Assessing the impacts of timing on the health benefits, cost-effectiveness and relative affordability of COVID-19 vaccination programmes in 27 African Countries

BackgroundThe COVID-19 vaccine supply shortage in 2021 constrained rollout efforts in Africa while populations experienced waves of epidemics. As supply picks up, a key question becomes if vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. MethodsWe assessed the impact of timing using an epidemiological and economic model. We fitted our mathematical epidemiological model to reported COVID-19 deaths in 27 African countries to estimate the existing immunity (resulting from infection) before substantial vaccine rollout. We then projected health outcomes for different programme start dates (2021-01-01 to 2021-12-01, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/ million population-day, respectively) for viral vector and mRNA vaccines. Rollout rates used were derived from observed uptake trajectories. We collected data on vaccine delivery costs by country income group. Lastly, we calculated incremental cost-effectiveness ratios and relative affordability. FindingsVaccination programmes with early start dates incur the most health benefits and are most cost-effective. While incurring the most health benefits, fast vaccine roll-outs are not always the most cost-effective. At a willingness-to-pay threshold of 0.5xGDP per capita, vaccine programmes starting in August 2021 using mRNA and viral vector vaccines were cost-effective in 6-10 and 17-18 of 27 countries, respectively. InterpretationAfrican countries with large proportions of their populations unvaccinated by late 2021 may find vaccination programmes less cost-effective than they could have been earlier in 2021. Lower vaccine purchasing costs and/or the emergence of new variants may improve cost-effectiveness. FundingBill and Melinda Gates Foundation, World Health Organization, National Institute of Health Research (UK), Health Data Research (UK)

Test to release from isolation after testing positive for SARS-CoV-2

O_LIThe rapid spread and high transmissibility of the Omicron variant of SARS-CoV-2 is likely to lead to a significant number of key workers testing positive simultaneously. C_LIO_LIUnder a policy of self-isolation after testing positive, this may lead to extreme staffing shortfalls at the same time as e.g. hospital admissions are peaking. C_LIO_LIUsing a model of individual infectiousness and testing with lateral flow tests (LFT), we evaluate test-to-release policies against conventional fixed-duration isolation policies in terms of excess days of infectiousness, days saved, and tests used. C_LIO_LIWe find that the number of infectious days in the community can be reduced to almost zero by requiring at least 2 consecutive days of negative tests, regardless of the number of days wait until testing again after initially testing positive. C_LIO_LIOn average, a policy of fewer days wait until initiating testing (e.g 3 or 5 days) results in more days saved vs. a 10-day isolation period, but also requires a greater number of tests. C_LIO_LIDue to a lack of specific data on viral load progression, infectivity, and likelihood of testing positive by LFT over the course of an Omicron infection, we assume the same parameters as for pre-Omicron variants and explore the impact of a possible shorter proliferation phase. C_LI

Dosing interval strategies for two-dose COVID-19 vaccination in 13 low- and middle-income countries of Europe: health impact modelling and benefit-risk analysis

BackgroundIn settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine could let more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals for low- and middle-income countries of Europe. MethodsWe fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 low- and middle-income countries in the World Health Organization European Region (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies related to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern into the model, and also conducted a benefit-risk assessment to quantify the trade-off between health benefits versus adverse events following immunisation. FindingsIn 12 of the 13 countries, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20-59 years). These strategies lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.2% [range: 4.0% - 22.5%; n = 13 (countries)] more deaths. There is generally a negative association between dosing interval and COVID-19 mortality within the range we investigated. Assuming a shorter first dose waning duration of 120 days, as opposed to 360 days in the base case, led to shorter optimal dosing intervals of 8-12 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. InterpretationWe infer that longer dosing intervals of over six months, which are substantially longer than the current label recommendation for most vaccine products, could reduce COVID-19 mortality in low- and middle-income countries of WHO/Europe. Certain vaccine features, such as fast waning of first doses, significantly shorten the optimal dosing intervals. FundingWorld Health Organization

Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK

Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Human movement can inform the spatial scale of interventions against COVID-19 transmission

BackgroundIn 2020, the UK enacted an intensive, nationwide lockdown on March 23 to mitigate transmission of COVID-19. As restrictions began to ease, resurgences in transmission were targeted by geographically-limited interventions of various stringencies. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to inform interventions targeted at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence. MethodsWe use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time. FindingsWe found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance journeys central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas. InterpretationWe propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions. Putting Research Into ContextO_ST_ABSEvidence before this studyC_ST_ABSLarge-scale intensive interventions in response to the COVID-19 pandemic have been implemented globally, significantly affecting human movement patterns. Mobility data show spatially-explicit network structure, but it is not clear how that structure changed in response to national or locally-targeted interventions. Added value of this studyWe used daily mobility data aggregated from Facebook users to quantify changes in the travel network in the UK during the national lockdown, and in response to local interventions. We identified changes in human behaviour in response to interventions and identified the community structure inherent in these networks. This approach to understanding changes in the travel network can help quantify the extent of strongly connected communities of interaction and their relationship to the extent of spatially-explicit interventions. Implications of all the available evidenceWe show that spatial mobility data available in near real-time can give information on connectivity that can be used to understand the impact of geographically-targeted interventions and in the future, to inform spatially-targeted intervention strategies. Data SharingData used in this study are available from the Facebook Data for Good Partner Program by application. Code and supplementary information for this paper are available online (https://github.com/hamishgibbs/facebook_mobility_uk), alongside publication.

Changing travel patterns in China during the early stages of the COVID-19 pandemic

Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigated the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020 and discussed their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower access to care. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and have not yet led to structural reorganisation of the transportation network at the time of this study. One sentence summaryUnderstanding travel before, during, and after the introduction of travel restrictions in China in response to the COVID-19 Pandemic.

The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak

BackgroundSome key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship. MethodsWe used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals. FindingsOn the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15. InterpretationAsymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19. FundingERC Starting Grant (#757699), Wellcome trust (208812/Z/17/Z), HDR UK (MR/S003975/1)