key: cord-0253814-jtwtw9uc authors: Cai, J.; Yang, J.; Deng, X.; Peng, C.; Chen, X.; Wu, Q.; Liu, H.; Zhang, J.; Zheng, W.; Zou, J.; Zhao, Z.; Ajelli, M.; Yu, H. title: Projecting the transition of COVID-19 burden towards the young population while vaccines are rolled out: a modelling study date: 2021-10-17 journal: nan DOI: 10.1101/2021.10.14.21265032 sha: add8b2921462040a181f908ff6077dafd81dc74c doc_id: 253814 cord_uid: jtwtw9uc SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 85% of individuals aged [≥]12 years have been vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while children aged 0-11 years are currently not eligible for vaccination (as of September 2021). The aim of this work is to assess whether the importation of Delta variant infections will shift the COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate the epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths. In the context of the vaccination programme targeting individuals aged [≥]12 years (as of September 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could lead to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the currently eligible age groups. The symptomatic SARS-CoV-2 infections and hospitalisation are projected to shift towards children and young adolescents, with 13% of symptomatic infections and 30% of hospitalisations occurring in those aged 0-11 years. Extending the vaccination roll-out to include children aged 3-11 years is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively), but would have a low impact on protecting infants (aged 0-2 years). Our findings highlight the need to strengthen vaccination efforts by simultaneously extending the target population and elevating vaccine effectiveness. Older age groups have the highest risk of severe illness and fatality from SARS-CoV-51 2 infection. While the vaccination coverage in China is highly skewed towards older 52 age groups. No study has quantified to what extent the spread of Delta variant 53 infections and lack of vaccination in younger age groups will shift the COVID-19 54 burden towards younger age groups and how this will affect the return to normal. To is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Introduction 67 The coronavirus disease 2019 (COVID-19) pandemic is still raging worldwide. The 68 highly contagious Delta variant (B.1.617.2) of the severe acute respiratory syndrome 69 coronavirus 2 (SARS-CoV-2) has become the dominant strain across the world [1] , [2] . 70 The global circulation of the Delta variant has led to a resurgence of COVID-19 cases 71 worldwide, including in areas with high vaccination coverage [3, 4] . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 115 We developed an age-structured (16 age groups, CoV-2 (Delta variant) and assess the health impact of age-targeted vaccination 118 campaigns ( Fig S1) . Detailed information about the model and adopted parameters are 119 described in S1 Text. A summary is presented here. The model is calibrated to represent the Chinese population and considers the age- is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint found to have a lower susceptibility to SARS-CoV-2 infection than other age groups, 125 which was confirmed by several independent studies[28] (Table S1) (Table S2 ) [35] . We simulated the daily distribution of vaccine doses 145 according to the observed vaccination capacity (S1 Text). We considered a two-dose vaccine with a 21-day interval between doses. Fourteen 148 days after the second dose, the vaccine efficacy in protecting against an infection 149 caused by the Delta variant was set at 54.3% [35] . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint "leaky" vaccine in which all vaccinated individuals are exposed to a lower risk of we calculated the rate ratios as the incidence rate per age group dividing the overall 173 incidence rate for each health outcome under different vaccination strategies. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint Baseline scenario 197 In the baseline scenario, we assumed that 40 individuals infected with the Delta 198 variant were introduced in the population on November 1, 2021, and the basic 199 reproduction number R0 was 6 in the absence of interventions and immunity [30] [31] [32] . 200 Given the actual vaccination rates, we project that the "adults+adolescents" 201 vaccination strategy could reach a 97% coverage of the target population (83% of the 202 total population) by November 1, 2021 ( Fig 1A) . November 1, 2021 (i.e., the "adults+adolescents+children" vaccination strategy). As 220 compared to the "adults+adolescents" vaccination strategy, this alternative strategy is 221 estimated to reduce the incidence of symptomatic cases, hospitalisations, ICU 222 admissions, and deaths by 6% (95% CI, 3-12%), 20% (95% CI, 17-27%), 8% (95% 223 CI, 4-15%), and 5% (95% CI, 1-13%), respectively (Fig 2) . Despite the beneficial is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint programme, should NPIs not be implemented (Fig S6) . respectively. We recall that the rate ratio is defined as the incidence rate per age group 234 divided by the overall incidence rate [49] . A higher increase is observed in the rate 235 ratios of hospitalisation for these two population groups: 178% and 191% for children 236 aged 0-2 and 3-11 years, respectively. At the same time, the rate ratios in adults aged 237 ≥60 years is estimated to decrease by 25%. Similar patterns are observed in the rate 238 ratios of ICU admissions and deaths (Fig 3) . Extending the vaccination to children 239 aged 3-11 years is projected to dramatically decrease the burden of symptomatic 240 infections and hospitalisations within the same age group by 54% and 81%, 241 respectively ( Fig S6) . However, due to the strong age-assortativity of contact patterns 242 of this age group (i.e., individuals aged 3-11 years primarily mix with other 243 individuals of the same age) (Fig S4A) , extending the vaccination to children does not 244 strongly impact the COVID-19 burden in other age groups (Fig S6) . No evident effect 245 is projected on the 0-2-year age group (Fig 3 and S6) . Under either the "adults+adolescents" or "adults+adolescents+children" vaccination 248 strategies, the mean incidence of symptomatic cases among unvaccinated individuals 249 is estimated to be 1.5-2.0 fold that of vaccinated individuals, with larger differences 250 observed in terms of the incidence of severe clinical outcomes (3.4-5.0 fold for 251 hospitalisation, 5.5-8.8 fold for ICU admission, and 4.1-8.8 fold for death) (Fig 2) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint increased to >84% from 54.3% used in the baseline [35] , the 258 "adults+adolescents+children" vaccination strategy is estimated to reduce the number 259 of deaths by 99% even in the absence of any NPIs, leading to <40,000 deaths over 1 260 year, similar to the annual excess respiratory disease deaths associated with influenza 261 in China[50] (Fig S7) . 276 In the baseline analysis, age-varying susceptibility to SARS-CoV-2 infection was 277 considered. That is, using adults aged 15-64 years as a reference group, children have 278 a 42% lower risk of infection than adults (Table S1 ) [27] . No estimates are available 279 for susceptibility to Delta variant infections by age. As such, we performed an 280 analysis assuming the same susceptibility to infection across all age groups. The 281 obtained results are consistent with those obtained in the baseline analysis, with 282 average variations lower than 12% (Fig S3) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint Another feature able to shape the epidemiology of COVID-19 is the contact pattern of 285 the population. In the baseline analysis, we used pre-pandemic mixing patterns to 286 represent a situation close to the objective of returning to a pre-COVID-19 pandemic 287 lifestyle[26] (Fig S4A) . However, whether mixing patterns will ever return to be the 288 same after the pandemic remains to be seen. As such, we tested the robustness of our 289 findings by considering an alternative contact matrix estimated in Shanghai, China, 290 right after the end of the lockdown in March 2020[51] (Fig S4B) . The obtained results 291 are consistent with those obtained with the pre-pandemic contact matrix, with mean 292 variations in the estimated burden lower than 6% (Fig S5) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. The data and code that support the findings of this study will be made available on is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint GitHub upon the acceptance of this manuscript. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint 488 . CC-BY-NC 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.14.21265032 doi: medRxiv preprint to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Weekly epidemiological update on COVID-19 -10 Delta Variant: What We Know About the Science WHO Coronavirus (COVID-19) Dashboard 2021 Data. 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