One vaccine to counter many diseases? Modeling the economics of oral polio vaccine against child mortality and COVID-19

Introduction Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19. Materials and methods We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, a susceptible-exposed-infectious-recovered model was developed to estimate the population benefits of two scenarios, in which OPV would be co-administered alongside COVID-19 vaccines. Incremental cost-effectiveness and benefit-cost ratios were modeled for ranges of intervention effectiveness estimates to supplement the headline numbers and account for heterogeneity and uncertainty. Results For child mortality, headline cost-effectiveness was $650 per child death averted. For COVID-19, assuming OPV had 20% effectiveness, incremental cost per death averted was $23,000–65,000 if it were administered simultaneously with a COVID-19 vaccine <200 days into a wave of the epidemic. If the COVID-19 vaccine availability were delayed, the cost per averted death would decrease to $2600–6100. Estimated benefit-to-cost ratios vary but are consistently high. Discussion Economic evaluation suggests the potential of OPV to efficiently reduce child mortality in high mortality environments. Likewise, within a broad range of assumed effect sizes, OPV (or another vaccine with NSE) could play an economically attractive role against COVID-19 in countries facing COVID-19 vaccine delays. Funding The contribution by DTJ was supported through grants from Trond Mohn Foundation (BFS2019MT02) and Norad (RAF-18/0009) through the Bergen Center for Ethics and Priority Setting.

Comparing the impact on COVID-19 mortality of self-imposed behavior change and of government regulations across 13 countries.

OBJECTIVE: Countries have adopted different approaches, at different times, to reduce the transmission of coronavirus disease 2019 (COVID-19). Cross-country comparison could indicate the relative efficacy of these approaches. We assess various nonpharmaceutical interventions (NPIs), comparing the effects of voluntary behavior change and of changes enforced via official regulations, by examining their impacts on subsequent death rates. DATA SOURCES: Secondary data on COVID-19 deaths from 13 European countries, over March-May 2020. STUDY DESIGN: We examine two types of NPI: the introduction of government-enforced closure policies and self-imposed alteration of individual behaviors in the period prior to regulations. Our proxy for the latter is Google mobility data, which captures voluntary behavior change when disease salience is sufficiently high. The primary outcome variable is the rate of change in COVID-19 fatalities per day, 16-20 days after interventions take place. Linear multivariate regression analysis is used to evaluate impacts. DATA COLLECTION/EXTRACTION METHODS: publicly available. PRINCIPAL FINDINGS: Voluntarily reduced mobility, occurring prior to government policies, decreases the percent change in deaths per day by 9.2 percentage points (pp) (95% confidence interval [CI] 4.5-14.0 pp). Government closure policies decrease the percent change in deaths per day by 14.0 pp (95% CI 10.8-17.2 pp). Disaggregating government policies, the most beneficial for reducing fatality, are intercity travel restrictions, canceling public events, requiring face masks in some situations, and closing nonessential workplaces. Other sub-components, such as closing schools and imposing stay-at-home rules, show smaller and statistically insignificant impacts. CONCLUSIONS: NPIs have substantially reduced fatalities arising from COVID-19. Importantly, the effect of voluntary behavior change is of the same order of magnitude as government-mandated regulations. These findings, including the substantial variation across dimensions of closure, have implications for the optimal targeted mix of government policies as the pandemic waxes and wanes, especially given the economic and human welfare consequences of strict regulations.

Achieving global mortality reduction targets and universal health coverage: The impact of COVID-19.

Wenhui Mao and coauthors discuss possible implications of the COVID-19 pandemic for health aspirations in low- and middle-income countries.

The East-West Divide in Response to COVID-19.

Coronavirus disease 2019 (COVID-19) deaths per million population in the countries of the West had often exceeded those in the countries of the East by factor of 100 by May 2021. In this paper, we refer to the West as represented by the United States plus the five most populous countries of Western Europe (France, Germany, Italy, Spain, and the United Kingdom), and the East as the 15 countries in East Asia and Oceania that are members of the Regional Comprehensive Economic Partnership, RCEP (Australia, Brunei, Cambodia, China, Indonesia, Japan, the Republic of Korea, Laos, Malaysia, Myanmar, New Zealand, Philippines, Singapore, Thailand, and Vietnam). This paper argues that currently available information points to the factors most responsible for the East-West divide. Warnings by early January 2020 about an atypical viral pneumonia in Wuhan, China, prompted rapid responses in many jurisdictions in East Asia. Publication of the virus's genome on 10 January 2020 provided essential information for making diagnostic tests and launching vaccine development. China's lockdown of Wuhan on 23 January 2020 provided a final, decisive signal of the danger of the new disease. By late March 2020, China had fully controlled its epidemic, and many other RCEP countries had taken early and decisive measures, including restrictions on travel, that aborted serious outcomes. Inaction during the critical month of February 2020 in the United States and most other Western countries allowed the disease to take hold and spread. In both the East and the West, stringent population-wide non-pharmaceutical interventions were widely implemented at great cost to societies, economies, and school systems. Without these measures, the outcomes could have been even worse. Most countries in the East also implemented tightly focused policies to isolate infectious individuals. Even today, most countries in the West allow infectious individuals to mingle with their families, coworkers, and communities. Much of the East-West divide plausibly results from failure in the West to implement the basic public health policies of early action and the isolation of infectious individuals. Widespread immunization in some RCEP and high-income countries will soon attenuate their outbreaks, while the slow rollout of vaccines in lower income countries is replacing the East-West divide in outcomes with a North-South one. The South is thus replacing the West as the breeding ground for more dangerous variants as exemplified by the highly contagious Delta variant, which may undermine hitherto successful control strategies in many countries.

Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics.

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.

Country performance against COVID-19: rankings for 35 countries.

OBJECTIVE: To generate rankings of 35 countries from all continents (except Africa) on performance against COVID-19. DESIGN: International time series, cross-sectional analysis. SELECTED COUNTRIES: Countries having 5500 or more cases (collectively including 85% of the world's cases) as of 16 April 2020 and that had reached 135 days into their pandemic by 30 July. MAIN OUTCOME MEASURES: The initial severity and late-pandemic performance of countries can reasonably be ranked by COVID-19 cases or deaths per million population. For guiding policy and informing public accountability during the pandemic, we propose mid-pandemic performance rankings based on doubling time in days of the total number of cases and deaths in a country. Rank orderings then follow. RESULTS: At day 25 into a country's pandemic, cross-country performance variation was modest: in most countries, cumulative deaths doubled in fewer than 5 days. By day 65, and even more so by day 135, great cross-country variation emerged. By day 135, 9 of the 10 top-performing countries on deaths were European, although they were initially hard hit by the pandemic. Thus, rankings change rapidly enough to point to the value of a dynamic indicator. Five countries-Brazil, Mexico, India, Indonesia and Israel-were among the seven poorest performers at day 135 on both cases and deaths. Doubling times for cases and for deaths are positively correlated, but differ sufficiently to point to the value of both indicators. CONCLUSIONS: Readily available data support transparently generated rankings of countries' performance against COVID-19 based on doubling times of cases and deaths. It is premature to judge the value of these rankings in practice, but the potential and early experience suggest they might help facilitate identification of good policies and inform judgements on national leadership.

Protecting essential health services in low-income and middle-income countries and humanitarian settings while responding to the COVID-19 pandemic.

In health outcomes terms, the poorest countries stand to lose the most from these disruptions. In this paper, we make the case for a rational approach to public sector health spending and decision making during and in the early recovery phase of the COVID-19 pandemic. Based on ethics and equity principles, it is crucial to ensure that patients not infected by COVID-19 continue to get access to healthcare and that the services they need continue to be resourced. We present a list of 120 essential non-COVID-19 health interventions that were adapted from the model health benefit packages developed by the Disease Control Priorities project.