ABSTRACT
BackgroundThe city of Melbourne, Australia experienced two waves of the COVID-19 epidemic peaking, the first in March and a more substantial wave in July 2020. During the second wave, a series of control measure were progressively introduced that initially slowed the growth of the epidemic then resulted in decreasing cases until there was no detectable local transmission. MethodsTo determine the relative efficacy of the progressively introduced intervention measures, we modelled the second wave as a series of exponential growth and decay curves. We used a linear regression of the log of daily cases vs time, using a four-segment linear spline model corresponding to implementation of the three successive major public health measures. The primary model used all reported cases between 14 June and 15 September then compared the projection of the model with observed cases predict future case trajectory up until the 31 October to assess the use of exponential models in projecting the future course and planning future interventions. The main outcome measures were the exponential daily growth constants, analysis of residuals and estimates of the 95% confidence intervals for the expected case distributions, comparison of predicted daily cases. ResultsThe exponential growth/decay constants in the primary analysis were: 0.122 (s.e. 0.004), 0.035 (s.e. 0.005), -0.037 (s.e. 0.011), and -0.069 (s.e. 0.003) for the initial growth rate, Stage 3, stage 3 + compulsory masks and Stage 4, respectively. Extrapolation of the regression model from the 14 September to the 31 October matched the decline in observed cases over this period. ConclusionsThe four-segment exponential model provided an excellent fit of the observed reported case data and predicted the day-to-day range of expected cases. The extrapolated regression accurately predicted the decline leading to epidemic control in Melbourne.
ABSTRACT
BackgroundIn clinical trials two vaccinations with mRNA vaccines have shown high efficacy in preventing COVID-19. However, in the context of a pandemic, the time to generation of protective immunity, the need for and timing of a second vaccination are matters of legitimate debate. This manuscript explores the efficacy and timing of the second dose COVID-19 vaccines, including a reanalysis of data from the Pfizer mRNA BNT162b2 mRNA SARS-CoV-2 vaccine phase 3 study. Methods and findingsA non-weighted three-segment, two knot linear regression was fitted to the published cumulative infection incidence from the Pfizer BNT162b2 vaccine Phase III trial using the lspine routine in R. The optimal knot days were estimated through sensitivity analysis and the confidence limits for efficacy estimates were determined by Monte Carlo Simulations. This analysis showed the vaccine was effective from day 11 post first vaccination. The estimated efficacy over the period 11 to 28 days post first vaccination was 0.94 and there was no detectable increase in efficacy following the second vaccination. The efficacy post first vaccination substantially preceded the development of detectable serum neutralizing antibody. ConclusionsStrongly protective immunity develops rapidly following a single vaccination and at least in the short period covered by the timetable of the Phase III trial, there was no additional benefit from a second vaccination. This increases options for use of this vaccine, e.g., for ring fence vaccination, for use in travelers and for mass vaccination rollout. It highlights the need for further research into duration of immunity following a single vaccination and for understanding mechanisms of protection.
