Countries of the World Health Organization (WHO) African Region have experienced a wide range of coronavirus disease 2019 (COVID-19) epidemics. This study aimed to identify predictors of the timing of the first COVID-19 case and the per capita mortality in WHO African Region countries during the first and second pandemic waves and to test for associations with the preparedness of health systems and government pandemic responses. Using a region-wide, country-based observational study, we found that the first case was detected earlier in countries with more urban populations, higher international connectivity and greater COVID-19 test capacity but later in island nations. Predictors of a high first wave per capita mortality rate included a more urban population, higher pre-pandemic international connectivity and a higher prevalence of HIV. Countries rated as better prepared and having more resilient health systems were worst affected by the disease, the imposition of restrictions or both, making any benefit of more stringent countermeasures difficult to detect. Predictors for the second wave were similar to the first. Second wave per capita mortality could be predicted from that of the first wave. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa that should be taken into account in future pandemic preparedness planning.

In this study we demonstrate that the adoption of a segmenting and shielding (S&S) strategy could increase scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection. The S&S strategy has an antecedent in the "cocooning" of infants by immunisation of close family members (Forsyth et al., 2015), and forms a pillar of infection, prevention and control (IPC) strategies (RCN, 2017). We are unaware of it being proposed as a major public health initiative previously. We illustrate the S&S strategy using a mathematical model that segments the vulnerable population and their closest contacts, the "shielders". We explore the effects on the epidemic curve of a gradual ramping up of protection for the vulnerable population and a gradual ramping down of restrictions on the non-vulnerable population over a period of 12 weeks after lockdown. The most important determinants of outcome are: i) post-lockdown transmission rates within the general population segment and between the general and vulnerable segments; ii) the fraction of the population in the vulnerable and shielder segments; iii) adherence with need to be protected; and iv) the extent to which population immunity builds up in all segments. We explored the effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population. We illustrate how the potential for the relaxation of restrictions interacts with specific policy objectives. We show that the range of options for relaxation in the general population can be increased by maintaining restrictions on the shielder segment and by intensive routine screening of shielders. We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. These relationships are difficult to quantify so close monitoring of the epidemic would be essential during and after the exit from lockdown. More generally, S&S has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes.

This study demonstrates that an adoption of a segmenting and shielding strategy could increase the scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection. We illustrate this using a mathematical model that segments the vulnerable population and their closest contacts, the ‘shielders’. Effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population are explored. Our study shows that the most important determinants of outcome are: (i) post-lockdown transmission rates within the general and between the general and vulnerable segments; (ii) fractions of the population in the vulnerable and shielder segments; (iii) adherence to protective measures; and (iv) build-up of population immunity. Additionally, we found that effective measures in the shielder segment, e.g. intensive routine screening, allow further relaxations in the general population. We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. This strategy has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.

Genes are commonly abstracted into a coding sequence and cis-regulatory elements (CREs), such as promoter and terminator regions, and short sequence motifs within these regions. Modern cloning techniques allow easy assembly of synthetic genetic constructs from discrete cis-regulatory modules. However, it is unclear how much the contributions of CREs to gene expression depend on other CREs in the host gene. Using budding yeast, we probe the extent of composability, or independent effects, of distinct CREs. We confirm that the quantitative effect of a terminator on gene expression depends on both promoter and coding sequence. We then explore whether individual cis-regulatory motifs within terminator regions display similar context dependence, focusing on putative regulatory motifs inferred using transcriptome-wide datasets of mRNA decay. We construct a library of diverse reporter genes, consisting of different combinations of motifs within various terminator contexts, paired with different promoters, to test the extent of composability. Our results show that the effect of a motif on RNA abundance depends both on its host terminator, and also on the associated promoter sequence. Consequently, this emphasises the need for improved motif inference algorithms that include both local and global context effects, which in turn could aid researchers in the accurate use of diverse CREs for the engineering of synthetic genetic constructs.

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