Meetings 45-46 of the CSA COVID-19 Expert Panel

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As part of the response to the COVID-19 pandemic, the Chief Science Advisor of Canada created the Expert Panel on COVID-19 to advise her on the latest and most relevant scientific developments. This information assists the Chief Science Advisor in providing current, cross-disciplinary and independent advice to the Prime Minister and government.

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Overview of discussions

Held by MS Teams on October 8 and 25, 2021

The following discussion reflects evidence and scientific knowledge up to October 24, 2021.

Participating expert panel members*:

• Mona Nemer PhD, Chief Science Advisor of Canada (chair)

Disease modelling

• Caroline Colijn PhD, Simon Fraser University (October 8)
• Daniel Coombs PhD, University of British Columbia

Risk and behavioural sciences

• Daniel Krewski PhD, University of Ottawa
• Kim Lavoie PhD, Université du Québec à Montréal
• Louise Lemyre PhD, University of Ottawa
• Steven Taylor PhD, University of British Columbia

Biomedical and clinical sciences

• Maziar Divangahi PhD, McGill University (October 8)
• Eleanor Fish PhD, University of Toronto
• Joanne Langley MD, Dalhousie University
• Allison McGeer MD, Mount Sinai Hospital, University of Toronto
• Samira Mubareka MD, Sunnybrook Research Institute
• Caroline Quach-Thanh MD, Université de Montréal (October 8)
• Supriya Sharma MD, Health Canada

Invited experts*:

• Isaac Bogoch MD, Toronto General Hospital (October 8)
• Eric Cohen MD, Institut de recherches cliniques de Montréal (October 8)
• Alan Forster MD, FRCPC, MSc, The Ottawa Hospital (October 8)
• Charu Kaushic PhD, McMaster University
• John Kim MD, PhD, Public Health Agency of Canada
• Richard Menzies MD, McGill International TB Centre
• Pascal Michel PhD, Public Health Agency of Canada
• Brent Moloughney MD, MSc, FRCPC, University of Toronto (October 8)
• Sarah Otto PhD, University of British Columbia
• Tracy Vaillancourt PhD, University of Ottawa

Other*:

• Lori Engler-Todd MSc, Office of the Chief Science Advisor (support)
• Vanessa Sung PhD, Office of the Chief Science Advisor (support)
• Nayaar Islam BHSc, MSc Candidate, Office of the Chief Science Advisor (support)
• Andreea-Diana Moisa BSc, Office of the Chief Science Advisor (support)

* participated in both meetings unless otherwise stated in brackets

Context

The CSA Expert Panel convened with invited guest experts to discuss scientific considerations for the preparation and management of an anticipated SARS-CoV-2 pandemic to endemic transition. The invited guests included infectious disease, health system and education specialists, evolutionary virologists. A summary of the key scientific observations and considerations going forward is included below.

Scientific observations

Characteristics of an endemic state

• During an epidemic or a pandemic state, infections spread rapidly and exponentially.
• If the virus does not fade out, it can circulate within a population for an extended period of time at a lower prevalence than at the peak of the epidemic – this is an endemic state^{Footnote 1}. Local outbreaks can occur in an endemic state.
• Lessons from other pathogens indicate that endemicity does not mean “no harm” and that there is no set path. Endemic also does not mean that incidence and prevalence will necessarily be very low, or low enough for some desired circumstance (for example, low demand for health care). Globally, some endemic infectious diseases have been well-controlled (e.g., measles and Ebola), whereas others have not (e.g., HIV, tuberculosis, influenza).
• There is growing consensus that SARS-CoV-2 will become endemic based on a number of factors, including:
  • An estimated doubling time for Omicron that is 4 to 5 times higher than for the Delta variant^{Footnote 2}
  • Asymptomatic and airborne transmission
  • Evidence of waning immunity post-vaccination or post-infection^{Footnote 1}
  • Absence of vaccine-induced sterilizing immunity^{Footnote 1}.
• Other countries (e.g., Israel, Brazil, New Zealand, UK) provide a glimpse of the path that COVID-19 could take moving forward. The factors that will affect an endemic steady state include:
  • The ability to limit transmission
  • The ability to prevent severe disease
  • The emergence of variants of concern^{Footnote 3 Footnote 4};
  • The development and availability of effective therapeutics
  • Vaccine coverage and effectiveness, as well as durability of immunity^{Footnote 3 Footnote 4}
  • Maintenance of behavioral, social, and environmental public health measures^{Footnote 3 Footnote 4}
  • Inequities associated with high-risk populations^{Footnote 3 Footnote 4}
  • Number of introductions of new variants of concern into Canada through travel.

Lessons learned from other endemic infectious diseases

Tuberculosis

• Tuberculosis (TB) is not as contagious as COVID-19, but similarly can be asymptomatic or latent. As such, TB can be spread via travel over long distances. There is treatment but no effective vaccine for TB.
• At the global level, TB is not well controlled, although TB rates are very low in most of Canada. Management of the disease has largely relied on general health conditions and social determinants of health, i.e., outbreaks occur when population health worsens, particularly among at-risk populations. Similarly, it is possible that the current disproportionate burden of COVID-19 will continue or worsen during the endemic phase of the virus.

Influenza

• Influenza is a chronic burden of infection on the population. In Canada, it is the cause of ~12,000 hospitalizations and 3,500 deaths per year^{Footnote 5}.
• In contrast to the current COVID-19 pandemic, endemic COVID-19 may have far less impact on Canadian communities, as fewer deaths and less morbidity are anticipated. This relies on high levels of immunity being maintained. However, at this time the overburdened healthcare system does not have the capacity to manage an influenza level of endemic COVID-19 hospitalizations and deaths.
• Additional approaches to reduce COVID-19 disease burden will likely be needed. This includes the maintenance of some behavioral, social and environmental measures as well as investments into health systems.

HIV

• There are major differences between HIV and SARS-CoV-2 (e.g., the former is a persistent long-term infection, the latter is an acute short-term infection albeit with potential long-term sequalae), however both have caused global pandemics and are good reminders that what happens in one part of the world can have global implications.
• It will be important to monitor COVID-19 developments (e.g., variants, immune evasion) in countries with fewer resources and low vaccine access.
• Lessons from HIV that could be applicable to SARS-CoV-2 include:
  • socio-behavioral considerations (e.g., stigma and subgroup culture),
  • intervention approaches and policy options (e.g., harm reduction)
  • the use of combination antiviral therapeutic interventions to limit the emergence of drug resistance and variants of concern.

Evolution of the virus

• SARS-CoV-2 gains a mutation every two weeks somewhere in the genome. In the first year of the pandemic, mutations accumulated but there was not much selection. Variants of concern began emerging in the second year.
• Given the dominance of the Delta variant, new variants of concern may emerge from this lineage as there are already subtypes of Delta (e.g., AY.25, AY.27, and AY.4.2) circulating^{Footnote 6}. However, undetected variants from previous strains may also be circulating, especially in places with limited to no capacity for genomic screening and surveillance.
• At this point, the virus has already explored all possible one-step and two-step mutations of the genome. With respect to the fitness of the virus, it is not yet known what is possible with recombination of mutations, but surveillance is underway.
• Evolutionary selection has favoured increased transmission until now^{Footnote 7}. Selection pressure moving forward may favour mutations that facilitate immune escape ( i.e. the virus evading the immune system) in an endemic state^{Footnote 8}.
  • Complete immune escape may not be easily achievable because vaccine-induced immunity is unique to an individual. This means there are many aspects of the immune response for the virus to overcome, unlike antibiotic resistance in bacteria. Immune evasion will likely need an accumulation of mutations, rather than a single mutation.
  • The best way to minimize the development and impact of immune escape variants is to focus efforts on both vaccinated and unvaccinated populations alike. Steps should be taken to reduce the emergence of variants and their transmission.
    • Immunosuppressed individuals require particular attention and protection as they are susceptible to prolonged COVID-19 infection which can lead to rapid viral evolution and highly mutated variants^{Footnote 9}.
    • Mutation-inducing drugs such as Molnupiravir should be used with caution.
    • Once a new variant of concern emerges, the spread can be slowed by rapid case detection and effective reduction transmission chains.

Considerations for managing endemic SARS-COV-2

The “long-game”

• There is growing consensus that, over the longer-term, it is likely that COVID-19 will transition to become another endemic and/or seasonal respiratory disease that the population lives with. Protocols with clear accountabilities to manage an outbreak or emerging variant of concern are essential within and across jurisdictions for rapid, effective emergency action.
• It will be necessary to use a number of indicators to activate additional public health interventions to prevent and manage COVID-19 outbreaks, including border measures. Such indicators include:
  • Real time number of cases or their rate of increase, test positivity rate, and number of respiratory PCR tests administered (noting these require that people get tested and that results are monitored)
  • Hospitalizations (rate or number of admissions to hospital), emergency department visits for influenza-like illnesses or pneumonia, and mortality (noting these indicators lag behind community transmission)
  • Wastewater surveillance signals from communities, vessels, and airports
  • Measures of health system capacity, such as wait times for indications other than COVID-19.
• It is particularly important to prevent provincial and territorial health systems from being overburdened by hospitalizations from COVID-19, given the burden from existing seasonal infectious diseases.
• Given the uncertainties around the post-pandemic reality, it will be important to prime the public to be adaptable by emphasizing the need to remain attentive to surveillance data and be willing to remain engaged with protective behavior, as needed. This includes masking, uptake of boosters, distancing, avoiding crowds, seeking testing and isolating when ill.
  • Rather than tying policy change to fixed dates, it would be better to link policy change to public health benchmarks, which points to the fluctuating nature of the situation.
  • Improvements in the COVID-19 situation (i.e., less transmission, morbidity, and mortality) are collective achievements resulting from the public’s uptake of vaccines and adherence to public health measures and should be communicated as such.
• Human behavior is the first line of defense which has inherent challenges, including:
  • Pandemic exhaustion – people want to just move on from the pandemic and its associated public health measures.
    • Canadians’ intentions to continue participating in protective behavior (e.g., masking) decreased from March to June 2021 for both vaccinated and unvaccinated populations, with a larger decrease in the unvaccinated, based on preliminary findings from an iCARE study survey (n=6000). These data suggest that unvaccinated individuals have a strong risk of continuing to propagate the SARS-CoV-2 virus.
  • Some subgroups have significant incentive to NOT know their infection status (e.g., loss of income). There continues to be a need to reduce the negative consequences of testing positive for COVID-19.
  • Misinformation and disinformation influence individuals’ own biases which may not be grounded in science and evidence, further eroding social cohesion.
• It may be helpful to reframe an “acceptable level of COVID-19 burden” in an endemic stage as an “acceptable means of protection”, i.e., based on the trade-offs people are willing to accept to be protected from COVID-19. A shutdown of the economy and not traveling are no longer acceptable to Canadians, whereas most find vaccination to be acceptable. A key question is “how can the acceptability of relatively minor inconveniences like wearing a mask, hand hygiene, and using vaccine certificates in certain contexts be sustained?”.

Knowledge gaps

Immunity

• More information is needed regarding the duration of protection against infection and severe disease, as related to age, health status, length of vaccine dose interval, and time since immunization or infection, specifically in Canadian populations.
• It is known that a person’s first exposure to influenza shapes the susceptibility to and outcomes of subsequent infections. Whether or not this is also the case for SARS-CoV-2 requires investigation.

Viral evolution

• SARS-CoV-2 will continue to evolve. Larger adaptations tend to happen more frequently when an organism first finds itself in a new environment (e.g., in the human population). Moving forward, adaptations leading to smaller advantages for the virus are expected, though there can be punctuated ‘shift’ events that substantially change a virus’ phenotype. However, it is not yet known recombination events might yield.
• The observed waning of neutralizing antibodies over time in vaccinated individuals seems largely due to the normal progression of immune systems. Cellular immunity, which plays a key role in long-term immunity, has so far been minimally affected by viral mutations, but this could change in the future and requires monitoring.
• The extent of SARS-CoV-2 transmission that is human-to-animal, animal-to-animal and animal-to-human in Canada is currently unknown. Research that increases knowledge of SARS-CoV-2 and other coronavirus prevalence, and risk factors for exposure and spillover at the human-animal-environment interface is required.

Impacts on children

• The impacts of COVID-19 on the health and welfare of children and youth have not been adequately measured in Canada in a nationally representative way, compared to peer nations.
• There are some efforts underway, such as the Child Health Survey on Children and Youth. It is important that these efforts have the resources to continue so that there is a better understanding of what is needed to support children and youth.

Co-circulation with other viruses

• While diagnostic laboratories regularly report on circulating respiratory viruses, more research is needed on the co-circulation of seasonal coronaviruses, co-infection with SARS-CoV-2, and potential health impacts of recombination.
• Development of differential diagnoses and tools (including point of care) is also needed for distinguishing SARS-CoV-2 from influenza, respiratory syncytial virus (RSV), and other potential co-circulating viruses.

Behavior

• Research on what activities Canadians value most (e.g., visiting family and friends, traveling) are needed so they can be supported to do them safely in the context of an ongoing pandemic/endemic. Statistics Canada could be well-placed to do nationally representative studies on COVID-19 related behavior.
• More granular epidemiology and mapping of outbreaks are needed to better understand what the riskiest settings, activities, and behavior are. This requires capacity and system for efficient contact tracing, especially for a new variant of concern. Communications could then shift from WHO is at risk of exposure to WHERE and WHAT, allowing people to make informed decisions and self-regulate.

Areas requiring continuous attention

In addition to research to address knowledge gaps, the six key areas outlined below will require continuous attention and action going forward as we transition to an endemic state.

1. Prevention and treatment

Prevention of infection and breaking chains of transmission are achieved through protective behavior, such as masking and vaccine acceptance and by reducing airborne transmission of SARS-CoV-2 indoors through proper ventilation and air circulation. Treatment will also continue to be important.

Protective behavior

• It would be more productive and sustainable in the long-term for public health guidance to communicate the relevant evidence, including the benefits, consequences of actions and uncertainty^{Footnote 10}. This would empower people to make decisions for themselves, moving away from government-mandated actions to self-motivated actions, including self-testing and self-isolation.
• Understanding motivation and concerns can focus messaging and improve the adoption of protective behaviors. For example, sociological research demonstrates that connection toward strangers can promote and sustain helping behavior during a crisis. This is consistent with iCARE surveys finding that a desire to protect themselves and others from infection was most predictive of vaccine intentions, and conversely, those who had high personal financial concerns were less likely to get vaccinated. A propensity for solidarity should continue to be leveraged for encouraging COVID-19 protective behavior^{Footnote 11 Footnote 12}.
• Guidelines regarding behavioral, social, and environmental measures should be updated to better align with the current understanding of SARS-CoV-2 transmission (e.g., less emphasis on fomite transmission and cleaning surfaces and more emphasis on airborne and asymptomatic transmission, and the role of ventilation).
• Guidance is needed on how to relax some measures without losing adherence to all protective behavior, and how to adapt them to different settings (e.g., family gatherings during the holidays).
• To improve effective evidence-based behavioral change, representative sampling of surveys on actual behavior with selected biomarkers is required.
• Similar to a UK model, Canada could also establish a science communication centre/research unit to research, design, test and evaluate messages for evidence-based effective communication for COVID-19 and a wide range of science-policy files.

Ventilation to reduce ongoing transmission

• SARS-CoV-2 spreads in the air, from an infected person to others through respiratory droplets and aerosols. The COVID-19 pandemic has revealed that uniform adherence to existing indoor air quality standards is lacking in Canada. This needs to be addressed to reduce transmission of SARS-CoV-2, as well as other existing and future pathogens and prevent outbreaks.
• While many schools in Canada have invested in HEPA filters for classrooms, improving indoor ventilation, air circulation and air quality should be a priority for all public buildings^{Footnote 13}.

Treatment

• Effective therapies to treat COVID-19 and reduce morbidity and mortality are still needed.
• Efforts are also needed to develop therapeutics for those suffering from long COVID.
• In an endemic state, there will continue to be unvaccinated individuals, i.e., not protected, as well as continuing breakthrough infections among vaccinated populations. As such, therapeutic interventions that focus on limiting viral transmission and preventing hospitalization will be important. These antiviral therapeutics will need to:
  • Demonstrate effective elimination of the virus at the earliest stage of infection, soon after exposure, to effectively limit transmission.
  • Address age-driven differences in disease outcomes.
  • Have broad spectrum effectiveness against different SARS-CoV-2 variants.
• The effect of therapeutics known to induce viral mutations (e.g., Molnupiravir) should be closely monitored to reduce the chance of emergence of new variants of concern and avoid viral divergence that shortens the time period during which vaccines remain effective.

2. Surveillance and early detection

Surveillance

• Heightened surveillance should be maintained through sentinel surveillance systems and targeted wastewater monitoring to effectively manage COVID-19 as the epidemiology changes and for early detection of new variants of concern with the potential for vaccine escape.
• Canada lacks the right data linkages and expertise in place to know if the “worst case scenario” is happening until it is already unpreventable. Going forward, surveillance activities should include:
  • A close monitoring of settings that are at high risk for exposure and outbreaks, such as long-term care facilities, congregate settings including schools, universities, public transport, and crowded workplaces like meat packing plants. Wastewater surveillance could be a very useful tool in these settings.
  • Data linkages between viral genetic sequences, immunization status and other case clinical and epidemiological data are essential for robust data modelling and evidence-informed policy. Without this, it will remain a challenge in Canada to analyze whether new variants are resulting in hospitalizations or if they can transmit effectively among immunized individuals.
  • Tapping into existing infectious disease networks (e.g., influenza, seasonal coronaviruses) to track the emergence of new outbreaks and variants. Regular, rigorous evaluations of existing surveillance platforms will be important for ensuring they are still fulfilling their purpose.
  • Taking a one-health approach, enhancing infectious disease monitoring of wildlife, domestic and peri-domestic animals, while ensuring that sequencing data are available to researchers. It is a strong possibility that climate change will result in more emerging zoonotic infectious diseases.
  • Addressing infrastructure needs such as for sample preservation and alternate safe lab space.
• Standard operational protocols with clear accountabilities need to be in place to rapidly respond to new variants of concern and other signals found domestically and internationally in surveillance data.

Early detection

• Screening and diagnostic PCR testing will continue to be important elements of COVID-19 management and early detection, as testing is the only way to know the status of the pandemic/endemic. Testing, contact tracing, isolation of positive cases and support are foundational elements for early detection and outbreak management.
• Rapid home tests (rapid antigen tests) can be an important tool in empowering individuals to self-monitor and manage their behavior responsibly, particularly those who are not vaccinated. For example, a negative rapid test in advance of visiting an older or more vulnerable person would help drive transmission rates down. Rapid tests are discrete and require no appointments, no transportation, and no time off work. Home tests will also help capture asymptomatic cases, especially among children. Incentives for home testing could also benefit communities by helping break chains of transmission. An important caveat is that not everyone who tests positive for SARS-CoV-2 at home will report their case to a public health unit. It is critical that rapid home tests are easily available and affordable so that they are accessible to the populations that need them the most.
  • In the United Kingdom, the government mailed boxes of rapid home tests to every home.
  • In other countries, rapid home tests are available cheaply in pharmacies.
  • In Canada, Health Canada has authorized six home tests but there are challenges around harmonizing distribution among provinces/territories and municipalities. They remain expensive to purchase privately.
  • Biases and under-reporting of test results could be estimated with a parallel representative random sampling study from Statistics Canada with biomarkers, questionnaires and interviews.

3. Vaccination and boosters

• A remaining ~16% of eligible people 12 and older across Canada are not yet vaccinated and children under 12 are not yet eligible. Given the transmissibility of the Delta variant, the target for immunity should be 90 to 95% of the population, either through vaccination or recovery from infection.
  • The development of a vaccine/booster strategy based on susceptibility and life stage harmonized across the country would be helpful. Furthermore, a targeted strategy for vaccination can provide added protection for individuals with weakened immune systems, whereby people around them are adequately immunized.

4. Border measures and travel

• The endemic steady state's incidence, prevalence, fluctuations and severity will depend to some degree on the number of introductions of infections and variants of concern from elsewhere. Heightened testing and surveillance systems are essential for rapid detection and isolation of a new variant of concern to limit its potential spread, especially in vulnerable populations.
• Evolving travel risks at all ports of entry must continue to be assessed and managed in an endemic state. Canadians also require evidence-based advice on risks when they travel outside of the country.

5. Healthcare system capacity

• After more than 20 months of managing this pandemic, Canada’s healthcare systems and healthcare workforce are fatigued and overburdened. There is rising skepticism toward medical and health officials as well as reports of rising violence against healthcare workers. Currently there are healthcare worker shortages, some leaving their profession due to working conditions.
• Excess deaths have resulted from delays or interruptions in surgeries and treatments for other illnesses due to the focus on COVID-19 during the pandemic, especially for individuals with multiple morbidities (iCARE study).
• Building overall sustainable health system capacity is essential going forward to manage endemic COVID-19. Addressing health human resources, wait times and delays in surgeries require particular attention going forward.

6. Ongoing risk assessment

• Going forward, individual and community-based measures will continue to change depending on the particular Canadian context. Risk assessment should consider both the direct health risks of the pandemic as well as the indirect effects of control measures^{Footnote 14}. COVID-19 related decisions are interdependent, requiring risk analysis and effective communication^{Footnote 15}.
• When determining acceptable levels of burden, the primary impacts on physical health as well as the secondary health and social costs must be considered. For example, the mental health and longer-term impacts are significant for all.
  • Before the pandemic, one in five children met the diagnostic criteria for mental health disorder, this has worsened during the pandemic. There are also developmental impacts on children, including lost learning and socialization opportunities^{Footnote 13}.
  • Research from SARS suggests that true mental health impacts were not evident until years later^{Footnote 16}. Ongoing community-based efforts are needed now to assess how people are doing and resources may be directed, accordingly.
  • Lasting health effects from long-COVID could affect a significant proportion of COVID-19 cases, particularly individuals who were more severely ill^{Footnote 17 Footnote 18}.
• Other secondary impacts observed include rising domestic violence, alcoholism and addiction, distrust in government, science, and official media, racism and discrimination, political conflict, and COVID-19 associated stigma.
• Risk assessment should also consider that certain sub-populations are disproportionately affected in order to avoid exacerbating existing inequities. These include:
  • Older adults
  • Women
  • Individuals with pre-existing health conditions, especially those with multiple chronic diseases
  • Youth and students (specifically, those in high school and older)
  • Indigenous populations
  • Racialized populations
  • Disadvantaged groups, including those with lower socioeconomic status