Viral Families With Pandemic Potential

Abstract

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A major challenge of pandemic preparedness is how to anticipate and prepare for future pandemic threats among the wide range of viral threats that can infect humans. Fortunately, only a subset of the 25 viral families that can infect humans have both the capability of widespread respiratory transmission in humans or animals, a prerequisite for pandemic-causing capability, as well a lack of medical countermeasures (MCMs) to prevent and treat the key viral species within them. Orthopoxviruses, for example, clearly have historically shown the capacity to cause terrible pandemics in humans, but vaccines and antivirals have been developed and stockpiled for this viral family that are cross-protective against multiple family members (unlike the case for the pandemic-causing orthomyxoviruses and coronaviruses). Therefore, for the purposes of identifying novel rapid-onset novel pandemics, they are not listed here as a viral family of pandemic potential with unmet research and development (R&D) requirements, although there is clear need for improved MCMs to both of these viral families.

Prior to coronavirus disease 2019 (COVID-19), most pandemic preparedness efforts, when they did occur, focused almost exclusively on influenza viruses. Pandemic preparedness was considered to be nearly synonymous with influenza preparedness. This has basis in experience as the only occurring pandemics for almost a century (spanning from at least 1918 to 2009) were all caused by influenza A viruses. However, a number of events of the past 20 years have shown the capacity of Coronaviridae to cause major epidemics and pandemics: severe acute respiratory syndrome coronavirus (SARS-CoV) 1 in 2003, Middle East respiratory syndrome coronavirus in 2012, and, most recently and obviously, SARS-CoV-2 in 2019–2020. It is critical now to plan for other viral threats that can cause huge epidemics or pandemics.

We were among the first to publish on the characteristics of pandemic pathogens, and in that effort, we emphasized conceptualizing the problem by putting specific focus on viral families of greatest pandemic potential, particularly families for which no MCMs were yet developed [1, 2]. There have been subsequent projects to categorize viral families with greatest pandemic potential; those that have been published have cast a wider net and have so far used inclusion criteria that are significantly broader than what we have used for the categorization in this work [3–5]. The benefit of the other organizations’ broader inclusion criteria is that they have encompassed substantially more viral families; the downside of such broader inclusion criteria is that it can include viral families with little evidence of their prospect of generating a new pandemic. This essay proposes a more tailored, focused approach to preparedness based on both pathogen pandemic potential and R&D.

Drawing on that prior work, here we describe with more detail the viral families that should be prioritized as those with greatest pandemic potential given their capacity for widespread respiratory transmission and the absence of MCMs: Orthomyxoviridae, Coronaviridae, Paramyxoviridae, Picornavirdae, Pneumoviridae, and Adenoviridae. These viral families all include viral species that have the capacity for efficient human-to-human spread via the respiratory route, seasonal endemic members, and zoonotic analogues. As we have argued in prior work [1], in the modern era, the respiratory mode of transmission is the distinguishing characteristic between epidemic and worldwide acutely disruptive pandemic viruses. The human immunodeficiency virus, by contrast, given its mode of transmission, did not have the same propensity for explosive growth. The special status of respiratory infectious diseases derives chiefly from the difficulty of public health interventions to arrest their spread and the potential for asymptomatic or minimally symptomatic contagiousness. Given that the great majority of new infectious disease threats are spillovers from animal viruses, it is likely that pandemic threats will spill over from animal viruses as well. SARS-CoV-2 is a case in point. However, the spillovers most likely to cause pandemic threats will emerge from a zoonotic virus that is a member of the respiratory viral families whose other members have shown the capacity to cause extensive respiratory infection in humans.

There are biological and medical characteristics for each of the 6 viral families that make them the most likely families to generate future pandemic viruses. Chiefly, they each have viral species within them that spread efficiently between humans. Within these viral families there is also a lack of MCMs for many of the serious potential viral threats. No other viral families so starkly possess these combined characteristics [1]. The lens we apply is in distinction to some other groups that use more inclusive criteria for pandemic capacity.

While the potential pandemic properties of Orthomyxoviridae and Coronaviridae are widely appreciated, it is valuable to highlight some of the characteristics of the other 4 less appreciated viral families with greatest pandemic potential [6] (see Table 1).

In conclusion, prioritizing the viral families with greatest pandemic preparedness should be a strong driver for focusing the research, development, and manufacturing agenda for preparedness in the US and globally. This preparedness work should include the following:

Of course, other viral families have the potential to cause serious illness, endemic disease, and high-consequence local or larger epidemics, and they merit scientific attention and MCM development commensurate with their substantial public health impact. However, R&D and manufacturing being pursued with the goal of preparing the country and the world for the next pandemic should first prioritize viral families with greatest pandemic potential. We are encouraged by the UK government's priority pathogen tool, which includes paramyxovirus and picornaviruses [13]. There are clear and tractable MCM development goals that should be pursued for these viral families. Accomplishing this work would substantially strengthen our collective capacity to diminish the suffering, illness, and deaths associated with future pandemics.