Which curve are we flattening? The disproportionate impact of COVID-19 among economically marginalized communities in Ontario, Canada, was unchanged from wild-type to omicron

Economically marginalized communities have faced disproportionately higher risks for infection and death from COVID-19 across Canada. It was anticipated that health disparities would dissipate over time and during subsequent waves. We used person-level surveillance and neighbourhood-level income data to explore, using Lorenz curves and Gini coefficients, magnitude of inequalities in COVID-19 hospitalizations and deaths over five waves of COVID-19 in Ontario, Canada (population 14 million) between February 26, 2020 and February 28, 2022. We found that despite attempts at equity-informed policies alongside fluctuating levels of public health measures, inequalities in hospitalizations and deaths by income remained at levels observed during the first wave - prior to vaccination, discussion or implementation of equity-informed policies - and despite rising levels of hybrid immunity. There was no change in the magnitude of inequalities across all waves evaluated. Our findings indicate that interventions did not sufficiently address differential exposure risks amplified at the intersections of household crowding and size, workplace exposures, and systemic barriers to prevention and care (including access to therapeutics). Equity and effectiveness of programs are inherently linked and ongoing evaluation of both is central to inform the public health response to future waves of COVID-19 and other rapidly emergent pandemics.

Area-level social and structural inequalities determine mortality related to COVID-19 diagnosis in Ontario, Canada: a population-based explanatory modeling study of 11.8 million people

ImportanceSocial determinants of health (SDOH) play an important role in COVID-19 outcomes. More research is needed to quantify this relationship and understand the underlying mechanisms. ObjectivesTo examine differential patterns in COVID-19-related mortality by area-level SDOH accounting for confounders; and to compare these patterns to those for non-COVID-19 mortality, and COVID-19 case fatality (COVID-19-related death among those diagnosed). Design, setting, and participantsPopulation-based retrospective cohort study including all community living individuals aged 20 years or older residing in Ontario, Canada, as of March 1, 2020 who were followed through to March 2, 2021. ExposureSDOH variables derived from the 2016 Canada Census at the dissemination area-level including: median household income; educational attainment; proportion of essential workers, racialized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. Main outcomes and measuresCOVID-19-related death was defined as death within 30 days following, or 7 days prior to a positive SARS-CoV-2 test. Cause-specific hazard models were employed to examine the associations between SDOH and COVID-19-related mortality, treating non-COVID-19 mortality as a competing risk. ResultsOf 11,810,255 individuals included, 3,880 (0.03%) died related to COVID-19 and 88,107 (0.75%) died without a positive test. After accounting for demographics, baseline health, and other SDOH, the following SDOH were associated with increased hazard of COVID-19-related death (hazard ratios [95% confidence intervals]) comparing the most to least vulnerable group): lower income (1.30[1.09-1.54]), lower educational attainment (1.27[1.10-1.47]), higher proportion essential workers (1.28[1.10-1.50]), higher proportion racialized groups (1.42[1.16-1.73]), higher proportion apartment buildings (1.25[1.11-1.41]), and larger vs. medium household size (1.30[1.13-1.48]). In comparison, areas with higher proportion racialized groups were associated with a lower hazard of non-COVID-19 mortality (0.88[0.85-0.92]). With the exception of income, SDOH were not independently associated with COVID-19 case fatality. Conclusions and relevanceArea-level social and structural inequalities determine COVID-19-related mortality after accounting for individual demographic and clinical factors. COVID-19 has reversed the pattern of lower non-COVID-19 mortality by racialized groups. Pandemic responses should include prioritized and community-tailored intervention strategies to address SDOH that mechanistically underpin disproportionate acquisition and transmission risks and shape barriers to the reach of, and access to prevention interventions. Key pointsO_ST_ABSQuestionC_ST_ABSAre area-level social determinants of health factors independently associated with coronavirus disease 2019 (COVID-19)-related mortality after accounting for demographics and clinical factors? FindingsIn this population-based cohort study including 11.8 million adults residing in Ontario, Canada and 3,880 COVID-19-related death occurred between Mar 1, 2020 and Mar 2, 2021, we found that areas characterized by lower SES (including lower income, lower educational attainment, and higher proportion essential workers), greater ethnic diversity, more apartment buildings, and larger vs. medium household size were associated with increased hazard of COVID-19-related mortality compared to their counterparts, even after accounting for individual-level demographics, baseline health, and other area-level SDOH. MeaningPandemic responses should include prioritized and community-tailored intervention strategies to address SDOH that mechanistically underpin inequalities in acquisition and transmission risks, and in the reach of, and access to prevention interventions.

Inhaled Corticosteroids for Outpatients with Covid-19: A Meta-Analysis

The role of inhaled corticosteroids for outpatient COVID-19 is evolving. We meta-analyzed reported clinical trials and estimated probability of any effect and number needed to treat of 50 or 20 for symptom resolution by day 14 [100%, 99.8%, 93.1%] and hospitalization [89.3%, 72.9%, 26.7%] respectively.

Increasing concentration of COVID-19 by socioeconomic determinants and geography in Toronto, Canada: an observational study

BackgroundInequities in the burden of COVID-19 observed across Canada suggest heterogeneity within community transmission. ObjectivesTo quantify the magnitude of heterogeneity in the wider community (outside of long-term care homes) in Toronto, Canada and assess how the magnitude in concentration evolved over time (January 21 to November 21, 2020). DesignRetrospective, population-based observational study using surveillance data from Ontarios Case and Contact Management system. SettingToronto, Canada. ParticipantsLaboratory-confirmed cases of COVID-19 (N=33,992). MeasurementsWe generated epidemic curves by SDOH and crude Lorenz curves by neighbourhoods to visualize inequities in the distribution of COVID-19 cases by social determinants of health (SDOH) and estimated the crude Gini coefficient. We examined the correlation between SDOH using Pearson correlation coefficients. ResultsThe Gini coefficient of cumulative cases by population size was 0.41 (95% CI: 0.36-0.47) and were estimated for: household income (0.20, 95%CI: 0.14-0.28); visible minority (0.21, 95%CI: 0.16-0.28); recent immigration (0.12, 95%CI: 0.09-0.16); suitable housing (0.21, 95%CI: 0.14-0.30); multi-generational households (0.19, 95%CI: 0.15-0.23); and essential workers (0.28, 95% CI: 0.23-0.34). Most SDOH were highly correlated. Locally acquired cases were concentrated in higher income neighbourhoods in the early phase of the epidemic, and then concentrated in lower income neighbourhoods. Mirroring the trajectory of epidemic curves by income, the Lorenz curve shifted over time from below to above the line of equality with a similar pattern across SDOH. LimitationsStudy relied on area-based measures of the SDOH and individual case counts of COVID-19. We cannot infer concentration of cases by specific occupational exposures given limitation to broad occupational categories. ConclusionCOVID-19 is increasingly concentrated by SDOH given socioeconomic inequities and structural racism. Primary Funding SourceCanadian Institutes of Health Research.

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

Introduction - Worldwide, nursing home residents have experienced disproportionately high COVID-19 mortality due to the intersection of congregate living, multimorbidity, and advanced age. Among 12 OECD countries, Canada has had the highest proportion of COVID-19 deaths in nursing home residents (78%), raising concerns about a skewed pandemic response that averted much transmission and mortality in community-dwelling residents, but did not adequately protect those in nursing homes. To investigate this, we measured temporal variations in hospitalizations among community and nursing home-dwelling decedents with COVID-19 during the first and second waves of the pandemic. Methods - We conducted a population-based cohort study of residents of Ontario, Canada with COVID-19 who died between March 11, 2020 (first COVID-19 death in Ontario) and October 28, 2020. We examined hospitalization prior to death as a function of 4 factors: community (defined as all non-nursing home residents) vs. nursing home residence, age in years (<70, 70-79, 80-89, [≥]90), gender, and month of death (1st wave: March-April [peak], May, June-July 2020 [nadir], 2nd wave: August-October 2020). Results - A total of 3,114 people with confirmed COVID-19 died in Ontario from March to October, 2020 (Table 1), of whom 1,354 (43.5%) were hospitalized prior to death (median: 9 days before death, interquartile range: 4-19). Among nursing home decedents (N=2000), 22.4% were admitted to hospital prior to death, but this varied substantially from a low of 15.5% in March-April (peak of wave 1) to a high of 41.2% in June-July (nadir of wave 1). Among community-dwelling decedents (N=1,114), admission to acute care was higher (81.4%) and remained relatively stable throughout the first and second waves. Similar temporal trends for nursing home versus community decedents were apparent in age-stratified analyses (Figure 1). Women who died were less likely to have been hospitalized compared to men in both community (80% women vs 84% men) and nursing home (21% women vs 24% men) settings. Discussion - Only a minority of Ontario nursing home residents who died of COVID-19 were hospitalized prior to death, and that there were substantial temporal variations, with hospitalizations reaching their lowest point when overall COVID-19 incidence peaked in mid-April, 2020. While many nursing home residents had pre-pandemic advance directives precluding hospitalization, the low admission rate observed in March-April 2020 (15.5%) was inconsistent with both higher admission rates in subsequent months (>30%), and comparatively stable rates among community-dwelling adults. Our findings substantiate reports suggesting that hospitalizations for nursing home residents with COVID-19 were low during the peak of the pandemics first wave in Canada, which may have contributed to the particularly high concentration of COVID-19 mortality in Ontarios nursing homes.

Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-{gamma} to TNF- ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-{gamma}g+ CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.

The Diagnostic Accuracy of Subjective Dyspnea in Detecting Hypoxemia Among Outpatients with COVID-19

ObjectivesThe majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnea is challenging to assess remotely, and the accuracy of subjective dyspnea measures in capturing hypoxemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnea in diagnosing hypoxemia in COVID-19 patients. MethodsThis is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from April 3, 2020 to June 8, 2020. Hypoxemia was defined by oxygen saturation <95%. Dyspnea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV), and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxemia. ResultsDuring the study period 64/298 (21.5%) of patients met criteria for home oxygen saturation monitoring, and of these 14/64 (21.9%) were diagnosed with hypoxemia. The presence/absence of dyspnea had limited accuracy for diagnosing hypoxemia, with SN 57% (95% CI 30-81%), SP 78% (63%-88%), NPV 86% (72%-94%), PPV 42% (21%-66%), +LR 2.55 (1.3-5.1), -LR 0.55 (0.3-1.0). An mMRC dyspnea score >1 (SP 97%, 95%CI 82%-100%), Roth Maximal Count <12 (SP 100%, 95%CI 75-100%), and Roth Counting time < 8 seconds (SP 93%, 95%CI 66%-100%) had high SP that could be used to rule in hypoxemia, but displayed low SN ([≤]50%). ConclusionsSubjective dyspnea measures have inadequate accuracy for ruling out hypoxemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.

Association Between Nursing Home Crowding and COVID-19 Infection and Mortality in Ontario, Canada

ImportanceNursing home residents have been disproportionately impacted by the COVID-19 epidemic. Prevention recommendations have emphasized frequent testing of healthcare personnel and residents, but additional strategies are needed to protect nursing home residents. ObjectiveWe developed a reproducible index of nursing home crowding and determined whether crowding was associated with incidence of COVID-19 in the first months of the COVID-19 epidemic. Design, Setting, and ParticipantsPopulation-based retrospective cohort study of over 78,000 residents of 618 distinct nursing homes in Ontario, Canada from March 29 to May 20, 2020. ExposureThe nursing home crowding index equalled the average number of residents per bedroom and bathroom. OutcomesPrimary outcomes included the cumulative incidence of COVID-19 infection and mortality, per 100 residents; introduction of COVID-19 into a home ([≥]1 resident case) was a negative tracer. ResultsOf 623 homes in Ontario, we obtained complete information on 618 homes (99%) housing 78,607 residents. A total of 5,218 residents (6.6%) developed COVID-19 infection, and 1,452 (1.8%) died with COVID-19 infection as of May 20, 2020. COVID-19 infection was distributed unevenly across nursing homes: 4,496 (86%) of infections occurred in just 63 (10%) of homes. The crowding index ranged across homes from 1.3 (mainly single-occupancy rooms) to 4.0 (exclusively quadruple occupancy rooms); 308 (50%) homes had high crowding index ([≥]2). Incidence in high crowding index homes was 9.7%, versus 4.5% in low crowding index homes (p<0.001), while COVID-19 mortality was 2.7%, versus 1.3%. The likelihood of COVID-19 introduction did not differ (31.3% vs 30.2%, p=0.79). After adjustment for regional, nursing home, and resident covariates, the crowding index remained associated with increased risk of infection (RR=1.72, 95% Confidence Interval [CI]: 1.11-2.65) and mortality (RR=1.72, 95%CI: 1.03-2.86). Propensity score analysis yielded similar conclusions for infection (RR=2.06, 95%CI: 1.34-3.17) and mortality (RR=2.09, 95%CI: 1.30-3.38). Simulations suggested that converting all 4-bed rooms to 2-bed rooms would have averted 988 (18.9%) infections of COVID-19 and 271 (18.7%) deaths. Conclusions and RelevanceCrowding was associated with higher incidence of COVID-19 infection and mortality. Reducing crowding in nursing homes could prevent future COVID-19 mortality.

Heterogeneity in risk, testing and outcome of COVID-19 across outbreak settings in the Greater Toronto Area, Canada: an observational study

BackgroundWe compared the risk of, testing for, and death following COVID-19 infection across three settings (long-term care homes (LTCH), shelters, the rest of the population) in the Greater Toronto Area (GTA), Canada. MethodsWe sourced person-level data from COVID-19 surveillance and reporting systems in Ontario, and examined settings with population-specific denominators (LTCH residents, shelters, and the rest of the population). We calculated cumulatively, the diagnosed cases per capita, proportion tested for COVID-19, daily and cumulative positivity, and case fatality proportion. We estimated the age- and sex-adjusted relative rate ratios for test positivity and case fatality using quasi-Poisson regression. ResultsBetween 01/23/2020-05/25/2020, we observed a shift in the proportion of cases: from travel-related and into LTCH and shelters. Cumulatively, compared to the rest of the population, the number of diagnosed cases per 100,000 was 59-fold and 18-fold higher among LTCH and shelter residents, respectively. By 05/25/2020, 77.2% of LTCH residents compared to 2.4% of the rest of the population had been tested. After adjusting for age and sex, LTCH residents were 2.5 times (95% confidence interval (CI): 2.3-2.8) more likely to test positive. Case fatality was 26.3% (915/3485), 0.7% (3/402), and 3.6% (506/14133) among LTCH residents, shelter population, and others in the GTA, respectively. After adjusting for age and sex, case fatality was 1.4-fold (95%CI: 1.1-1.9) higher among LTCH residents than the rest of the population. InterpretationHeterogeneity across micro-epidemics among specific populations in specific settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.