COVID-19: The Road Ahead

In just three months, spread of the novel coronavirus SARS-CoV-2 grew from a localized outbreak in Wuhan, China, into a pandemic that has touched every continent, infected more than 2.6 million people, placed unimaginable strain on healthcare systems, and devastated global economies. As infection rates in some hotspots, including New York, show signs of waning, questions about the road ahead—including how to safely reopen society and the economy—loom large.

On April 22, 2020, three experts on pandemic control and preparedness joined with the Academy for a virtual discussion of these timely issues. Peter Daszak, PhD, a zoologist, infectious disease researcher, and president of EcoHealth Alliance, Michael T. Osterholm, PhD, MPH, Director of the Center for Infectious Disease Research and Policy at the University of Minnesota, and Nahid Bhadelia, MD, MA, of the National Emerging Infectious Diseases Laboratory at Boston University School of Medicine, shared their thoughts on what the scientific and healthcare communities have learned about the virus itself and COVID-19 disease, strategies for identifying future pandemics, and the role of diagnostic and serological testing in paving a path to a new normal.

The Pandemic Era

Key Takeaways

• Pandemic illnesses such as COVID-19 are increasing in both frequency and impact, due in part to human activities.

• Efforts to prevent future pandemics involve identifying animal viruses with pandemic potential and preemptively developing treatments or vaccine candidates.

Peter Daszak’s work studying zoonotic diseases—human infections caused by pathogens that originate in animals—has taken him all over the world, including to the wildlife markets in China, where scientists believe the new coronavirus made its fateful leap from bats to humans . These markets, with their dense crowds and diversity of wildlife, are “amazing places for viruses to spread,” according to Daszak, who explained that SARS-CoV-2 is just the latest zoonotic virus to cause pandemic illness—a list that also includes SARS, Spanish flu, H1N1 influenza, and HIV. “Pandemics are not only increasing in frequency, but in impact,” said Daszak, landing us in “a sort of pandemic era.”

COVID-19 is the third potentially deadly coronavirus to emerge from bats in the past two decades, and despite its genetic similarity to SARS, it is far more contagious than either SARS or MERS. Daszak, who has identified more than 50 SARS-related coronaviruses in bats, estimates that there are 10-20,000 unknown coronaviruses circulating in bat populations, and “maybe 1.7 million unknown viruses in wildlife of the viral families that we know can infect people.” While most of those viruses are unlikely to cause problems, the catastrophic potential of a single virus motivates Daszak and his collaborators to seek ways to identify—and hopefully prevent—future pandemics. “We need to start thinking about...going out to wildlife and doing a better job of understanding what viruses they carry, what risks they represent to public health,” he said.

Daszak’s studies of bats from various locations in China have revealed that it is possible not only to identify new coronaviruses, but to determine which can infect human cells in the lab and may have pandemic potential.

Mitigating Drivers of Pandemic Emergence

The wildlife trade is just one driver of pandemic emergence. Describing the factors that make a region a potential pandemic hotspot, Daszak noted “strong correlations where there are dense populations of people interacting with diverse populations of wildlife.” Beyond markets like those where this virus is thought to have emerged, land use change, intensive agriculture and livestock production, and expansion of urban centers into remote areas can contribute to encroachment on wildlife habitat. In order to counteract these impacts, behavior change is necessary, noted Daszak, "If we're part of the problem, that gives us the power to be part of the solution.”

Reopening the Country: When is it Safe?

Key Takeaways

• The coronavirus will continue to spread until a vaccine is available, likely in phases of intense flareups followed by periods of slower transmission.

• To safely reopen, regions must be able to meet testing needs, provide protective equipment for healthcare workers, manage surges in hospital admissions, and implement symptom surveillance.

Michael Osterholm discussed three possible scenarios for the course of COVID-19 in the United States over the next 12 to 18 months, while acknowledging that “we don’t know how this pandemic will unfold.” Due to statewide shutdowns and social distancing, most people in the country—and in the world at large—have not been infected with SARS-CoV-2. “Even using the best data, nobody estimates that more than 5% of the world has been infected,” Osterholm said. As herd immunity for this virus appears to depend on at least 65 percent of the population becoming infected and recovering, he commented that in every model of the near-term future, “cases will continue.”

In one scenario, an initially large outbreak—such as those that occurred in China and New York—ultimately wanes, giving way to additional peaks as the virus flares up, calms down, then flares again until the population attains herd or vaccine-induced immunity. A second possibility is that the initial wave is followed by an even larger wave six months later, as has occurred in each of the last 10 pandemics, according to Osterholm. The third possibility is a sustained period of frequent, smaller flare-ups alternating with periods of lower virus activity. “This virus may be on its own time schedule,” Osterholm said, “When we talk about reopening and being prepared for the future, we’re in the long haul here.”

Failing the Test

Testing is “one of the few tools we have,” said Osterholm, but multiple missteps and challenges have resulted in a shortage of accurate diagnostic testing for COVID-19 in the United States. Osterholm described how, after a series of difficulties with test development at the Centers for Disease Control, the Food and Drug Administration issued an emergency use authorization that cleared more than 45 different PCR-based diagnostic tests and 90 serologic (antibody) tests. Many tests entered the U.S. market with little oversight, and issues with accuracy have been significant—reports of false negative rates range from 15 percent to as high as 30 percent .

Beyond accuracy, PCR-based tests pose other long-term challenges, namely a global shortage of the reagents needed to run them. In the face of sustained, global demand for reagents, “we wouldn’t have enough even if we had a canal full of it,” Osterholm said, noting that there has been “no meaningful effort...to develop an international consensus about expanding the availability of reagents.” Innovation in this area, either by addressing the reagent shortage or ramping up availability of tests that don’t utilize them, is critical to the reopening plansadvocated by public health experts and many governors. Given the above challenges, Osterholm warned, “These plans are well-meaning and I give them credit...but right now they’re just not credible.”

Identifying Immunity

Serology testing to identify those who have developed coronavirus antibodies has been widely touted as a critical component of reopening the economy. Osterholm cautions against heavy reliance on antibody testing, noting that little is known about the degree or duration of protection antibodies confer against future coronavirus infection. Here too, he explained, testing accuracy is an issue, with far more dire consequences for false results. Proposals for “immunity passports” or similar measures that “clear” those with antibodies to return to normal life place the country “on a collision course with destiny,” said Osterholm. He explained that amid the currently low prevalence of disease (≤5 percent of the population), even a test more sensitive and specific than those currently in use would identify an equal number of true positives as false positives. “If you’re a nurse, a physician, a first responder, and I told you there was a 1 in 2 chance that your [test] is really positive, would you trust that?”

Realistic Benchmarks

The benchmarks Osterholm feels that regions must meet before beginning to loosen restrictions on work and mobility include: the ability to test every person who needs a test on any given day; equipping healthcare workers with adequate personal protective equipment; ensuring that hospitals have capacity to manage a rapid 25% surge in patients requiring intensive care; and implementing syndromic surveillance, which includes monitoring populations for disease indicators before they seek medical care or receive a diagnosis.

Osterholm didn’t mince words when it comes to the importance of beginning to re-open society. “There are many consequences [of a shutdown] that are not about dollars and cents—there are health effects of depressed economies,” he said. “We will have tough months ahead, but I think by...trying to figure out how to keep society from shutting down while protecting people at highest risk of serious disease, we can somehow thread the rope through the needle.”

Healthcare: The Challenges Ahead

Key Takeaways

• Healthcare facilities and workersremain vulnerable to being overwhelmed as the virus continues to spread.

• Physicians, researchers and policymakers must balance the need to learn about emerging infectious diseases with the need to care for patients.

Straight from a shift caring for patients at Boston University Medical Center, Nahid Bhadelia shared a frontline perspective on how medical facilities are coping with the pandemic, as well as the healthcare challenges ahead. “Pandemics break us at our fault lines, and the biggest fault line for most hospitals, both here (in the U.S.) and in resource-limited settings, is lack of surge capacity,” said Bhadelia, who has studied and responded to disease outbreaks throughout Africa, Asia, and Latin America. As the new coronavirus continues its march across the globe, healthcare facilities have improvised and innovated, especially when it comes to preserving resources in short supply, including ventilators and personal protective equipment. The pandemic has triggered an ongoing process of reinventing and reevaluating safety protocols and future supply needs based on disease prediction models that, along with the progression of the outbreak itself, are ever-changing.

Infectious disease outbreaks pose similar challenges to healthcare workers and policymakers regardless of the illness itself, noted Bhadelia, especially when the underlying pathogen is newly emergent. “When you have pathogens that you're still learning about, how do you shape medical policies or healthcare workers’ safety policies while you’re learning?” she said. The same quandary applies to patient treatment, an area where Bhadelia says some of the most difficult, ethically fraught decisions must be made.

Compassionate Use and Data Collection

With no known treatment for COVID-19 infection, physicians have grappled with the ethics of trying unproven medications—whether FDA-approved or experimental—on patients with severe disease. “How much evidence is enough evidence for us to try a drug?” Bhadelia asked, “and what kind of protection are patients getting in terms of us giving them something that might be promising, but could potentially harm them?” Compassionate use of medications—a system of accessing what is often a pre-approval compound by patients with life-threatening disease and no treatment options—has long been plagued by a lack of data collection. Compassionate use exists outside the framework of randomized control trials, making it difficult or impossible to evaluate whether a drug is effective. Amid the coronavirus pandemic, where multiple experimental or unproven drugs are being provided on a compassionate use basis, Bhadelia reports that a new framework for collecting data has been established to link physicians across the globe and increase information sharing with regards to safety and patient outcomes. This program offers hope for some evidence-based learning while we wait for outcomes from more robust clinical trials.

Science, Compassion, and Care

By definition, pandemics have global impact, and Daszak, Osterholm, and Bhadelia emphasized the need for a coordinated, global response rooted in science-based policymaking, compassion, and care for patients and citizens. As Bhadelia remarked, in closing, “if anything, this pandemic has shown us how connected we are.”

Watch the complete archived webinar here.