The call came on Sunday morning, Jan. 19, 2020, and Chas DeBolt, MPH, answered it. She had to: as a senior epidemiologist for the Washington Department of Health, in Seattle, DeBolt was on call, over the holiday weekend. She listened as a clinician described a 35-year-old patient who thought he had a fever and definitely had a mild cough. X-rays didn’t reveal anything suspicious, but the clinician heard rattling sounds—known as rhonchi—when the patient breathed. His temperature barely registered above normal. He tested negative for an array of probable causes for his condition, including influenza A and B, adenovirus, rhinovirus and 4 known human coronaviruses.

He'd returned from visiting family in Wuhan, China, 4 days earlier.

In January, DeBolt and her colleagues had received alerts that a new respiratory illness with pneumonia-like symptoms was spreading quickly in the area around Wuhan, and the novel coronavirus behind the infection had been identified (a pneumonia outbreak was recognized in December 2019). If clinicians learned of anyone who'd recently been to the region and met certain vague criteria—a fever, lower respiratory illness—then staffers were instructed to call the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta.

Which is what DeBolt did. "I really wasn’t sure the CDC would want to test him because he had a pretty minimal temperature and a clear chest film," she says. But they did. "They were definitely being conservative," she says. DeBolt and a microbiologist from her office drove one county north, where the patient lived, to collect samples. They packaged the samples and drove to the airport, where they met a courier who flew the package to Atlanta. The CDC scanned the patient's sample for viral fragments.

The next day, the CDC confirmed that the patient had been infected with the new coronavirus, which has since been named SARS-CoV-2. Scientists in China had made the genomic sequence of the virus available on Jan. 10. The disease, which causes pneumonia-like symptoms, is named COVID-19 (from CO-rona VI-rus D-isease 2019). DeBolt says she has managed multiple outbreaks over her 15-year career, but remains surprised that the CDC caught that first case, based on such slight criteria.

"I still marvel at that," she says. "To me, it's just amazing that they decided to test."

The World Health Organization (WHO) declared a world health emergency in late January. It has ignited efforts to get trustworthy diagnostic kits to the populations who need them. Microbiologists, virologists and epidemiologists around the world are racing to better understand the pathogen, with the goal of developing a safe and effective vaccine. That process, however, will likely take at least 12-18 months, because before it can be approved by the FDA, an experimental vaccine has to go through a series of clinical trials that ensure it's safe and effective. Experts warn that a rushed vaccine could exacerbate the problem.

The pandemic is also sparking heated debates about fatality rates and other statistics, and has produced torrents of misinformation that similarly spread like a virus. National and international travel, tourism and trade have been disrupted. So has education: as of mid-April, the United Nations estimated that schools had closed in 191 countries around the world, affecting more than 91 percent of schoolchildren.

This is how the pandemic began. How and when it will end remain open questions.

"This is very much an evolving situation," says Robin Patel, M.D., president of the American Society for Microbiology and head of the Infectious Diseases Research Laboratory at the Mayo Clinic in Rochester, Minn. "We're learning day by day, sometimes hour by hour, about what's happening."

Getting to Know SARS-CoV-2

Coronaviruses make up a large and contagious family of pathogens that can infect animals or people. Four are known to cause mild respiratory infections, including the common cold. A fifth, identified in 2002, causes severe acute respiratory syndrome, or SARS, which infected 8,098 people and killed 774 during a 2003 outbreak. The sixth causes Middle East Respiratory Syndrome, or MERS, which was identified in 2012. In an outbreak that same year that spread to 27 countries, about 2,500 people contracted MERS and 858 died as a result, suggesting that the virus kills more than a third of people who become infected (though that rate is debatable, as an unknown number of cases likely went unreported).

The new coronavirus is the seventh known to be able to infect people. On Feb. 11, 2020, the International Committee on the Taxonomy of Viruses—the organization charged with naming and classifying new viruses—reported that the new coronavirus, a "sister virus" to the one that causes SARS, would be named severe acute respiratory coronavirus 2, or SARS-CoV-2.

The viruses behind MERS, SARS and COVID-19 all originated in animals and jumped to people. At first, researchers believed MERS-COV began in bats, but studies later confirmed dromedary camels as the animal reservoirs. Experts suspect that both SARS-CoV and SARS-CoV-2 originated in bats.

"Where there are bats, there are coronaviruses," says Lin-Fa Wang, Ph.D., director of Duke-NUS Medical School’s Programme in Emerging Infectious Diseases in Singapore. There are other viruses, too: bats can harbor the Ebola virus, Marburg virus, Nipah virus and Hendra virus, without showing symptoms. Wang is currently developing technologies that could speed up the sequencing process of new viruses, with the ultimate goal of building a genetic library of bat coronaviruses. Such a resource, he says, could help researchers better surveil pathogens and track outbreaks.

In the case of SARS-CoV-2, researchers suspect that the virus may have jumped from bats to another animal before infecting humans, but an intermediate host—or hosts—hasn't been identified.

To Travel or Not To Travel?

COVID-19 has had a ripple effect on the world, the end of which is not yet in sight. Its origins are murky, though genetic analyses show that it likely began in bats. Many of the people first diagnosed with the disease had recently visited a seafood market in Wuhan, leading epidemiologists to suspect that the virus had jumped species there. But that's not certain: a study published in The Lancet in late January reported that the first patient had symptoms beginning Dec. 1 and didn't have a known link to later cases or the market. That suggests the patient may have contracted the virus in November and raises the possibility that someone carried the virus into the market before it reverberated outward.

The next population to be diagnosed with the disease included people who had been in contact with people at the market, or who had been in the vicinity (such as the first U.S. case, near Seattle). In late February, the CDC reported cases of the disease in people in the U.S. with no obvious route of transmission—suggesting the possibility of community spread.

Even in mid-March, it was likely that the numbers of reported cases lagged behind the actual situation, and that the virus had been moving through large populations for weeks. A series of setbacks delayed the ability of local health departments to test local patients. The first involved getting a reliable test.

"Prior to this emergency, we did not have tests for SARS-CoV-2," says Patel. The CDC's first effort at distributing tests was botched when the agency sent out hundreds of kits that turned out to be faulty. The test looks for 3 specific genetic sequences, but it wasn't working correctly. "Ultimately what we saw was a problem with the assay, and many of those tests ended up being recalled," said Dr. Michael Mina, M.D., Ph.D., from Harvard University, during a Feb. 28 panel discussion hosted by the USC Annenberg Center for Health Journalism. That misstep, he says, did "significant damage" by hampering efforts to estimate the number of new cases.

A second roadblock, says Patel, emerged when the U.S. declared the situation to be a public health emergency, which meant that local laboratories, outside the CDC and public health departments, would not be permitted to use their own tests for SARS-CoV-2. That restriction effectively prevented researchers from being able to test patients at the local level.

"Many members of ASM develop and offer their own lab-developed tests," says Patel. On Feb. 28, ASM sent a letter to the Food and Drug Administration (FDA) to change the requirements, noting that the SARS-CoV-2 regulations were more stringent than for other viral tests. On Feb. 29, the FDA issued a new policy that relaxed the restrictions. "There hasn’t been enough access to testing," says Patel, but that will likely change as labs put their own tests into play.

The ripple effect hasn't only moved through populations and public health agencies; it's also significantly dampened travel, tourism and trade. Passengers on cruise ships were quarantined away from home as they waited for test results. The American Physics Society canceled its largest annual meeting in March because of the virus, and at least two dozen other major medical or scientific conferences have been called off out of fear of spreading the outbreak.

The U.S. Travel Association, a nonprofit advocacy group, estimates that as people begin to make decisions based on the risks of the coronavirus and face government restrictions, international inbound travel to the United States will fall by 6% over the next 3 months, representing the steepest decline since the financial crisis in 2007 and 2008. For perspective, Chinese citizens make up the third-largest group of international travelers who visit the United States, with each spending about $6,500 during their trip.

On a broader scale, economists note that the outbreak has fueled more volatility in financial markets, evidenced by historic drops in the stock market in the first week of March. "The truth is that uncertainty is becoming the new normal," noted Kristalina Georgieva, managing director of the International Monetary Fund, on Feb. 19.

Diagnostics, Treatment and Vaccines Outlook

Emerging studies have begun to identify how the virus attacks cells, especially in the lungs, and how those mechanisms might be exploited for new therapies. In March, for example, researchers reported that the virus attaches to angiotensin-converting enzyme 2, or ACE2, receptors in the lungs. The FDA hasn't approved any drugs shown to effectively treat coronavirus infections. But there is a frontrunner: an antiviral called remdesivir. In a paper published Feb. 13 in the Proceedings of the National Academy of Sciences, NIH researchers reported that the drug successfully prevented rhesus macaques from being infected with the MERS coronavirus, which is closely related to SARS-CoV-2.

How it works has remained a mystery, in large part. In a study published Feb. 24 in the Journal of Biological Chemistry, Canadian and American researchers—including some from Gilead, the company that makes remdesivir—made some headway. They showed that the virus incorporates the drug molecule, which resembles a chunk of RNA, into an enzyme needed for replication. That process inhibits the virus from making additional copies of itself.

But who would benefit the most from the drug? Patterns are starting to emerge, but they're not clear yet. Epidemiologists and other scientists have struggled to make meaningful estimates of how quickly the virus will spread, and how lethal it will be.

Notably, they're trying to make sense of the case fatality rate. At a press conference on March 3, Tedros Adhanom Ghebreyesus, Director-General of the WHO, noted that "Globally, about 3.4 percent of reported COVID-19 cases have resulted in death." That number is based on a basic calculation, dividing the number of deaths by the number of known diagnosed cases. However, other experts caution that the numerator and denominator of that ratio change quickly, and that number may not reflect an accurate picture of the viral danger.

In a study conducted on more than 1,000 patients in China and published in the New England Journal of Medicine, researchers reported a case fatality rate of 1.4% in the study population. In the paper, they similarly noted that estimating the rate is subject to high likely error. In particular, patients without debilitating symptoms may not have sought medical attention—and wouldn't have been captured in the study data—which means the real-world rate might be even lower, even below 1%.

"If you look at the weight of the data, the risk group is very, very clear," said immunologist Anthony Fauci, M.D., Director of the National Institute of Allergy and Infectious Diseases, at a press conference on March 6. Elderly patients—especially those with other underlying medical conditions like heart disease, chronic lung disease, diabetes and obesity—are much more likely to get very sick or die. Case studies show that some younger people have also died from the disease, but the risk is much lower.

At the other end of the spectrum, the rate for children less than 19 years old is nearly negligible, and even the incidence rate is almost undetectable. "I don’t totally understand it, the lack of detectable infections in children," Fauci said. It's not as though they’re not getting infected—they have to be, he added. "Why they're not developing clinical disease is really interesting, and it's something that we really need to study."

Finding Reliable Information

Keeping abreast of current and correct information during an outbreak can be a challenge, says Patel. NewsGuard, a misinformation watchdog group started by journalists, recently launched a Coronavirus Misinformation Tracking Center, which collects articles about the outbreak published on fake news sites. That number, since the launch of the tool in late February, has grown to more than 100. During a 90-day period this spring, the group reported some sobering figures: people "engaged with" information from the CDC or WHO a few hundred thousand times. For comparison, people engaged with information from notably unreliable sources more than 52 million times.

To find credible information, the CDC recommends people stick to vetted organizations like the WHO and studies published in peer-reviewed journals. News articles that cite—and link to—published studies can easily be checked for accuracy. Finally, a number of journals and professional organizations, including ASM, have established online information portals with the latest published findings.

DeBolt, back in Washington state, says the case of SARS-CoV-2 is unusual not only because of how quickly it spreads, but also because of the rapid dissemination of information, good and bad.

As of March 20, more than 10,000 cases of COVID-19 have been identified in the United States, and 150 people have died. Several studies estimate that the number of infected people doubles about every 6 days, which means it's following a pattern of exponential growth. If that continues, the number could reach 4 million by the middle of May. In the worst-case scenario, COVID-19 cases could overwhelm the U.S. health system.

How will it end? In late February, the WHO reported that the number of cases in China had peaked, and since then the rate of new diagnoses has fallen steadily there—even as the outbreak spreads elsewhere. In a comment published online March 6 in The Lancet, epidemiologists from the United Kingdom point to efforts like social isolation, voluntary and required quarantine and closing institutions where infections have emerged as effective ways to slow the spread of the virus. "Individual behaviour will be crucial to control the spread of COVID-19," the authors noted.

However, some experts say the virus has spread too far, too quickly, for its effects to be controlled by containment. Some estimate that the virus could ultimately infect between 20 and 60 percent of the world’s population before an effective vaccine has been developed. Even though 80% of cases of COVID-19 are mild, such a large number of infections means millions of people could die.

"How is it different from previous outbreaks? We just don't know yet," says DeBolt. "But we do know that the CDC is learning about the virus, right along with Washington state."

Keep up to date on COVID-19 research with ASM's curated COVID-19 Research Registry.