Superspreading, overdispersion and their implications in the SARS-CoV-2 (COVID-19) pandemic: a systematic review and meta-analysis of the literature.

BACKGROUND: A recurrent feature of infectious diseases is the observation that different individuals show different levels of secondary transmission. This inter-individual variation in transmission potential is often quantified by the dispersion parameter k. Low values of k indicate a high degree of variability and a greater probability of superspreading events. Understanding k for COVID-19 across contexts can assist policy makers prepare for future pandemics. METHODS: A literature search following a systematic approach was carried out in PubMed, Embase, Web of Science, Cochrane Library, medRxiv, bioRxiv and arXiv to identify publications containing epidemiological findings on superspreading in COVID-19. Study characteristics, epidemiological data, including estimates for k and R0, and public health recommendations were extracted from relevant records. RESULTS: The literature search yielded 28 peer-reviewed studies. The mean k estimates ranged from 0.04 to 2.97. Among the 28 studies, 93% reported mean k estimates lower than one, which is considered as marked heterogeneity in inter-individual transmission potential. Recommended control measures were specifically aimed at preventing superspreading events. The combination of forward and backward contact tracing, timely confirmation of cases, rapid case isolation, vaccination and preventive measures were suggested as important components to suppress superspreading. CONCLUSIONS: Superspreading events were a major feature in the pandemic of SARS-CoV-2. On the one hand, this made outbreaks potentially more explosive but on the other hand also more responsive to public health interventions. Going forward, understanding k is critical for tailoring public health measures to high-risk groups and settings where superspreading events occur.

COVID-19 vaccine hesitancy and social contact patterns in Pakistan: results from a national cross-sectional survey.

BACKGROUND: Vaccination is a key tool against COVID-19. However, in many settings it is not clear how acceptable COVID-19 vaccination is among the general population, or how hesitancy correlates with risk of disease acquisition. In this study we conducted a nationally representative survey in Pakistan to measure vaccination perceptions and social contacts in the context of COVID-19 control measures and vaccination programmes. METHODS: We conducted a vaccine perception and social contact survey with 3,658 respondents across five provinces in Pakistan, between 31 May and 29 June 2021. Respondents were asked a series of vaccine perceptions questions, to report all direct physical and non-physical contacts made the previous day, and a number of other questions regarding the social and economic impact of COVID-19 and control measures. We examined variation in perceptions and contact patterns by geographic and demographic factors. We describe knowledge, experiences and perceived risks of COVID-19. We explored variation in contact patterns by individual characteristics and vaccine hesitancy, and compared to patterns from non-pandemic periods. RESULTS: Self-reported adherence to self-isolation guidelines was poor, and 51% of respondents did not know where to access a COVID-19 test. Although 48.1% of participants agreed that they would get a vaccine if offered, vaccine hesitancy was higher than in previous surveys, and greatest in Sindh and Baluchistan provinces and among respondents of lower socioeconomic status. Participants reported a median of 5 contacts the previous day (IQR: 3-5, mean 14.0, 95%CI: 13.2, 14.9). There were no substantial differences in the number of contacts reported by individual characteristics, but contacts varied substantially among respondents reporting more or less vaccine hesitancy. Contacts were highly assortative, particularly outside the household where 97% of men's contacts were with other men. We estimate that social contacts were 9% lower than before the COVID-19 pandemic. CONCLUSIONS: Although the perceived risk of COVID-19 in Pakistan is low in the general population, around half of participants in this survey indicated they would get vaccinated if offered. Vaccine impact studies which do not account for correlation between social contacts and vaccine hesitancy may incorrectly estimate the impact of vaccines, for example, if unvaccinated people have more contacts.

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy;reliable estimates of waiting times and ‘patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees' movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males;p<0.001) and attending with a baby (18.8 minutes longer than those without;p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700;p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46–100]) than outdoors (2.5% [IQR 0–35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1–75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow.

What, how and who: Cost-effectiveness analyses of COVID-19 vaccination to inform key policies in Nigeria.

While safe and efficacious COVID-19 vaccines have achieved high coverage in high-income settings, roll-out remains slow in sub-Saharan Africa. By April 2022, Nigeria, a country of over 200 million people, had only distributed 34 million doses. To ensure the optimal use of health resources, cost-effectiveness analyses can inform key policy questions in the health technology assessment process. We carried out several cost-effectiveness analyses exploring different COVID-19 vaccination scenarios in Nigeria. In consultation with Nigerian stakeholders, we addressed three key questions: what vaccines to buy, how to deliver them and what age groups to target. We combined an epidemiological model of virus transmission parameterised with Nigeria specific data with a costing model that incorporated local resource use assumptions and prices, both for vaccine delivery as well as costs associated with care and treatment of COVID-19. Scenarios of vaccination were compared with no vaccination. Incremental cost-effectiveness ratios were estimated in terms of costs per disability-adjusted life years averted and compared to commonly used cost-effectiveness ratios. Viral vector vaccines are cost-effective (or cost saving), particularly when targeting older adults. Despite higher efficacy, vaccines employing mRNA technologies are less cost-effective due to high current dose prices. The method of delivery of vaccines makes little difference to the cost-effectiveness of the vaccine. COVID-19 vaccines can be highly effective and cost-effective (as well as cost-saving), although an important determinant of the latter is the price per dose and the age groups prioritised for vaccination. From a health system perspective, viral vector vaccines may represent most cost-effective choices for Nigeria, although this may change with price negotiation.

Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.

BACKGROUND: The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. METHODS: We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. RESULTS: Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable. CONCLUSION: Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.

Is there a role for RDTs as we live with COVID-19? An assessment of different strategies.

INTRODUCTION: By 2022, high levels of past COVID-19 infections, combined with substantial levels of vaccination and the development of Omicron, have shifted country strategies towards burden reduction policies. SARS-CoV-2 rapid antigen tests (rapid diagnostic tests (RDTs)) could contribute to these policies by helping rapidly detect, isolate and/or treat infections in different settings. However, the evidence to inform RDT policy choices in low and middle-income countries (LMICs) is limited. METHOD: We provide an overview of the potential impact of several RDT use cases (surveillance; testing, tracing and isolation without and with surveillance; hospital-based screening to reduce nosocomial COVID-19; and testing to enable earlier/expanded treatment) for a range of country settings. We use conceptual models and literature review to identify which use cases are likely to bring benefits and how these may change with outbreak characteristics. Impacts are measured through multiple outcomes related to gaining time, reducing the burden on the health system and reducing deaths. RESULTS: In an optimal scenario in terms of resources and capacity and with baseline parameters, we find marginal time gains of 4 days or more through surveillance and testing tracing and isolation with surveillance, a reduction in peak intensive care unit (ICU) or ICU admissions by 5% or more (hospital-based screening; testing, tracing and isolation) and reductions in COVID-19 deaths by over 6% (hospital-based screening; test and treat). Time gains may be used to strengthen ICU capacity and/or boost vulnerable individuals, though only a small minority of at-risk individuals could be reached in the time available. The impact of RDTs declines with lower country resources and capacity, more transmissible or immune-escaping variants and reduced test sensitivity. CONCLUSION: RDTs alone are unlikely to dramatically reduce the burden of COVID-19 in LMICs, though they may have an important role alongside other interventions such as vaccination, therapeutic drugs, improved healthcare capacity and non-pharmaceutical measures.

Correction: COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

[This corrects the article DOI: 10.1371/journal.pmed.1003815.].

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics.

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and 'patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees' movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36-3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46-100]) than outdoors (2.5% [IQR 0-35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1-75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow.

Impact of COVID-19 restrictive measures on income and health service utilization of tuberculosis patients in India.

BACKGROUND: The nationwide lockdown (March 25 to June 8, 2020) to curb the spread of coronavirus infection had significant health and economic impacts on the Indian economy. There is limited empirical evidence on how COVID-19 restrictive measures may impact the economic welfare of specific groups of patients, e.g., tuberculosis patients. We provide the first such evidence for India. METHODS: A total of 291 tuberculosis patients from the general population and from a high-risk group, patients from tea garden areas, were interviewed at different time points to understand household income loss during the complete lockdown, three and eight months after the complete lockdown was lifted. Income loss was estimated by comparing net monthly household income during and after lockdown with prelockdown income. Tuberculosis service utilization patterns before and during the lockdown period also were examined. Household income loss, travel and other expenses related to tuberculosis drug pickup were presented in 2020 US dollars (1 US$ = INR 74.132). RESULTS: 26% of households with tuberculosis patients in tea garden areas and 51% of households in the general population had zero monthly income during the complete lockdown months (April-May 2020). Overall income loss slowly recovered during July-August compared to April-May 2020. Approximately 7% of patients in the general population and 4% in tea garden areas discontinued their tuberculosis medicines because of the complete lockdown. CONCLUSION: Discontinuation of medicine will have an additional burden on the tuberculosis elimination program in terms of additional cases, including multidrug resistant tuberculosis cases. Income loss for households and poor restoration of income after the lockdown will likely have an impact on the nutrition of tuberculosis patients and families. Tuberculosis patients working in the informal sector were the worst affected group during the nationwide lockdown. This emphasizes that a policy priority must continue to protect those working in informal sectors from the economic consequences of such restrictive measures, including paid sick leave, additional food support, and direct benefit transfers. Alongside ensuring widespread access to COVID-19 vaccines, these policy actions remain pivotal in ensuring the well-being of those who are unfortunate enough to be living with tuberculosis.

Optimal health and economic impact of non-pharmaceutical intervention measures prior and post vaccination in England: a mathematical modelling study.

Background. Even with good progress on vaccination, SARS-CoV-2 infections in the UK may continue to impose a high burden of disease and therefore pose substantial challenges for health policy decision makers. Stringent government-mandated physical distancing measures (lockdown) have been demonstrated to be epidemiologically effective, but can have both positive and negative economic consequences. The duration and frequency of any intervention policy could, in theory, be optimized to maximize economic benefits while achieving substantial reductions in disease. Methods. Here, we use a pre-existing SARS-CoV-2 transmission model to assess the health and economic implications of different strengths of control through time in order to identify optimal approaches to non-pharmaceutical intervention stringency in the UK, considering the role of vaccination in reducing the need for future physical distancing measures. The model is calibrated to the COVID-19 epidemic in England and we carry out retrospective analysis of the optimal timing of precautionary breaks in 2020 and the optimal relaxation policy from the January 2021 lockdown, considering the willingness to pay (WTP) for health improvement. Results. We find that the precise timing and intensity of interventions is highly dependent upon the objective of control. As intervention measures are relaxed, we predict a resurgence in cases, but the optimal intervention policy can be established dependent upon the WTP per quality adjusted life year loss avoided. Our results show that establishing an optimal level of control can result in a reduction in net monetary loss of billions of pounds, dependent upon the precise WTP value. Conclusion. It is vital, as the UK emerges from lockdown, but continues to face an on-going pandemic, to accurately establish the overall health and economic costs when making policy decisions. We demonstrate how some of these can be quantified, employing mechanistic infectious disease transmission models to establish optimal levels of control for the ongoing COVID-19 pandemic.

Stark choices: exploring health sector costs of policy responses to COVID-19 in low-income and middle-income countries.

OBJECTIVES: COVID-19 has altered health sector capacity in low-income and middle-income countries (LMICs). Cost data to inform evidence-based priority setting are urgently needed. Consequently, in this paper, we calculate the full economic health sector costs of COVID-19 clinical management in 79 LMICs under different epidemiological scenarios. METHODS: We used country-specific epidemiological projections from a dynamic transmission model to determine number of cases, hospitalisations and deaths over 1 year under four mitigation scenarios. We defined the health sector response for three base LMICs through guidelines and expert opinion. We calculated costs through local resource use and price data and extrapolated costs across 79 LMICs. Lastly, we compared cost estimates against gross domestic product (GDP) and total annual health expenditure in 76 LMICs. RESULTS: COVID-19 clinical management costs vary greatly by country, ranging between <0.1%-12% of GDP and 0.4%-223% of total annual health expenditure (excluding out-of-pocket payments). Without mitigation policies, COVID-19 clinical management costs per capita range from US$43.39 to US$75.57; in 22 of 76 LMICs, these costs would surpass total annual health expenditure. In a scenario of stringent social distancing, costs per capita fall to US$1.10-US$1.32. CONCLUSIONS: We present the first dataset of COVID-19 clinical management costs across LMICs. These costs can be used to inform decision-making on priority setting. Our results show that COVID-19 clinical management costs in LMICs are substantial, even in scenarios of moderate social distancing. Low-income countries are particularly vulnerable and some will struggle to cope with almost any epidemiological scenario. The choices facing LMICs are likely to remain stark and emergency financial support will be needed.

Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.

BACKGROUND: How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes. METHODS: We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed. RESULTS: The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage. CONCLUSION: The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.

COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

BACKGROUND: Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million). METHODS AND FINDINGS: We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question. CONCLUSIONS: COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.

Exploring equity in health and poverty impacts of control measures for SARS-CoV-2 in six countries.

BACKGROUND: Policy makers need to be rapidly informed about the potential equity consequences of different COVID-19 strategies, alongside their broader health and economic impacts. While there are complex models to inform both potential health and macro-economic impact, there are few tools available to rapidly assess potential equity impacts of interventions. METHODS: We created an economic model to simulate the impact of lockdown measures in Pakistan, Georgia, Chile, UK, the Philippines and South Africa. We consider impact of lockdown in terms of ability to socially distance, and income loss during lockdown, and tested the impact of assumptions on social protection coverage in a scenario analysis. RESULTS: In all examined countries, socioeconomic status (SES) quintiles 1-3 were disproportionately more likely to experience income loss (70% of people) and inability to socially distance (68% of people) than higher SES quintiles. Improving social protection increased the percentage of the workforce able to socially distance from 48% (33%-60%) to 66% (44%-71%). We estimate the cost of this social protection would be equivalent to an average of 0.6% gross domestic product (0.1% Pakistan-1.1% Chile). CONCLUSIONS: We illustrate the potential for using publicly available data to rapidly assess the equity implications of social protection and non-pharmaceutical intervention policy. Social protection is likely to mitigate inequitable health and economic impacts of lockdown. Although social protection is usually targeted to the poorest, middle quintiles will likely also need support as they are most likely to suffer income losses and are disproportionately more exposed.

The potential health and economic value of SARS-CoV-2 vaccination alongside physical distancing in the UK: a transmission model-based future scenario analysis and economic evaluation.

BACKGROUND: In response to the COVID-19 pandemic, the UK first adopted physical distancing measures in March, 2020. Vaccines against SARS-CoV-2 became available in December, 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing in the UK to gain insights about possible future scenarios in a post-vaccination era. METHODS: We used an age-structured dynamic transmission and economic model to explore different scenarios of UK mass immunisation programmes over 10 years. We compared vaccinating 75% of individuals aged 15 years or older (and annually revaccinating 50% of individuals aged 15-64 years and 75% of individuals aged 65 years or older) to no vaccination. We assumed either 50% vaccine efficacy against disease and 45-week protection (worst-case scenario) or 95% vaccine efficacy against infection and 3-year protection (best-case scenario). Natural immunity was assumed to wane within 45 weeks. We also explored the additional impact of physical distancing on vaccination by assuming either an initial lockdown followed by voluntary physical distancing, or an initial lockdown followed by increased physical distancing mandated above a certain threshold of incident daily infections. We considered benefits in terms of quality-adjusted life-years (QALYs) and costs, both to the health-care payer and the national economy. We discounted future costs and QALYs at 3·5% annually and assumed a monetary value per QALY of £20 000 and a conservative long-run cost per vaccine dose of £15. We explored and varied these parameters in sensitivity analyses. We expressed the health and economic benefits of each scenario with the net monetary value: QALYs × (monetary value per QALY) - costs. FINDINGS: Without the initial lockdown, vaccination, and increased physical distancing, we estimated 148·0 million (95% uncertainty interval 48·5-198·8) COVID-19 cases and 3·1 million (0·84-4·5) deaths would occur in the UK over 10 years. In the best-case scenario, vaccination minimises community transmission without future periods of increased physical distancing, whereas SARS-CoV-2 becomes endemic with biannual epidemics in the worst-case scenario. Ongoing transmission is also expected in intermediate scenarios with vaccine efficacy similar to published clinical trial data. From a health-care perspective, introducing vaccination leads to incremental net monetary values ranging from £12·0 billion to £334·7 billion in the best-case scenario and from -£1·1 billion to £56·9 billion in the worst-case scenario. Incremental net monetary values of increased physical distancing might be negative from a societal perspective if national economy losses are persistent and large. INTERPRETATION: Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Smaller outbreaks could continue even with vaccines, but population-wide implementation of increased physical distancing might no longer be justifiable. Our study provides early insights about possible future post-vaccination scenarios from an economic and epidemiological perspective. FUNDING: National Institute for Health Research, European Commission, Bill & Melinda Gates Foundation.

Integrating economic and health evidence to inform Covid-19 policy in low- and middle- income countries [version 1;peer review: awaiting peer review]

Covid-19 requires policy makers to consider evidence on both population health and economic welfare. Over the last two decades, the field of health economics has developed a range of analytical approaches and contributed to the institutionalisation of processes to employ economic evidence in health policy. We present a discussion outlining how these approaches and processes need to be applied more widely to inform Covid-19 policy;highlighting where they may need to be adapted conceptually and methodologically, and providing examples of work to date. We focus on the evidential and policy needs of low- and middle-income countries;where there is an urgent need for evidence to navigate the policy trade-offs between health and economic well-being posed by the Covid-19 pandemic.