RESUMO
SARS-CoV-2 lipid nanoparticle mRNA therapeutics continue to be administered as the predominant therapeutic intervention to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series, and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities, remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series and a subset of 137 individuals who then received a booster dose. We find the booster dose elicits a 71-84\% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses drops as a function of increased year of age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis Test we find no difference between male and female decay kinetics, however, a multivariate approach utilizing Lasso regression for feature selection reveals a statistically significant (p-value <10 -3 ), albeit small, bias in favour of longer-lasting humoral immunity amongst males.
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COVID-19 , Síndrome Respiratória Aguda Grave , AsmaRESUMO
ABSTRACT Background Since December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategy focused on vaccinating the elderly to prevent hospitalizations and deaths. With vaccines becoming available to the broader population, we aimed to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence. Methods We developed a compartmental deterministic SEIR model to simulate the lifting of NPIs under different vaccination rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020 and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity. Results We found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20-39 and 40-59 years, whereby first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% by mid-June, postponing reopening from August 2021 to September 2021can reduce case counts and severe outcomes by roughly 80% by December 31, 2021. Conclusions Our results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, lifting NPIs to pre-pandemic levels is not advisable since a resurgence is expected to occur, especially with earlier reopening.
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COVID-19RESUMO
BackgroundThe closure of communities, including schools, has been adopted to control the coronavirus disease 2019 (COVID-19) epidemic in most countries. Operating schools safely during the pandemic requires a balance between health risks and the need for in-person learning. We use compartmental models to explore school reopening scenarios. MethodsUsing demographic and epidemiological data between July 31 and November 23, 2020 from the city of Toronto, we developed a Susceptible-Exposed-Asymptomatic-Infectious-Recovered-Hospitalized-Isolated model. Our model with age, household, and community transmission allow us to study the impact of schools open in September 2020. The model mimics the transmission in households, the community, and schools, accounting for differences in infectiousness between adults and children and youth and adults working status. We assessed the extent to which school opening may have contributed to COVID-19 resurgence in the fall and simulated scenarios for the safe reopening of schools up to May 31, 2021. We further considered the impact of the introduction of the new variant of concern. FindingsThough a slight increase in infections among adults (2.8%) and children (5.4%) is anticipated by the end of the year, safe school opening is possible with stringent nonpharmaceutical interventions (NPIs) decreasing the risk of transmission in the community and the household. We found that while school reopening was not the key driver in virus resurgence, but rather it was community spread that determined the outbreak trajectory, brief school closures did reduce infections when transmission risk within the home was low. When considered possible cross-infection amongst households, communities, and schools, we found that home transmission was crucial for mitigating the epidemic and safely operating schools. Simulating the introduction of a new strain with higher infectiousness, we observed substantial increases in infections, even when both schools and communities are closed. InterpretationSchools can open safely under strict maintenance of strict public health measures in the community. The gradual opening of schools and communities can only be achieved by maintaining NPIs and mitigating household transmission risk to avoid the broader escape of infections acquired in schools into the community via households. If the new COVID-19 strain is more infectious for children, public spaces, including schools, should be closed, and additional NPIs, including the use of masks, should be extended to toddlers. FundingThis research was supported by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, and York University Research Chair program. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe design of a gradual school reopening strategy remains at the heart of decision-making on reopening after shut-downs to control the epidemic. Although available studies have assessed the risk of school reopening by modelling the transmission across schools and communities, it remains unclear whether the risk is due to increased transmission in adults or children and youth.We used GoogleScholar and PubMed searches to identify previous published works. We used te following terms: "school closure", "covid 19 school closure", "reopening schools", "reopening screening school", "school household second wave model". The search of the studies ended in January 2021. Papers in other languages than English and letters were excluded from the search. Two modelling studies examined the effects of screening and delayed school reopening, two other agent-based modelling studies explored the epidemic spread across different age groups. Added-value of this studyWe find that the resurgence of COVID-19 in Toronto in fall 2020 mainly resulted from the increase of contact rate among adults in the community, and that the degree of in-person attendance had the most significant impact on transmission in schools. To our knowledge, our work is the first to investigate the resurgence in infections following school reopening and the impact of risk mitigation measures in schools operation during the pandemic. Our novel and comprehensive model considers the age and household structure, but also considers three different settings, school, household and community. We further examined the effects of self-screening procedures, class size, and schooling days on transmission, which enabled us to compare scenarios of school reopening separately for both adults and children and youth, and model the cross-infection between them to avoid potential underestimation. We found that after schools opened, reducing household transmission was crucial for mitigating the epidemic since it can reduce cross-infection amongst households, communities and schools. Lastly, given the recent report of SARS-CoV-2 variant (VOC202012/01), we investigated the impact of the new variant that may be more infectious in children and youth. Implications of all the available evidenceOur analysis can inform policymakers of planning the safe reopening of schools during COVID-19. We suggest that integrating strict NPIs and school control measures are crucial for safe reopening. When schools are open, reducing transmission risk at home and community is paramount in curbing the spread of COVID-19. Lastly, if children are more susceptible to the new COVID-19 VOC, both schools and community must be closed, the time children spend in essential services locations minimized, and NPIs for those aged less than three years enforced.
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COVID-19 , Infecção HospitalarRESUMO
Background In many parts of the world, restrictive non-pharmaceutical interventions (NPI) that aim to reduce contact rates, including stay-at-home orders, limitations on gatherings, and closure of public places, are being lifted, with the possibility that the epidemic resurges if alternative measures are not strong enough. Here we aim to capture the combination of use of NPIs and reopening measures which will prevent an infection rebound. Methods We employ a SEAIR model with a household structure able to capture the stay-at-home policy (SAHP). To reflect the changes in the SAHP over the course of the epidemic, we vary the SAHP compliance rate, assuming that the time to compliance of all the people requested to stay-at-home follows a Gamma distribution. Using confirmed case data for the City of Toronto, we evaluate basic and instantaneous reproduction numbers and simulate how the average household size, the stay-at-home rate, the efficiency and duration of SAHP implementation, affect the outbreak trajectory. Findings The estimated basic reproduction number R_0 was 2.36 (95% CI: 2.28, 2.45) in Toronto. After the implementation of the SAHP, the contact rate outside the household fell by 39%. When people properly respect the SAHP, the outbreak can be quickly controlled, but extending its duration beyond two months (65 days) had little effect. Our findings also suggest that to avoid a large rebound of the epidemic, the average number of contacts per person per day should be kept below nine. This study suggests that fully reopening schools, offices, and other activities, is possible if the use of other NPIs is strictly adhered to. Interpretation Our model confirmed that the SAHP implemented in Toronto had a great impact in controlling the spread of COVID-19. Given the lifting of restrictive NPIs, we estimated the thresholds values of the maximum number of contacts, probability of transmission and testing needed to ensure that the reopening will be safe, i.e. maintaining an R_t<1.
Assuntos
COVID-19RESUMO
Background: In many parts of the world, restrictive non-pharmaceutical interventions (NPI) that aim to reduce contact rates, including stay-at-home orders, limitations on gatherings, and closure of public places, are being lifted, with the possibility that the epidemic resurges if alternative measures are not strong enough. Here we aim to capture the combination of use of NPI’s and reopening measures which will prevent an infection rebound.Methods: We employ an SEAIR model with household structure able to capture the stay-at-home policy (SAHP). To reflect the changes in the SAHP over the course of the epidemic, we vary the SAHP compliance rate, assuming that the time to compliance of all the people requested to stay-at-home follows a Gamma distribution. Using confirmed case data for the City of Toronto, we evaluate basic and instantaneous reproduction numbers and simulate how the average household size, the stay-at-home rate, the efficiency and duration of SAHP implementation, affect the outbreak trajectory.Findings: The estimated basic reproduction number R_0 was 2.36 (95% CI: 2.28, 2.45) in Toronto. After the implementation of the SAHP, the contact rate outside the household fell by 39%. When people properly respect the SAHP, the outbreak can be quickly controlled, but extending its duration beyond two months (65 days) had little effect. Our findings also suggest that to avoid a large rebound of the epidemic, the average number of contacts per person per day should be kept below nine. This study suggests that fully reopening schools, offices, and other activities, is possible if the use of other NPIs is strictly adhered to.Interpretation: Our model confirmed that the SAHP implemented in Toronto had a great impact in controlling the spread of COVID-19. Given the lifting of restrictive NPIs, we estimated the thresholds values of maximum number of contacts, probability of transmission and testing needed to ensure that the reopening will be safe, i.e. maintaining an Rt <1.Funding Statement: This research was supported by Canadian Institutes of Health Research (CIHR), Canadian COVID-19 Math Modelling Task Force (NO, BS, JH, JA, JB, JW, JD, HZ), the Natural Sciences and Engineering Research Council of Canada (JH, JA, JB, JW, JD, IM, HZ) and York University Research Chair program (HZ). Declaration of Interests: The authors declare no conflict of interest.