Ready for the Next Pandemic? (Spoiler Alert: It’s Coming)

In a way, SARS-CoV-2 resembled science fiction’s hypothetical dark matter: Its existence could be inferred but couldn’t be clearly defined—until it appeared. In other words, coronavirus disease 2019 (COVID-19) may have taken a lot of people by surprise, but its possibility wasn’t in doubt. As Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), and David Morens, MD, NIAID’s senior scientific adviser, write, this has been “but the latest example of an unexpected, novel, and devastating pandemic disease…[w]e have entered a pandemic era.”1

But while coronaviruses aren’t new to us, COVID-19 shifted our recent experiences with SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) into hyperspeed. “We weren’t prepared for it. It put us on our heels,” David Aronoff, MD, tells Infection Control Today®. He speaks to the way infectious disease experts live now—always on the qui vive for the next pathogenic threat. “We’re constantly concerned that something will be around the corner. And we’re living on a street that’s all corners.”

Aronoff is director of the Division of Infectious Diseases, Department of Medicine, and professor and Addison B. Scoville Jr. Chair in Medicine at Vanderbilt University Medical Center. He has a lot to do in his regular jobs, but like his colleagues in infectious disease, he pretty much dropped everything else to concentrate on COVID-19—“to just lean into it,” he says. That includes, for instance, giving 2 lectures on COVID-19 one day, and 3 the next.

But that doesn’t mean that he, or others in the field, have abandoned preparations for other pathogenic threats. There’s always something else on the radar. In fact, “we haven’t gone a generation without emerging threats,” Aronoff says. “It characterizes the profession that we’re confronted by them on a regular basis.”

With the current pandemic running everyone in health care ragged, this may not be the best time to ask, “What’s next?” But…what’s next? What pathogen(s) not called COVID-19 should we be most concerned about? And where will it (they) be coming from?

You Can Run But…

On Aronoff’s list of concerns: Diseases that might not cause pandemics, but cause small epidemics. “I get particularly nervous about antibiotic-resistant infections that we thought we had control over, but then lost control of. Gonorrhea is a good example. It’s increasingly hard to treat with antibiotics, and increasingly easy to spread.”

Priya Nori, MD, also puts antibiotic-resistant infections at the top of her list. Nori is associate professor of medicine (infectious diseases) and of orthopedics at Albert Einstein College of Medicine and medical director of the Antimicrobial Stewardship Program at Montefiore Health System. She also co-developed the Infectious Diseases Society of America and the Centers for Disease Control and Prevention (CDC)’s COVID-19 Real-Time Learning Network2 resource page for stewardship during COVID-19. This includes up-to-date information from infectious diseases physicians, pharmacists, and infection preventionists (IPs) on personal protective equipment, vaccines, therapeutics, stewardship—“anything you can think of related to the pandemic,” she says.

As she speaks on a Zoom call, enormous COVID-19 molecules loom over her shoulders, a sad metaphor for these days (“I put the background up for a med student lecture weeks ago, and now I don’t know how to take it down,” she says).

“If we think of it in the immediate COVID-19 aftermath, we’re greatly concerned that we’ll see emergence of lots of multidrug-resistant bacteria and fungi,” Nori says. “And these are not novel pathogens necessarily, these are things we had before but that were starting to get lots of attention the past few years before COVID-19 because they had become so widespread. These are the most concerning things, I think, to the folks [who] practice infection prevention and ID [infectious disease]. As soon as COVID-19 starts calming down because of control measures and vaccinations, I think we’re going to unmask all these other things that COVID-19 left in its wake.”

One reason, she says, is that there was a lot of excess antibiotic use, especially in the early stages of the pandemic, which has probably abated now that people are more aware of how the disease works and its long-term effects. “But we’re worried because lots of patients, if they’re fortunate enough to survive COVID-19, unfortunately end up in a sort of chronically medicalized state. There’s a whole new population of long-term-care residents who are now bedbound, plugged in to lots of devices, meaning catheters, tracheostomy tubes, PEG [percutaneous endoscopic gastrostomy] tubes, urinary catheters. This is exactly the type of host who becomes colonized with multidrug-resistant pathogens, which can spread within health care facilities, like long-term care and acute care.”

One of the things that CDC infectious disease experts have found to be a problem, possibly re-emergent due to the COVID-19 pandemic, is carbapenem-resistant Acinetobacter, Nori says. “Any kind of carbapenem-resistant Enterobacteriaceae, especially the extensively drug-resistant ones, like New Delhi metallo-beta-lactamase–producing Enterobacteriaceae, these are definitely the things to watch for.”

Moreover, people who have been hospitalized with COVID-19 are particularly vulnerable to all the “old” hospital-acquired infections. They may have survived COVID-19, but they survive with substantial damage, immunologically and to organs, and then pick up other infections along the way.

However, in some interesting ways, COVID-19 may actually have contributed to the benefits side of the ratio in hospitals. Nori says, “Because of the really heightened control measures for COVID-19 in hospitals, somehow Clostridioides difficile has not played a role in this as we initially thought. Part of that is that we were not testing as much for C diff, but even if you correct for that, it seems like C diff has maybe not been as much of an issue as some of these other pathogens.”

Does that good thing balance out some of the bad things? “Potentially,” Nori says. “But then you worry that you’re just sort of squeezing the balloon, and that one thing gets better but at the expense of another thing. So, it’s probably a little too early to celebrate. Maybe 3 years down the road, if it seems this really mitigated that issue, then I think it is definitely a win.”

Small World

In addition to home-grown pathogens, we have to worry about others that come from far-flung regions. Both Aronoff and Nori point to what some of our deadliest contagions have had in common: The viruses were transferred via air. “If you look back over the history of the world,” Nori says, “it’s really respiratory viral pandemics that have been the ones that have infected and killed people across borders and have gone on and on for many years and sometimes revisit.

“As far as long-term concerns,” she adds, “definitely what’s likely to lead to a pandemic state is another respiratory viral pathogen, without a doubt, because these are the things that spread most quickly, that are most transmissible between human beings, and have extensively high viral loads that make it very easy to spread between individuals.”

What’s more, it’s very likely, she predicts, that the next pandemic could be due to a respiratory viral pathogen that hasn’t been seen before, because of some kind of mixing of genetic elements from different species. The species-mixing element concerns Aronoff as well: As we’ve discovered, many viruses that live in animals can jump to humans.

However, the next big threat could also very well be an old one. In many ways, the world has been becoming more hospitable to pathogens we thought we’d seen the end of. And it’s hard to fight the 2 main things that drive the threat, Aronoff says: evolution and opportunism. Pathogens like cholera, diphtheria, tuberculosis (TB), and malaria take advantage of people gathering or living in crowded spaces, people with already poor health.

“Infectious disease is a kind of barometer for other causes, geopolitical, social disturbances or inequities, even political,” says Aronoff. “TB is a great example. It hits on all cylinders: crowding, lack of effective vaccines, malnutrition, poverty. It’s a disease that’s been around forever, but scares us in ID as a newly forming threat. It’s both a looming and perennial threat.”

On the other hand, Nori says, “That’s what makes this whole area of study so fascinating. It’s the convergence of the climate crisis, politics, conflicts…. Infectious diseases that we previously eradicated, or things that really should be under control in the year 2021, like cholera, diphtheria, those are reemerging because of regional conflicts.”

Another factor, climate change, is also driving changes in infectious disease. As animals and people migrate, searching for a more livable environment, we see vector-borne or insect-borne diseases shift with them. “There may not be emerging or entirely new diseases, but arrival in new areas,” Aronoff says.

Now add in human mobility (as in global travel), and it’s a recipe for another worldwide catastrophe. The reality is that plagues have been a part of human life since hunter-gatherer days—it’s just that nowadays the diseases get around the world much faster. It took the Black Plague roughly 2 years to travel from Italy to Scandinavia. It took SARS-CoV-2 about 4 months to travel from China to Seattle, Washington, to New York, New York. Dengue, chikungunya, Zika—they’re all on the move. Zika, for one, started out in a relatively small area of the world, and is now found in 86 countries and territories.3

Getting Ready…Again

It all sounds ominous, but Aronoff is reassuring, in a restrained sort of way. We might not have been prepared for COVID-19, he says, “but we’ve learned lessons about how to deal with other pathogens. It’s possible to be frozen in anxiety and fear about what’s next, but this is what we’re trained to do. We’re trained to look for emerging threats and figure out how to deal with them.”

What can be done to make the next pandemic—and there will be one—less traumatic? “We need more,” Nori says. “We need more advocacy, we need more resources diverted toward really bolstering very strong IP programs in hospitals and long-term care. The decisions we make, the policies we put into place, they’re impacting the entire system, and not just the one patient at a time. I hope that resources are allocated accordingly after all this, whereby it’s a more proactive approach, rather than trying to fix a problem after it’s too late. If you really invest in that workforce, the ones leading prevention and patient safety, then collateral damage to the system won’t be nearly as bad.

“Health leaders recognize it, definitely, now. They see where the holes are. Unfortunately, where hospitals find themselves now in terms of the bottom line, that type of resources investment is probably not going to be possible for a long time. What’s awesome, though, is that the new CDC director [Rochelle Walensky, MD, MPH,] is an infectious disease physician who practiced medicine. She gets it. She gets what we all do, and I think once the dust settles on all this, she’s going to be a tremendous advocate for IPs.”

As we scrounge for silver linings to the COVID-19 cloud, one might be the growing recognition of how crucial the IP job is. “It’s certainly been a really interesting year for our discipline,” Nori says. “Finally, I think people understand what we try to do on a day-to-day basis. Infection prevention has really come into the forefront.”

In fact, given all that’s been going on, and all that could be going on, Nori thinks it’s time for a loud shout-out to IPs. “I want to advocate for our people. They’re holding this whole thing together. And by extension, infectious disease physicians. We hold the fort. We’re the glue. We keep the hospital running, make sure elective surgeries can still happen. We continue to think about these things when everybody else goes to sleep at night.

“If this country, the world, successfully emerge from this whole crisis…thank your neighborhood IP, basically.” She chuckles. “Give ’em a hug and kiss. Well, maybe not a kiss.”

When the world gets back to some kind of normal, maybe it will include some positive change coming out of this health crisis. In the meantime, to avoid turning the world into one huge disaster movie, Aronoff warns, “It’s really important that we keep our head in the game.”

“We remain at risk for the foreseeable future,” say both Fauci and Morens. “COVID-19 is among the most vivid wake-up calls in over a century. It should force us to begin to think in earnest and collectively about living in more thoughtful and creative harmony with nature, even as we plan for nature’s inevitable, and always unexpected, surprises.”

JAN DYER is a writer and editor specializing in clinical topics. She lives in Suffern, New York.

References

1. Morens DM, Fauci AS. Emerging pandemic diseases: How we got to COVID-19. Cell. 2020;182(5):1077-1092. doi:10.1016/j.cell.2020.08.021
2. COVID-19 real-time learning network. Infectious Diseases Society of America and Centers for Disease Control and Prevention. Accessed February 4, 2021. https://www.idsociety.org/covid-19-real-time-learning-network/
3. Zika Virus. World Health Organization. July 20, 2018. Accessed February 24, 2021. https://www.who.int/news-room/fact-sheets/detail/zika-virus