Modelling the impact of extending dose intervals for COVID-19 vaccines in Canada

AbstractBackgroundDual dose SARS-CoV-2 vaccines demonstrate high efficacy and will be critical in public health efforts to mitigate the COVID-19 pandemic and its health consequences; however, many jurisdictions face very constrained vaccine supply. We examined the impacts of extending the interval between two doses of mRNA vaccines in Canada in order to inform deliberations of Canada’s National Advisory Committee on Immunization.MethodsWe developed an age-stratified, deterministic, compartmental model of SARS-CoV-2 transmission and disease to reproduce the epidemiologic features of the epidemic in Canada. Simulated vaccination comprised mRNA vaccines with explicit examination of effectiveness against disease (67% [first dose], 94% [second dose]), hospitalization (80% [first dose], 96% [second dose]), and death (85% [first dose], 96% [second dose]) in adults aged 20 years and older. Effectiveness against infection was assumed to be 90% relative to the effectiveness against disease. We used a 6-week mRNA dose interval as our base case (consistent with early program rollout across Canadian and international jurisdictions) and compared extended intervals of 12 weeks, 16 weeks, and 24 weeks. We began vaccinations on January 1, 2021 and simulated a third wave beginning on April 1, 2021.ResultsExtending mRNA dose intervals were projected to result in 12.1-18.9% fewer symptomatic cases, 9.5-13.5% fewer hospitalizations, and 7.5-9.7% fewer deaths in the population over a 12-month time horizon. The largest reductions in hospitalizations and deaths were observed in the longest interval of 24 weeks, though benefits were diminishing as intervals extended. Benefits of extended intervals stemmed largely from the ability to accelerate coverage in individuals aged 20-74 years as older individuals were already prioritized for early vaccination. Conditions under which mRNA dose extensions led to worse outcomes included: first-dose effectiveness < 65% against death; or protection following first dose waning to 0% by month three before the scheduled 2nd dose at 24-weeks. Probabilistic simulations from a range of likely vaccine effectiveness values did not result in worse outcomes with extended intervals.ConclusionUnder real-world effectiveness conditions, our results support a strategy of extending mRNA dose intervals across all age groups to minimize symptomatic cases, hospitalizations, and deaths while vaccine supply is constrained.

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Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across All Ages: A Popula-Tion-Based Modeling Study Using the UK as an Example

Vaccines ◽

10.3390/vaccines9101180 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1180

Author(s):

Tinevimbo Shiri ◽

Marc Evans ◽

Carla A. Talarico ◽

Angharad R. Morgan ◽

Maaz Mussad ◽

...

Keyword(s):

Disease Transmission ◽

Age Groups ◽

Population Level ◽

Vital Role ◽

Morbidity And Mortality ◽

Transmission Model ◽

Base Case ◽

Global Public Health ◽

The Uk ◽

The Impact

Debate persists around the risk–benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we present a novel SEIR mathematical disease transmission model that quantifies the impact of different vaccination strategies on population-level SARS-CoV-2 infections and clinical outcomes. The model employs both age- and time-dependent social mixing patterns to capture the impact of changes in restrictions. The model was used to assess the impact of vaccinating adolescents and children on the natural history of the COVID-19 pandemic across all age groups, using the UK as an example. The base case model demonstrates significant increases in COVID-19 disease burden in the UK following a relaxation of restrictions, if vaccines are limited to those ≥18 years and vulnerable adolescents (≥12 years). Including adolescents and children in the vaccination program could reduce overall COVID-related mortality by 57%, and reduce cases of long COVID by 75%. This study demonstrates that vaccinating adolescents and children has the potential to play a vital role in reducing SARS-CoV-2 infections, and subsequent COVID-19 morbidity and mortality, across all ages. Our results have major global public health implications and provide valuable information to inform a potential pandemic exit strategy.

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Traumatic Stress in Older Adults

The Oxford Handbook of Traumatic Stress Disorders ◽

10.1093/oxfordhb/9780195399066.013.0009 ◽

2012 ◽

pp. 118-127

Author(s):

Joan M. Cook ◽

Tatyana Biyanova ◽

Diane L. Elmore

Keyword(s):

Older Adults ◽

World War Ii ◽

Functional Impairment ◽

Stress Disorder ◽

Acute Stress ◽

Age Groups ◽

Care Utilization ◽

Older Individuals ◽

Delayed Recognition ◽

The Impact

This chapter focuses on older adult trauma survivors. Information is presented on prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD); course, functional impairment, suicide risk, and health care utilization in older adults with PTSD; and the impact of demographic factors such as gender, ethnicity, and race on PTSD in older individuals. In general, rates of ASD and PTSD are lower in older adults compared to other age groups. PTSD in older adults has been linked to suicidal ideation and attempts, functional impairment, physical health, and increased healthcare utilization. Although delayed onset of PTSD has been empirically verified in some military samples with World War II veterans and younger adult civilians, it is rare in the absence of any prior symptoms and might more accurately be labeled “delayed recognition.” More information on trauma and PTSD in diverse populations of older adults is needed, such as racial and ethnic minorities, those with severe physical or mental impairment, noncommunity-residing groups, and those from nonindustrialized countries.

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A simulation study on the relative role of age groups under differing pertussis transmission scenarios

10.1101/247007 ◽

2018 ◽

Cited By ~ 2

Author(s):

Ana I. Bento ◽

Aaron A. King ◽

Pejman Rohani

Keyword(s):

Herd Immunity ◽

Age Groups ◽

Transmission Model ◽

Relative Role ◽

Older Individuals ◽

Age Cohorts ◽

Relative Risks ◽

Transmission Mechanisms ◽

Acellular Vaccines ◽

The Impact

AbstractPertussis has resurged in many countries where it was once regarded as under control, with the recent outbreaks showing a shift in incidence towards teens and older individuals. Here, using an age-stratified transmission model, we tested two potential causes for underlying changes in pertussis transmission dynamics. We did so assuming hypothesized mechanisms supporting present-day pertussis epidemiology: (I) improved diagnostics, (II) acellular vaccines leading to asymptomatic transmission (III) both. We used the relative risks and odds ratio methods to examine the impact of these differing assumptions on signatures of relative roles of key age groups through time, allowing us to explore those age cohorts that disproportionately account for transmission. Our findings show that for epidemics after the vaccine switch, a scenario with increased adult reporting and no asymptomatic transmission reflect a loss of signal, where no age group appears to be key. While scenarios with asymptomatic transmission, reflect a population where children (1-10 years old) are still disproportionally at risk. These results demonstrate that understanding the underlying transmission mechanisms in a population are paramount for vaccination policies in attaining herd immunity and eventually eradication.

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Antibody response after COVID-19 mRNA vaccination in relation to age, sex, and side effects

10.1101/2021.04.19.21255714 ◽

2021 ◽

Author(s):

Paul Naaber ◽

Virge Jürjenson ◽

Ainika Adamson ◽

Epp Sepp ◽

Liina Tserel ◽

...

Keyword(s):

Immune Response ◽

Side Effects ◽

Immune Responses ◽

Antibody Response ◽

Older Individuals ◽

High Efficacy ◽

Vaccine Response ◽

Antibody Levels ◽

The Impact ◽

Older Males

AbstractBackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations.FindingsOur findings show a robust immune response to the Spike protein’s RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine.FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.Research in contextEvidence before this studyThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms “SARS-CoV-2”, “COVID-19”, “vaccine response”, “mRNA vaccine”, up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects.Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose.Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.

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Impact of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority on Disease Dynamics. Implications for SARS-CoV-2

10.1101/2021.12.14.21267742 ◽

2021 ◽

Author(s):

Ashleigh Tuite ◽

Afia Amoako ◽

David Fisman

Keyword(s):

Compartmental Model ◽

Vaccine Development ◽

Health And Safety ◽

Infection Risk ◽

Base Case ◽

Disease Dynamics ◽

Population Mixing ◽

Contact Frequency ◽

Random Mixing ◽

The Impact

Background: The speed of vaccine development has been a singular achievement during the SARS-CoV-2 pandemic. However, anti-vaccination movements and disinformation efforts have resulted in suboptimal uptake of available vaccines. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. Our objective was to explore the impact of mixing of vaccinated and unvaccinated populations on risk among vaccinated individuals. Methods: We constructed a simple Susceptible-Infectious-Recovered (SIR) compartmental model of a respiratory infectious disease with two connected sub-populations: vaccinated individuals and unvaccinated individuals (Figure 1). We modeled the non-random mixing of these two groups using a matrix approach with a mixing constant varied to simulate a spectrum of patterns ranging from random mixing to complete assortativity. We evaluated the dynamics of an epidemic within each subgroup, and in the population as a whole, and also evaluated the contact-frequency-adjusted contribution of unvaccinated individuals to risk among the vaccinated. Results: As expected, the relative risk of infection was markedly higher among unvaccinated individuals than among vaccinated individuals. However, the contact-adjusted contribution of unvaccinated individuals to infection risk during the epidemic was disproportionate with unvaccinated individuals contributing to infection risk among the vaccinated at a rate up to 6.4 times higher than would have been expected based on contact numbers alone in the base case. As assortativity increased the final attack rate decreased among vaccinated individuals, but the contact-adjusted contribution to risk among vaccinated individuals derived from contact with unvaccinated individuals increased. Interpretation: While risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to the unvaccinated, the choices of these individuals are likely to impact the health and safety of vaccinated individuals in a manner disproportionate to the fraction of unvaccinated individuals in the population.

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LESSONS FROM THE COVID-19 THIRD WAVE IN CANADA: THE IMPACT OF VARIANTS OF CONCERN AND SHIFTING DEMOGRAPHICS

10.1101/2021.08.27.21261857 ◽

2021 ◽

Author(s):

Finlay A McAlister ◽

Majid Nabipoor ◽

Anna Chu ◽

Douglas Lee ◽

Lynora Saxinger ◽

...

Keyword(s):

Age Groups ◽

Vaccine Hesitancy ◽

First Year ◽

Third Wave ◽

Wild Type ◽

Lengths Of Stay ◽

Younger Age ◽

Canadian Provinces ◽

Event Rates ◽

The Impact

Importance: With the emergence of more transmissible SARSCoV2 variants of concern (VOC), there is an urgent need for evidence about disease severity and the health care impacts of VOC in North America, particularly since a substantial proportion of the population have declined vaccination thus far. Objective: To examine 30day outcomes in Canadians infected with SARSCoV2 in the first year of the pandemic and to compare event rates in those with VOC versus wild type infection. Design: Retrospective cohort study using linked healthcare administrative datasets. Setting: Alberta and Ontario, the two Canadian provinces that experienced the largest third wave in the spring of 2021. Participants: All individuals with a positive SARSCoV2 reverse transcriptase polymerase chain reaction swab from March 1, 2020 until March 31, 2021, with genomic confirmation of VOC screen positive tests during February and March 2021 (wave 3). Exposure of Interest: VOC versus wild type SARSCoV2 Main Outcomes and Measures: All-cause hospitalizations or death within 30 days after a positive SARSCoV2 swab. Results: Compared to the 372,741 individuals with SARSCoV2 infection between March 2020 and January 2021 (waves 1 and 2 in Canada), there was a shift in transmission towards younger patients in the 104,232 COVID19 cases identified in wave 3. As a result, although third wave patients were more likely to be hospitalized (aOR 1.34 [1.29 to 1.39] in Ontario and aOR 1.53 [95%CI 1.41 to 1.65] in Alberta), they had shorter lengths of stay (median 5 vs. 7 days, p<0.001) and were less likely to die within 30 days (aOR 0.66 [0.60 to 0.71] in Ontario and aOR 0.74 [0.62 to 0.89] in Alberta). However, within the third wave, patients infected with VOC (91% Alpha) exhibited higher risks of death (aOR 1.52 [1.27 to 1.81] in Ontario and aOR 1.67 [1.13 to 2.48] in Alberta) and hospitalization (aOR 1.57 [1.47 to 1.69] in Ontario and aOR 1.88 [1.74 to 2.02] in Alberta) than those with wild-type SARSCoV2 infections during the same timeframe. Conclusions and Relevance: On a population basis, the shift towards younger age groups as the COVID19 pandemic has evolved translates into more hospitalizations but shorter lengths of stay and lower mortality risk than seen in the first 10 months of the pandemic in Canada. However, on an individual basis, infection with a VOC is associated with a higher risk of hospitalization or death than the original wild type SARSCoV2; this is important information to address vaccine hesitancy given the increasing frequency of VOC infections now.

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Traumatic Stress in Older Adults

The Oxford Handbook of Traumatic Stress Disorders, Second Edition ◽

10.1093/oxfordhb/9780190088224.013.9 ◽

2020 ◽

Author(s):

Joan M. Cook ◽

Vanessa Simiola

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Healthcare Utilization ◽

Functional Impairment ◽

Stress Disorder ◽

Acute Stress ◽

Age Groups ◽

Accelerated Aging ◽

Older Individuals ◽

The Impact

This chapter focuses on older adult trauma survivors. Information is presented on prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD); course, functional impairment, suicide risk, cognitive impairment, accelerated aging, healthcare utilization in older adults with PTSD, and the impact of demographic factors such as gender, ethnicity, and race on PTSD in older individuals. In general, rates of ASD and PTSD are lower in older adults compared to other age groups. PTSD in older adults has been linked to suicidal ideation and attempts, functional impairment, physical health, cognitive impairment, accelerated aging, and increased healthcare utilization. Although delayed onset of PTSD has been empirically verified in some military samples with veterans and younger adult civilians, it is rare in the absence of any prior symptoms and might more accurately be labeled “delayed recognition.” More information on trauma and PTSD in diverse populations of older adults is needed, such as racial/ethnic as well as sexual and gender minorities, those with severe physical or mental impairment, non–community-residing groups, and those from non-industrialized countries.

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Evaluating COVID-19 booster vaccination strategies in a partially vaccinated population: a modeling study.

10.21203/rs.3.rs-1143391/v1 ◽

2021 ◽

Author(s):

Clément Massonnaud ◽

Jonathan Roux ◽

Vittoria Colizza ◽

Pascal Crépey

Keyword(s):

Compartmental Model ◽

Age Groups ◽

Booster Vaccination ◽

Primary Vaccination ◽

Effective Strategy ◽

Younger Adults ◽

Vaccination Strategies ◽

Admission Data ◽

Vaccination Campaigns ◽

The Impact

Abstract Background. Several countries are implementing COVID-19 booster vaccination campaigns. The objective of this study was to model the impact of different primary and booster vaccination strategies. Methods. We used a compartmental model fitted to hospital admission data in France to analyze the impact of primary and booster vaccination strategies on morbidity and mortality, assuming waning of immunity and various levels of virus transmissibility during winter. Results. Strategies prioritizing primary vaccinations were systematically more effective than strategies prioritizing boosters. Regarding booster strategies targeting different age groups, their effectiveness varied with immunity and virus transmissibility levels. If waining of immunity affects all adults, people aged 30 to 49 years should be boosted in priority, even for low transmissibility levels. Discussion. Increasing the primary vaccination coverage should remain a priority. If a plateau has been reached, boosting immunity of younger adults could be the most effective strategy, especially if SARS-CoV-2 transmissibility is high.

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Modelling the impact of age-stratified public health measures on SARS-CoV-2 transmission in Canada

Royal Society Open Science ◽

10.1098/rsos.210834 ◽

2021 ◽

Vol 8 (11) ◽

Author(s):

Vanessa Gabriele-Rivet ◽

Kelsey L. Spence ◽

Nicholas H. Ogden ◽

Aamir Fazil ◽

Patricia Turgeon ◽

...

Keyword(s):

Public Health ◽

Vulnerable Populations ◽

Age Groups ◽

Older Individuals ◽

Agent Based Model ◽

Agent Based ◽

Avoidable Deaths ◽

Health Measures ◽

Large Numbers ◽

The Impact

Public health measures applied exclusively within vulnerable populations have been suggested as an alternative to community-wide interventions to mitigate SARS-CoV-2 transmission. With the population demography and healthcare capacity of Canada as an example, a stochastic age-stratified agent-based model was used to explore the progression of the COVID-19 epidemic under three intervention scenarios (infection-preventing vaccination, illness-preventing vaccination and shielding) in individuals above three age thresholds (greater than or equal to 45, 55 and 65 years) while lifting shutdowns and physical distancing in the community. Compared with a scenario with sustained community-wide measures, all age-stratified intervention scenarios resulted in a substantial epidemic resurgence, with hospital and ICU bed usage exceeding healthcare capacities even at the lowest age threshold. Individuals under the age threshold were severely impacted by the implementation of all age-stratified interventions, with large numbers of avoidable deaths. Among all explored scenarios, shielding older individuals led to the most detrimental outcomes (hospitalizations, ICU admissions and mortality) for all ages, including the targeted population. This study suggests that, in the absence of community-wide measures, implementing interventions exclusively within vulnerable age groups could result in unmanageable levels of infections, with serious outcomes within the population. Caution is therefore warranted regarding early relaxation of community-wide restrictions.

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Does the choosiness of female crickets change as they age?

Journal of Experimental Biology ◽

10.1242/jeb.241802 ◽

2021 ◽

Author(s):

Edith Julieta Sarmiento-Ponce ◽

Stephen Rogers ◽

Berthold Hedwig

Keyword(s):

Carrier Frequency ◽

Age Groups ◽

Older Individuals ◽

Young Females ◽

Auditory Response ◽

Male Calling ◽

Song Types ◽

The Impact ◽

Best Responses ◽

Relative Preferences

For crickets, which approach singing males by phonotaxis, the female choosiness hypothesis postulates that young females should be more selective of male calling song patterns than older individuals. However, there is no information about the behavioural preferences of females over their complete adulthood. We analysed phonotaxis in female Gryllus bimaculatus throughout their entire adult lifetime and measured the impact of sound amplitude, carrier frequency, and the temporal pattern of test songs on their auditory response. Females of all ages demonstrated their best responses to male calling songs with a pulse period of 34-42 ms, a carrier frequency of 4.5 kHz and a sound pressure level of 75dB SPL. The response profile to somewhat less optimal song types did vary with age, but not in a manner consistent with a simple loosening of selectiveness in older females. Age however had an effect on the overall strength of phonotaxis, as very old females showed an overall diminishing response to all song types. Our data suggest that although there are minor changes in the relative preferences of crickets to individual song elements as they age, the breadth of song patterns that they will perform phonotaxis to remains similar across age groups.

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