The COVID-19 pandemic may be the deadliest viral outbreak the world has seen in more than a century. But statistically, such extreme events aren't as rare as we may think, asserts a new analysis of novel disease outbreaks over the past 400 years.

The study, appearing the week of Aug. 23 in the Proceedings of the National Academy of Sciences, used a newly assembled record of past outbreaks to estimate the intensity of those events and the yearly probability of them recurring.

It found the probability of a pandemic with similar impact to COVID-19 is about 2% in any year, meaning that someone born in the year 2000 would have about a 38% chance of experiencing one by now. And that probability is only growing, which the authors say highlights the need to adjust perceptions of pandemic risks and expectations for preparedness.

"The most important takeaway is that large pandemics like COVID-19 and the Spanish flu are relatively likely," said William Pan, PhD, associate professor of global environmental health at Duke and one of the paper's co-authors. Understanding that pandemics aren't so rare should raise the priority of efforts to prevent and control them in the future, he said.

The study, led by Marco Marani, PhD, of the University of Padua in Italy, used new statistical methods to measure the scale and frequency of disease outbreaks for which there was no immediate medical intervention over the past four centuries. Their analysis, which covered a murderer's row of pathogens including plague, smallpox, cholera, typhus and novel influenza viruses, found considerable variability in the rate at which pandemics have occurred in the past. But they also identified patterns that allowed them to describe the probabilities of similar-scale events happening again.

In the case of the deadliest pandemic in modern history—the Spanish flu, which killed more than 30 million people between 1918 and 1920—the probability of a pandemic of similar magnitude occurring ranged from 0.3% to 1.9% per year over the time period studied. Taken another way, those figures mean it is statistically likely that a pandemic of such extreme scale would occur within the next 400 years.

But the data also show the risk of intense outbreaks is growing rapidly. Based on the increasing rate at which novel pathogens such as SARS-CoV-2 have broken loose in human populations in the past 50 years, the study estimates that the probability of novel disease outbreaks will likely grow three-fold in the next few decades.

Using this increased risk factor, the researchers estimate that a pandemic similar in scale to COVID-19 is likely within a span of 59 years, a result they write is "much lower than intuitively expected." Although not included in the PNAS paper, they also calculated the probability of a pandemic capable of eliminating all human life, finding it statistically likely within the next 12,000 years.

That is not to say we can count on a 59-year reprieve from a COVID-like pandemic, nor that we're off the hook for a calamity on the scale of the Spanish flu for another 300 years. Such events are equally probable in any year during the span, said Gabriel Katul, PhD, the Theodore S. Coile Distinguished Professor of Hydrology and Micrometeorology at Duke and another of the paper's authors.

"When a 100-year flood occurs today, one may erroneously presume that one can afford to wait another 100 years before experiencing another such event," Katul says. "This impression is false. One can get another 100-year flood the next year."

As an environmental health scientist, Pan can speculate on the reasons outbreaks are becoming more frequent, noting that population growth, changes in food systems, environmental degradation and more frequent contact between humans and disease-harboring animals all may be significant factors. He emphasizes the statistical analysis sought only to characterize the risks, not to explain what is driving them.

But at the same time, he hopes the study will spark deeper exploration of the factors that may be making devastating pandemics more likely—and how to counteract them.

"This points to the importance of early response to disease outbreaks and building capacity for pandemic surveillance at the local and global scales, as well as for setting a research agenda for understanding why large outbreaks are becoming more common," Pan said.

Marani, the paper's lead author, holds an adjunct appointment at Duke, where he previously was a professor of civil and environmental engineering. Another co-author, Anthony Parolari, PhD, of Marquette University, is a former Duke postdoctoral researcher.