Saying it out loud: explicit equity prompts for public health organization resilience.

Introduction: In the early days of the COVID-19 pandemic there were numerous stories of health equity work being put "on hold" as public health staff were deployed to the many urgent tasks of responding to the emergency. Losing track of health equity work is not new and relates in part to the need to transfer tacit knowledge to explicit articulation of an organization's commitment to health equity, by encoding the commitment and making it visible and sustainable in policy documents, protocols and processes. Methods: We adopted a Theory of Change framework to develop training for public health personnel to articulate where and how health equity is or can be embedded in their emergency preparedness processes and documents. Results: Over four sessions, participants reviewed how well their understanding of disadvantaged populations were represented in emergency preparedness, response and mitigation protocols. Using equity prompts, participants developed a heat map depicting where more work was needed to explicitly involve community partners in a sustained manner. Participants were challenged at times by questions of scope and authority, but it became clear that the explicit health equity prompts facilitated conversations that moved beyond the idea of health equity to something that could be codified and later measured. Over four sessions, participants reviewed how well their understanding of disadvantaged populations were represented in emergency preparedness, response and mitigation protocols. Using equity prompts, participants developed a heat map depicting where more work was needed to explicitly involve community partners in a sustained manner. Participants were challenged at times by questions of scope and authority, but it became clear that the explicit health equity prompts facilitated conversations that moved beyond the idea of health equity to something that could be codified and later measured. Discussion: Using the indicators and prompts enabled the leadership and staff to articulate what they do and do not know about their community partners, including how to sustain their involvement, and where there was need for action. Saying out loud where there is - and is not - sustained commitment to achieving health equity can help public health organizations move from theory to true preparedness and resilience.

Effect of Flight Connectivity on Introduction and Evolution of COVID-19 in Canadian Cities.

BACKGROUND: The COVID-19 pandemic has challenged health services and governments in Canada and around the world. Our research aims to evaluate the effect of domestic and international air travel patterns on the COVID-19 pandemic in Canadian provinces and territories. METHODS: Air travel data were obtained through licensed access to the 'BlueDot Intelligence Platform', BlueDot Inc. Daily provincial and territorial COVID-19 cases for Canada and global figures, including mortality, cases recovered, and population data were downloaded from public datasets. The effects of domestic and international air travel and passenger volume on the number of local and non-local infected people in each Canadian province and territory were evaluated with a semi-Markov model. Provinces and territories are grouped into large (>100 000 confirmed COVID-19 cases and > 1 000 000 inhabitants) and small jurisdictions (≤100 000 confirmed COVID-19 cases and ≤ 1 000 000 inhabitants). RESULTS: Our results show a clear decline in passenger volumes from March 2020 due to public health policies, interventions, and other measures taken to limit or control the spread of COVID-19. As the measures were eased, some provinces and territories saw small increases in passenger volumes, although travel remained below pre-pandemic levels. During the early phase of disease introduction, the burden of illness is determined by the connectivity of jurisdictions. In provinces with a larger population and greater connectivity, the burden of illness is driven by case importation, although local transmission rapidly replaces imported cases as the most important driver of increasing new infections. In smaller jurisdictions, a steep increase in cases is seen after importation, leading to outbreaks within the community. CONCLUSIONS: Historical travel volumes, combined with data on an emerging infection, are useful to understand the behaviour of an infectious agent in regions of Canada with different connectivity and population size. Historical travel information is important for public health planning and pandemic resource allocation.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination.

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ increase in number ~12 days following the first and second doses, by 0.31 and 0.43 log10 cells per swab respectively (p = 0.058 and p = 0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decrease post-vaccination. Similar increases in nasal CD8+CD69+CD103- T cells are observed, particularly following the second dose. CD4+ cells co-expressing CCR6 and CD161 are also increased in abundance following both doses. Stimulation of nasal CD8+ T cells with SARS-CoV-2 spike peptides elevates expression of CD107a at 2- and 6-months (p = 0.0096) post second vaccine dose, with a subset of donors also expressing increased cytokines. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

Impact of non-pharmaceutical interventions and vaccination on COVID-19 outbreaks in Nunavut, Canada: a Canadian Immunization Research Network (CIRN) study.

BACKGROUND: Nunavut, the northernmost Arctic territory of Canada, experienced three community outbreaks of the coronavirus disease 2019 (COVID-19) from early November 2020 to mid-June 2021. We sought to investigate how non-pharmaceutical interventions (NPIs) and vaccination affected the course of these outbreaks. METHODS: We used an agent-based model of disease transmission to simulate COVID-19 outbreaks in Nunavut. The model encapsulated demographics and household structure of the population, the effect of NPIs, and daily number of vaccine doses administered. We fitted the model to inferred, back-calculated infections from incidence data reported from October 2020 to June 2021. We then compared the fit of the scenario based on case count data with several counterfactual scenarios without the effect of NPIs, without vaccination, and with a hypothetical accelerated vaccination program whereby 98% of the vaccine supply was administered to eligible individuals. RESULTS: We found that, without a territory-wide lockdown during the first COVID-19 outbreak in November 2020, the peak of infections would have been 4.7 times higher with a total of 5,404 (95% CrI: 5,015-5,798) infections before the start of vaccination on January 6, 2021. Without effective NPIs, we estimated a total of 4,290 (95% CrI: 3,880-4,708) infections during the second outbreak under the pace of vaccination administered in Nunavut. In a hypothetical accelerated vaccine rollout, the total infections during the second Nunavut outbreak would have been 58% lower, to 1,812 (95% CrI: 1,593-2,039) infections. Vaccination was estimated to have the largest impact during the outbreak in April 2021, averting 15,196 (95% CrI: 14,798-15,591) infections if the disease had spread through Nunavut communities. Accelerated vaccination would have further reduced the total infections to 243 (95% CrI: 222-265) even in the absence of NPIs. CONCLUSIONS: NPIs have been essential in mitigating pandemic outbreaks in this large, geographically distanced and remote territory. While vaccination has the greatest impact to prevent infection and severe outcomes, public health implementation of NPIs play an essential role in the short term before attaining high levels of immunity in the population.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Changes in the incidence of seasonal influenza in response to COVID-19 social distancing measures: an observational study based on Canada's national influenza surveillance system.

OBJECTIVES: Seasonal influenza is an acute respiratory infection that presents a significant annual burden to Canadians and the Canadian healthcare system. Social distancing measures that were implemented to control the 2019-2020 novel coronavirus outbreak were investigated for their ability to lessen the incident cases of seasonal influenza. METHODS: We conducted an ecological study using data from Canada's national influenza surveillance system to investigate whether social distancing measures to control COVID-19 reduced the incident cases of seasonal influenza. Data taken from three separate time frames facilitated analysis of the 2019-2020 influenza season prior to, during, and following the implementation of COVID-19-related measures and enabled comparisons with the same time periods during three preceding flu seasons. The incidence, which referred to the number of laboratory-confirmed cases of specific influenza strains, was of primary focus. Further analysis determined the number of new laboratory-confirmed influenza or influenza-like illness outbreaks. RESULTS: Our results indicate a premature end to the 2019-2020 influenza season, with significantly fewer cases and outbreaks being recorded following the enactment of many COVID-19 social distancing policies. The incidence of influenza strains A (H3N2), A (unsubtyped), and B were all significantly lower at the tail end of the 2019-2020 influenza season as compared with preceding seasons (p = 0.0003, p = 0.0007, p = 0.0019). CONCLUSION: Specific social distancing measures and behaviours may serve as effective tools to limit the spread of influenza transmission moving forward, as they become more familiar.

RéSUMé: OBJECTIFS: La grippe saisonnière est une infection aiguë des voies respiratoires qui représente un important fardeau annuel pour la population et pour le système de soins de santé du Canada. Nous avons cherché à déterminer si les mesures de distanciation sociale appliquées pour contrôler l'éclosion du nouveau coronavirus en 2019­2020 ont pu atténuer les cas incidents de grippe saisonnière. MéTHODES: Nous avons mené une étude écologique à l'aide des données du système national de surveillance de l'activité grippale au Canada pour déterminer si les mesures de distanciation sociale appliquées pour contrôler la COVID-19 ont réduit les cas incidents de grippe saisonnière. Des données provenant de trois périodes distinctes ont facilité l'analyse de la saison grippale 2019­2020 avant, pendant et après l'application des mesures liées à la COVID-19 et permis des comparaisons avec les mêmes intervalles durant trois saisons grippales antérieures. L'incidence, c'est-à-dire le nombre de cas confirmés en laboratoire de souches grippales particulières, était notre principal objectif. Des analyses plus poussées ont permis de déterminer le nombre de nouvelles éclosions de syndrome grippal ou de grippe confirmée en laboratoire. RéSULTATS: Selon nos résultats, la saison grippale 2019­2020 a connu une fin prématurée; un nombre sensiblement moins élevé de cas et d'éclosions ont été enregistrés après la mise en place des nombreuses politiques de distanciation sociale liées à la COVID-19. L'incidence des souches grippales A (H3N2), A (non sous-typée) et B a été sensiblement moins élevée vers la fin de la saison grippale 2019­2020 comparativement aux saisons précédentes (p = 0,0003, p = 0,0007, p = 0,0019). CONCLUSION: Des mesures et des comportements de distanciation sociale particuliers peuvent être des outils efficaces pour limiter la propagation de la grippe maintenant qu'ils sont plus familiers.

Extraction-free RT-LAMP to detect SARS-CoV-2 is less sensitive but highly specific compared to standard RT-PCR in 101 samples.

The current scale of public and private testing cannot be expected to meet the emerging need for higher levels of community-level and repeated screening of asymptomatic Canadians for SARS-CoV-2. Rapid point-of-care techniques are increasingly being offered to fill the gap in screening levels required to identify undiagnosed individuals with high viral loads. However, rapid, point-of-care tests often have lower sensitivity in practice. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) for SARS-CoV-2 has proven sensitive and specific and provides visual results in minutes. Using a commercially available kit for RT-LAMP and primer set targetting nucleocapsid (N), we tested a blinded set of 101 archived nasopharyngeal (NP) swab samples with known RT-PCR results. RT-LAMP reactions were incubated at 65 °C for 30 min, using heat-inactivated nasopharyngeal swab sample in viral transport medium, diluted tenfold in water, as input. RT-LAMP agreed with all RT-PCR defined negatives (N = 51), and all positives with cycle threshold (Ct) less than 20 (N = 24), 65% of positives with Ct between 20-30 (N = 17), and no positives with Ct greater than 30 (N = 9). RT-LAMP requires fewer and different core components, so may not compete directly with the mainline testing workflow, preserving precious central laboratory resources for those with the greatest need. Careful messaging must be provided when using less-sensitive tests, so that people are not falsely reassured by negative results, but this caveat must be weighed against the clear benefits of reliably identifying those with high levels of virus in prioritized samples at the point of care.

Knowledge brokering on infectious diseases for public health.

The National Collaborating Centres (NCCs) for Public Health (NCCPH) were established in 2005 as part of the federal government's commitment to renew and strengthen public health following the severe acute respiratory syndrome (SARS) epidemic. They were set up to support knowledge translation for more timely use of scientific research and other knowledges in public health practice, programs and policies in Canada. Six centres comprise the NCCPH, including the National Collaborating Centre for Infectious Diseases (NCCID). The NCCID works with public health practitioners to find, understand and use research and evidence on infectious diseases and related determinants of health. The NCCID has a mandate to forge connections between those who generate and those who use infectious diseases knowledge. As the first article in a series on the NCCPH, we describe our role in knowledge brokering and the numerous methods and products that we have developed. In addition, we illustrate how NCCID has been able to work with public health to generate and share knowledge during the coronavirus disease 2019 (COVID-19) pandemic.

Simulating the effect of school closure during COVID-19 outbreaks in Ontario, Canada.

BACKGROUND: The province of Ontario, Canada, has instituted indefinite school closures (SC) as well as other social distancing measures to mitigate the impact of the novel coronavirus disease 2019 (COVID-19) pandemic. We sought to evaluate the effect of SC on reducing attack rate and the need for critical care during COVID-19 outbreaks, while considering scenarios with concurrent implementation of self-isolation (SI) of symptomatic cases. METHODS: We developed an age-structured agent-based simulation model and parameterized it with the demographics of Ontario stratified by age and the latest estimates of COVID-19 epidemiologic characteristics. Disease transmission was simulated within and between different age groups by considering inter- and intra-group contact patterns. The effect of SC of varying durations on the overall attack rate, magnitude and peak time of the outbreak, and requirement for intensive care unit (ICU) admission in the population was estimated. Secondly, the effect of concurrent community-based voluntary SI of symptomatic COVID-19 cases was assessed. RESULTS: SC reduced attack rates in the range of 7.2-12.7% when the duration of SC increased from 3 to 16 weeks, when contacts among school children were restricted by 60-80%, and in the absence of SI by mildly symptomatic persons. Depending on the scenario, the overall reduction in ICU admissions attributed to SC throughout the outbreak ranged from 3.3 to 6.7%. When SI of mildly symptomatic persons was included and practiced by 20%, the reduction of attack rate and ICU admissions exceeded 6.3% and 9.1% (on average), respectively, in the corresponding scenarios. CONCLUSION: Our results indicate that SC may have limited impact on reducing the burden of COVID-19 without measures to interrupt the chain of transmission during both pre-symptomatic and symptomatic stages. While highlighting the importance of SI, our findings indicate the need for better understanding of the epidemiologic characteristics of emerging diseases on the effectiveness of social distancing measures.