Phase 2 clinical trials demonstrated that vaccine immunogenicity was lower among older individuals than in younger adults And for other inactivated vaccines such as influenza vaccine, a lower VE is observed in children compared with young adults Accordingly, we assumed an age-dependent VE. A scenario without age-specific variations in VE was explored as sensitivity analysis SA Individuals vaccinated with the first dose could still develop infections without any immune protection, while the second dose vaccination could produce the expected VE after an average of 14 days.
In the main analysis we assume both natural infection-induced and vaccine-induced immunity to SARS-CoV-2 infection does not wane within the considered time horizon 2 years. In additional sensitivity analyses, we considered an average duration of vaccine-induced protection of 6 months SA12 and 1 year SA We also consider a sensitivity analysis assuming that vaccination is effective in preventing symptomatic illness but not infection SA11 , and another one assuming an all-or-nothing vaccine, that is, the vaccine confers full protection to VE percent of vaccinated individuals SA Different priority orders are explored as sensitivity analyses.
Healthcare workers and the other essential workers listed above are fixed in tier 1 and 2 of vaccination, while the remaining population is vaccinated as described in Supplementary Table 2 by considering different orders of prioritization only based on age and disregarding the presence of underlying conditions SA first prioritization to old adults; SA first prioritization to working-age groups; SA first prioritization to school-age groups.
We explore the impact of 5, initial cases on the prioritization strategy SA To understand the impact in terms of number of infections by age, we compare the prioritization strategy when we account for the uncertainty in the contact matrix and in the susceptibility to infection by age, or not in this context, median values of contact numbers and relative susceptibility are used.
The main output of above transmission model is the age-specific number of new infections per day in the subpopulation with or without underlying conditions. We computed the age-specific number of symptomatic infections in individuals with and without underlying conditions on a daily basis by applying an age-specific probability of respiratory symptoms of We assume that individuals with and without underlying conditions have the same age-specific probability of developing symptoms.
The daily age-specific number of hospital admissions in the two subpopulations was computed by applying the age-specific proportion of laboratory-confirmed symptomatic cases requiring hospitalization Supplementary File 4 , delayed by an average time of 3.
The daily age-specific number of patients admitted to ICU in the two subpopulations was computed by applying to hospitalized cases an age-specific probability of being admitted to ICU 19 , and distinguishing patients requiring intensive care in survivors and non-survivors. Survivors are admitted to ICU after an average time of 7 days from hospitalization.
Non-survivors are admitted to ICU after an average time of 8 days after hospitalization The daily age-specific number of deaths in the two subpopulations was computed by applying the age-specific fatality ratio among symptomatic cases Supplementary File 4 , delayed by an average time of For each scenario, stochastic model realizations were performed. The outcome of these simulations determined the distributions of the number of symptomatic infections, hospitalizations, ICU admissions and deaths.
We used a Bayesian approach to estimate R t from the time series of symptomatic cases by date of symptom onset and the distribution of the serial interval The methods are described in detail in Supplementary File 5.
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