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$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

Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies—Acting Now before It Is Too Late—A Joint Call for Action

Contains fulltext : 225815.pdf (publisher's version ) (Open Access)The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics [...].4 p

Workshop #4: Public Messaging: Risk Communication for Disaster Preparedness, Evacuation, and Sheltering: After-Action Report (AAR)

Participants in the breakout sessions for the CONVERGE COVID-19 Working Group’s Workshop 4 (Public Messaging) identified key issues that included the need to provide timely and effective communication to the public, increasing awareness around using shelters as a refuge of last resort, addressing the risks associated with COVID-19 exposure at shelters, and using various inclusive forms of public messaging to reach a wide audience. Workshop participants emphasized the importance of timely and effective communications to support informed decision making. There is ongoing concern over balancing the need to communicate the risks of COVID-19 exposure as it relates to evacuation shelters (to create public awareness and informed decision making) and the potential to create unnecessary fear. This balance will entail clear and consistent communications from regional, state, and local authorities. The messaging also will need to emphasize that shelters are a last resort option and to highlight the importance of personal preparedness. This includes “know your zone” and “know your home.” For some people, staying at their house and not evacuating could be less risky than going to an evacuation shelter; messaging to create this public awareness is essential. One proposal was to encourage people to reach out to family and friends preemptively, identifying evacuation plans that avoiding shelters in advance of the hurricane season. Public messaging also should include information on how personal preparedness kits should be adjusted or augmented to account for the additional hazards this hurricane season from COVID-19. Workshop participants simultaneously recognized that COVID-19 has already created additional burdens on the population that might impede evacuees from adequately preparations. Based on these conversations, early communication and preparedness are urgently needed. In addition to identifying what should be communicated to the public, participants also discussed the types of questions the public might ask and what data will be used to respond. They suggested that effective communications should include awareness of underlying fears and other emotions that the public may experience. It is critical that shelter management guidelines—such as social distancing and mask requirements—are communicated to the public to increase transparency and to provide information on what will be expected. Suggested items to mention to the public before a hurricane makes landfall include, but are not limited to, what resources will be available at shelters (e.g., will masks be provided or will they need to bring their own), what the intake process will involve, and how people will be isolated if they appear symptomatic or have been identified as COVID-positive. Furthermore, information regarding evacuation shelters will require a greater degree of specificity for medically fragile individuals and other vulnerable populations

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$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

Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK.

BACKGROUND: To mitigate and slow the spread of COVID-19, many countries have adopted unprecedented physical distancing policies, including the UK. We evaluate whether these measures might be sufficient to control the epidemic by estimating their impact on the reproduction number (R0, the average number of secondary cases generated per case). METHODS: We asked a representative sample of UK adults about their contact patterns on the previous day. The questionnaire was conducted online via email recruitment and documents the age and location of contacts and a measure of their intimacy (whether physical contact was made or not). In addition, we asked about adherence to different physical distancing measures. The first surveys were sent on Tuesday, 24 March, 1 day after a "lockdown" was implemented across the UK. We compared measured contact patterns during the "lockdown" to patterns of social contact made during a non-epidemic period. By comparing these, we estimated the change in reproduction number as a consequence of the physical distancing measures imposed. We used a meta-analysis of published estimates to inform our estimates of the reproduction number before interventions were put in place. RESULTS: We found a 74% reduction in the average daily number of contacts observed per participant (from 10.8 to 2.8). This would be sufficient to reduce R0 from 2.6 prior to lockdown to 0.62 (95% confidence interval [CI] 0.37-0.89) after the lockdown, based on all types of contact and 0.37 (95% CI = 0.22-0.53) for physical (skin to skin) contacts only. CONCLUSIONS: The physical distancing measures adopted by the UK public have substantially reduced contact levels and will likely lead to a substantial impact and a decline in cases in the coming weeks. However, this projected decline in incidence will not occur immediately as there are significant delays between infection, the onset of symptomatic disease, and hospitalisation, as well as further delays to these events being reported. Tracking behavioural change can give a more rapid assessment of the impact of physical distancing measures than routine epidemiological surveillance

The potential impact of COVID-19-related disruption on tuberculosis burden.

Before the coronavirus disease 2019 (COVID-19) pandemic, over 4000 people were dying from tuberculosis (TB) every day. As with past emergencies, the impact of COVID-19 on TB outcomes is a serious cause for concern but is currently unknown. Health system overload, due to high numbers of COVID-19 cases, as well as interventions necessary to limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could result in severe reductions in health service availability and access for the detection and treatment of TB cases. However, physical distancing interventions could also limit Mycobacterium tuberculosis transmission outside of households, where most transmission occurs. This has not been adequately explored in concurrent work, and it is currently unclear whether social distancing could compensate for disruptions in TB services, and what the impact of these combined COVID-19 disruption effects on TB burden is likely to be

Epidemiology of Confirmed COVID-19 Deaths in Adults, England, March-December 2020

Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas

Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7.

SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike (S) gene target (known as S gene target failure (SGTF)1). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39-72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8-1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42-82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness

Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01.

VOC 202012/01, a SARS-CoV-2 variant first detected in the United Kingdom in September 2020, has spread to multiple countries worldwide. Several studies have established that this novel variant is more transmissible than preexisting variants of SARS-CoV-2, but have not identified whether the new variant leads to any change in disease severity. We analyse a large database of SARS-CoV-2 community test results and COVID-19 deaths for England, representing approximately 47% of all SARS-CoV-2 community tests and 7% of COVID-19 deaths in England from 1 September 2020 to 22 January 2021. Fortuitously, these SARS-CoV-2 tests can identify VOC 202012/01 because mutations in this lineage prevent PCR amplification of the spike gene target (S gene target failure, SGTF). We estimate that the hazard of death among SGTF cases is 30% (95% CI 9-56%) higher than among non-SGTF cases after adjustment for age, sex, ethnicity, deprivation level, care home residence, local authority of residence and date of test. In absolute terms, this increased hazard of death corresponds to the risk of death for a male aged 55-69 increasing from 0.56% to 0.73% (95% CI 0.60-0.86%) over the 28 days following a positive SARS-CoV-2 test in the community. Correcting for misclassification of SGTF, we estimate a 35% (12-64%) higher hazard of death associated with VOC 202012/01. Our analysis suggests that VOC 202012/01 is not only more transmissible than preexisting SARS-CoV-2 variants but may also cause more severe illness

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region.

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine roll-out speed. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted country-specific age-stratified compartmental transmission models to reported COVID-19 mortality in the WHO European Region to inform the immunity level before vaccine roll-out. Building upon broad recommendations from the WHO Strategic Advisory Group of Experts on Immunisation (SAGE), we examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incremental expansion to successively younger five-year age groups. We explored four roll-out scenarios based on projections or recent observations (R1-4) - the slowest scenario (R1) covers 30% of the total population by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy (cLE), comorbidity- and quality-adjusted life years (cQALY), and the value of human capital (HC). Six sets of infection-blocking and disease-reducing vaccine efficacies were considered. FINDINGS: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics and roll-out speeds. Overall, V60 consistently performed better than or comparably to V75. There were greater benefits in prioritising older adults when roll-out is slow and when VE is low. Under faster roll-out, V+ was the most desirable option. INTERPRETATION: A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust. RESEARCH IN CONTEXT: Evidence before this study: We searched PubMed and medRxiv for articles published in English from inception to 9 Jun 2021, with the search terms: ("COVID-19" OR "SARS-CoV-2") AND ("priorit*) AND ("model*") AND ("vaccin*") and identified 66 studies on vaccine prioritization strategies. Of the 25 studies that compared two or more age-based prioritisation strategies, 12 found that targeting younger adults minimised infections while targeting older adults minimised mortality; an additional handful of studies found similar outcomes between different age-based prioritisation strategies where large outbreaks had already occurred. However, only two studies have explored age-based vaccine prioritisation using models calibrated to observed outbreaks in more than one country, and no study has explored the effectiveness of vaccine prioritisation strategies across settings with different population structures, contact patterns, and outbreak history.Added-value of this study: We evaluated various age-based vaccine prioritisation strategies for 38 countries in the WHO European Region using various health and economic outcomes for decision-making, by parameterising models using observed outbreak history, known epidemiologic and vaccine characteristics, and a range of realistic vaccine roll-out scenarios. We showed that while targeting older adults was generally advantageous, broadly targeting everyone above 60 years might perform better than or comparably to a more detailed strategy that targeted the oldest age group above 75 years followed by those in the next younger five-year age band. Rapid vaccine roll-out has only been observed in a small number of countries. If vaccine coverage can reach 80% by the end of 2021, prioritising older adults may not be optimal in terms of health and economic impact. Lower vaccine efficacy was associated with greater relative benefits only under relatively slow roll-out scenarios considered.Implication of all the available evidence: COVID-19 vaccine prioritization strategies that require more precise targeting of individuals of a specific and narrow age range may not necessarily lead to better outcomes compared to strategies that prioritise populations across broader age ranges. In the WHO European Region, prioritising all adults equally or younger adults first will only optimise health and economic impact when roll-out is rapid, which may raise between-country equity issues given the global demand for COVID-19 vaccines