We did not know about the SARS-CoV-2 virus until it appeared in humans. But previous experience with other coronaviruses that have jumped into humans (SARS and MERS) had told us that something like COVID-19 could pose a risk. Coronaviruses are common in a number of species that frequently come into contact with humans, and they have a clear history of adapting to human cells.
Knowing about viruses that have similar properties can help us identify threats to future pandemics. Now researchers are taking the results of a massive virus study and publishing a public database of hundreds of viruses, all assessed for how much risk the viruses pose to humans. And all the viruses we discover can be plugged into the framework they have developed so that we can get quick information on whether they are threatening.
The effort grew out of a USAID-sponsored program called PREDICT, which was part of a set of efforts focused on zoonotic diseases, those that can cross species barriers and infect humans. Together, the PREDICT project conducted a massive survey of animal viruses, with more than half a million individual samples taken from 75,000 animals. From that data, the project identified more than 700 new viruses and another that had never been seen in the animal in which it was found.
By itself, the genome sequence of the viruses does not tell us much about the risk that the viruses pose to humans. We can find out which proteins encode the viruses, but we are not at the point where we can look at these proteins and find out if they make the virus more likely to infect humans. And besides, it is not only infectivity that poses a risk. If the virus normally circulates in rare animals that occur in humans, the chances of it spreading to us are slim.
There are many factors, as well as disagreement among experts about how important those factors are. Finding out how to evaluate these new viruses posed a challenge.
To find out what is important, the researchers asked 150 virology and public health experts to consider 50 different potential risk factors, ranging from the host species it carried to where it was found to its evolutionary relationships to known viruses. The experts were asked to rate the importance of each of these risk factors, and the PREDICT team evaluated each of their ratings based on the person’s expertise in each issue. (So, for example, the opinion of a virologist may be less likely to account for problems related to how often the host animal interacts with humans.)
Some of the key risk factors that were consistently highly assessed were obvious: frequency of interactions with humans and our livestock, ability to infect a variety of hosts, and transfer modes. But not every factor was considered very important, and seven of those evaluated were considered important. But we just do not have enough data on most viruses to allow evaluation.
Score from spillover
The net result is a spillover score, the best estimate of the risk that each of these viruses has for humans, awkwardly rated on a score of 1 to 155 (this happens when you start with a 50 factor score of 1-5, they weigh in varying degrees, and then throws out some of it). As a test of its validity, the researchers looked at the top-scoring viruses; already from the first decades it was already known that they had infected people.
SARS-CoV-2 stood just between two viruses that have caused multiple outbreaks of hemorrhagic fever in Africa: Lassa and Ebola. It did not come on top because these other viruses have caused multiple outbreaks (SARS-CoV-2 has only had one, but has let it count). We also know a lot more about their normal hosts, while we did not identify the type of SARS-CoV-2 before it moved into humans.
All analysis is made available through the Spillover website, which contains a ranking of all viruses analyzed so far. A quick view of each breaks down the risk into three categories (based on the host in which it was found, the environment of that host, and the genetics of the virus). A detailed view breaks down each individual factor that we have enough data to evaluate.
In addition to providing the data on these new viruses, Spillover is also a flexible sharing platform. Flexible, as we learn more about what makes a virus a zoonotic threat, the researchers promise to update the analyzes for all viruses in the database. And share, because the PREDICT team hopes the research community will add new viruses to be assessed once they are discovered. It is possible to create a risk score with as few as half a dozen viral properties.
While these many new viruses are a great start, there are a few clear limitations. For one, because they are already being closely monitored, the researchers do not add flu viruses to their database. Second, although it represents a lot of work, the hundreds of viruses described here are a drop in the bucket compared to the estimated 1.7 million viruses that infect mammals and birds. We have a lot more work to do if we really want to prevent the next pandemic from engulfing us.
Nevertheless, the project represents a valuable start. Several of the viruses not previously described are considered to be more dangerous than viruses that we already know can make the leap in humans. Of course, focusing on those for study and more careful oversight has the potential for a significant payoff, especially compared to the global cost of the COVID-19 pandemic.
PNAS, 2021. DOI: 10.1073 / pnas.2002324118 (About DOIs).