We did not know about the SARS-CoV-2 virus until it appeared in humans. But previous experience with other coronaviruses that had jumped into humans (SARS and MERS) had told us that something like COVID-19 could pose a risk. Coronavirus is widespread in a number of species that have frequent contact with humans and they have a clear history of being able to adapt to human cells.
Being aware of viruses that have similar properties can help us recognize threats to future pandemics. Now, researchers are taking the results of a massive virus study and releasing a public database of hundreds of viruses, all of which are being assessed for the risk posed by the virus to humans. And all the viruses that we detect can be linked to the framework they have developed so that we can get quick information on whether they are threatening.
What’s out there?
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. Overall, the PREDICT project conducted a massive study of animal viruses using over half a million individual samples taken from 75,000 animals. From this data, the project identified over 700 new viruses and another that had never been seen in the animal where it was found.
Knowing the virus genome sequence does not tell us much about the risk that the virus poses to humans. We can find out which proteins viruses encode, 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 usually circulates in rare animals that avoid humans, the chances of it spreading to us are slim.
Factors are found in abundance as well as disagreement among experts about how important these factors are. So it was a challenge to figure out how to evaluate these new viruses.
To find out what’s important, the researchers got 150 virology and public health experts to consider 50 different potential risk factors, ranging from the host species that carried it where it was found to its evolutionary relationship to known viruses. The experts were asked to rank the importance of each of these risk factors, and the PREDICT team weighed each of its assessments based on the person’s expertise in each topic. (So, for example, a virologist’s opinion may rely less on questions related to how often its host animals interact with humans.)
Some of the important risk factors that were consistently rated highly were clear: the frequency of interactions with humans and our domestic animals, the ability to infect a variety of hosts, and modes of transmission. However, not all factors were rated as very significant, and seven of those evaluated were rated as important. But we simply do not have enough data on most viruses to make it possible to evaluate them.
Exceeding the score
The net result is a spillover score, the best estimate of the risk that each of these viruses poses to humans, awkwardly rated at a score of 1 to 155 (this happens when you start with 50 factors scored from 1-5, weighing them to varying degrees, and then throw some of them out). As a test of its validity, the researchers looked at the top-scoring viruses; all the first dozen were already known to have infected humans.
SARS-CoV-2 ranked right between two viruses that have caused several outbreaks of hemorrhagic fever in Africa: Lassa and Ebola. It did not come on top because the other viruses have caused several outbreaks (SARS-CoV-2 has only had one, but has made it count). We also know much more about their normal hosts, while we have not identified the species SARS-CoV-2 was in before it moved into humans.
All the analysis is made available via the Spillover website, which contains a ranking of all the viruses analyzed so far. A quick overview of each divides the risk into three categories (based on the host it is in, the environment of that host, and the genetics of the virus). A detailed view divides each factor, which we have enough data to evaluate.
In addition to making the data on these new viruses available, Spillover is also a flexible sharing platform. Flexible, as researchers promise that as we learn more about what makes a virus a zoonotic threat, they will update the analyzes for all viruses in the database. And sharing because the PREDICT team hopes the research community will add new viruses to be classified when they are discovered. It is possible to create a risk score with as few as half a dozen viral properties.
While so many new viruses are a good start, there are a few obvious limitations. First, because they are already being tracked intensively, researchers are not adding influenza viruses to their database. Second, while 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 avoid the next pandemic creeping up on us.
Nevertheless, the project represents a valuable start. Several of the viruses that had not been described before are considered more threatening than viruses that we already know can make the leap to humans. It is clear that targeting them for investigation and more careful monitoring has the potential for a significant payout, especially compared to the global costs of the COVID-19 pandemic.
PNAS, 2021. DOI: 10.1073 / pnas.2002324118 (About DOIs).