The relentless spread of coronavirus disease 2019 (COVID-19) and its penetration into the least developed, fragile, and conflict-affected countries (LDFCAC) is a certainty. Expansion of the pandemic will be expedited by factors such as an abundance of at-risk populations, inadequate COVID-19 mitigation efforts, sheer inability to comply with community mitigation strategies, and constrained national preparedness. This situation will reduce the benefits achieved through decades of disease control and health promotion measures, and the economic progress made during periods of global development. Without interventions, and as soon as international travel and trade resume, reservoirs of COVID-19 and other vaccine-preventable diseases in LDFCAC will continue ‘feeding’ developed countries with repeated infection seeds. Assuring LDFCAC equity in access to medical countermeasures, funds to mitigate the pandemic, and a paradigm change in the global development agenda, similar to the post-World War II Marshall Plan for Europe, are urgently needed. We argue for a paradigm change in strategy, including a new global pandemic financing mechanism for COVID-19 and other future pandemics. This approach should assist LDFCAC in gaining access to and membership of a global interdisciplinary pandemic taskforce to enable in-country plans to train, leverage, and maintain essential functioning and also to utilize and enhance surveillance and early detection capabilities. Such a task force will be able to build on and expand research into the management of pandemics, protect vulnerable populations through international laws/treaties, and reinforce and align the development agenda to prevent and mitigate future pandemics. Lifting LDFCAC from COVID-related failure will offer the global community the best economic dividends of the century.

The COVID-19 pandemic can no longer be mitigated by a nationwide approach of individual nations alone. Given its scale and accelerating expansion, COVID-19 requires a coordinated and simultaneous Whole- of-World approach that galvanizes clear global leadership and solidarity from all governments of the world. Considering an ‘all hands-on deck’ concept, we present a comprehensive list of tools and entities responsible for enabling them, as well a conceptual framework to achieve the maximum impact. The list is drawn from pandemic mitigation tools developed in response to past outbreaks including influenza, coronaviruses, and Ebola, and includes tools to minimize transmission in various settings including person-to-person, crowd, funerals, travel, workplace, and events and gatherings including business, social and religious venues. Included are the roles of individuals, communities, government and other sectors such as school systems, health, institutions, and business. While individuals and communities have significant responsibilities to prevent person-to-person transmission, other entities can play a significant role to enable individuals and communities to make use of the tools. Historic and current data indicate the role of political will, whole-of-government approach, and the role of early introduction of mitigation measures. There is also an urgent need to further elucidate the immunologic mechanisms underlying the epidemiological characteristics such as the low disease burden among women, and the role of COVID-19 in inducing Kawasaki-like syndromes in children. Understanding the role of and development of anti-inflammatory strategies based on our understanding of pro-inflammatory cytokines (IL1, IL-6) is also critical. Similarly, the role of oxygen therapy as an anti-inflammatory strategy is evident and access to oxygen therapy should be prioritized to avoid the aggravation of COVID-19 infection. We highlight the need for global solidarity to share both mitigation commodities and infrastructure between countries. Given the global reach of COVID-19 and potential for repeat waves of outbreaks, we call on all countries and communities to act synergistically and emphasize the need for synchronized pan-global mitigation efforts to minimize everyone's risk, to maximize collaboration, and to commit to shared progress.