The changing impact of vaccines in the COVID-19 pandemic (preprint)

The Omicron wave has left a global imprinting of immunity which changes the COVID landscape. In this study, we simulate six hypothetical variants emerging over the next year and evaluate the impact of existing and improved vaccines. We base our study on South Africa's infection- and vaccination-derived immunity. Our findings illustrate that variant-chasing vaccines will only add value above existing vaccines in the setting where a variant emerges if we can shorten the window between variant introduction and vaccine deployment to under three weeks, an impossible time-frame without significant NPI use. This strategy may have global utility, depending on the rate of spread from setting to setting. Broadly neutralizing and durable next-generation vaccines could avert over three-times as many deaths from an immune-evading variant compared to existing vaccines. Our results suggest it is crucial to develop next-generation vaccines and redress inequities in vaccine distribution to tackle future emerging variants.

Susceptibility of zero community transmission regimes to new variants of SARS-CoV-2: a modelling study of Queensland (preprint)

Objectives: To assess the risk of sustained community transmission of SARS-CoV-2/COVID-19 in Queensland (Australia) in the presence of high-transmission variants of the virus. Design: We used an agent-based model Covasim and the demographics, policies, and interventions implemented in the state. Using the calibrated model, we simulated possible epidemic trajectories that could eventuate due to leakage of infected cases with high-transmission variants, during a period of zero community transmission. Setting: Model calibration covered the first-wave period from early March 2020 to May 2020. Predicted epidemic trajectories were simulated from early February 2021 to late March 2021. Participants: None (simulation study). Main outcomes: A calibrated model of COVID-19 epidemiology in Queensland; the conditions that could lead to an outbreak; and how likely that situation is to occur. Results: Simulations showed that one infected agent with the ancestral (A.2.2) variant has a 14% chance of crossing a threshold of sustained community transmission (i.e., > 5 infections per day, more than 3 days in a row), assuming no change in the prevailing preventative and counteracting policies. However, one agent carrying a more infectious variant (e.g., B.1.1.7) has a 43% chance of crossing the same threshold; a threefold increase. Doubling the average number of daily tests results in a decrease of this probability from 43% to 23%. Conclusions: The introduction of even a small number of people infected with high-transmission variants dramatically increases the probability of sustained community transmission in Queensland.

Mechanistic modeling of SARS-CoV-2 immune memory, variants, and vaccines (preprint)

Early waves of the SARS-CoV-2 pandemic were driven by importation events and subsequent policy responses. However, epidemic dynamics in 2021 are largely driven by the spread of more transmissible and/or immune-evading variants, which in turn are countered by vaccination programs. Here we describe updates to the methodology of Covasim (COVID-19 Agent-based Simulator) to account for immune trajectories over time, correlates of protection, co-circulation of different variants and the roll-out of multiple vaccines. We have extended recent work on neutralizing antibodies (NAbs) as a correlate of protection to account for protection against infection, symptomatic COVID-19, and severe disease using a joint estimation approach. We find that NAbs are strongly correlated with infection blocking and that natural infection provides stronger protection than vaccination for the same level of NAbs, though vaccines typically produce higher NAbs. We find only relatively weak correlations between NAbs and the probability of developing symptoms given a breakthrough infection, or the probability of severe disease given symptoms. A more refined understanding of breakthrough infections in individuals with natural and vaccine-derived immunity will have implications for timing of booster vaccines, the impact of emerging variants of concern on critical vaccination thresholds, and the need for ongoing non-pharmaceutical interventions.

Modelling the impact of reopening schools in early 2021 in the presence of the new SARS-CoV-2 variant and with roll-out of vaccination against COVID-19 (preprint)

Background Following the resurgence of the COVID-19 epidemic in the UK in late 2020 and the emergence of the new variant of the SARS-CoV-2 virus, B.1.1.7, a third national lockdown was imposed from January 5, 2021. Following the decline of COVID-19 cases over the remainder of January 2021, it is important to assess the conditions under which reopening schools from early March is likely to lead to resurgence of the epidemic. This study models the impact of a partial national lockdown with social distancing measures enacted in communities and workplaces under different strategies of reopening schools from March 8, 2021 and compares it to the impact of continual full national lockdown remaining until April 19, 2021. Methods We used our previously published model, Covasim, to model the emergence of B.1.1.7 over September 1, 2020 to January 31, 2021. We extended the model to incorporate the impacts of the roll-out of a two-dose vaccine against COVID-19, assuming 200,000 daily doses of the vaccine in people 75 years or older with vaccination that offers 95% reduction in disease acquisition and 10% reduction of transmission blocking. We used the model, calibrated until January 25, 2021, to simulate the impact of a full national lockdown (FNL) with schools closed until April 19, 2021 versus four different partial national lockdown (PNL) scenarios with different elements of schooling open: 1) staggered PNL with primary schools and exam-entry years (years 11 and 13) returning on March 8, 2021 and the rest of the schools years on March 15, 2020; 2) full-return PNL with both primary and secondary schools returning on March 8, 2021; 3) primary-only PNL with primary schools and exam critical years (Y11 and Y13) going back only on March 8, 2021 with the rest of the secondary schools back on April 19, 2021 and 4) part-Rota PNL with both primary and secondary schools returning on March 8, 2021 with primary schools remaining open continuously but secondary schools on a two-weekly rota-system with years alternating between a fortnight of face-to-face and remote learning until April 19, 2021. Across all scenarios, we projected the number of new daily cases, cumulative deaths and effective reproduction number R until April 30, 2020. Results Our calibration across different scenarios is consistent with the new variant B.1.1.7 being around 60% more transmissible. Strict social distancing measures, i.e. national lockdowns, are required to contain the spread of the virus and control the hospitalisations and deaths during January and February 2021. The national lockdown will reduce the number of cases by early March levels similar to those seen in October with R also falling and remaining below 1 during the lockdown. Infections start to increase when schools open but if other parts of society remain closed this resurgence is not sufficient to bring R above 1. Reopening primary schools and exam critical years only or having primary schools open continuously with secondary schools on rotas will lead to lower increases in cases and R than if all schools open. Under the current vaccination assumptions and across the set of scenarios considered, R would increase above 1 if society reopens simultaneously, simulated here from April 19, 2021. Findings Our findings suggest that stringent measures are necessary to mitigate the increase in cases and bring R below 1 over January and February 2021. It is plausible that a PNL with schools partially open from March 8, 2021 and the rest of the society remaining closed until April 19, 2021 may keep R below 1, with some increase evident in infections compared to continual FNL until April 19, 2021. Reopening society in mid-April, with the vaccination strategy we model, could push R above 1 and induce a surge in infections, but the effect of vaccination may be able to control this in future depending on the transmission blocking properties of the vaccines.

The potential contribution of face coverings to the control of SARS-CoV-2 transmission in schools and broader society in the UK: a modelling study (preprint)

Recent findings suggest that an adequate test-trace-isolate (TTI) strategy is needed to prevent a secondary COVID-19 wave with the reopening of society in the UK. Here we assess the potential importance of mandatory masks in the parts of community and in secondary schools. We show that, assuming current TTI levels, adoption of masks in secondary schools in addition to community settings can reduce the size of a second wave, but will not prevent it; more testing of symptomatic people, tracing and isolating of their contacts is also needed. To avoid a second wave, with masks mandatory in secondary schools and in certain community settings, under current tracing levels, 68% or 46% of those with symptomatic infection would need to be tested if masks' effective coverage were 15% or 30% respectively, compared to 76% and 57% if masks are mandated in community settings but not secondary schools.

Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave (preprint)

Background In order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing (lockdown) measures including school 'dismissals' since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. Methods We use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals' contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Findings We found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. Interpretation To prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals.