and that 2 doses are likely to provide even higher protection.

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

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 (preprint)

Objectives: To estimate the effectiveness of one and two doses of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design: Using a test-negative design study and linked laboratory, vaccination, and health administrative databases, we estimated adjusted vaccine effectiveness (aVE) against symptomatic infection and severe outcomes (hospitalization or death) using multivariable logistic regression. Setting: Ontario, Canada between 14 December 2020 and 19 April 2021. Participants: Community-dwelling adults aged [≥]16 years who were tested for SARS-CoV-2 and had COVID-19 symptoms. Interventions: Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273 vaccine. Main outcome measures: Laboratory-confirmed SARS-CoV-2 identified by RT-PCR; hospitalization or death associated with SARS-CoV-2 infection. Results: Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received 1 or more vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. aVE against symptomatic infection 14 days or more 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. aVE 7 days or more after receiving 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, aVE 14 days or more after receiving 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 or more, whereas aVE 7 days or more after receiving 2 doses was 98% (95%CI, 88 to 100%). For adults aged 70 years and older, aVE estimates were lower after receiving 1 dose, but were comparable to younger adults after 28 days. After 2 doses, we observed high aVE against E484K-positive variants. Conclusions: Two doses of BNT162b2 and mRNA-1273 vaccines are highly effective against both symptomatic infection and severe outcomes. Effectiveness is lower after only a single dose, 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 (preprint)

Background: In 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. Methods: We 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. Results: Residents 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%). Discussion: Heterogeneous 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.

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

IMPORTANCE: Higher 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 OBJECTIVE: To compare secondary attack rates in households with VOC versus non-VOC index cases. DESIGN: A retrospective cohort study of household index cases reported from February 7-27, 2021. A propensity-score matched cohort was derived to calculate adjusted estimates. SETTING: Ontario, Canada. PARTICIPANTS: A 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. EXPOSURE: VOC 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 MEASURE: Household 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. RESULTS: We 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 RELEVANCE: This 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 (preprint)

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.

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

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.

Factors Associated with Timely Test Seeking, Test Turnaround, and Public Reporting of COVID-19: a retrospective analysis in Ontario, Canada (preprint)

Background Minimizing 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. Methods We 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. Findings Among 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. Interpretation Individual, 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.

Risk factors for retirement home COVID-19 outbreaks in Ontario, Canada: A population-level cohort study (preprint)

BackgroundThe epidemiology of COVID-19 in retirement homes (also known as assisted living facilities) is largely unknown. We examined the association between retirement home and community level characteristics and the risk of COVID-19 outbreaks in retirement homes during the first wave of the COVID-19 epidemic. MethodsWe conducted a population-based retrospective cohort study of licensed retirement homes in Ontario, Canada, from March 1st - September 24th, 2020. Our primary outcome was a COVID-19 outbreak ([≥]1 resident or staff confirmed case by validated nucleic acid amplification assay). We used time-dependent proportional hazards methods to model the associations between retirement home and community level characteristics and COVID-19 outbreaks. ResultsOur cohort included all 770 licensed retirement homes in Ontario, which housed 56,491 residents. There were 172 (22.3%) COVID-19 retirement home outbreaks involving 1,045 (1.9%) residents and 548 staff (1.5%). COVID-19 cases were distributed unevenly across retirement homes, with 1,593 (92.2%) resident and staff cases occurring in 77 (10%) of homes. The adjusted hazard of a COVID-19 outbreak in a retirement home was positively associated with homes that had a large resident capacity, homes that were co-located with a long-term care facility, large corporate owned chains, homes that offered many services onsite, increases in regional COVID-19 incidence, and a higher community-level ethnic concentration. InterpretationReadily identifiable retirement home-level characteristics are independently associated with COVID-19 outbreaks and may support risk identification. A higher ethnic concentration of the community surrounding a retirement home is associated COVID-19 outbreaks, with an uncertain mechanism.

Increased Prescribing of Psychotropic Medications to Ontario Nursing Home Residents during the COVID-19 Pandemic (preprint)

In this population-based study of all Ontario nursing home residents, we found increased prescribing of psychotropic drugs at the onset of the COVID-19 pandemic that persisted through September 2020. Increases in prescribing were out of proportion to expected secular trends, and distinct from observed prescribing changes in other drugs during the pandemic. Our findings underscore the urgency of balancing infection prevention and control measures in nursing homes with the mental wellbeing of residents.

COVID-19 Workplace Outbreaks by Industry Sector and their Associated Household Transmission, Ontario, Canada, January to June, 2020 (preprint)

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 community What 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.

Impact of a public policy restricting staff mobility between long-term care homes in Ontario, Canada during the COVID-19 pandemic (preprint)

ObjectivesTo assess changes in the mobility of staff between long-term care homes in Ontario, Canada before and after enactment of public policy restricting staff from working at multiple homes. DesignPre-post observational study. Setting and Participants623 long-term cares homes in Ontario, Canada between March 2020 and June 2020. MethodsWe used anonymized mobile device location data to approximate connectivity between all 623 long-term care homes in Ontario during the 7 weeks before (March 1 - April 21) and after (April 22 - June 13) the policy restricting staff movement was implemented. We visualized connectivity between long-term care homes in Ontario using an undirected network and calculated the number of homes that had a connection with another long-term care home and the average number of connections per home in each period. We calculated the relative difference in these mobility metrics between the two time periods and compared within-home changes using McNemars test and the Wilcoxon rank-sum test. ResultsIn the period preceding restrictions, 266 (42.7%) long-term care homes had a connection with at least one other home, compared to 79 (12.7%) homes during the period after restrictions, a drop of 70.3% (p <0.001). The average number of connections in the before period was 3.90 compared to 0.77 in after period, a drop of 80.3% (p < 0.001). In both periods, mobility between long-term care homes was higher in homes located in larger communities, those with higher bed counts, and those part of a large chain. Conclusions and ImplicationsMobility between long-term care homes in Ontario fell sharply after an emergency order by the Ontario government limiting long-term care staff to a single home, though some mobility persisted. Reducing this residual mobility should be a focus of efforts to reduce risk within the long-term care sector during the COVID-19 pandemic.

Temporal Variations in the Intensity of Care Provided to Community and Nursing Home Residents Who Died of COVID-19 in Ontario, Canada (preprint)

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 (<70, 70-79, 80-89, [≥]90), gender, and month of death (1st wave: March-April [peak], May, June-July 2020 [nadir], 2nd wave: August-October 2020). 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.

Characteristics associated with household transmission of SARS-CoV-2 in Ontario, Canada (preprint)

BACKGROUND: Within-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. METHODS: Using 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. FINDINGS: Between 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. INTERPRETATION: It 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.

COVID-19 seroprevalence surveys and antibody decline - A note of caution on antibody decline (preprint)

We analyzed 21,676 residual specimens from Ontario, Canada collected between March-August, 2020 to investigate the effect of antibody decline on SARS-CoV-2 seroprevalence estimates. Testing specimens orthogonally using the Abbott (anti-nucleocapsid) and then the Ortho (anti-spike) assays, seroprevalence estimates ranged from 0.4%-1.4%, despite ongoing disease activity. The geometric mean concentration (GMC) of antibody-positive specimens decreased over time (p=0.015), and the GMC of antibody-negative specimens increased over time (p=0.0018). The association between the two tests decreased each month (p<0.001), suggesting anti-N antibody decline. Lowering the Abbott index cut-off from 1.4 to 0.7 resulted in a 16% increase in positive specimens.