Over the past few decades, two to three new viruses never before discovered in humans have been identified each year, a number that has remained roughly stable since the 1960s, but only a handful of these have turned into global public health crises. Some new viruses leave only sporadic records in medical literature and then disappear quietly into oblivion, while others, like HIV-1 discovered in 1983 and SARS-CoV-2 discovered in 2020, heralded the arrival of AIDS and the new coronavirus epidemic and have claimed tens of millions of lives.
A team of researchers at the University of Edinburgh in Scotland is trying to answer a key question: When scientists discover a rare or unknown virus in a patient, how can they tell whether it is likely to develop into a global public health emergency on the scale of AIDS or COVID-19? Drawing on the historical experience of virus evolution and epidemiology, they systematically sorted out RNA viruses known to be infective to humans and constructed a "catalogue of high-risk viruses" in an attempt to outline the outline of the next pandemic before new pathogens emerge.
Most of the recent major pandemics have been caused by RNA viruses, whose genetic material is in the form of RNA rather than the more common form of DNA. Thousands of RNA virus species have been identified so far, with the potential total number reaching millions, but only 239 of them are capable of infecting humans. The database released by the research team sorted out these 239 human-infectious RNA viruses and evaluated key factors such as disease type, severity, and mode of transmission. They pointed out that if a virus cannot be continuously transmitted between humans, even if it can cause serious disease, it will be difficult to set off a global pandemic; on the contrary, viruses with efficient human-to-human transmission capabilities are the real potential threats.
Transmission route is one of the core indicators for risk assessment. The virus can be transmitted between humans through physical contact, inhalation of virus-containing air particles, contact with blood or feces, or bites from vector insects such as mosquitoes and ticks. In this list of viruses, about two-thirds are "zoonotic viruses", that is, the infection mainly comes from animals, and there is almost no human-to-human transmission. Rabies is a typical example. This fact is comforting to a certain extent. However, viruses evolve rapidly, and the scientific community has long been worried that some zoonotic viruses will acquire the ability to spread continuously among human populations. This is one of the reasons why the world is currently paying high attention to avian influenza. It is worth noting that there are no confirmed cases showing that a certain RNA zoonotic virus has completed the transition from "only transmitted from animals to humans" to "efficiently transmitted among humans." Although rabies causes tens of thousands of cases worldwide every year, it is still stuck in the stage of animal-to-human transmission.
The real big threat comes from viruses that have the ability to spread from person to person. Once this type of virus further enhances its transmission efficiency, immune evasion ability or environmental adaptability, it may continue to increase the spread of the epidemic like a series of new coronavirus mutant strains. Studies have pointed out that these viruses often initially jump from animals into humans in a form that can be transmitted between humans. Historically, diseases such as measles, mumps and rubella, as well as many viruses that cause common colds and gastrointestinal infections, are thought to have originated from similar cross-species events.
There is another type of virus that deserves vigilance. They have been able to spread within the population, but currently only cause local outbreaks because their basic reproduction number (R value) is low. The so-called R value refers to the average number of people an infected person can infect. If this value is not enough to maintain continued transmission, the infection chain will naturally terminate. However, the R value is not fixed. When the virus moves from remote villages into densely populated big cities, the chances of transmission increase sharply, and the R value may rise significantly. The Zaire Ebola virus outbreak in West Africa in 2014 is an example of this. After the virus spread from local transmission to urban environments, it caused an unprecedented large-scale outbreak.
An "outbreak virus list" maintained by the research team currently only has a few dozen names, but it has been proven to have strong prediction capabilities for public health events. Zaire Ebola virus, chikungunya virus, Zika virus and Oropoche virus transmitted by mosquitoes, as well as monkeypox (DNA virus), which has broken out in many regions in recent years, were all early members on this list, and later triggered major regional or transnational epidemics. At the same time, some previously little-known viruses have begun to appear frequently in international public health notifications, such as the Andean hantavirus that recently caused an outbreak on a cruise ship, and the Bandibugyo Ebola virus is currently spreading in central Africa.
These data are used not only to track outbreaks, but also to deduce the possible shape of the "next pandemic virus" - a hypothetical pathogen often referred to as "Disease X" by the World Health Organization and related agencies. The COVID-19 epidemic is a typical example of this early warning approach. As early as 2019, the research team pointed out through analysis that highly transmissible viruses are often closely related to a known type of human-to-human transmission virus, but they themselves are a "new branch" that emerged independently from the animal kingdom. This description is highly consistent with the later emergence of SARS-CoV-2. The new coronavirus is genetically very similar to the SARS virus in 2003, but it is considered to be another evolutionary branch independently (or indirectly) derived from bats. Just the year before, the World Health Organization listed “SARS-like coronavirus” as a candidate for “Disease
In contrast, the Andean hantavirus currently causing the cruise ship epidemic and the currently spreading Bandibugyo Ebola virus do not fit the typical picture of a "global pandemic" in terms of transmission characteristics and host range. However, the research team pointed out that if a new virus with biological characteristics close to measles emerges in the future - that is, extremely contagious and has a wide range of susceptible people - it may trigger a global emergency far worse than the new coronavirus. The risk of this type of hypothetical virus is that it not only has a similar structure and transmission efficiency to highly contagious viruses, but may also develop new mutations in immune evasion or pathogenic mechanisms, thus posing unprecedented challenges to the prevention and control system.
The recent Andean hantavirus and Bandibugyo Ebola virus outbreaks have reinforced an important lesson: these outbreaks circulated in communities for weeks before they were officially recognized, as did the COVID-19 outbreak. When pathogens spread secretly "beyond the radar", the prevention and control system will miss the critical window period in the initial stage, providing the virus with a valuable first-mover advantage. Researchers call on countries to speed up the discovery and characterization of new viruses and shorten the time span from the emergence of the first abnormal case to the completion of pathogen identification as much as possible through more efficient surveillance networks, laboratory testing capabilities and data sharing mechanisms. They believe that if the goal of "discovering, reporting and responding to a new virus can be completed within the first seven days after the emergence of a new virus," it will be expected to significantly reduce the scale and lethality of the next pandemic and reduce the long-term impact on lives and livelihoods.