key: cord-1028953-nkad3p9d
authors: Raina MacIntyre, C; Costantino, Valentina; Trent, Mallory
title: Modelling of COVID-19 vaccination strategies and herd immunity, in scenarios of limited and full vaccine supply in NSW, Australia
date: 2021-04-24
journal: Vaccine
DOI: 10.1016/j.vaccine.2021.04.042
sha: e48c0a511e4a9f4f3947d1d80cc383e92352114a
doc_id: 1028953
cord_uid: nkad3p9d

Several vaccines for SARS-CoV-2 are expected to be available in Australia in 2021. Initial supply is likely to be limited and will require a judicious vaccination strategy until supply is unrestricted. If vaccines have efficacy as post-exposure prophylaxis (PEP) in contacts, this provides more policy options. We used a deterministic mathematical model of epidemic response with limited supply (age-targeted or ring vaccination) and mass vaccination for the State of New South Wales (NSW) in Australia. For targeted vaccination, the effectiveness of vaccinating health workers, young people and older adults was compared. For mass vaccination, we tested varying vaccine efficacy (VE) and distribution capacities. With a limited vaccine stockpile of 1 million doses in NSW, if there is efficacy as PEP, the most efficient way to control COVID-19 will be ring vaccination, however at least 90% of contacts per case needs to be traced and vaccinated. Health worker vaccination is required for health system resilience. Age based strategies with restricted doses make minimal impact on the epidemic, but vaccinating older people prevents more deaths. Herd immunity can only be achieved with mass vaccination. With 90% VE, herd immunity can be achieved by vaccinating 66% of the population. A vaccine with less than 70% VE cannot achieve herd immunity and will result in ongoing risk of outbreaks. For mass vaccination, distributing at least 60,000 doses per day is required to achieve control. Slower rates of vaccination will result in the population living with COVID-19 longer, and higher cases and deaths.

Abstract: Several vaccines for SARS-CoV-2 are expected to be available in Australia in 2021. 24 Initial supply is likely to be limited and will require a judicious vaccination strategy until 25 supply is unrestricted. If vaccines have efficacy as post-exposure prophylaxis (PEP) in 26 contacts, this provides more policy options. We used a deterministic mathematical model of 27 epidemic response with limited supply (age-targeted or ring vaccination) and mass 28 vaccination for the State of New South Wales (NSW) in Australia. For targeted vaccination, 29 the effectiveness of vaccinating health workers, young people and older adults was 30 compared. For mass vaccination, we tested varying vaccine efficacy (VE) and distribution 31 capacities. With a limited vaccine stockpile of 1 million doses in NSW, if there is efficacy as 32 PEP, the most efficient way to control COVID-19 will be ring vaccination, however at least 33 90% of contacts per case needs to be traced and vaccinated. Health worker vaccination is 34 required for health system resilience. Age based strategies with restricted doses make 35 minimal impact on the epidemic, but vaccinating older people prevents more deaths. Herd 36 immunity can only be achieved with mass vaccination. With 90% VE, herd immunity can be 37 achieved by vaccinating 66% of the population. A vaccine with less than 70% VE cannot 38 achieve herd immunity and will result in ongoing risk of outbreaks. For mass vaccination, 39 distributing at least 60,000 doses per day is required to achieve control. Slower rates of 40 vaccination will result in the population living with COVID-19 longer, and higher cases and 41 deaths.

Introduction 45 Coronavirus disease 19 (COVID-19) has caused an unprecedented pandemic, with 46 catastrophic health, social and economic impacts 1 . Without available drugs or vaccines, 47 nations require ongoing or intermittent use of non-pharmaceutical approaches such as 48 lockdowns, border closures and social distancing to control COVID-19 2,3 . In addition, case 49 finding through increased testing and surveillance, with contact tracing and quarantine, are 50 the mainstays of epidemic control 4 . While Australia has achieved good control over the 51 pandemic through border closures, testing, contact tracing and hotel quarantine, the risk of 52 intermittent outbreaks of COVID-19 will continue until an effective vaccine is available 3 and 53 administered appropriately to a large enough proportion of the population. The societal 54 impact of ongoing restrictions and border closure cannot be under-estimated. 55 There is a massive global effort to fast-track the development of COVID-19 vaccines 5,6 . 56 Currently, there are 48 COVID-19 vaccine candidates undergoing clinical evaluation, with 11 57 already in phase 3 clinical trials 7 . Preliminary reports from phase 3 trials suggest that mRNA 58 vaccines have over 90% efficacy against COVID-19 infection 8, 9 . The ChAdOx1 nCoV-19, the 59 largest component of the planned Australian vaccine stockpile, has efficacy of 62% against 60 symptomatic infection in the intended two-dose schedule 10 . On December 11 it was 61 announced that the second largest component of the Australian stockpile had been 62 withdrawn from further development 11 . A small proportion of the Australian vaccine plan 63 includes the BNT162b2 mRNA vaccine, which has 95% efficacy against symptomatic 64 infection 11,12 . As more vaccine candidates become available through 2021, we will continue 65 to see variation in efficacy and safety between them. 66 It is likely there will be initial vaccine shortages. Thus, an effective vaccination strategy will 67 need to be developed to best utilise limited vaccine supply in the early phases of vaccine 68 rollout 13 , with a plan for expanded vaccination at a later stage. 69 Several COVID-19 vaccination strategies have been proposed, 13 such as prioritising 70 healthcare and aged care workers and other frontline responders at high risk of disease 71 transmission, and sociodemographic groups at significantly higher risk of severe disease, 72 such as older adults or people with high risk chronic health conditions 13,14 . However, 73 prioritizing children or young people may impact transmission more, since vaccines are 4 74 more effective in younger people, and transmission is highest in young adults 15 . 75 Alternatively, a ring vaccination strategy could be utilized, which involves identifying the 76 close contacts of a confirmed case and vaccinating them. This strategy was used effectively 77 against Ebola, and also smallpox in settings where mass vaccination was not possible, 78 despite efficacy being half that of primary prevention [16] [17] [18] [19] . Many vaccines including 79 measles, hepatitis A and smallpox, are effective as post-exposure prophylaxis (PEP) and can 80 be given to contacts during an outbreak, albeit with lower efficacy than primary prevention 81 20 . Whether COVID-19 vaccines will be effective as PEP is unknown as yet, but may well be 82 given the long incubation period 21 . 83 In Australia, the stated priority groups for early unlimited supply assumptions, as described in more detail below. We used the NSW 96 population and age distribution from 2020 24 , stratified into 16 five-year age groups from 0 97 to 74 years old and the last age group comprising people 75 years and over. 98 The model moves the population in 17 mutually exclusive compartments, each divided by (Figure 1 ). The duration of stay in each compartment 106 determines the rate at which people move from one compartment to another for the 107 epidemiological disease states. The duration of the latent period is assumed to be 5.2 days 108 25 , of which the last two days before symptoms onset are considered infectious 26 . 109 The transmission was distributed over the infectious period with 44 % of transmissions 110 occurring in the last two days of the pre-symptomatic state. We assume that the viral load is 111 very high on the first day of symptoms and then decreases to a lower infectious level, 112 spread over the following 6 days 26 , so 36% of transmissions occur in the first day of 113 symptoms and 20% in the following 6 days of symptoms 26 . Of the total people infected, 114 35% are considered asymptomatic and never develop symptoms, however we assumed that 115 asymptomatic cases are as equally infectious as symptomatic ones 27-29 . In conjunction with 116 vaccination, other disease control interventions such as case finding, contacts tracing, 117 quarantine, isolation and hospital, ICU treatments were included, however we did not 118 include additional measures such as universal masking or lockdowns, neither of which are in 119 effect in NSW. 120 The force of infection that moves people from susceptible to infected is an age specific rate 121 calculated as a combination of average age specific number of close contacts per day in 122 Australia 30 , the proportion of infectious people and the probability of infection per contact, 123 which is estimated to reproduce an R0 of 2.5 28 . Once infected, a person enters the latent 124 compartment, and after 3.2 days will become infectious and pre-symptomatic for 2 days, 125 where if traced will be quarantined with a 50% reduction in transmissions 31 and upon 126 symptoms onset will take 1 day on average to get isolated with no more transmissions after 127 isolation. However, if an infected person is not traced in latency, it will take 5 days to get 128 isolated following symptom onset 32 . Hospitalizations and admission to ICU follow age-129 specific rates 33 . The model assumes that 80% of all close contacts are traced and 130 quarantined for 14 days and 90% of the symptomatic cases are isolated after 5 days. 131 There are no data on COVID-19 vaccines as PEP, but early data from phase three trials 132 indicate efficacy in excess of 90% as primary prevention of mRNA vaccines 8 PEP has a 50% reduction in protection from vaccination (from 90% to 45%). Successful 142 vaccination is considered to give immunity to the infection for at least 12 months. Duration 143 of immunity beyond 12 months is not considered, as long term follow up data are not 144 available yet to inform the modelling of waning immunity. Figure 1 shows model diagrams, 145 and in Table 1 are described all parameters used in the model, while the differential 

A restricted supply (for 1 million people) will not be enough to control the epidemic, with all 205 scenarios resulting in a large number of cases and deaths after 500 days. population (approximately 5.384 million people) will provide herd immunity and reduce the 230 R0 to less than 1, while efficacy below 60% cannot achieve herd immunity. A minimum VE of 231 85% is required to achieve herd immunity at 70% population coverage. A VE of 80% will 232 require 75% of the population to be vaccinated, and VE of 60% will require 100% of the 233 population to be vaccinated to achieve herd immunity. Supplementary Table 1 is the best way to achieve epidemic control, but the majority of the population will remain 286 non-immune and susceptible to outbreaks. Recurrent breaches in hotel quarantine 51 and 287 associated with cruise ships have resulted in community transmission, and without herd 288 immunity, this risk will continue and will hamper economic recovery 52 . 289 During the period of initial restricted supply, health and aged care workers should be the 290 highest priority, as protecting health workers and other first responders is essential for We showed that for mass vaccination, a slow trickle approach will leave us living with 317 COVID-19 longer with all the associated societal and economic implications -rapid speed of 318 vaccination will be the best strategy to reduce morbidity and mortality. The logistics of rapid 319 delivery is key, and we show that slower uptake will result in more cases and deaths and a 320 longer epidemic risk. Rapid vaccine uptake requires concerted planning for vaccination 321 infrastructure, including training more accredited vaccinators, planning mass vaccination 322 clinics, and testing the capacity to deliver 300,000 or more vaccine doses a day, which 323 provides the best outcomes. We assumed in the base case scenario for mass vaccination 324 that the health system will be able to deliver 125,000 Vaccine hesitancy may also affect the ability to achieve rapid, high uptake and must also be 361 addressed well in advance of vaccination programs to ensure that programmatic 362 competency to achieve high uptake rapidly will not be met by unexpected social or 

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