Understanding an evolving pandemic: An analysis of the clinical time delay distributions of COVID-19 in the United Kingdom.

Understanding and monitoring the epidemiological time delay dynamics of SARS-CoV-2 infection provides insights that are key to discerning changes in the phenotype of the virus, the demographics impacted, the efficacy of treatment, and the ability of the health service to manage large volumes of patients. This paper analyses how the pandemic has evolved in the United Kingdom through the temporal changes to the epidemiological time delay distributions for clinical outcomes. Using the most complete clinical data presently available, we have analysed, through a doubly interval censored Bayesian modelling approach, the time from infection to a clinical outcome. Across the pandemic, for the periods that were defined as epidemiologically distinct, the modelled mean ranges from 8.0 to 9.7 days for infection to hospitalisation, 10.3 to 15.0 days for hospitalisation to death, and 17.4 to 24.7 days for infection to death. The time delay from infection to hospitalisation has increased since the first wave of the pandemic. A marked decrease was observed in the time from hospitalisation to death and infection to death at times of high incidence when hospitals and ICUs were under the most pressure. There is a clear relationship between age groups that is indicative of the youngest and oldest demographics having the shortest time delay distributions before a clinical outcome. A statistically significant difference was found between genders for the time delay from infection to hospitalisation, which was not found for hospitalisation to death. The results by age group indicate that younger demographics that require clinical intervention for SARS-CoV-2 infection are more likely to require earlier hospitalisation that leads to a shorter time to death, which is suggestive of the largely more vulnerable nature of these individuals that succumb to infection. The distinction found between genders for exposure to hospitalisation is revealing of gender healthcare seeking behaviours.

Does infection with or vaccination against SARS-CoV-2 lead to lasting immunity?

Many nations are pursuing the rollout of SARS-CoV-2 vaccines as an exit strategy from unprecedented COVID-19-related restrictions. However, the success of this strategy relies critically on the duration of protective immunity resulting from both natural infection and vaccination. SARS-CoV-2 infection elicits an adaptive immune response against a large breadth of viral epitopes, although the duration of the response varies with age and disease severity. Current evidence from case studies and large observational studies suggests that, consistent with research on other common respiratory viruses, a protective immunological response lasts for approximately 5-12 months from primary infection, with reinfection being more likely given an insufficiently robust primary humoral response. Markers of humoral and cell-mediated immune memory can persist over many months, and might help to mitigate against severe disease upon reinfection. Emerging data, including evidence of breakthrough infections, suggest that vaccine effectiveness might be reduced significantly against emerging variants of concern, and hence secondary vaccines will need to be developed to maintain population-level protective immunity. Nonetheless, other interventions will also be required, with further outbreaks likely to occur due to antigenic drift, selective pressures for novel variants, and global population mobility.

Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis.

OBJECTIVES: Importations of novel variants of concern (VOC), particularly B.1.617.2, have become the impetus behind recent outbreaks of SARS-CoV-2. Concerns around the impact on vaccine effectiveness, transmissibility and severity are now driving the public health response to these variants. This paper analyses the patterns of growth in hospitalisations and confirmed cases for novel VOCs by age groups, geography and ethnicity in the context of changing behaviour, non-pharmaceutical interventions (NPIs) and the UK vaccination programme. We seek to highlight where strategies have been effective and periods that have facilitated the establishment of new variants. DESIGN: We have algorithmically linked the most complete testing and hospitalisation data in England to create a data set of confirmed infections and hospitalisations by SARS-CoV-2 genomic variant. We have used these linked data sets to analyse temporal, geographic and demographic distinctions. SETTING AND PARTICIPANTS: The setting is England from October 2020 to July 2021. Participants included all COVID-19 tests that included RT-PCR CT gene target data or underwent sequencing and hospitalisations that could be linked to these tests. METHODS: To calculate the instantaneous growth rate for VOCs we have developed a generalised additive model fit to multiple splines and varying day of the week effects. We have further modelled the instantaneous reproduction number Rt for the B.1.1.7 and B.1.617.2 variants and included a doubly interval censored model to temporally adjust the confirmed variant cases. RESULTS: We observed a clear replacement of the predominant B.1.1.7 by the B.1.617.2 variant without observing sustained exponential growth in other novel variants. Modelled exponential growth of RT PCR gene target triple-positive cases was initially detected in the youngest age groups, although we now observe across all ages a very small doubling time of 10.7 (95% CI 9.1 to 13.2) days and 8 (95% CI 6.9 to 9.1) days for cases and hospitalisations, respectively. We observe that growth in RT PCR gene target triple-positive cases was first detected in the Indian ethnicity group in late February, with a peak of 0.06 (95% CI 0.07 to 0.05) in the instantaneous growth rate, but is now maintained by the white ethnicity groups, observing a doubling time of 6.8 (95% CI 4.9 to 11) days. Rt analysis indicates a reproduction number advantage of 0.45 for B.1.617.2 relative to B.1.1.7, with the Rt value peaking at 1.85 for B.1.617.2. CONCLUSIONS: Our results illustrate a clear transmission advantage for the B.1.617.2 variant and the growth in hospitalisations illustrates that this variant is able to maintain exponential growth within age groups that are largely doubly vaccinated. There are concerning signs of intermittent growth in the B.1.351 variant, reaching a 28-day doubling time peak in March 2021, although this variant is presently not showing any evidence of a transmission advantage over B.1.617.2. Step 1b of the UK national lockdown easing was sufficient to precipitate exponential growth in B.1.617.2 cases for most regions and younger adult age groups. The final stages of NPI easing appeared to have a negligible impact on the growth of B.1.617.2 with every region experiencing sustained exponential growth from step 2. Nonetheless, early targeted local NPIs appeared to markedly reduced growth of B.1.617.2. Later localised interventions, at a time of higher prevalence and greater geographic dispersion of this variant, appeared to have a negligible impact on growth.