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BackgroundLate outbreak identification is a common risk factor mentioned in case reports of large respiratory infection outbreaks in long-term care (LTC) homes.AimTo systematically measure the association between late SARS-CoV-2 outbreak identification and secondary SARS-CoV-2 infection and mortality in residents of LTC homes.MethodsWe studied SARS-CoV-2 outbreaks across LTC homes in Ontario, Canada from March to November 2020, before the COVID-19 vaccine rollout. Our exposure (late outbreak identification) was based on cumulative infection pressure (the number of infectious resident-days) on the outbreak identification date (early: ≤ 2 infectious resident-days, late: ≥ 3 infectious resident-days), where the infectious window was -2 to +8 days around onset. Our outcome consisted of 30-day incidence of secondary infection and mortality, based on the proportion of at-risk residents with a laboratory-confirmed SARS-CoV-2 infection with onset within 30 days of the outbreak identification date.ResultsWe identified 632 SARS-CoV-2 outbreaks across 623 LTC homes. Of these, 36.4% (230/632) outbreaks were identified late. Outbreaks identified late had more secondary infections (10.3%; 4,437/42,953) and higher mortality (3.2%; 1,374/42,953) compared with outbreaks identified early (infections: 3.3%; 2,015/61,714; p < 0.001, mortality: 0.9%; 579/61,714; p < 0.001). After adjustment for 12 LTC home covariates, the incidence of secondary infections in outbreaks identified late was 2.90-fold larger than that of outbreaks identified early (OR: 2.90; 95% CI: 2.04-4.13).ConclusionsThe timeliness of outbreak identification could be used to predict the trajectory of an outbreak, plan outbreak measures and retrospectively provide feedback for quality improvement, with the objective of reducing the impacts of respiratory infections in LTC home residents.

Background: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status., Methods: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts., Results: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively)., Conclusions: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation., Competing Interests: Potential conflicts of interest. S. C. J. J. received a grant from the Canadian Immunization Research Network. J. C. K. received grants from the Public Health Agency of Canada and the Canadian Institutes of Health Research and is supported by a Clinician-Scientist Award from the University of Toronto Department of Family and Community Medicine. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: There are limited data on the viral dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children. Understanding viral load changes over the course of illness and duration of viral shedding may provide insight into transmission dynamics to inform public health and infection-control decisions., Methods: We conducted a prospective cohort study of children aged 18 years and younger with polymerase chain reaction-confirmed SARS-CoV-2 between 1 February 2022 and 14 March 2022. SARS-CoV-2 testing occurred on daily samples for 10 days; a subset of participants completed daily rapid antigen tests (RATs). Viral RNA trajectories were described in relation to symptom onset and resolution. The associations between both time since symptom onset/resolution and non-infectious viral load were evaluated using a Cox proportional hazards model., Results: Among 101 children aged 2 to 17 years, the median time to study-defined non-infectious viral load was 5 days post-symptom onset, with 75% meeting this threshold by 7 days and 90% by 10 days. On the day of and day after symptom resolution, 43 (49%) and 52 (60%) of 87 had met the non-infectious thresholds, respectively. Of the 50 participants completing a RAT, positivity at symptom onset and on the day after symptom onset was 67% (16/24) and 75% (14/20). On the first day where the non-infectious threshold was met, 61% (n = 27/44) of participant RAT results were positive., Conclusions: Children often met the study-defined non-infectiousness threshold on the day after symptom resolution. The RATs were often negative early in the course of illness and should not be relied on to exclude infection. Clinical Trials Registration. clinicaltrials.org; NCT05240183., Competing Interests: Potential conflicts of interest. L. M. reports support for attending meetings and/or travel from Queen's University and Northern Ontario Medical School Public Health and Preventive Medicine residency programs to travel to and attend residency program events in 2022; other financial or nonfinancial interests: employment as a Public Health Physician at Public Health Ontario. C. B. B. reports voluntary unpaid leadership or a fiduciary role as the Board Chair of Kennedy House. P. J. reports payment as an expert witness on vaccine mandates for universities, hospitals, and municipalities from Hicks Morley Hamilton Stewart Storie LLP, City of Toronto, and Baker McKenzie LLP; other financial or nonfinancial interests: Abbott Vascular, Terumo, serves as an unpaid member of the steering group of trials funded by Abbott Vascular (EXCEL trial: https://clinicaltrials.gov/ct2/show/NCT01205776; comparing XIENCE Stent in subjects with unprotected left main coronary artery disease with coronary artery bypass graft surgery; no active involvement for >3 years, no co-authored publication but still listed as an original member of the statistical executive committee) and Terumo (MASTER DAPT trial: https://www.clinicaltrials.gov/ct2/show/NCT0302 3020; comparing abbreviated DAPT (dual antiplatelet therapy) with prolonged DAPT in patients with a drug-eluting stent; ongoing active involvement as a member of the steering group). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine COVID-19 vaccine uptake among physicians in Ontario, Canada from 14 December 2020 to 13 February 2022., Design: Population-based retrospective cohort study., Setting: All registered physicians in Ontario, Canada using data from linked provincial administrative healthcare databases., Participants: 41 267 physicians (including postgraduate trainees) who were Ontario residents and registered with the College of Physicians and Surgeons of Ontario were included. Physicians who were out of province, had not accessed Ontario Health Insurance Plan-insured services for their own care for ≥5 years and those with missing identifiers were excluded., Primary and Secondary Outcome Measures: Primary outcomes were the proportions of physicians who were recorded to have received at least one, at least two and three doses of a Health Canada-approved COVID-19 vaccine by study end date. Secondary outcomes were how uptake varied by physician characteristics (including age, sex, specialty and residential location) and time elapsed between doses., Results: Of 41 267 physicians, (56% male, mean age 47 years), 39 359 (95.4%) received at least one dose, 39 148 (94.9%) received at least two doses and 35 834 (86.8%) received three doses of a COVID-19 vaccine. Of those who received three doses, the proportions were 90.4% among those aged ≥60 years and 81.2-89.5% among other age groups; 88.7% among family physicians and 89% among specialists. 1908 physicians (4.6%) had no record of vaccination, and this included 3.4% of family physicians and 4.1% of specialists; however, 28% of this group had missing specialty information., Conclusions: In Ontario, within 14 months of COVID-19 vaccine availability, 86.8% of physicians had three doses of a COVID-19 vaccine, compared with 45.6% of the general population. Findings may signify physicians' confidence in the safety and effectiveness of COVID-19 vaccines., Competing Interests: Competing interests: MS has received speaker fees from AstraZeneca. No other competing interests were declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We assessed protection from coronavirus disease 2019 (COVID-19) vaccines and/or prior severe acute respiratory syndrome coronavirus 2 (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, polymerase chain reaction (PCR)-tested adults aged ≥50 years in Ontario, Canada, between 2 January 2022 and 30 June 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% confidence interval [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., Conclusions: 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., Competing Interests: Potential conflicts of interest. N. L. has previously received honoraria for consultancy work, speaking in educational programs, and/or travel support from: Shionogi Inc., Gilead Sciences Canada Inc., Janssen Inc., GlaxoSmithKline plc., Sanofi Pasteur Ltd., F. Hoffmann-La Roche Ltd., Genentech Inc., CIDARA Therapeutics Inc., Clarion Healthcare, bioStrategies, Technospert, Aligos; all unrelated to this work. K. W. is a shareholder and board member and Co-founder and Chief Scientific Officer of CANImmunize Inc. and has served on independent scientific advisory boards for Medicago (Independent Data Monitoring Committee) and Moderna (Global Advisory Core Consultancy Group). J. G. reports a position as a paid consultant scientific editor for GIDEON Informatics, Inc., which is unrelated to the current work. S. E. W. reports being a co-investigator on a grant related to public health surveillance of invasive pneumococcal disease (no involvement in administration of funds) for the Canadian Immunization Research Network and a co-investigator on a grant on immunization data in Canada (no involvement in administration of funds) for CIRN; travel support to attend the Future of Vaccinology conference in October 2023 as an invited speaker from McMaster University (Hamilton, ON) and a role as an unpaid volunteer member for Canada's National Advisory Committee on Immunization (NACI). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines., Competing Interests: Potential conflicts of interest . K. W. is a shareholder and board member of CANImmunize Inc and has served on independent scientific advisory boards for Medicago and Moderna. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures., Competing Interests: The authors declare no conflict of interest.

Importance: Widespread and frequent testing for COVID-19 was an important strategy to identify infected patients to isolate and control the spread of the disease during the pandemic. The nasopharyngeal swab (NPS) global supply chain and access to trained healthcare professionals for standard NPS collection were often compromised. Patient discomfort and limited access challenged health systems to reach large numbers for testing in adult and pediatric populations. Our study revealed that swish and gargle saliva (SGS) was comparable to NPS in detecting SARS-CoV-2 and more patient-friendly than NPS. Patients were more likely to repeat the test with SGS. SGS was amenable to self-collection instead of relying on skilled professionals. This comprehensive evaluation highlights the challenges of comparing the accuracy of new methods to imperfect gold standards and identifies additional patient-centric factors that should be considered when defining such standards. Thus, SGS is an advantageous alternative specimen collection for outpatient en masse testing., Competing Interests: The authors declare no conflict of interest.

Importance: The study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19-related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence., Objective: To determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes., Design, Setting, and Participants: This population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023., Exposure: Maternal mRNA COVID-19 vaccination (1 or more doses) during pregnancy., Main Outcomes and Measures: Severe neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery., Results: In total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05)., Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.

Background: Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction-confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses., Results: We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4-1) and 0.3 (0.3-0.4), respectively., Conclusions: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19-vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19., Competing Interests: Potential conflicts of interest. D. B. reports grants or contracts from the Public Health Agency of Canada, CIHR, Natural Sciences and Engineering Research Council of Canada, and Weston Family Foundation; occasional honoraria for invited talks; payment for expert testimony and a volunteer role for the government of Canada in 3 lawsuits on vaccine mandates; and support for attending meetings and/or travel when invited to speak at conferences. M. S. reports speaker's honorarium for an educational event from the government of Canada; and a role as Chair of the Canadian Society of Hospital Pharmacists Foundation Education Grant Committee (unpaid role to lead the committee to review submissions for the Education Grant competition). S. R. reports payment or honoraria paid to author from Merck for presentation on the role of antimicrobial stewardship pharmacists and facilitator for talk on hospital-acquired pneumonias, and a role as volunteer Board Director and Corporate Secretary with Momiji Health Care Society for a seniors’ supportive housing facility in Toronto. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years., Methods: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval., Results: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, -11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, -20% to 85%) after ≥120 days., Conclusions: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

We estimated the effectiveness of booster doses of monovalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults in Ontario, Canada. We used a test-negative design to estimate vaccine effectiveness (VE) against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years from January 2 to October 1, 2022, stratified by age and time since vaccination. We also compared VE during BA.1/BA.2 and BA.4/BA.5 sublineage predominance. We included 11,160 cases and 62,880 tests for test-negative controls. Depending on the age group, compared to unvaccinated adults, VE was 91-98% 7-59 days after a third dose, waned to 76-87% after ≥240 days, was restored to 92-97% 7-59 days after a fourth dose, and waned to 86-89% after ≥120 days. VE was lower and declined faster during BA.4/BA.5 versus BA.1/BA.2 predominance, particularly after ≥120 days. Here we show that booster doses of monovalent mRNA COVID-19 vaccines restored strong protection against severe outcomes for at least 3 months after vaccination. Across the entire study period, protection declined slightly over time, but waned more during BA.4/BA.5 predominance., (© 2023. Crown.)

Background: Studies conducted during the COVID-19 pandemic have shown that crowding in nursing homes is associated with high incidence of SARS-CoV-2 infections, but this effect has not been shown for other respiratory pathogens. We aimed to measure the association between crowding in nursing homes and outbreak-associated respiratory infection incidence and related mortality before the COVID-19 pandemic., Methods: We conducted a retrospective cohort study of nursing homes in Ontario, Canada. We identified, characterised, and selected nursing homes through the Ontario Ministry of Long-Term Care datasets. Nursing homes that were not funded by the Ontario Ministry of Long-Term Care and homes that closed before January, 2020 were excluded. Outcomes consisting of respiratory infection outbreaks were obtained from the Integrated Public Health Information System of Ontario. The crowding index equalled the mean number of residents per bedroom and bathroom. The primary outcomes were the incidence of outbreak-associated infections and mortality per 100 nursing home residents per year. We examined the incidence of infections and deaths as a function of the crowding index by use of negative binomial regression with adjustment for three home characteristics (ie, ownership, number of beds, and region) and nine mean resident characteristics (ie, age, female sex, dementia, diabetes, chronic heart failure, renal failure, cancer, chronic obstructive pulmonary disease, and activities of daily living score)., Findings: Between Sept 1, 2014, and Aug 31, 2019, 5107 respiratory infection outbreaks in 588 nursing homes were recorded, of which 4921 (96·4%), involving 64 829 cases of respiratory infection and 1969 deaths, were included in this analysis. Nursing homes with a high crowding index had higher incidences of respiratory infection (26·4% vs 13·8%; adjusted rate ratio per one resident per room increase in crowding 1·89 [95% CI 1·64-2·17]) and mortality (0·8% vs 0·4%; 2·34 [1·88-2·92]) than did homes with a low crowding index., Interpretation: Respiratory infection and mortality rates were higher in nursing homes with high crowding index than in homes with low crowding index, and the association was consistent across various respiratory pathogens. Decreasing crowding is an important safety target beyond the COVID-19 pandemic to help to promote resident wellbeing and decrease the transmission of prevalent respiratory pathogens., Funding: None., Competing Interests: Declaration of interests AMG reports consulting fees from Sienna Senior Living; honoraria from AstraZeneca, Merck, Biogen, and Moderna; and advisory board participation for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, AstraZeneca, Novavax, and Sanofi. All other authors declare no competing interests., (Copyright Crown Copyright © 2023 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Background: A randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir-ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate., Methods: We conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir-ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1-30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding., Results: The final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir-ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir-ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47-0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39-0.62). Our findings were similar across strata of age, drug-drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43-80), which varied across strata., Interpretation: Nirmatrelvir-ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease., Competing Interests: Competing interests: Tara Gomes has received a stipend from Indigenous Services Canada for their role on the Drugs and Therapeutics Advisory Committee. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Objective: To estimate the effectiveness of maternal mRNA covid-19 vaccination during pregnancy against delta and omicron severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and hospital admission in infants., Design: Test negative design study., Setting: Community and hospital testing in Ontario, Canada., Participants: Infants younger than six months of age, born between 7 May 2021 and 31 March 2022, who were tested for SARS-CoV-2 between 7 May 2021 and 5 September 2022., Intervention: Maternal mRNA covid-19 vaccination during pregnancy., Main Outcome Measures: Laboratory confirmed delta or omicron infection or hospital admission of the infant. Multivariable logistic regression estimated vaccine effectiveness, with adjustments for clinical and sociodemographic characteristics associated with vaccination and infection., Results: 8809 infants met eligibility criteria, including 99 delta cases (4365 controls) and 1501 omicron cases (4847 controls). Infant vaccine effectiveness from two maternal doses was 95% (95% confidence interval 88% to 98%) against delta infection and 97% (73% to 100%) against infant hospital admission due to delta and 45% (37% to 53%) against omicron infection and 53% (39% to 64%) against hospital admission due to omicron. Vaccine effectiveness for three doses was 73% (61% to 80%) against omicron infection and 80% (64% to 89%) against hospital admission due to omicron. Vaccine effectiveness for two doses against infant omicron infection was highest with the second dose in the third trimester (53% (42% to 62%)) compared with the first (47% (31% to 59%)) or second (37% (24% to 47%)) trimesters. Vaccine effectiveness for two doses against infant omicron infection decreased from 57% (44% to 66%) between birth and eight weeks to 40% (21% to 54%) after 16 weeks of age., Conclusions: Maternal covid-19 vaccination with a second dose during pregnancy was highly effective against delta and moderately effective against omicron infection and hospital admission in infants during the first six months of life. A third vaccine dose bolstered protection against omicron. Effectiveness for two doses was highest with maternal vaccination in the third trimester, and effectiveness decreased in infants beyond eight weeks of age., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Public Health Agency of Canada, the Canadian Institutes of Health Research, and the Ontario Ministry of Health and the Ministry of Long term Care for the submitted work; KW is chief executive officer of CANImmunize and serves on the data safety board for the Medicago covid-19 vaccine trial., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Setting: Rapid antigen screening can be effective in identifying infectious individuals in occupational settings to reduce transmission and outbreaks. We report results from a pilot project at the Greater Toronto Airports Authority (GTAA) and describe the operationalization. Toronto Pearson is a large international airport encompassing over 400 employers and, pre-pandemic, with approximately 50,000 employees., Intervention: An employee screening program was piloted between March 8 and May 28, 2021, to implement rapid antigen testing for asymptomatic employees. Recruitment targeted enrolment of 400 employees and yielded participation of 717 from 58 companies. Employees were recommended to book three times per week for nasal swabs on site, and were tested on the Abbot Panbio TM rapid antigen test. No action was taken from a negative result, and if positive, the employee was told to isolate at home and obtain a confirmatory polymerase chain reaction test., Outcomes: A total of 5117 tests were performed on 717 individuals over 12 weeks; 5091 tests were negative (99.5%), and 22 individuals tested positive (3.1% positivity rate). One hundred twenty-four (17%) completed the post-participation survey. All respondents reported that testing did not change their behaviour at work with respect to public health recommendations, and only 1 (1%) reported behaviour change outside of work (socializing with family) as a result of the program., Implications: This pilot program identified 22 (3.1%) potentially infectious employees. Onsite testing was feasible and highly accepted by this group of employees who completed the survey. Education resulted in reasonable uptake and no substantial change in behaviour, although the survey response rate may limit generalizability. Home-based testing may facilitate larger recruitment., (© 2022. The Author(s) under exclusive license to The Canadian Public Health Association.)

Importance: Wearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation., Objective: To evaluate the effect of wearing a face mask on hand-to-face contact by children while at school., Design, Setting, and Participants: This prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes., Interventions: Participants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be maintained (grade 5 and up)., Main Outcomes and Measures: The primary outcome was the number of hand-to-face contacts per student per hour on day 2 of the simulation. Secondary outcomes included hand-to-mucosa contacts and hand-to-nonmucosa contacts. A mixed Poisson regression model was used to derive rate ratios (RRs), adjusted for age and sex with a random intercept for class with bootstrapped 95% CIs., Results: A total of 174 students underwent randomization and 171 students (mask group, 50.6% male; control group, 52.4% male) attended school on day 2. The rate of hand-to-face contacts did not differ significantly between the mask and the control groups (88.2 vs 88.7 events per student per hour; RR, 1.00; 95% CI, 0.78-1.28; P = >.99). When compared with the control group, the rate of hand-to-mucosa contacts was significantly lower in the mask group (RR, 0.12; 95% CI, 0.07-0.21), while the rate of hand-to-nonmucosa contacts was higher (RR, 1.40; 95% CI, 1.08-1.82)., Conclusions and Relevance: In this clinical trial of simulated school attendance, hand-to-face contacts did not differ among students required to wear face masks vs students not required to wear face masks; however, hand-to-mucosa contracts were lower in the face mask group. This suggests that mask wearing is unlikely to increase infection risk through self-inoculation., Trial Registration: ClinicalTrials.gov Identifier: NCT04531254.

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

Background: Health care workers have a higher risk of acquiring SARS-CoV-2 infection than the general population. Our study reports on SARS-CoV-2 testing, infection and associated outcomes in Ontario physicians before SARS-CoV-2 vaccination became available on Dec. 14, 2020., Methods: We conducted a descriptive, population-based cohort study of physicians in Ontario, Canada, from Jan. 25 to Dec. 31, 2020. We included physicians and postgraduate medical trainees who were residents of Ontario and registrants with the College of Physicians and Surgeons of Ontario during the study period. We examined the proportion of physicians tested for SARS-CoV-2 infection, the proportion who tested positive, and how testing and infections varied by certain physician characteristics. We reported on clinical outcomes associated with infection, including hospital admission and death., Results: Of 41 208 physicians (mean age 47 yr; 56.1% male), 19 116 (46.4%) were tested at least once for SARS-CoV-2 infection; 358 tested positive (0.9%). No physicians died within 30 days of testing positive; however, 20/358 (5.6%) were admitted to hospital. By specialty, the proportion tested was highest among postgraduate medical trainees (2531/4125 [61.4%]), emergency physicians (281/478 [58.8%]), infectious disease physicians (33/67 [49.3%]) and family physicians (8857/18 553 [47.7%]). The proportion who tested positive was highest among internal medicine physicians (44/3499 [1.3%]), postgraduate medical trainees (47/4125 [1.1%]) and family physicians (171/18 553 [0.9%]). Of 2290 physicians who worked in long-term care, 1636 (71.4%) were tested and 25 (1.1%) tested positive., Interpretation: During the prevaccination period of the COVID-19 pandemic in Ontario, nearly half of all physicians in the province were tested at least once for SARS-CoV-2 infection, 0.9% tested positive and none died. These findings may reflect the public health measures that were implemented in the province during this period., Competing Interests: Competing interests: Manish Sood reports receiving speaker fees from AstraZeneca. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Objectives: The COVID-19 pandemic has had an effect on the incidence of infectious diseases and medical care. This study aimed to describe the impact of the COVID-19 pandemic on community-level antibiotic use., Methods: Using national antibiotic dispensing data from IQVIA's CompuScript database, this ecological study investigated antibiotic dispensing through community retail pharmacies in Canada from November 2014 to October 2020. Analyses were stratified by age, sex, prescription origin and approximate indication., Results: Adjusting for seasonality, the national rate of antibiotic dispensing in Canada decreased by 26.5% (50.4 to 37.0 average prescriptions per 1000 inhabitants) during the first 8 months of the Canadian COVID-19 period (March to October 2020), compared with the pre-COVID-19 period. Prescribing rates in children ≤18 years decreased from 43.7 to 12.2 prescriptions per 1000 inhabitants in males (-72%) and from 46.8 to 14.9 prescriptions per 1000 inhabitants in females (-68%) in April 2020. Rates in adults ≥65 decreased from 74.9 to 48.8 prescriptions per 1000 inhabitants in males (-35%) and from 91.7 to 61.3 prescriptions per 1000 inhabitants in females (-33%) in May 2020. Antibiotic prescriptions from family physicians experienced a greater decrease than from surgeons and infectious disease physicians. Prescribing rates for antibiotics for respiratory indications decreased by 56% in May 2020 (29.2 to 12.8 prescriptions per 1000 inhabitants), compared with prescribing rates for urinary tract infections (9.4 to 7.8 prescriptions per 1000 inhabitants; -17%) and skin and soft tissue infections (6.4 to 5.2 prescriptions per 1000 inhabitants; -19%)., Discussion: The first 8 months of the COVID-19 pandemic reduced community antibiotic dispensing by 26.5% in Canada, compared with the marginal decrease of 3% in antibiotic consumption between 2015 and 2019. Further research is needed to understand the implications and long-term effects of the observed reductions on antibiotic use on antibiotic resistance in Canada., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: As 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., Objective: To determine whether there are differences in the odds of household transmission by younger children compared with older children., Design, Setting, and Participants: This population-based cohort study took place between June 1 and December 31, 2020, in Ontario, Canada. Private households in which the index case individual of laboratory-confirmed SARS-CoV-2 infection was younger than 18 years were included. Individuals were excluded if they resided in apartments missing suite information, in households with multiple index cases, or in households where the age of the index case individual was missing., Exposures: Age group of pediatric index cases categorized as 0 to 3, 4 to 8, 9 to 13, and 14 to 17 years., Main Outcomes and Measures: Household transmission, defined as households where at least 1 secondary case occurred 1 to 14 days after the pediatric index case., Results: A total of 6280 households had pediatric index cases, and 1717 households (27.3%) experienced secondary transmission. The mean (SD) age of pediatric index case individuals was 10.7 (5.1) years and 2863 (45.6%) were female individuals. Children aged 0 to 3 years had the highest odds of transmitting SARS-CoV-2 to household contacts compared with children aged 14 to 17 years (odds ratio, 1.43; 95% CI, 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2 to 14 days or 4 to 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 to 8 years and 9 to 13 years also had increased odds of transmission (aged 4-8 years: odds ratio, 1.40; 95% CI, 1.18-1.67; aged 9-13 years: odds ratio, 1.13; 95% CI, 0.97-1.32)., Conclusions and Relevance: This study suggests that younger children may be more likely to transmit SARS-CoV-2 infection compared with older children, and the highest odds of transmission was observed for children aged 0 to 3 years. Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.

Background: Health care workers have a critical role in the pandemic response to COVID-19 and may be at increased risk of infection. The objective of this study was to assess the seroprevalence of SARS-CoV-2 immunoglobulin G (IgG) antibodies among health care workers during and after the first wave of the pandemic., Methods: We conducted a prospective multicentre cohort study involving health care workers in Ontario, Canada, to detect IgG antibodies against SARS-CoV-2. Blood samples and self-reported questionnaires were obtained at enrolment, at 6 weeks and at 12 weeks. A community hospital, tertiary care pediatric hospital and a combined adult-pediatric academic health centre enrolled participants from Apr. 1 to Nov. 13, 2020. Predictors of seropositivity were evaluated using a multivariable logistic regression, adjusted for clustering by hospital site., Results: Among the 1062 health care workers participating, the median age was 40 years, and 834 (78.5%) were female. Overall, 57 (5.4%) were seropositive at any time point (2.5% when participants with prior infection confirmed by polymerase chain reaction testing were excluded). Seroprevalence was higher among those who had a known unprotected exposure to a patient with COVID-19 ( p < 0.001) and those who had been contacted by public health because of a nonhospital exposure ( p = 0.003). Providing direct care to patients with COVID-19 or working on a unit with a COVID-19 outbreak was not associated with higher seroprevalence. In multivariable logistic regression, presence of symptomatic contacts in the household was the strongest predictor of seropositivity (adjusted odds ratio 7.15, 95% confidence interval 5.42-9.41)., Interpretation: Health care workers exposed to household risk factors were more likely to be seropositive than those not exposed, highlighting the need to emphasize the importance of public health measures both inside and outside of the hospital., Competing Interests: Competing interests: Shelly Bolotin has received grants for COVID-19 work, unrelated to this manuscript, from the Canadian Institutes of Health Research (CIHR), the Public Health Agency of Canada (PHAC), the COVID-19 Immunity Task Force (CITF) and the Canadian Immunity Research Network; has participated on the executive management committee for the MOSAIC COVID-19 vaccine clinical trial (CITF funded); and is a member of the PHAC Vaccine Surveillance Reference Group and the Canadian Immunization Research Network Management Committee. Michael Silverman reports an unrestricted grant paid to Western University from the Academic Medical Organization of Southwestern Ontario. Allison McGeer reports research grants to her institution from Sanofi Pasteur, Pfizer, Merck, CIHR, CITF, University of Toronto and Appili Therapeutics; funding from AstraZeneca for the preparation and delivery of webinars about vaccination; and participation on a data safety monitoring board or advisory board regarding COVID-19 therapy and vaccines for AstraZeneca, Janssen, Moderna, Pfizer, GlaxoSmithKline, Sanofi Pasteur, Merck, Medicago and Novavax. Upton Allen reports an honorarium provided to SickKids from the St. Jude Pediatric Infectious Diseases course. Jerome Leis reports a grant payment from the University of Toronto COVID-19 Action Initiative to his organization, Sunnybrook Health Sciences Centre, as a participant site; and payment for expert testimony regarding COVID-19 infection prevention and control management for the Ontario Hospital Association and the Ontario Ministry of the Attorney General. Jeffrey Pernica reports grant funding from bioMérieux to his institution for a clinical trial and from MedImmune to his institution for a prospective cohort study; and payment for an educational event from the Canadian Paediatric Review. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Introduction: There is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset., Methods: Laboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences., Results: In Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12-28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18-34). Long-term care residents had 3-5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2-4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2-3 days were observed at the 25th% of the distribution in those aged 20-49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14., Conclusions: Viral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection., Competing Interests: The authors have read the journal’s policy and have the following competing interests: IQVIA Solutions Canada Inc. provided the Drug Information File. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Competing Interests: Competing interests: Isaac Bogoch has received consultant fees from BlueDot, a social benefit corporation that tracks the spread of emerging infectious diseases. No other competing interests were declared.

Importance: Nursing home residents have been disproportionately affected by coronavirus disease 2019 (COVID-19). Prevention recommendations emphasize frequent testing of health care personnel and residents, but additional strategies are needed., Objective: To develop a reproducible index of nursing home crowding and determine whether crowding was associated with COVID-19 cases and mortality in the first months of the COVID-19 epidemic., Design, Setting, and Participants: This population-based retrospective cohort study included more than 78 000 residents across more than 600 nursing homes in Ontario, Canada, and was conducted from March 29 to May 20, 2020., Exposures: The nursing home crowding index equaled the mean number of residents per bedroom and bathroom., Main Outcomes and Measures: The cumulative incidence of COVID-19 cases confirmed by a validated nucleic acid amplification assay and mortality per 100 residents; the introduction of COVID-19 into a home (≥1 resident case) was a negative tracer., Results: Of 623 homes in Ontario, we obtained complete information on 618 homes (99%) housing 78 607 residents (women, 54 160 [68.9%]; age ≥85 years, 42 919 [54.6%]). A total of 5218 residents (6.6%) developed COVID-19 infection, and 1452 (1.8%) died of COVID-19 infection as of May 20, 2020. COVID-19 infection was distributed unevenly across nursing homes; 4496 infections (86%) occurred in 63 homes (10%). The crowding index ranged across homes from 1.3 (mainly single-occupancy rooms) to 4.0 (exclusively quadruple occupancy rooms); 308 homes (50%) had a high crowding index (≥2). Incidence in high crowding index homes was 9.7% vs 4.5% in low crowding index homes (P < .001), while COVID-19 mortality was 2.7% vs 1.3%, respectively (P < .001). The likelihood of COVID-19 introduction did not differ (high = 31.3% vs low = 30.2%; P = .79). After adjustment for regional, nursing home, and resident covariates, the crowding index remained associated with an increased incidence of infection (relative risk [RR] = 1.73, 95% CI, 1.10-2.72) and mortality (RR, 1.69; 95% CI, 0.99-2.87). A propensity score analysis yielded similar conclusions for infection (RR, 2.09; 95% CI, 1.30-3.38) and mortality (RR, 1.83; 95% CI, 1.09-3.08). Simulations suggested that converting all 4-bed rooms to 2-bed rooms would have averted 998 COVID-19 cases (19.1%) and 263 deaths (18.1%)., Conclusions and Relevance: In this cohort of Canadian nursing homes, crowding was common and crowded homes were more likely to experience larger and deadlier COVID-19 outbreaks.

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.

Introduction: Protecting healthcare workers (HCWs) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a priority to maintain a safe and functioning healthcare system. Our objective was to describe and compare the epidemiology, clinical characteristics, and lethality of SARS-CoV-2 infections among HCWs compared to non-HCWs., Methods: Using reportable disease data at Public Health Ontario, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with SARS-CoV-2 infections as of 30 September 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. We evaluated the risk of death using a multivariable logistic regression model adjusting for age, sex, comorbidities, symptoms, and long-term care home exposure., Results: There were 7,050 (12.5%) HCW SARS-CoV-2 infections in Ontario, Canada, of whom 24.9% were nurses, 2.3% were physicians, and the remaining 72.8% other specialties, including personal support workers. Overall HCWs had an infection rate of 1,276 per 100,000 compared to non-HCWs of 346 per 100,000 (3.7 times higher). This difference decreased from a 7 times higher rate in April to no difference in September 2020. Twenty-six percent of HCWs had a household member with SARS-CoV-2 infection; 6.8% were probable acquisitions, 12.3% secondary transmissions, and 6.9% unknown direction of transmission. Death among HCWs was 0.2% compared to 6.1% of non-HCWs. The risk of death in HCWs remained significantly lower than non-HCWs after adjustment (adjusted odds ratio 0.09; 95%CI 0.05-0.17)., Conclusion: HCWs represent a disproportionate number of diagnosed SARS-CoV-2 infections in Ontario, however this discrepancy is at least partially explained by limitations in testing earlier in the pandemic for non-HCWs. We observed a low risk of death in HCWs which could not be completely explained by other factors., Competing Interests: The authors have declared that no competing interests exist.

Background: A randomized controlled trial involving a high-risk, unvaccinated population that was conducted before the Omicron variant emerged found that nirmatrelvir–ritonavir was effective in preventing progression to severe COVID-19. Our objective was to evaluate the effectiveness of nirmatrelvir–ritonavir in preventing severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population-based cohort study in Ontario that included all residents who were older than 17 years of age and had a positive polymerase chain reaction test for SARS-CoV-2 between Apr. 4 and Aug. 31, 2022. We compared patients treated with nirmatrelvir–ritonavir with patients who were not treated and measured the primary outcome of hospital admission from COVID-19 or all-cause death at 1–30 days, and a secondary outcome of all-cause death. We used weighted logistic regression to calculate weighted odds ratios (ORs) with confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177 545 patients, 8876 (5.0%) who were treated with nirmatrelvir–ritonavir and 168 669 (95.0%) who were not treated. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. We found that the occurrence of hospital admission or death was lower in the group given nirmatrelvir–ritonavir than in those who were not (2.1% v. 3.7%; weighted OR 0.56, 95% CI 0.47–0.67). For death alone, the weighted OR was 0.49 (95% CI 0.39–0.62). Our findings were similar across strata of age, drug–drug interactions, vaccination status and comorbidities. The number needed to treat to prevent 1 case of severe COVID-19 was 62 (95% CI 43–80), which varied across strata. Interpretation: Nirmatrelvir–ritonavir was associated with significantly reduced odds of hospital admission and death from COVID-19, which supports use to treat patients with mild COVID-19 who are at risk for severe disease. [ABSTRACT FROM AUTHOR]

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

The COVID-19 pandemic affected access to care, and the associated public health measures influenced the transmission of other infectious diseases. The pandemic has dramatically changed antibiotic prescribing in the community. We aimed to determine the impact of the COVID-19 pandemic and the resulting control measures on oral antibiotic prescribing in long-term care facilities (LTCFs) in Alberta and Ontario, Canada using linked administrative data. Antibiotic prescription data were collected for LTCF residents 65 years and older in Alberta and Ontario from 1 January 2017 until 31 December 2020. Weekly prescription rates per 1000 residents, stratified by age, sex, antibiotic class, and selected individual agents, were calculated. Interrupted time series analyses using SARIMA models were performed to test for changes in antibiotic prescription rates after the start of the pandemic (1 March 2020). The average annual cohort size was 18,489 for Alberta and 96,614 for Ontario. A significant decrease in overall weekly prescription rates after the start of the pandemic compared to pre-pandemic was found in Alberta, but not in Ontario. Furthermore, a significant decrease in prescription rates was observed for antibiotics mainly used to treat respiratory tract infections: amoxicillin in both provinces (Alberta: −0.6 per 1000 LTCF residents decrease in weekly prescription rate, p = 0.006; Ontario: −0.8, p < 0.001); and doxycycline (−0.2, p = 0.005) and penicillin (−0.04, p = 0.014) in Ontario. In Ontario, azithromycin was prescribed at a significantly higher rate after the start of the pandemic (0.7 per 1000 LTCF residents increase in weekly prescription rate, p = 0.011). A decrease in prescription rates for antibiotics that are largely used to treat respiratory tract infections is in keeping with the lower observed rates for respiratory infections resulting from pandemic control measures. The results should be considered in the contexts of different LTCF systems and provincial public health responses to the pandemic. [ABSTRACT FROM AUTHOR]

Background Nonpharmaceutical interventions such as physical distancing and mandatory masking were adopted in many jurisdictions during the coronavirus disease 2019 pandemic to decrease spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined the effects of these interventions on incidence of healthcare utilization for other infectious diseases. Methods Using a healthcare administrative dataset, we employed an interrupted time series analysis to measure changes in healthcare visits for various infectious diseases across the province of Ontario, Canada, from January 2017 to December 2020. We used a hierarchical clustering algorithm to group diagnoses that demonstrated similar patterns of change through the pandemic months. Results We found that visits for infectious diseases commonly caused by communicable respiratory pathogens (eg, acute bronchitis, acute sinusitis) formed distinct clusters from diagnoses that often originate from pathogens derived from the patient's own flora (eg, urinary tract infection, cellulitis). Moreover, infectious diagnoses commonly arising from communicable respiratory pathogens (hierarchical cluster 1: highly impacted diagnoses) were significantly decreased, with a rate ratio (RR) of 0.35 (95% confidence interval [CI],.30–.40; P  < .001) after the introduction of public health interventions in April–December 2020, whereas infections typically arising from the patient's own flora (hierarchical cluster 3: minimally impacted diagnoses) did not demonstrate a sustained change in incidence (RR, 0.95 [95% CI,.90–1.01]; P  = .085). Conclusions Public health measures to curtail the incidence of SARS-CoV-2 were widely effective against other communicable respiratory infectious diseases with similar modes of transmission but had little effect on infectious diseases not strongly dependent on person-to-person transmission. [ABSTRACT FROM AUTHOR]

Background The coronavirus disease 2019 (COVID-19) pandemic has potentially impacted outpatient antibiotic prescribing. Investigating this impact may identify stewardship opportunities in the ongoing COVID-19 period and beyond. Methods We conducted an interrupted time series analysis on outpatient antibiotic prescriptions and antibiotic prescriptions/patient visits in Ontario, Canada, between January 2017 and December 2020 to evaluate the impact of the COVID-19 pandemic on population-level antibiotic prescribing by prescriber specialty, patient demographics, and conditions. Results In the evaluated COVID-19 period (March–December 2020), there was a 31.2% (95% CI, 27.0% to 35.1%) relative reduction in total antibiotic prescriptions. Total outpatient antibiotic prescriptions decreased during the COVID-19 period by 37.1% (95% CI, 32.5% to 41.3%) among family physicians, 30.7% (95% CI, 25.8% to 35.2%) among subspecialist physicians, 12.1% (95% CI, 4.4% to 19.2%) among dentists, and 25.7% (95% CI, 21.4% to 29.8%) among other prescribers. Antibiotics indicated for respiratory infections decreased by 43.7% (95% CI, 38.4% to 48.6%). Total patient visits and visits for respiratory infections decreased by 10.7% (95% CI, 5.4% to 15.6%) and 49.9% (95% CI, 43.1% to 55.9%). Total antibiotic prescriptions/1000 visits decreased by 27.5% (95% CI, 21.5% to 33.0%), while antibiotics indicated for respiratory infections/1000 visits with respiratory infections only decreased by 6.8% (95% CI, 2.7% to 10.8%). Conclusions The reduction in outpatient antibiotic prescribing during the COVID-19 pandemic was driven by less antibiotic prescribing for respiratory indications and largely explained by decreased visits for respiratory infections. [ABSTRACT FROM AUTHOR]

Although antigen tests are not perfect as diagnostic tests, they are a helpful and currently underutilized public health screening tool in Canada's COVID-19 response. More meaningful than test accuracy is the extent to which rapid antigen testing identifies cases of COVID-19 during the infectious period and whether ongoing transmission is reduced. With this context and goal, test sensitivity of rapid antigen tests compared with testing using reverse transcription-polymerase chain reaction (RT-PCR) is only 1 important characteristic, and a sole focus on sensitivity is misguided. [Extracted from the article]

In response to the I CMAJ i news article, "Communication, transparency key as Canada faces new coronavirus threat,"[1] we would like to share the public health response to the first Canadian cases of coronavirus disease 2019 (COVID-19). On Jan. 29, 1 close contact developed symptoms of cough; however, nasopharyngeal and throat swabs were negative for COVID-19. Non-close-contact passengers were advised to self-monitor and contact public health if they became symptomatic; 5 of these passengers became symptomatic, were tested and found by nasopharyngeal and throat swabs to be negative for COVID-19. [Extracted from the article]