Individual and social determinants of SARS-CoV-2 testing and positivity in Ontario,Canada: a population-wide study

BACKGROUND:Optimizing the public health response to reduce the burden of COVID-19 necessitates characterizing population-level heterogeneity of risks for the disease. However, heterogeneity in SARS-CoV-2 testing may introduce biased estimates depending on analytic design. We aimed to explore the potential for collider bias in a large study of disease determinants, and evaluate individual, environmental and social determinants associated with SARS-CoV-2 testing and diagnosis among residents of Ontario, Canada.METHODS:We explored the potential for collider bias and characterized individual, environmental and social determinants of being tested and testing positive for SARS-CoV-2 infection using cross-sectional analyses among 14.7 million community-dwelling people in Ontario, Canada. Among those with a diagnosis, we used separate analytic designs to compare predictors of people testing positive versus negative; symptomatic people testing positive versus testing negative; and people testing positive versus people not testing positive (i.e., testing negative or not being tested). Our analyses included tests conducted between Mar. 1 and June 20, 2020.RESULTS:Of 14 695 579 people, we found that 758 691 were tested for SARS-CoV-2, of whom 25 030 (3.3%) had a positive test result. The further the odds of testing from the null, the more variability we generally observed in the odds of diagnosis across analytic design, particularly among individual factors. We found that there was less variability in testing by social determinants across analytic designs. Residing in areas with the highest household density (adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 1.75–1.98), highest proportion of essential workers (adjusted OR 1.58, 95% CI 1.48–1.69), lowest educational attainment (adjusted OR 1.33, 95% CI 1.26–1.41) and highest proportion of recent immigrants (adjusted OR 1.10, 95% CI 1.05–1.15) were consistently related to increased odds of SARS-CoV-2 diagnosis regardless of analytic design.INTERPRETATION:Where testing is limited, our results suggest that risk factors may be better estimated using population comparators rather than test-negative comparators. Optimizing COVID-19 responses necessitates investment in and sufficient coverage of structural interventions tailored to heterogeneity in social determinants of risk, including household crowding, occupation and structural racism.

The spread of SARS-CoV-2, the virus causing COVID-19, has resulted in a pandemic with heterogeneity in exposure and risk of transmission.^1–4Heterogeneity in social determinants of COVID-19 may exist at the individual and community (e.g., by housing density^5–7) levels. In addition, social determinants of health, including barriers to health care, occupation, structural racism and xenophobia, have been implicated in COVID-19 risk.^8,9 Environmental determinants such as ambient air pollution may also play a role, as evidence indicates that higher ambient air pollution increases risk for infection with other respiratory viruses^10,11 and the development of severe COVID-19.^12,13 Environmental factors are linked with structural racism (e.g., in the context of low-quality housing).^12,14Using observational data to identify risk factors for COVID-19 relies on SARS-CoV-2 testing, a service that is not equally distributed.¹⁵ Differential testing introduces the potential for selection biases,^16,17 including collider bias.¹⁷ Collider bias may be introduced into epidemiologic studies of COVID-19 risk factors if the factors under investigation are related both to developing an infection and to the likelihood of being tested.^17–19 For example, data suggest that people with diabetes are more likely to develop severe COVID-19 if infected with SARS-CoV-2.^20,21 Thus, if infected, people with diabetes may be more likely to be tested, and consequently, diabetes may appear to be associated with a diagnosis of COVID-19 in studies of those tested for SARS-CoV-2, even if diabetes is not a risk factor for infection.¹⁷ The opposite may occur with underlying respiratory diseases (e.g., asthma) that have symptoms similar to those caused by SARS-CoV-2, leading to the appearance of potentially “protective” associations with COVID-19.²²Our objectives were to explore the potential for collider bias in a large study of COVID-19 determinants and examine individual, environmental and social determinants associated with testing and diagnosis among 14.7 million people in Ontario, Canada.¹⁷     

Risk factors for outbreaks of SARS-CoV-2 infection at retirement homes in Ontario,Canada: a population-level cohort study

BACKGROUND:The epidemiology of SARS-CoV-2 infection in retirement homes (also known as assisted living facilities) is largely unknown. We examined the association between home-and community-level characteristics and the risk of outbreaks of SARS-CoV-2 infection in retirement homes since the beginning of the first wave of the COVID-19 pandemic.METHODS:We conducted a population-based, retrospective cohort study of licensed retirement homes in Ontario, Canada, from Mar. 1 to Dec. 18, 2020. Our primary outcome was an outbreak of SARS-CoV-2 infection (≥ 1 resident or staff case confirmed 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 outbreaks of SARS-CoV-2 infection.RESULTS:Our cohort included all 770 licensed retirement homes in Ontario, which housed 56 491 residents. There were 273 (35.5%) retirement homes with 1 or more outbreaks of SARS-CoV-2 infection, involving 1944 (3.5%) residents and 1101 staff (3.0%). Cases of SARS-CoV-2 infection were distributed unevenly across retirement homes, with 2487 (81.7%) resident and staff cases occurring in 77 (10%) homes. The adjusted hazard of an outbreak of SARS-CoV-2 infection in a retirement home was positively associated with homes that had a large resident capacity, were co-located with a long-term care facility, were part of larger chains, offered many services onsite, saw increases in regional incidence of SARS-CoV-2 infection, and were located in a region with a higher community-level ethnic concentration.INTERPRETATION:Readily identifiable characteristics of retirement homes are independently associated with outbreaks of SARS-CoV-2 infection and can support risk identification and priority for vaccination.

Frail older adults living in congregate care settings have been at the centre of the COVID-19 pandemic in Canada and internationally.^1,2 Long-term care facilities — whose residents are the congregate living population most affected by COVID-19 — have been the subject of immense scientific and public interest during the pandemic.³ Retirement homes (often known as assisted living facilities) have received far less examination despite also housing many vulnerable older adults.^4–7 In contrast to long-term care facilities, retirement homes are private residential complexes that provide a range of supportive care and lifestyle services that are purchased out of pocket by residents or their families.⁸ Although residents of retirement homes access supportive care services, they are substantially less frail and dependent than residents of long-term care homes.⁵ Inconsistent regulation of these facilities throughout Canada and the United States has limited research into the epidemiology of SARS-CoV-2 infection in retirement homes.⁹There are 770 licensed retirement homes in Ontario, Canada’s most populous province, that house more than 50 000 older adults, a population size that approaches the number of Ontario residents of long-term care homes.¹⁰ Since the onset of the COVID-19 pandemic in Ontario, the number of positive cases and deaths in retirement homes has continued to grow. As of Apr. 11, 2021, retirement home residents accounted for about 8% of deaths from COVID-19 in Ontario (596/7552).¹¹ Outbreaks of SARS-CoV-2 infection surged in retirement homes during the first and second waves in Canada and the US,^11,12 and there has been limited examination in the literature beyond early reports of case surveillance.¹³We examined the association between home- and community-level characteristics and the risk of outbreaks of SARS-CoV-2 infection during the first wave of the COVID-19 epidemic in Ontario’s retirement homes. Consistent with our previous population-level work in Ontario long-term care homes,^2,14 we hypothesized that home size and regional incidence of SARS-CoV-2 infection would be associated with the risk of an outbreak.     

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

BACKGROUND:Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose of the BNT162b2 SARS-CoV-2 vaccine is efficacious in the general population, but responses in patients receiving hemodialysis are uncertain.METHODS:We obtained serial plasma from patients receiving hemodialysis and health care worker controls before and after vaccination with 1 dose of the BNT162b2 mRNA vaccine, as well as convalescent plasma from patients receiving hemodialysis who survived COVID-19. We measured anti–receptor binding domain (RBD) immunoglobulin G (IgG) levels and stratified groups by evidence of previous SARS-CoV-2 infection.RESULTS:Our study included 154 patients receiving hemodialysis (135 without and 19 with previous SARS-CoV-2 infection), 40 controls (20 without and 20 with previous SARS-CoV-2 infection) and convalescent plasma from 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG was undetectable at 4 weeks in 75 of 131 (57%, 95% confidence interval [CI] 47% to 65%) patients receiving hemodialysis, compared with 1 of 20 (5%, 95% CI 1% to 23%) controls (p < 0.001). No patient with nondetectable levels at 4 weeks developed anti-RBD IgG by 8 weeks. Results were similar in non-immunosuppressed and younger individuals. Three patients receiving hemodialysis developed severe COVID-19 after vaccination. Among those with previous SARS-CoV-2 infection, median anti-RBD IgG levels at 8 weeks in patients receiving hemodialysis were similar to controls at 3 weeks (p = 0.3) and to convalescent plasma (p = 0.8).INTERPRETATION:A single dose of BNT162b2 vaccine failed to elicit a humoral immune response in most patients receiving hemodialysis without previous SARS-CoV-2 infection, even after prolonged observation. In those with previous SARS-CoV-2 infection, the antibody response was delayed. We advise that patients receiving hemodialysis be prioritized for a second BNT162b2 dose at the recommended 3-week interval.

Patients with end-stage kidney disease receiving incentre hemodialysis have been uniquely vulnerable during the COVID-19 pandemic. For these patients, unlike for most other people, self-isolation to avoid exposure to SARS-CoV-2 is impossible. Most patients receiving hemodialysis must leave their homes 3 times weekly to receive their life-saving treatments, often in shared spaces for hours at a time. COVID-19 case fatality rates are 20%–30% for patients receiving hemodialysis —10 times higher than in the general population.^1,2 Advanced age, multiple comorbidities and blunted immune response likely all contribute to the high COVID-19 death rates in this population. Some hemodialysis centres have thus prioritized these patients for vaccination.To facilitate wider vaccine distribution during current shortages, ³ the National Advisory Committee on Immunization of Canada has recommended delaying the second dose of the BNT162b2 vaccine from 3 to 16 weeks.⁴ In a randomized controlled trial (RCT), the clinical efficacy of the BNT162b2 was reported to be greater than 80% at 3 weeks after the first dose.⁵ However, no patients receiving hemodialysis were enrolled in this trial.⁵ Patients with end-stage kidney disease receiving hemodialysis often have impairments in both humoral and cellular immune responses⁶ and are noted to have lower antibody responses to other vaccines.⁷ Whether patients receiving hemodialysis develop robust immune responses after vaccination against SARS-CoV-2 remains uncertain.⁸ Data are required to better inform Canadian public health policy on whether second doses of vaccine can be safely delayed in this population.Usually, once clinical trials are completed, antibody levels can be used as surrogate measures of vaccine efficacy, such as with hepatitis B⁹ and influenza.¹⁰ With respect to the novel coronavirus SARS-CoV-2, although there is increasing understanding of the antibodies that best correlate with viral neutralization and T-cell responses,^11,12 assays vary from laboratory to laboratory and as yet there are no internationally accepted standards defining what antibody levels constitute immunity.¹³ The only way to evaluate vaccine efficacy using antibody levels, therefore, is through direct experimental comparison with controls who are known to reliably develop immunity after vaccination (i.e., healthy individuals similar to those enrolled in the RCT showing vaccine efficacy⁵) or who have developed immunity after natural infection (i.e., survivors of COVID-19).We sought to determine whether short-term antibody responses after a single dose of the BNT162b2 mRNA vaccine are comparable between patients receiving hemodialysis and healthy individuals, and how this compares with antibody responses in patients receiving hemodialysis who survived natural infection with SARS-CoV-2.     

The mobility gap: estimating mobility thresholds required to control SARS-CoV-2 in Canada

BACKGROUND:Nonpharmaceutical interventions remain the primary means of controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures to quantify the mobility level needed to control SARS-CoV-2 (i.e., mobility threshold), and the difference relative to the observed mobility level (i.e., mobility gap).METHODS:We conducted a time-series study of the weekly incidence of SARS-CoV-2 in Canada from Mar. 15, 2020, to Mar. 6, 2021. The outcome was weekly growth rate, defined as the ratio of cases in a given week versus the previous week. We evaluated the effects of average time spent outside the home in the previous 3 weeks using a log-normal regression model, accounting for province, week and mean temperature. We calculated the SARS-CoV-2 mobility threshold and gap.RESULTS:Across the 51-week study period, a total of 888 751 people were infected with SARS-CoV-2. Each 10% increase in the mobility gap was associated with a 25% increase in the SARS-CoV-2 weekly case growth rate (ratio 1.25, 95% confidence interval 1.20–1.29). Compared to the prepandemic baseline mobility of 100%, the mobility threshold was highest in the summer (69%; interquartile range [IQR] 67%–70%), and dropped to 54% in winter 2021 (IQR 52%–55%); a mobility gap was present in Canada from July 2020 until the last week of December 2020.INTERPRETATION:Mobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control SARS-CoV-2 through spring 2021. Mobility measures from anonymized smartphone data can be used to guide provincial and regional loosening and tightening of physical distancing measures.

The global toll of coronavirus disease 2019 (COVID-19) continues to grow, despite the promise of recently approved vaccines. A surge is occurring in many countries in the Northern Hemisphere, including Canada, that may take a considerable toll before vaccination is sufficiently widespread to achieve herd immunity. Nonpharmaceutical public health interventions, including physical distancing, remain the primary population-based means of controlling COVID-19.¹ Since early in the second wave, which started in September 2020, polling has suggested that most people in Canada have supported and adhered to government-directed restrictions,² and many favour strengthened measures to control community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral agent of COVID-19.³SARS-CoV-2 is spread primarily through close contact with people who are infected.⁴ As with any infectious disease, contact rates are a primary driver of SARS-CoV-2 transmission.⁵ Mobility measures capturing human activity through anonymized tracking of smartphones are believed to be reasonable proxies of contact rates outside of one’s own home; these measures can provide more timely and reliable sources of information on contact rates compared with time-use surveys or contact tracing.^6–8Aggregated smartphone mobility data are provided by a number of software developers and have been used to quantify the impact of policy on mobility in Canada,⁹ the effectiveness of lockdowns aiming to reduce the spread of SARS-CoV-2^10–12 and loopholes from excessively localized measures.¹³ Mobility metrics are helpful for gauging the effect of restrictions on behaviour, but do not, on their own, show decision-makers whether restrictions in place at the time are sufficient to curtail the spread of SARS-CoV-2. In this study, we evaluated the association between smartphone mobility measures and the spread of SARS-CoV-2 in Canada, both nationally and provincially, between March 2020 and March 2021. We also sought to quantify the mobility level needed to control COVID-19 (i.e., the mobility threshold), and the difference between observed mobility levels and the threshold (i.e., the mobility gap). We hypothesized that lower mobility levels may be needed in provinces with larger urban populations in the winter compared with more rural provinces in the summer.¹⁴     

COVID-19 in patients undergoing long-term dialysis in Ontario

BACKGROUND:Patients undergoing long-term dialysis may be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of associated disease and mortality. We aimed to describe the incidence, risk factors and outcomes for infection in these patients in Ontario, Canada.METHODS:We used linked data sets to compare disease characteristics and mortality between patients receiving long-term dialysis in Ontario who were diagnosed SARS-CoV-2 positive and those who did not acquire SARS-CoV-2 infection, between Mar. 12 and Aug. 20, 2020. We collected data on SARS-CoV-2 infection prospectively. We evaluated risk factors for infection and death using multivariable logistic regression analyses.RESULTS:During the study period, 187 (1.5%) of 12 501 patients undergoing dialysis were diagnosed with SARS-CoV-2 infection. Of those with SARS-CoV-2 infection, 117 (62.6%) were admitted to hospital and the case fatality rate was 28.3%. Significant predictors of infection included in-centre hemodialysis versus home dialysis (odds ratio [OR] 2.54, 95% confidence interval [CI] 1.59–4.05), living in a long-term care residence (OR 7.67, 95% CI 5.30–11.11), living in the Greater Toronto Area (OR 3.27, 95% CI 2.21–4.80), Black ethnicity (OR 3.05, 95% CI 1.95–4.77), Indian subcontinent ethnicity (OR 1.70, 95% CI 1.02–2.81), other non-White ethnicities (OR 2.03, 95% CI 1.38–2.97) and lower income quintiles (OR 1.82, 95% CI 1.15–2.89).INTERPRETATION:Patients undergoing long-term dialysis are at increased risk of SARS-CoV-2 infection and death from coronavirus disease 2019. Special attention should be paid to addressing risk factors for infection, and these patients should be prioritized for vaccination.

As of Aug. 20, 2020, in Ontario, Canada’s most populous province, almost 41 000 people had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19),¹ which represented 0.3% of the provincial population. Close to 2800 people had died, a case fatality rate of 6.8%.²Patients undergoing dialysis have high rates of comorbid conditions, are often older adults, have varying degrees of immunosuppression and are more likely to reside in long-term care, which puts them at risk of both acquiring SARS-CoV-2 and developing complicated disease.^3,4 Furthermore, in Ontario, those who receive in-centre hemodialysis typically have 3 treatments per week in outpatient units located in or affiliated with hospitals, and the consequent inability to fully self-isolate means that patients undergoing hemodialysis likely have an even higher risk of SARS-CoV-2 infection.^3,4 Recent studies support this but do not compare infection rates with those in the local population of patients not undergoing dialysis.^5–10 Several studies have reported SARS-CoV-2 infection in single or multicentre cohorts of patients undergoing dialysis,^5–10 but we are unaware of any that have identified risk factors for infection at the level of a large region. Some studies have found that patients with SARS-CoV-2 infection who are undergoing dialysis are at high risk of severe illness and death.^6–10     

A population-based analysis of the impact of the COVID-19 pandemic on common abdominal and gynecological emergency department visits

BACKGROUND:Reduced use of the emergency department during the COVID-19 pandemic may result in increased disease acuity when patients do seek health care services. We sought to evaluate emergency department visits for common abdominal and gynecologic conditions before and at the beginning of the pandemic to determine whether changes in emergency department attendance had serious consequences for patients.METHODS:We conducted a population-based analysis using administrative data to evaluate the weekly rate of emergency department visits pre-COVID-19 (Jan. 1–Mar. 10, 2020) and during the beginning of the COVID-19 pandemic (Mar. 11–June 30, 2020), compared with a historical control period (Jan. 1–July 1, 2019). All residents of Ontario, Canada, presenting to the emergency department with appendicitis, cholecystitis, ectopic pregnancy or miscarriage were included. We evaluated weekly incidence rate ratios (IRRs) of emergency department visits, management strategies and clinical outcomes.RESULTS:Across all study periods, 39 691 emergency department visits met inclusion criteria (40.2 % appendicitis, 32.1% miscarriage, 21.3% cholecystitis, 6.4% ectopic pregnancy). Baseline characteristics of patients presenting to the emergency department did not vary across study periods. After an initial reduction in emergency department visits, presentations for cholecystitis and ectopic pregnancy quickly returned to expected levels. However, presentations for appendicitis and miscarriage showed sustained reductions (IRR 0.61–0.80), with 1087 and 984 fewer visits, respectively, after the start of the pandemic, relative to 2019. Management strategies, complications and mortality rates were similar across study periods for all conditions.INTERPRETATION:Although our study showed evidence of emergency department avoidance in Ontario during the first wave of the COVID-19 pandemic, no adverse consequences were evident. Emergency care and outcomes for patients were similar before and during the pandemic.

Avoidance of the emergency department for conditions that may require urgent surgery has been a global concern during the COVID-19 pandemic, and could result in higher case severity and morbidity.^1–3 Resource constraints and provider concerns around the safety of surgery^4–6 may influence rates of nonoperative management for abdominal and gynecological emergencies,⁷ even when existing nonoperative options are not optimal. Limited data suggest that patients with appendicitis and cholecystitis, the 2 most common abdominal emergencies that routinely require operative management,^8,9 may be more likely to avoid the hospital,¹⁰ present with more severe illness^9,10 and be managed nonoperatively during the pandemic, with uncertain consequences for patient outcomes.^10–13 Similarly, the management of early pregnancy complications (i.e., miscarriage and ectopic pregnancy) may be medical or surgical, depending on patient preference and pregnancy characteristics (e.g., stability, gestational age).¹⁴ Up to 80% of women experiencing miscarriage routinely access emergency services; however, there are concerns that women requiring emergency care for miscarriages are avoiding the emergency department.¹⁵ Reduced access to emergency care for early pregnancy complications may result in more adverse outcomes; a study in Italy found an increased rate of ruptured ectopic pregnancy in the early months of the pandemic.¹⁶We sought to characterize the impact of COVID-19 on emergency department visits for and management of appendicitis, cholecystitis, miscarriage and ectopic pregnancy. We aimed to determine if there was a difference in the rate of patients presenting to the emergency department before and during the pandemic, whether a reduction in emergency department visits for these conditions resulted in adverse patient outcomes and whether the proportion of patients undergoing operative management differed before and during the pandemic.     

Total knee replacement after high tibial osteotomy: time-to-event analysis and predictors

BACKGROUND:An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it.METHODS:We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery.RESULTS:Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m², 95% CI 1.12–1.53).INTERPRETATION:We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO.

The burden of knee osteoarthritis (OA) on patients and health care systems is substantial and growing.¹ The current treatment strategy that relies largely on total knee replacement (TKR) for end-stage disease may not be sustainable.^2–5 Reduced quality of life and loss of productivity due to knee OA in middle-aged people in the workforce is particularly problematic.^5–8 The global prevalence of knee OA peaks at about 50 years of age.⁹ Worldwide, the estimated years lived with disability is 2.4 million for people younger than 50 years of age, the approximate age of peak prevalence for knee OA.^9,10 Accordingly, the number of middle-aged patients seeking treatment for knee OA, including TKR, is increasing. ¹¹ Joint replacement may not be the most appropriate treatment for these patients.¹² Earlier TKR is associated with prosthesis infection, ¹³ lower patient satisfaction¹⁴ and revision surgery;^15–18 about 25% of all TKRs are considered “likely inappropriate.”¹⁹ Clinicians have identified a clear treatment gap between exhausting nonoperative management and appropriateness for TKR, resulting in years of pain, decreased function, productivity losses and associated costs.^5–9,20,21 It is therefore imperative to identify additional effective treatments for the large group of patients with knee OA.Medial opening wedge high tibial osteotomy (HTO) is a limb realignment surgery intended for patients with medial compartment knee OA who are not suitable candidates for TKR because of less severe disease, younger age and greater physical demands. The purpose of HTO is to correct malalignment, thereby shifting load away from the more involved knee compartment and limit OA progression.^22,23 Substantial shifts in knee loading^24,25 have resulted in clinically important improvements in pain and function after HTO^26,27 and the procedure is cost-effective,^28,29 yet the surgery is uncommon in Canada.³⁰ Unlike the high and increasing rates of other knee surgical procedures including arthroscopy³¹ and TKR,³² rates of HTO remain low.^33,34High tibial osteotomy may help fill the treatment gap between nonsurgical treatments and definitive TKR. At the London Health Sciences Centre in London, Ontario, HTO is performed frequently with a goal of preventing or delaying the need for TKR. Thus, it is appropriate to investigate the duration of benefit of HTO, and the preoperative characteristics associated with it. When quantified as conversion from HTO to TKR, registries using administrative data enable large sample sizes (> 2500 patients) to estimate cumulative incidence of TKR.^30,35,36 However, there can be limitations in using only administrative data, including confirming the correct procedure, limb and diagnosis. Administrative data often lack detailed information assessed preoperatively, such as radiographic features (e.g., disease severity and lower limb alignment) and patient-reported outcome measures. Previously reported predictors of conversion to TKR such as female sex and greater age^30,35–39 may be influenced (perhaps confounded) by other clinical characteristics not typically included in administrative data. Therefore, our objective was to investigate the cumulative incidence of TKR after medial opening wedge HTO and potential predictors using data collected prospectively from a single Canadian centre that focuses on HTO. Specifically, we evaluated the time to conversion from HTO to TKR and investigated the association of HTO preoperative characteristics with subsequent TKR.     

Changes over time in means of suicide in Canada: an analysis of mortality data from 1981 to 2018

BACKGROUND:Ongoing surveillance of the means of suicide is necessary for effective prevention. We examined how mortality rates owing to different means of suicide changed in Canada from 1981 to 2018.METHODS:We obtained data from 1981 to 2018 on suicide deaths of individuals aged 10 years and older, from the Canadian Vital Statistics Death Database. We used joinpoint regression analysis to examine changes over time in the suicide mortality rate for the 3 most common means of suicide.RESULTS:The age-standardized suicide mortality rate declined in earlier decades for both sexes, but did not significantly change in recent decades for either sex. The age-standardized rate of suicide by suffocation increased from 1993 for females (2.1% per year) and from 1996 for males (0.4% per year). The age-standardized rate of suicide by poisoning decreased for females (2.2% per year) and males (2.1% per year) from 1981 to 2018. The age-standardized rate of suicide by firearm decreased from 1981 to 2008 (7.4% per year) but did not significantly change there-after for females; for males, it decreased 2.1% per year from 1981 to 1993 and 5.7% per year from 1993 to 2007, but did not significantly change thereafter.INTERPRETATION:For both sexes, the rate of suicide by poisoning is decreasing, the rate of suicide by suffocation is increasing, and the rate of suicide by firearm has not significantly changed in the last decade. Given the high proportion of suicide deaths by suffocation, its increasing rate and the difficulty of restricting the means of suffocation, other approaches to suicide prevention are needed.

The overall suicide mortality rate in Canada is lower than it was a few decades ago, but continued declines have been absent in recent years and the impact of suicide remains high.^1,2 Suicide was the ninth leading cause of death in 2018.³ More than three-quarters of suicide deaths in Canada are a result of suffocation, poisoning and firearms.^4–6 Suffocation is the predominant suicide method in most countries.⁴ However, the prevalence of different means of suicide can vary over time because of changes in the accessibility of certain means.⁷ Evidence suggests that the relative frequency of different means of suicide has changed in Canada, but those studies have not included data from more recent years.^8,9 Ongoing surveillance of the means of suicide and understanding changes over time are essential for designing and implementing prevention programs.¹⁰It is especially important to consider sex and age in suicide surveillance, because of differences across these sociodemographic characteristics. For instance, females are more likely to self-report thoughts of suicide and to be admitted to hospital owing to self-inflicted injuries,^5,11 while suicide mortality rates are about 3 times higher among males than females in Canada.^2,3,6 Higher suicide mortality rates for males have been observed in almost all countries,¹ and have been attributed, in part, to more lethal means of suicide (e.g., firearms).^5,6,12 Suicide-related behaviour also varies across the lifespan, with the suicide mortality rate tending to be high in middle-aged adults and males older than 80 years, but hospital admissions owing to self-inflicted injuries tending to occur during adolescence (particularly among females).^2,3,5,6,13Canadian data from 2000 to 2009 indicated that suicide by suffocation was more prevalent among individuals aged 15–39 years, while suicide by firearm was more prevalent among individuals aged 60 years and older.⁶ Canadian data for 2001 to 2011 suggested that rates of suicide by firearm and poisoning declined for males aged 15 years and older, but were unchanged among females during this period.⁹ Less is known about whether the means used by age and sex groups have fluctuated over longer periods and in more recent years. We sought to document the means of suicide deaths in Canada in 2018 (the most recent data available at the time of writing) and investigate how the use of different means has changed for males and females and across age groups since 1981.     

Postpartum mental illness during the COVID-19 pandemic: a population-based,repeated cross-sectional study

BACKGROUND:It is unclear whether the clinical burden of postpartum mental illness has increased during the COVID-19 pandemic. We sought to compare physician visit rates for postpartum mental illness in Ontario, Canada, during the pandemic with rates expected based on prepandemic patterns.METHODS:In this population-based, repeated cross-sectional study using linked health administrative databases in Ontario, Canada, we used negative binomial regression to model expected visit rates per 1000 postpartum people for March–November 2020 based on prepandemic data (January 2016–February 2020). We compared observed visit rates to expected visit rates for each month of the pandemic period, generating absolute rate differences, incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). The primary outcome was a visit to a primary care physician or a psychiatrist for any mental disorder. We stratified analyses by maternal sociodemographic characteristics.RESULTS:In March 2020, the visit rate was 43.5/1000, with a rate difference of 3.11/1000 (95% CI 1.25–4.89) and an IRR of 1.08 (95% CI 1.03–1.13) compared with the expected rate. In April, the rate difference (10.9/1000, 95% CI 9.14–12.6) and IRR (1.30, 95% CI 1.24–1.36) were higher; this level was generally sustained through November 2020. From April–November, we observed elevated visit rates across provider types and for diagnoses of anxiety, depressive and alcohol or substance use disorders. Observed increases from expected visit rates were greater for people 0–90 days postpartum compared with 91–365 days postpartum; increases were small among people living in low-income neighbourhoods. Public health units in the northern areas of the province did not see sustained elevations in visit rates after July; southern health units had elevated rates through to November.INTERPRETATION:Increased visits for mental health conditions among postpartum people during the first 9 months of the COVID-19 pandemic suggest an increased need for effective and accessible mental health care for this population as the pandemic progresses.

Postpartum mental illness affects as many as 1 in 5 mothers,¹ and can result in maternal suffering and diminished functioning.² Related impaired mother–infant interactions are linked to poor social, cognitive and behavioural outcomes in children across their lifespan.³ When mental illness becomes chronic and recurrent, its effects can extend to the entire family and across generations.⁴ With emergence of the novel coronavirus (SARS-CoV-2), the World Health Organization declared a global COVID-19 pandemic on Mar. 11, 2020. Globally, efforts to contain the virus have led to widespread travel restrictions, physical distancing and work limitations, causing broad social and financial disruption that has been associated with substantial mental health effects.^5,6During the COVID-19 pandemic, people have been reporting concerns about postpartum infection,⁷ and difficulty accessing the extended postpartum social support networks and key community programs that protect against mental illness, such as home visits from public health nurses, breastfeeding clinics and support groups, owing to public health measures.⁸ In Canadian surveys, about 50% of pregnant people reported psychological distress in spring 2020,⁹ and alcohol use increased among women, particularly among those with young children.¹⁰ Whether this represents an increased clinical burden of mental illness or need for care is unknown.Using routinely collected health care data from Ontario, Canada, (population of about 14.6 million), we aimed to examine whether rates of maternal visits to physicians for postpartum mental illness from March to November 2020 differed from expected visit rates based on pre-COVID-19 patterns, and to identify variation by provider type, clinical diagnosis, postpartum timing, parity, income, ethnicity and region of residence.     

Characteristics and outcomes of hospital admissions for COVID-19 and influenza in the Toronto area

BACKGROUND:Patient characteristics, clinical care, resource use and outcomes associated with admission to hospital for coronavirus disease 2019 (COVID-19) in Canada are not well described.METHODS:We described all adults with COVID-19 or influenza discharged from inpatient medical services and medical–surgical intensive care units (ICUs) between Nov. 1, 2019, and June 30, 2020, at 7 hospitals in Toronto and Mississauga, Ontario. We compared patient outcomes using multivariable regression models, controlling for patient sociodemographic factors and comorbidity level. We validated the accuracy of 7 externally developed risk scores to predict mortality among patients with COVID-19.RESULTS:There were 1027 hospital admissions with COVID-19 (median age 65 yr, 59.1% male) and 783 with influenza (median age 68 yr, 50.8% male). Patients younger than 50 years accounted for 21.2% of all admissions for COVID-19 and 24.0% of ICU admissions. Compared with influenza, patients with COVID-19 had significantly greater in-hospital mortality (unadjusted 19.9% v. 6.1%, adjusted relative risk [RR] 3.46, 95% confidence interval [CI] 2.56–4.68), ICU use (unadjusted 26.4% v. 18.0%, adjusted RR 1.50, 95% CI 1.25–1.80) and hospital length of stay (unadjusted median 8.7 d v. 4.8 d, adjusted rate ratio 1.45, 95% CI 1.25–1.69). Thirty-day readmission was not significantly different (unadjusted 9.3% v. 9.6%, adjusted RR 0.98, 95% CI 0.70–1.39). Three points-based risk scores for predicting in-hospital mortality showed good discrimination (area under the receiver operating characteristic curve [AUC] ranging from 0.72 to 0.81) and calibration.INTERPRETATION:During the first wave of the pandemic, admission to hospital for COVID-19 was associated with significantly greater mortality, ICU use and hospital length of stay than influenza. Simple risk scores can predict in-hospital mortality in patients with COVID-19 with good accuracy.

International studies report that patients admitted to hospital with coronavirus disease 2019 (COVID-19) have high rates of critical illness and mortality.^1–5 Two small Canadian case series have described care for critically ill patients with COVID-19 and found mortality rates of up to 25%.^6,7 However, outcomes of patients admitted to hospital for COVID-19 in Canada are not well described, particularly outside of intensive care units (ICUs). Case fatality rates for COVID-19 vary dramatically worldwide,⁸ and outcomes of patients admitted to hospital for COVID-19 in Canada may differ from other countries because of differences in populations, public health and health care systems.Seasonal influenza is a useful comparator for COVID-19^9–11 as it is another respiratory virus, familiar to the general public, with high rates of morbidity and mortality. The purpose of this study was to describe patient characteristics, resource use, clinical care and outcomes for patients admitted to hospital with COVID-19 in Ontario, Canada, using influenza as a comparator. We also validated the performance of various prognostic risk scores for in-hospital mortality among patients with COVID-19.     

Birth outcomes following cesarean delivery on maternal request: a population-based cohort study

BACKGROUND:Data on the effect of cesarean delivery on maternal request (CDMR) on maternal and neonatal outcomes are inconsistent and often limited by inadequate case definitions and other methodological issues. Our objective was to evaluate the trends, determinants and outcomes of CDMR using an intent-to-treat approach.METHODS:We designed a population-based retrospective cohort study using data on low-risk pregnancies in Ontario, Canada (April 2012–March 2018). We assessed temporal trends and determinants of CDMR. We estimated the relative risks for component and composite outcomes used in the Adverse Outcome Index (AOI) related to planned CDMR compared with planned vaginal delivery using generalized estimating equation models. We compared the Weighted Adverse Outcome Score (WAOS) and the Severity Index (SI) across planned modes of delivery using analysis of variance.RESULTS:Of 422 210 women, 0.4% (n = 1827) had a planned CDMR and 99.6% (n = 420 383) had a planned vaginal delivery. The prevalence of CDMR remained stable over time at 3.9% of all cesarean deliveries. Factors associated with CDMR included late maternal age, higher education, conception via in vitro fertilization, anxiety, nulliparity, being White, delivery at a hospital providing higher levels of maternal care and obstetrician-based antenatal care. Women who planned CDMR had a lower risk of adverse outcomes than women who planned vaginal delivery (adjusted relative risk 0.42, 95% confidence interval [CI] 0.33 to 0.53). The WAOS was lower for planned CDMR than planned vaginal delivery (mean difference −1.28, 95% CI −2.02 to −0.55). The SI was not statistically different between groups (mean difference 3.6, 95% CI −7.4 to 14.5).Interpretation:Rates of CDMR have not increased in Ontario. Planned CDMR is associated with a decreased risk of short-term adverse outcomes compared with planned vaginal delivery. Investigation into the long-term implications of CDMR is warranted.

Cesarean delivery is the most common inpatient surgical procedure in North America,^1,2 where rates often exceed World Health Organization recommendations (10%–15% of deliveries).³ Given the financial and resource implications of cesarean deliveries on health care systems, the contribution of cesarean deliveries on maternal request (CDMR) to rising cesarean section rates is of ongoing interest. Women may prefer CDMR for many reasons, including scheduling convenience, anxiety regarding labour pain, perceptions that the quality of obstetrical care is better for women who have cesarean deliveries, and concerns about possible urinary incontinence and sexual dysfunction after vaginal delivery.^4–7 Challenges in characterizing the epidemiology of CDMR include the lack of internationally accepted case definitions and inconsistencies in documentation that hinder meaningful comparisons across jurisdictions.^8–11 In Canada, the prevalence of CDMR has been estimated at 2% of cesarean deliveries,¹² but robust contemporary data are lacking.The benefits of vaginal delivery are well known and include a lower risk of transient tachypnea of the newborn, newborn exposure to the vaginal microbiome, shorter maternal hospital stays and lower risk of complications associated with abdominal surgeries. The findings of 1 Canadian study suggest that midpelvic operative vaginal delivery is associated with a greater risk of severe birth and obstetric trauma than cesarean delivery.¹³ Evidence on the risks and benefits of CDMR is sparse, and existing data are inconsistent.^14–19 Analyses are frequently limited by inadequate case definitions and unaddressed confounding from baseline maternal and neonatal factors.^4,11 Professional organizations in the United States, Canada and Europe do not recommend CDMR over vaginal delivery.^11,20–22 Patient counselling is suggested to inform patients of pain management options, and of potential benefits and harms related to cesarean deliveries. However, obstetrical care providers often accede to patient preferences, given the ethical imperative of patient autonomy. ^23–27 Contemporary, high-quality observational studies leveraging robust population-based data are required. Our objective was to evaluate the trends, determinants and outcomes of CDMR compared with planned vaginal delivery using an intent-to-treat approach.     

Postoperative outcomes for Indigenous Peoples in Canada: a systematic review

Background:Substantial health inequities exist for Indigenous Peoples in Canada. The remote and distributed population of Canada presents unique challenges for access to and use of surgery. To date, the surgical outcome data for Indigenous Peoples in Canada have not been synthesized.Methods:We searched 4 databases to identify studies comparing surgical outcomes and utilization rates of adults of First Nations, Inuit or Métis identity with non-Indigenous people in Canada. Independent reviewers completed all stages in duplicate. Our primary outcome was mortality; secondary outcomes included utilization rates of surgical procedures, complications and hospital length of stay. We performed meta-analysis of the primary outcome using random effects models. We assessed risk of bias using the ROBINS-I tool.Results:Twenty-eight studies were reviewed involving 1 976 258 participants (10.2% Indigenous). No studies specifically addressed Inuit or Métis populations. Four studies, including 7 cohorts, contributed adjusted mortality data for 7135 participants (5.2% Indigenous); Indigenous Peoples had a 30% higher rate of death after surgery than non-Indigenous patients (pooled hazard ratio 1.30, 95% CI 1.09–1.54; I² = 81%). Complications were also higher for Indigenous Peoples, including infectious complications (adjusted OR 1.63, 95% CI 1.13–2.34) and pneumonia (OR 2.24, 95% CI 1.58–3.19). Rates of various surgical procedures were lower, including rates of renal transplant, joint replacement, cardiac surgery and cesarean delivery.Interpretation:The currently available data on postoperative outcomes and surgery utilization rates for Indigenous Peoples in Canada are limited and of poor quality. Available data suggest that Indigenous Peoples have higher rates of death and adverse events after surgery, while also encountering barriers accessing surgical procedures. These findings suggest a need for substantial re-evaluation of surgical care for Indigenous Peoples in Canada to ensure equitable access and to improve outcomes. Protocol registration:PROSPERO-CRD42018098757

Safe, timely and affordable access to surgical care is essential to overall population health, as conditions amenable to surgical intervention account for one-third of the global burden of disease.^1,2 Surgery is responsible for 65% of cancer cure and control, it is key to trauma management, and access to cesarean delivery reduces neonatal deaths by up to 70%.¹ The magnitude and ubiquity of surgical conditions makes tracking their prevalence and treatment within local and national monitoring systems essential to fully capture the health and welfare of populations in Canada, including Indigenous Peoples.About 1.67 million people in Canada are Indigenous, representing 4.9% of the total population (58% First Nations, 4% Inuit, 35% Métis).³ Health inequities exist for the Indigenous population; life expectancy at birth is 5–11 years shorter than for non-Indigenous Peoples^4,5 and higher rates of communicable and noncommunicable diseases, unintentional injury and suicide are well documented.^4,6–14 These health inequities are direct impacts of the social determinants of health, which are in turn effects of colonialism and government policies, including the Indian residential school system.^8,11 People living in remote regions have less access to publicly funded health care than other people in Canada, with worse outcomes.¹⁵Given the substantial impact of surgical disease on population health and the recognized disparities in health care access for Indigenous Peoples in Canada, understanding access to surgical services and subsequent outcomes is a key step to addressing health inequities. To date, limited research has been conducted on surgical and postoperative care involving Indigenous Peoples in Canada and the available literature has not been synthesized. Our objective was to systematically review studies comparing postoperative outcomes between Indigenous and non-Indigenous Peoples in Canada.     

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis

BACKGROUND:The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections.METHODS:In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.RESULTS:Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study (n = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza (n = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference −1.62, 95% CI −3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence).INTERPRETATION:Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.

Coronavirus disease 2019 (COVID-19) has been diagnosed in nearly 3 million individuals around the globe, of whom around 0.2 million have died.¹ Many patients with COVID-19 develop severe acute respiratory illness requiring admission to intensive care units (ICU) and often mechanical ventilation.² The case fatality rate in COVID-19 may be as high as 2.3% overall² and from 10% to 40% among severely affected individuals. ^3,4 There is an urgent need for effective therapies.Emerging epidemiologic and clinical data show both similarities and differences between severe COVID-19 and severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).⁵ Similarly, treatment strategies for severe influenza infections tested during the H1N1 pandemic and H5N1 and H7N9 outbreaks could inform the care of patients with severe COVID-19.⁶Of the treatment options proposed for COVID-19,⁷ convalescent plasma has evidence suggesting a mortality benefit for Ebola virus infection.⁸ This intervention has also been tested in other severe acute viral respiratory infections.^6,9,10 “Convalescent plasma” refers to plasma obtained from individuals recently recovered from a viral illness, which is expected to contain the highest levels of polyclonal antibodies directed against the virus.¹¹ Similarly, “hyperimmune plasma” is collected from donors exhibiting high titres of neutralizing antibodies, independent of time elapsed since viral illness. Authors have used the terms interchangeably, and because viral neutralization is only one of the postulated mechanisms by which antibodies exert their antiviral effect, the importance of the distinction between the 2 products remains unclear (Figure 1).Open in a separate windowFigure 1:Potential mechanisms of action of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in coronavirus disease 2019 (COVID-19). This figure illustrates the normal entry of SARS-CoV-2 in a host cell, in which membrane fusion is mediated by the interaction between the SARS-CoV-2 spike glycoprotein (red) and the angiotensin-converting enzyme 2 (ACE2) receptor (green) on the host cell, either through the cytoplasmic or endosomal route. Antibodies directed against the receptor-binding domain (RBD) of the spike protein can interfere with its interaction with the ACE2 receptor and prevent viral entry in the host cell (panel A). Antibodies directed against epitopes outside the RBD can also exert antiviral functions through other mechanisms (panels B, C and D). The relative importance of these various functions in rescuing patients from an active SARS-CoV-2 infection is unknown. Importantly, neutralization assays generally used to qualify hyperimmune products measure only 1 of the 4 mechanisms depicted here and do not necessarily correlate with the others.Clinicians have typically administered convalescent plasma to patients with viral infections whose condition deteriorated despite supportive care.⁶ Although the primary postulated mechanism of action of convalescent plasma is reduction in viremia (passive immunity),¹² an increase in host immune response (active immunity) has also been proposed.¹³ We describe in Figure 1 the possible mechanisms by which convalescent plasma inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Systematic summaries of the available evidence regarding safety and effectiveness can inform the use of convalescent plasma in patients with COVID-19. We therefore conducted a systematic review to summarize the evidence for convalescent plasma to support a guideline on COVID-19 management.¹⁴ Because we anticipated a paucity of direct evidence addressing the use of convalescent plasma in COVID-19, we summarized the available evidence addressing convalescent plasma in the treatment of SARS, MERS and influenza, including H1N1, H7N9 and H5N1, as well as addressing possible adverse effects in patients with Ebola disease.     

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec,Canada: a cross-sectional study

Background:The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity.Methods:Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence.Results:Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63–6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03–1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12–1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13–1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30–0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39–0.98).Interpretation:Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

The COVID-19 pandemic has disproportionately affected health care workers. In France, Spain, Italy, Germany and the United States, at least 10% of cases reported in spring 2020 were in health care workers.¹ In Quebec, 25% (14 177 of 56 565) of all cases declared during the first wave of the pandemic, from March to July 2020, were in health care workers,² about one-third of whom were working in acute care hospitals.¹ The Montréal area was the most affected region in Quebec and Canada during the first wave, reaching a COVID-19 incidence rate of 1336 per 100 000 population.²The number of COVID-19 cases reported among health care workers underestimated the number of those infected with SARS-CoV-2 during that period, given limited testing leading to undiagnosed asymptomatic or paucisymptomatic infections.³ Seroprevalence studies are an important tool to determine the proportion of people infected with SARS-CoV-2, both in the general population and among health care workers.⁴ After the first wave in Quebec, SARS-CoV-2 seroprevalence in adults aged 18–69 years was found to be low (3.1% in Montréal and 1.3% in less affected regions), but this proportion could be much higher among health care workers who had to work despite the general shutdown of social and economic activities, especially if they were exposed to major outbreaks.⁵Only 2 other Canadian studies provide SARS-CoV-2 seroprevalence estimates among health care workers, and both studies were from a single centre.^6,7 Outside Canada, most seroprevalence studies among health care workers include a single site and do not provide a representative estimate for a defined region.⁸ Several studies have reported a higher seroprevalence among health care workers from units treating patients with COVID-19 (COVID-19 units) compared with other units (non–COVID-19 units), emergency departments or intensive care units.^9,10 Other studies have not identified such associations.^11,12 In this study, we aimed to assess the seroprevalence of SARS-CoV-2 antibody among hospital health care workers from a variety of settings after the first pandemic wave in Quebec, and to explore factors associated with SARS-CoV-2 seropositivity.     

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020

Background:Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.Methods:We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.Results:Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.Interpretation:Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

As of Dec. 31, 2020, Canada had 581 427 confirmed cases of SARS-CoV-2 infection.¹ Similar to other countries, most confirmed infections were in adults, in part because of initial testing policies that targeted older and at-risk populations, as well as prolonged societal containment measures to minimize children’s risk of exposure. Although fewer SARS-CoV-2 infections in children were reported relative to adults during Canada’s first waves of the pandemic,² recent surges in pediatric cases across North America have challenged the notion that children are infected at a lower frequency than adults.^3,4 However, the severity of infection in children appears to be substantially lower, with fewer overall hospital admissions reported and substantially lower mortality compared with adults.^5,6Although risk factors for more severe outcomes of COVID-19 have been well described in adults,⁷ similar risks are less well described in children.⁸ Experience with other viral respiratory infections, including influenza and respiratory syncytial virus, has shown that patient-level factors can increase risk for severe disease in children.^9,10 Understanding populations at risk for severe disease is essential for developing evidence-informed testing strategies, recommendations around reducing exposure (including guidance informing in-person schooling) and potential prioritization of SARS-CoV-2 vaccines in children.To date, few published data have characterized admissions to hospital with SARS-CoV-2 infection among children in Canada. We sought to describe pediatric hospital admissions associated with acute SARS-CoV-2 infection in Canada and identify risk factors for severe disease among children admitted to hospital.     

Burden of noninfluenza respiratory viral infections in adults admitted to hospital: analysis of a multiyear Canadian surveillance cohort from 2 centres

BACKGROUND:Data on the outcomes of noninfluenza respiratory virus (NIRV) infections among hospitalized adults are lacking. We aimed to study the burden, severity and outcomes of NIRV infections in this population.METHODS:We analyzed pooled patient data from 2 hospital-based respiratory virus surveillance cohorts in 2 regions of Canada during 3 consecutive seasons (2015/16, 2016/17, 2017/18; n = 2119). We included patients aged ≥ 18 years who developed influenza-like illness or pneumonia and were hospitalized for management. We included patients confirmed positive for ≥ 1 virus by multiplex polymerase chain reaction assays (respiratory syncytial virus [RSV], human rhinovirus/enterovirus (hRV), human coronavirus (hCoV), metapneumovirus, parainfluenza virus, adenovirus, influenza viruses). We compared patient characteristics, clinical severity conventional outcomes (e.g., hospital length-of stay, 30-day mortality) and ordinal outcomes (5 levels: discharged, receiving convalescent care, acute ward or intensive care unit [ICU] care and death) for patients with NIRV infections and those with influenza.RESULTS:Among 2119 adults who were admitted to hospital, 1156 patients (54.6%) had NIRV infections (hRV 14.9%, RSV 12.9%, hCoV 8.2%) and 963 patients (45.4%) had influenza (n = 963). Patients with NIRVs were younger (mean 66.4 [standard deviation 20.4] yr), and more commonly had immunocompromising conditions (30.3%) and delay in diagnosis (median 4.0 [interquartile range (IQR) 2.0–7.0] days). Overall, 14.6% (12.4%–19.5%) of NIRV infections were acquired in hospital. Admission to ICU (18.2%, median 6.0 [IQR 3.0–13.0] d), hospital length-of-stay (median 5.0 [IQR 2.0–10.0] d) and 30-day mortality (8.4%; RSV 9.5%, hRV 6.6%, hCoV 9.2%) and the ordinal outcomes were similar for patients with NIRV infection and those with influenza. Age > 60 years, immunocompromised state and hospital-acquired viral infection were associated with worse outcomes. The estimated median cost per acute care admission was $6000 (IQR $2000–$16 000).INTERPRETATION:The burden of NIRV infection is substantial in adults admitted to hospital and associated outcomes may be as severe as for influenza, suggesting a need to prioritize therapeutics and vaccines for at-risk people.

The global burden of lower respiratory tract infections is substantial, leading to many hospital admissions and deaths, especially among young children and older adults.¹ Respiratory viruses are responsible for almost half of such infections in adults that require in-hospital management; previous studies estimate that 28%–62% are caused by noninfluenza respiratory viruses (NIRVs).^2–4 With some geographical and seasonal variations, respiratory syncytial virus (RSV), human rhinovirus (hRV) and human coronavirus (hCoV) are among the most frequently identified NIRV infections.^1–7 Most infected adults develop mild, self-limiting illnesses, but increasing evidence suggest that NIRVs, either alone or with coinfecting bacteria, can result in severe pneumonia and death.^8,9 For instance, RSV has been shown to cause severe respiratory failure, with fatality rates comparable to or exceeding those observed among adults admitted to hospital with influenza.^10–12 Data on hRV, hCoV and other NIRVs are more limited, owing to the lack of accurate diagnostics and systematic case-finding approaches.^7–9 However, with the increasing availability of multiplex polymerase chain reaction (PCR) assays that can simultaneously detect influenza and NIRVs, these infections are now readily diagnosed as part of a syndromic approach in patients who present with acute respiratory illnesses.^2–5,13,14 The burden, clinical significance and impacts of NIRVs on the health care system remain inadequately characterized.To address this gap, we analyzed the relative frequencies, patient characteristics, location of acquisition (community or hospital), severity and clinical outcomes of patients with NIRV and influenza infections diagnosed by multiplex PCR in a cohort of adults admitted to hospital in 2 large Canadian health care centres during a 3-year surveillance period. The associated health care resource use was also estimated.     

Sex differences in mortality: results from a population-based study of 12 longitudinal cohorts

BACKGROUND:Women generally have longer life expectancy than men but have higher levels of disability and morbidity. Few studies have identified factors that explain higher mortality in men. The aim of this study was to identify potential factors contributing to sex differences in mortality at older age and to investigate variation across countries.METHODS:This study included participants age ≥ 50 yr from 28 countries in 12 cohort studies of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. Using a 2-step individual participant data meta-analysis framework, we applied Cox proportional hazards modelling to investigate the association between sex and mortality across different countries. We included socioeconomic (education, wealth), lifestyle (smoking, alcohol consumption), social (marital status, living alone) and health factors (cardiovascular disease, diabetes, mental disorders) as covariates or interaction terms with sex to test whether these factors contributed to the mortality gap between men and women.RESULTS:The study included 179 044 individuals. Men had 60% higher mortality risk than women after adjustment for age (pooled hazard ratio [HR] 1.6; 95% confidence interval 1.5–1.7), yet the effect sizes varied across countries (I² = 71.5%, HR range 1.1–2.4). Only smoking and cardiovascular diseases substantially attenuated the effect size (by about 22%).INTERPRETATION:Lifestyle and health factors may partially account for excess mortality in men compared with women, but residual variation remains unaccounted for. Variation in the effect sizes across countries may indicate contextual factors contributing to gender inequality in specific settings.

Life expectancy has increased over the last 6 decades in many societies around the world.¹ Women generally have longer life expectancy than men, yet have higher levels of disability and morbidity.^2,3 Male:female mortality ratios increased from the beginning of the 19th century and slightly decreased over the last 3 decades.^4,5 It has been suggested that the biological differences between the sexes, including genetics and hormones, provide stronger resilience to disadvantageous situations for women than men.⁶ However, biological sex is related to gender, a construct that also incorporates cultural and social differences between men and women. Although some studies suggest that the recent reduction in the male:female mortality ratio is likely a result of improvements in men’s health, lifestyle or occupational environments, others attribute it to women’s changing societal roles and increasing mortality from diseases such as lung cancer, which have traditionally affected mostly men.^3,7–9 Many studies have examined the potential impact of social, behavioural and biological factors on sex differences in mortality,^10,11 but few have been able to investigate potential variation across countries. Different cultural traditions, historical contexts, and economic and societal development may influence gender experiences in different countries, and thus variably affect the health status of men and women.We aimed to identify factors that may explain the difference in mortality risk between men and women at older age and to investigate potential variation across countries, using the harmonized data set of 12 cohort studies from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium.¹²