The macroeconomic and epidemiological impacts of Covid-19 in Pakistan. (preprint)

'Coronavirus Disease 2019' (C19) is a respiratory illness caused by 'new Coronavirus' SARS-CoV-2. The C19 pandemic, which engulfed the world in 2021, also caused a national C19 epidemic in Pakistan, who responded with initial forced lockdowns (15-30 March 2020) and a subsequent switch to a smart lockdown strategy, and, by 31 December 2020, Pakistan had managed to limit confirmed cases and case fatalities to 482,506 (456 per 100,000) and 10,176 (4.8 per 100,000). The early switch to a smart lockdown strategy, and successful follow-up move to central coordination and effective communication and enforcement of Standard Operating Procedures, was motivated by a concern over how broad-based forced lockdowns would affect poor households and day-labour. The current study aims to investigate how the national Pakistan C19 epidemic would have unfolded under an uncontrolled baseline scenario and an alternative set of controlled non-pharmaceutical intervention (NPI) policy lockdown scenarios, including health and macroeconomic outcomes. We employ a dynamically-recursive version of the IFPRI Standard Computable General Equilibrium model framework (Lofgren, Lee Harris and Robinson 2002), and a, by now, well-established epidemiological transmission-dynamic model framework (Davies, Klepac et al 2020) using Pakistan-specific 5-year age-group contact matrices on four types of contact rates, including at home, at work, at school, and at other locations (Prem, Cook & Jit 2017), to characterize an uncontrolled spread of disease. Our simulation results indicate that an uncontrolled C19 epidemic, by itself, would have led to a 0.12% reduction in Pakistani GDP (-721mn USD), and a total of 0.65mn critically ill and 1.52mn severely ill C19 patients during 2020-21, while 405,000 Pakistani citizens would have lost their lives. Since the majority of case fatalities and symptomatic cases, respectively 345,000 and 35.9mn, would have occurred in 2020, the case fatality and confirmed case numbers, observed by 31. December 2020 represents an outcome which is far better than the alternative. Case fatalities by 31. December 2020 could possibly have been somewhat improved either via a more prolonged one-off 10 week forced lockdown (66% reduction) or a 1-month forced lockdown/2-months opening intermittent lockdown strategy (33% reduction), but both sets of strategies would have carried significant GDP costs in the order of 2.2%-6.2% of real GDP.

Is there a role for RDTs as we live with COVID? An assessment of different strategies (preprint)

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 toward burden reduction policies. SARS-CoV-2 rapid antigen 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 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; 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 at least a week through surveillance and testing tracing and isolation with surveillance, a reduction in peak ICU or ICU admissions by 6% or more (hospital-based screening; testing, tracing and isolation), and reductions in COVID 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.

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

Background: The 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. Methods: We 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. Findings: Vaccination 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. Interpretation: African 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. Funding: Bill and Melinda Gates Foundation, World Health Organization, National Institute of Health Research (UK), Health Data Research (UK)

Waiting times, patient flow, and occupancy density in South African primary health care clinics: implications for infection prevention and control (preprint)

Background 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. In clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa, we estimated clinic visit duration, time spent indoors and outdoors, and occupancy density of waiting rooms. Methods We used unique barcodes to track attendees’ movements in 11 clinics in two provinces, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. Results 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) and attendance for tuberculosis or ante/postnatal care (24.8 and 32.6 minutes shorter, respectively, than HIV/acute care; p<0.01). 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/m 2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system), occupancy density did not exceed 1.0 persons/m 2 despite higher overall attendance. Conclusions Longer waiting times were associated with early arrival, being female, and attending with a young child. Attendees generally waited where they were asked to. Regular estimation of occupancy density (as patient flow proxy) may help staff assess for risk of infection transmission and guide intervention to reduce time spent in risky spaces.

Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review (preprint)

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 systematically 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. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed. Findings: The search identified 1820 studies. 36 studies met the inclusion criteria and were narratively synthesised. 83% of studies described outcomes in high-income countries. 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 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. Interpretation: 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.

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

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, could be optimised to maximise 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 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 willingness to pay (WTP) per QALY 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. Conclusions 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.

Health impact and cost-effectiveness of COVID-19 vaccination in Sindh Province, Pakistan (preprint)

Background Multiple 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 We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020 using varying assumptions about the timing of the first case and the duration of infection-induced immunity. We then projected cases and deaths 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 cost-effectiveness for each scenario. Findings A one-year vaccination campaign using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5 year duration of protection is projected to avert around 0.93 (95% Credible Interval: 0.91, 1.0) million cases, 7.3 (95% CrI: 7.2, 7.4) thousand deaths and 85.1 (95% CrI: 84.6, 86.8) thousand DALYs, and be net cost saving from the health system perspective. However, paying a high price for vaccination ($10/dose) may not be cost-effective. Vaccinating the older (65+) population first would prevent slightly more deaths and a similar number of cases as vaccinating everyone aged 15+ at the same time, at similar cost-effectiveness. Interpretation 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, but the advantage of focusing initially on older, high-risk populations may be smaller in generally younger populations where many people have already been infected, typical of many low- and -middle income countries, as long as vaccination gives good protection against infection as well as disease.

Exploring Equity in Health and Poverty Impacts of Control Measures for SARS-CoV-2 in Six Countries (preprint)

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, United Kingdom, Philippines, and South Africa. We consider impact of lockdown in terms of inability to socially distance, and income loss during lockdown, and tested the impact of assumptions on social protection coverage in a scenario analysis.Findings: In all examined countries, lower socioeconomic quintiles were likely to experience disproportionately more income loss and greater inability to socially distance during lockdown. Improving social protection increased the percentage of the workforce able to socially distance from 40% (30% Chile - 55% UK) to 60% (57% Chile - 67% UK). We estimate the cost of this social protection would be equivalent to an average of 0.5% GDP.Interpretation: We illustrate the potential for using publicly available data to rapidly assess the equity implications of social protection and non-pharmaceutical intervention policy. We highlight potential for social protection 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 suffer the worst income losses and are disproportionately more exposed.Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [grant number 221303/Z/20/Z].Declaration of Interests: We declare no competing interests.

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

Background In response to the coronavirus disease 2019 (COVID-19), the UK adopted mandatory physical distancing measures in March 2020. Vaccines against the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may become available as early as late 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing scenarios in the UK. Methods We used an age-structured dynamic-transmission and economic model to explore different scenarios of immunisation programmes over ten years. Assuming vaccines are effective in 5-64 year olds, we compared vaccinating 90% of individuals in this age group to no vaccination. We assumed either vaccine effectiveness of 25% and 1-year protection and 90% re-vaccinated annually, or 75% vaccine effectiveness and 10-year protection and 10% re-vaccinated annually. Natural immunity was assumed to last 45 weeks in the base case. We also explored the additional impact of physical distancing. We considered benefits from disease prevented in terms of quality-adjusted life-years (QALYs), and costs to the healthcare payer versus the national economy. We discounted at 3.5% annually and monetised health impact at 20,000 per QALY to obtain the net monetary value, which we explored in sensitivity analyses. Findings Without vaccination and physical distancing, we estimated 147.9 million COVID-19 cases (95% uncertainty interval: 48.5 million, 198.7 million) and 2.8 million (770,000, 4.2 million) deaths in the UK over ten years. Vaccination with 75% vaccine effectiveness and 10-year protection may stop community transmission entirely for several years, whereas SARS-CoV-2 becomes endemic without highly effective vaccines. Introducing vaccination compared to no vaccination leads to economic gains (positive net monetary value) of 0.37 billion to +1.33 billion across all physical distancing and vaccine effectiveness scenarios from the healthcare perspective, but net monetary values of physical distancing scenarios may be negative from societal perspective if the daily national economy losses are persistent and large. Interpretation Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Given uncertainty around both characteristics of the eventually licensed vaccines and long-term COVID-19 epidemiology, our study provides early insights about possible future scenarios in a post-vaccination era from an economic and epidemiological perspective.

The health sector cost of different policy responses to COVID-19 in low- and middle- income countries (preprint)

Much attention has focussed in recent months on the impact that COVID-19 has on health sector capacity, including critical care bed capacity and resources such as personal protective equipment. However, much less attention has focussed on the overall cost to health sectors, including the full human resource costs and the health system costs to address the pandemic. Here we present estimates of the total costs of COVID-19 response in low- and middle-income countries for different scenarios of COVID-19 mitigation over a one year period. We find costs vary substantially by setting, but in some settings even mitigation scenarios place a substantial fiscal impact on the health system. We conclude that the choices facing many low- and middle- income countries, without further rapid emergency financial support, are stark, between fully funding an effective COVID-19 reponse or other core essential health services.

The impact of Coronavirus disease 2019 (COVID-19) on health systems and household resources in Africa and South Asia (preprint)

Background. Coronavirus disease 2019 (COVID-19) epidemics strain health systems and households. Health systems in Africa and South Asia may be particularly at risk due to potential high prevalence of risk factors for severe disease, large household sizes and limited healthcare capacity. Methods. We investigated the impact of an unmitigated COVID-19 epidemic on health system resources and costs, and household costs, in Karachi, Delhi, Nairobi, Addis Ababa and Johannesburg. We adapted a dynamic model of SARS-CoV-2 transmission and disease to capture country-specific demography and contact patterns. The epidemiological model was then integrated into an economic framework that captured city-specific health systems and household resource use. Findings. The cities severely lack intensive care beds, healthcare workers and financial resources to meet demand during an unmitigated COVID-19 epidemic. A highly mitigated COVID-19 epidemic, under optimistic assumptions, may avoid overwhelming hospital bed capacity in some cities, but not critical care capacity. Interpretation. Viable mitigation strategies encompassing a mix of responses need to be established to expand healthcare capacity, reduce peak demand for healthcare resources, minimise progression to critical care and shield those at greatest risk of severe disease.