This Pandemic Is Not Even the ‘Big One’
Covid-19 is merely a wake-up call to scenarios that keep infectious-disease experts up at night
Robert Roy Britt
Robert Roy Britt
Jan 19·8 min read
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Image: Andriy Onufriyenko/Getty Images

As bad as Covid-19 seems, the world has grown increasingly vulnerable to an even deadlier global outbreak that experts expect is inevitable. It’s unclear when and where a more aggressive pathogen will emerge, but scientists say it will almost surely threaten an even worse pandemic than Covid-19.

“This pandemic has been very severe, has spread around the world extremely quickly, it has affected every corner of this planet. But this is not necessarily the big one,” says Mike Ryan, MD, an expert on emerging epidemics and executive director of the Emergencies Program at the World Health Organization (WHO). “This virus is very transmissible,” Ryan says. “But its current case fatality rate is reasonably low in comparison to other emerging diseases. This is a wake-up call.”

Other infectious disease experts agree. “While Covid-19 has been terrible, what is more concerning is a virus that would be both highly transmissible and more virulent than SARS-CoV-2 has been to date,” says Tara C. Smith, PhD, a professor of infectious disease epidemiology at Kent State University.

“This virus is very transmissible. But its current case fatality rate is reasonably low in comparison to other emerging diseases. This is a wake-up call.”

Importantly, the global community — and particularly the United States — won’t be prepared to battle the “big one” unless more is invested in research and preparedness and, critically, if we don’t collectively learn from the history we’re currently living through. “I think the United States’ response to SARS-CoV-2 shows that pretty dramatically,” Smith tells Elemental. “Other places have done better — such as South Korea, Australia, New Zealand — but globally, response overall has been dire.”
A spectrum of virulence

There are some 1.6 million known viruses circulating in animals. At least 600,000 of them have the potential to cross the species barrier and infect humans. Concern is fueled by outdoor markets in parts of Asia — though these are increasingly being banned — and also by burgeoning populations near areas of dense wildlife.

“The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover,” researchers write in a December study in One Health. Air travel to and from cities in or near animal-human interfaces makes global spread all but inevitable, they say. “Increasing animal-human interface has also occurred in concert with both increasing globalization and failing health systems, resulting in a trifecta with dire implications for human and animal health.”

The fear is not far-fetched. “A new pathogen with substantial potential for human harm is discovered every year, on average,” says Tom Frieden, MD, former director of the U.S. Centers for Disease Control and Prevention. “Covid-19 is the latest but far from the last health emergency the world will face.”

Coronaviruses exemplify the range of threats from just one type of pathogen. At one end of the virulence spectrum, some common colds are caused by coronaviruses yet rarely bring severe symptoms or death.

Covid-19 is thought to kill around 2% of those known to be infected, but this “case fatality rate” is grossly misleading. A large yet unknown number of people have had the disease with mild or no symptoms and were never diagnosed, so the actual “death rate,” when calculated using the true total case count, is lower; the case fatality rate varies dramatically by age — around 0.01% at age 25 and 15% at age 85, according to one study.

Mortality for two other coronaviruses was much worse and more mathematically definitive, because both caused mostly symptomatic cases, so the case fatality rate was roughly in line with the actual death rate. A 2003 outbreak of a coronavirus (named SARS-CoV) killed about 10% of all those who contracted it and did not discriminate much between young and old. Emerging in 2012, a coronavirus causing a disease dubbed MERS kills around 35% of its victims.
The biggest concerns

Scientists fret over a range of “emergent, zoonotic viruses coming from animals hunted for food or otherwise in close contact with humans, and antibiotic-resistant bacterial pathogens that could escape current treatments,” Smith says. Here are a few of the plausible scenarios:
Other coronaviruses

Mark Cameron, PhD, an immunologist and medical researcher in the School of Medicine at Case Western Reserve University in Ohio, worries about a new coronavirus or even an emerging variant of the current menace that gains higher transmissibility, as is happening now with SARS-CoV-2, and has these other characteristics:

Spreads by people without symptoms, same as the current virus
Causes higher mortality, both among older people and younger people
Mutates enough to nullify vaccines

Retroviruses

“That’s all very bad,” Cameron says of the coronavirus possibilities. “But what really keeps me up at night are the retroviruses, like HIV.”

The human immunodeficiency virus, which transmits through blood and other bodily fluids but is not airborne like the coronavirus, is thought to have jumped from animals to humans long before the AIDS crisis began, in the 1920s and perhaps even earlier by some accounts. It was circulating in the United States at least by the late 1970s. Yet, the first U.S. case of AIDS was not reported until 1981. Since then about 700,000 Americans have died from the disease, and in 2019 alone it killed a similar number of people worldwide.

“HIV has high transmissibility, near-total mortality without treatment or high health-burden and cost-burden with lifelong treatment, a slow and insidious nature of hiding inside our own cells, and has evaded our vaccine efforts for decades,” Cameron points out. “An emerging respiratory virus with a selection of the above menu combinations would be a nightmare,” he says. “We can’t get caught like this again; this was a tremendous wake-up call.”
Drug-resistant bacteria

“In terms of bacteria, the gears of the ‘big one’ are already turning — antibiotic-resistant bacteria outstripping our development of new antibiotic drugs,” Cameron says.

Smith worries about this a lot. “While the emergence of new viruses are often more dramatic and get more attention, the increase in antibiotic resistance over the last 50 years is more of a slow burn like climate change,” she says. “The danger is there, but because it has been slower to cause us harm as a global population, it’s easier to ignore.”

Some of the most efficient killers can actually be contained more easily, if officials react quickly.

The SARS outbreak of 2003 is a classic example. The virus fizzled out quickly because people got so sick, so fast, health experts were able to quickly isolate most of them before they infected others.

Ebola, which first caused outbreaks in 1976, swiftly kills half its victims, and a person doesn’t spread it until they experience symptoms (unlike SARS-CoV-2, in which more than half of new cases are caused by people who have no symptoms).
What can be done to prevent a pandemic worse than Covid-19

A detailed pandemic-response plan and infrastructure developed during the Obama administration, rooted in the experience of the 2009 swine flu outbreaks, was cast aside by the Trump administration. Throughout the Covid-19 pandemic, the majority of response and leadership was ceded to the states. Deaths in the U.S. will likely reach half a million before the end of February.

“This cycle of ‘panic-then-forget’ has prevented the development of effective health emergency preparedness across the globe,” the WHO states. “The world needs to break this cycle once and for all.”

“Over the years we have had many reports, reviews, and recommendations all saying the same thing: The world is not prepared for a pandemic,” Tedros Adhanom Ghebreyesus, PhD, WHO director-general, said recently. “Covid-19 has laid bare the truth: When the time came, the world was still not ready.”

Among practical measures, scientists and physicians need more resources to keep a closer eye on everything from pathogens circulating in animals to better observations and reporting on people who develop surprising or inexplicable illnesses, says Krutika Kuppalli, MD, an assistant professor of infectious diseases at Medical University of South Carolina. Local, countrywide, and global plans to react and cooperate upon detection of an emerging, potentially dangerous microbe need to be improved, so that when one makes its way into the human population, it can more rapidly be identified and isolated.

Critically, Kuppalli says, health experts also need to expect the unexpected.

Nobody expected the 2014 Ebola outbreak in West Africa to occur where and how it did, Kuppalli says. But once it was identified, the power of scientific research kicked in, illustrating the necessity of investing in disease research and prevention before outbreaks occur.

Ebola is thought to have originated with a toddler playing in a hollowed-out, bat-infested tree in his backyard in a remote village in a region of Guinea that had been deforested. In retrospect, scientists speculate the deforestation forced the bats and other wild animals closer to the village. However, other Ebola infections have been linked to antelopes, gorillas, and chimpanzees, and it remains uncertain whether bats are the primary animal reservoir of the disease or not.

Later, infectious disease modelers predicted that an area near the border of Uganda and the Democratic Republic of the Congo had a high chance of being the site of a future Ebola outbreak. Kuppalli went there as part of a U.S. government-funded project to do research should an outbreak occur. One did, as predicted, and there have been several in the area since.
Proactiveness is key

Successes in staunching Ebola outbreaks and failures to do the same with Covid-19 illustrate the need for better early detection of emerging pathogens, improved cooperation and communication among health officials in all countries, and more investment in research to trace pathogenetic origins, transmission characteristics and diseases, Kuppalli says.

“A big reason we’re in the problem we’re in right now is a lack of investment and preparedness. We have a problem in this country of being very reactive. We’re not proactive.”

The budget of the CDC, charged with researching and controlling infectious diseases, rose through about 2010 but has been flat or falling since, declining 4.5% in 2019 and 10.3% in 2020. Right now, due to a lack of coordinated planning, investment, and federal leadership, states are stumbling and struggling to quickly set up vital vaccination efforts.

“A big reason we’re in the problem we’re in right now is a lack of investment and preparedness,” Kuppalli says. “We have a problem in this country of being very reactive. We’re not proactive.”

“We saw in 2020 that the result of underfunding this type of work for decades came home to roost,” says Smith, the Kent State epidemiologist. “I hope no one wants that to happen again.”
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