BACKGROUND:Public health emergencies require rapid generation, synthesis, and translation of clinical evidence into practice guidelines; yet, systematic synthesis of the challenges and lessons from these processes remains limited. OBJECTIVES:The purpose of this study was to examine how evidence on anticoagulation in COVID-19 was generated and translated into clinical guidance, using randomized controlled trials (RCTs) as a case study, and to contextualize these processes with an individual participant data meta-analysis (IPDMA). METHODS:Systematic searches identified RCTs comparing therapeutic- vs nontherapeutic-dose anticoagulation in noncritically ill patients hospitalized for COVID-19. Trial characteristics, evidence accumulation, and associated guideline recommendations were summarized over time. An IPDMA was performed to estimate summary treatment effects using mixed-effects logistic regression. RESULTS:Evidence evolved from an early coordinated platform RCT (preprint May 2021) to subsequent RCTs published between June 2021 and July 2023. In exploratory counterfactual sequential IPDMA, the pooled treatment effect on organ support or death became statistically significant in May 2021, approximately 13 months after first patient enrollment (adjusted OR: 0.73; 95% CI: 0.58-0.91; 6 RCTs, n = 3,944). Guideline recommendations shifted from uniform endorsement of prophylactic-dose anticoagulation in 2020 to recommendations supporting therapeutic-dose anticoagulation in 2022, with variation in certainty across guidelines. Individual participant data were obtained after completion of data transfer in April 2024 and included 7 RCTs comprising 6,362 patients. Therapeutic-dose anticoagulation reduced the odds of organ support or death (12.9% vs 16.2%; adjusted OR: 0.81; 95% CI: 0.67-0.97). Major bleeding was rare (0.8% vs 0.5%). CONCLUSIONS:The COVID-19 anticoagulation experience highlights how delays in coordination, data sharing, and synthesis can slow the translation of evidence into practice. Therapeutic-dose anticoagulation was associated with reduced odds of organ support or death and, in this context, serves as a case study of how evidence emerges and is acted upon under conditions of uncertainty. Strengthening coordinated research networks, platform trial infrastructures, prioritized funding, and near-real-time cross-trial synthesis may improve the timeliness, reliability, and responsiveness of evidence systems during future health emergencies.

Background The Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID) is a multi-provincial adaptive platform trial (APT) evaluating outpatient therapeutics for individuals with mild to moderate SARS-CoV-2 infection at high risk of severe outcomes. Conducted across six Canadian provinces from January 2023 to March 2025, this paper describes its implementation and lessons for future APTs. Methods We conducted a structured reflection on trial implementation across six domains: governance, stakeholder engagement, recruitment strategies, consent and enrollment processes, operational challenges, and cross-trial collaboration. Insights were derived from documentation of trial operations, governance records, protocol amendments, monitoring reports, and discussions among trial leadership and committee members. Lessons were synthesized across domains and translated into recommendations to support future APT implementation. Results CanTreatCOVID highlighted the need for a centralized governance model. While the Steering Committee and Data Safety Monitoring Committee provided strategic oversight and safety monitoring, complementary committees for statistical methods, therapeutic selection, and recruitment addressed trial-specific needs. Regular stakeholder engagement supported trial design and implementation. Proactive communication with ethics boards facilitated regulatory approvals. Pre-negotiated agreements and national ethics review pathways were critical enablers accelerating site activation. Recruitment required multi-faceted strategies that adapted to evolving standards of care, supported by flexible, remote consent and online screening processes that reduced participant burden. Finally, aligning eligibility criteria, outcomes, and analytic approaches with international APTs enabled pooled analyses and strengthened evidence generation. Conclusion CanTreatCOVID demonstrates feasibility of decentralized APTs in community settings. These lessons and recommendations provide a framework to optimize future APTs.Trial registration: ClinicalTrials.gov (NCT05614349).

Abstract Wastewater-based surveillance of SARS-CoV-2 RNA has been implemented at building, neighbourhood, and city levels throughout the world. Implementation strategies and analysis methods differ, but they all aim to provide rapid and reliable information about community COVID-19 health states. A viable and sustainable SARS-CoV-2 surveillance network must not only provide reliable and timely information about COVID-19 trends, but also provide for scalability as well as accurate detection of known or unknown emerging variants. Emergence of the SARS-CoV-2 variant of concern Omicron in late Fall 2021 presented an excellent opportunity to benchmark individual and aggregated data outputs of the Ontario Wastewater Surveillance Initiative in Canada; this public health-integrated surveillance network monitors wastewaters from over 10 million people across major population centres of the province. We demonstrate that this coordinated approach provides excellent situational awareness, comparing favourably with traditional clinical surveillance measures. Thus, aggregated datasets compiled from multiple wastewater-based surveillance nodes can provide sufficient sensitivity (i.e., early indication of increasing and decreasing incidence of SARS-CoV-2) and specificity (i.e., allele frequency estimation of emerging variants) with which to make informed public health decisions at regional- and state-levels.

What do we know so far? Adenoviral vector COVID-19 vaccines, including the AstraZeneca/COVISHIELD vaccine and the Janssen/Johnson & Johnson vaccine, are associated with immune thrombosis that is similar to heparin-induced thrombocytopenia (HIT). Women and young people appear to be slightly overrepresented in reported cases, and thrombosis seems to occur 4 to 28 days after vaccination. Affected individuals have antibodies targeted […]

Key MessageSARS-CoV-2 infection has taken a disproportionate toll on Ontario older adults, and on residents of disadvantaged and racialized urban neighbourhoods throughout the province.Prioritizing and implementing vaccine distribution for Ontarians based on both age and neighbourhood of residence could ensure that those at the highest risk of SARS-CoV-2 infection, and hospitalization, ICU admission or death from COVID-19 will be among the first to receive vaccines.This vaccine strategy will maximize the prevention of deaths and long-term morbidity, and best maintain health care system capacity by reducing hospitalizations and ICU admissions due to COVID-19 as compared with a strategy that prioritizes vaccination based on age alone (Figure 1).The strategy would not interfere with the ongoing and future vaccination of any specific high-risk population, as it is intended to guide the mass distribution of vaccines to the general Ontario population.Figure 1.Projected Number of Prevented COVID-19 Hospitalizations, ICU Admissions and Deaths by Two Strategies for Mass Distribution of Vaccines in Ontario, March 1 to May 31, 2021 Bar graph presenting the projected number of prevented hospitalizations, ICU admissions and deaths due to COVID-19 in Ontario from March 1-May 31, 2021 under two strategies for mass distribution of vaccines: 1) prioritization based on age alone (blue bars) and 2) prioritization based on age and neighbourhood of residence (orange bars).The brackets above the bar graphs report the relative difference (%) in prevented outcomes between the two strategies for mass distribution of vaccines.See Table 1 below for the number of projected events associated with the different distribution strategies.

Tocilizumab is an anti-inflammatory medication that acts by inhibiting interleukin-6 (IL-6) and is shown to improve outcomes including mortality in patients hospitalized with COVID-19 requiring supplemental oxygen. Ontario supply of tocilizumab is limited, and tocilizumab demand in Ontario might exceed supply in the near future. A strategy that includes using a fixed, single intravenous dose of 400 mg for eligible patients will help extend available supply and is likely effective in treatment of COVID-19. Sarilumab, another IL-6 inhibitor, can be considered as a substitute. Additional options to consider to optimize tocilizumab use include the use of a provincial dashboard to help monitor and allocate use and estimating supply-to-demand adequacy. Likewise, a centralized allocation lottery system could be employed as soon as predicted demand exceeds supply to help ensure fair allocation. However, other issues may need to be taken into account for allocation decisions, as appropriate.

Administering Pfizer-BioNTech’s COVID-19 vaccine during the early stage of the vaccine rollout (January/February 2021) to as many individuals as possible would prevent more COVID-19 cases in Ontario as compared to reserving half of the initial allotments as second booster doses (Figure 1). On-label use of the vaccine with the administration of two doses is important, as the second dose significantly boosts the immune response and results in a substantial increase in neutralizing antibodies. However, using 100% of the initial allotments immediately to vaccinate as many individuals as possible does not preclude on-label use with two doses, even though the interval between first and second booster dose may become longer than 21 days.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.

The rate of SARS-CoV-2 infection in pregnancy does not appear to be higher than in the general population; however, compared to their non-pregnant counterparts, pregnant individuals have higher morbidity and mortality, with a higher risk of intensive care unit (ICU) admission, mechanical ventilation, and need for extracorporeal membrane oxygenation (ECMO). They also have a higher frequency of pre-eclampsia, Cesarean delivery, and a higher rate of preterm birth. Care of the critically ill pregnant patient with COVID-19 requires a multidisciplinary team that includes obstetrics, neonatology, anesthesia, infectious diseases, medicine, and critical care. Potentially life-saving evidence-based therapies such as corticosteroids and tocilizumab should not be withheld from pregnant individuals with severe COVID-19. Vaccines against SARS-CoV-2 are safe to use among pregnant individuals and vaccination is highly recommended in this population.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs. The Drugs & Biologics Clinical PracticeGuidelines Working Group is a group of clinicians and scientists with recognized expertise in drugs, biologics, and clinical care.The Working Group evaluates existing scientific data, disease epidemiology, drug availability, and implementation issues in order to develop Clinical Practice Guidelines for the treatment of COVID-19 using drugs and biologics.The Working Group reports its findings to the public and the Science Table .Its findings are also summarized in Science Briefs.

Homebound individuals face substantial barriers to receiving COVID-19 vaccines as they cannot or rarely leave their homes because of medical, psychiatric, cognitive, functional, transportation-related and social reasons. There are at least 75,000 Ontarians aged 65 years and above who are homebound, with the majority being women and people aged 85 years and above. Much of this older homebound population requires mobile in-home COVID-19 vaccination, which could be prioritized by residence in high SARS-CoV-2 risk neighbourhoods.

Multiple jurisdictions have adopted or adapted paid sick leave policies to reduce the likelihood of employees infected with SARS-CoV-2 presenting to work, which can lead to the spread of infection in workplaces. During the COVID-19 pandemic, paid sick leave has been associated with an increased likelihood of workers staying at home when symptomatic. Paid sick leave can support essential workers in following public health measures. This includes paid time off for essential workers when they are sick, have been exposed, need to self-isolate, need time off to get tested, when it is their turn to get vaccinated, and when their workplace closes due to an outbreak. In the United States, the introduction of a temporary paid sick leave, resulted in an estimated 50% reduction in the number of COVID-19 cases per state per day. The existing Canada Recovery Sickness Benefit (CRSB) cannot financially protect essential workers in following all public health measures, places the administrative burden of applying for the benefit on essential workers, and neither provides sufficient, nor timely payments. Table 1 lists the characteristics of a model paid sick leave program as compared with the CRSB. Implementation of the model program should be done in a way that is easy to navigate and quick for employers.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.The Drugs & Biologics Clinical Practice Guidelines Working Group is a group of clinicians and scientists with recognized expertise in drugs, biologics, and clinical care.The Working Group evaluates existing scientific data, disease epidemiology, drug availability, and implementation issues in order to develop Clinical Practice Guidelines for the treatment of COVID-19 using drugs and biologics.The Working Group reports its findings to the public and the Science Table.Its findings are also summarized in Science Briefs.

overall well-being of children and youth.Therefore, barring catastrophic circumstances, schools should remain open for in-person learning.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.The Congregate Care Setting Working Group is a group of internationally recognized researchers with expertise in older people living in congregate care settings.The Working Group evaluates emerging scientific evidence related to congregate care settings to inform Ontario's response to the COVID-19 pandemic.The Working Group reports its findings to the public and the Science Table.Its findings are also summarized in Science Briefs.

About Us: The Ontario COVID-19 Science Advisory Table is a group of scientific experts and health system leaders who evaluate and report on emerging evidence relevant to the COVID-19 pandemic, to inform Ontario's response.Our mandate is to provide weekly summaries of relevant scientific evidence for the COVID-19 Health Coordination Table of the Province of Ontario, integrating information from existing scientific tables, Ontario's universities and agencies, and the best global evidence.The Science Table summarizes its findings for the Health Coordination Table and the public in Science Briefs.

Naturally occurring retirement communities (NORCs) are apartment, condo, co-op and social housing buildings that while not purpose-built for older adults, have become home to a high number of them. In Toronto, there are 489 residential buildings that are NORCs. Of these, 256 are located in neighbourhoods with the highest cumulative incidence of SARS-CoV-2, and are home to 40,955 older adults 65 years of age and above, including 18,144 older adults 80 years of age and above. Prioritizing COVID-19 vaccination by both age and neighbourhood of residence is an effective strategy to minimize deaths, morbidity, and hospitalization. Targeting people living in NORCs in high-risk neighbourhoods for early vaccination is a practical application of that strategy, which will also address barriers to vaccination in this population.

Key MessageThe rollout of COVID-19 vaccines to Ontario's long-term care (LTC) homes has substantially reduced SARS-CoV-2 infections, COVID-19 hospitalizations, and deaths among LTC residents and health care workers.Completing and maximizing the uptake of the full COVID-19 vaccine series according to recommended schedules will maximize the safety and well-being of Ontario's LTC residents and staff. Summary BackgroundWhile only accounting for 0.5% of Ontario's population, long-term care (LTC) residents across the province have had disproportionately high rates of SARS-COV-2 infections and COVID-19 deaths.Ontario's COVID-19 vaccine rollout began in mid-December 2020, with LTC residents and staff identified as Phase 1 priority populations for vaccination. QuestionWhat was the early impact of the COVID-19 vaccine on SARS-CoV-2 cases, COVID-19 hospitalizations and deaths among Ontario's LTC residents and health care workers (HCWs)? FindingsLTC home staff were the first to receive the vaccine in clinics starting on December 14, 2020.Most LTC home residents started receiving first doses of the COVID-19 vaccine after December 23, 2020.All LTC residents in Ontario were offered at least the first dose of a COVID-19 vaccine by February 13, 2021.As of February 23, 2021, more than 64,000 Ontario LTC residents (92%) received at least one dose of a COVID-19 vaccine, with over 46,500 of residents having received both doses.Over 55,000 Ontario LTC staff (55%) also received at least one dose of a COVID-19 vaccine, with more than 44,600 having received both doses.As of February 23, 2021, COVID-19 vaccination in LTC homes prevented an estimated 2,079 SARS-CoV-2 infections, 249 COVID-19 hospitalizations, and 615 COVID-19 deaths in residents, and an estimated 330 SARS-CoV-2 infections, and 8 COVID-19 hospitalizations and 1 COVID-19 death in HCWs.Version 1.