How bad will the coronavirus outbreak get in the U.S.?

The spreading coronavirus is shaping up as a pandemic of potentially historic proportions, possibly on the scale ofthe global outbreak of influenza in 1957 but unlikely to be as catastrophic as the Spanish Flu of 1918, according to projections by infectious disease experts who are still struggling to understand this novel pathogen.

The many unknowns about the virus impede efforts to predict its trajectory. Modeling new diseases is inherently uncertain, and scientists have at times overestimated the severity of epidemics, including in 2009, when the H1N1 flu turned out to be milder than expected, and in 2014, when the Ebola outbreak in West Africa killed far fewer people than projected early in that crisis.

But the coronavirus has already spread at surprising speed. Most cases are mild; about 16% of confirmed cases in China have resulted in serious illnesses. The coronavirus has killed more than 3,000 people, the vast majority in central China.

Most new coronavirus cases are now outside of China, with 64 countries reporting cases as of Tuesday. In the U.S., where the death toll Tuesday stood at six, the coming days, weeks and months could see social and economic disruptions as infections spread and public health systems try to cope with a surge of patients.

Currently there are no travel restrictions and, outside some communities in Washington State, only scattered disruptions to daily life in the U.S. How soon the virus may become common across the country is hard to predict, but events could unfold quickly.

"It could be weeks to months. Certainly we're hoping for months," said Paul Biddinger, chief of emergency preparedness at Massachusetts General Hospital in Boston. "Some of the spread across the world and across the United States has been faster than we might have predicted."

Infectious disease experts in recent days have said the coronavirus could create a pandemic on a similar scale to, or even surpassing, the 1957 influenza contagion. That pandemic was caused by a virus related to one found in birds that entered the human population somewhere in Southeast Asia and sickened a quarter billion people, killing more than a million, including 70,000 in the United States. The flu and the current outbreak are caused by different viruses.

The ultimate impact of the new virus, officially named SARS-CoV-2, which causes the disease covid-19, depends on multiple factors that cannot be precisely calculated at present. They include how widely and quickly it spreads, its virulence (the degree to which is sickens and kills people), and the ability of health systems to handle illnesses.

It also depends on individual behavior - the extent to which people follow best practices for hygiene, staying home when they're sick, and avoiding close contact with people who could be infected.

"You may need to take a break from your normal daily routine for two weeks," said Nancy Messonnier, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, in a news conference Tuesday. "Staying home when you are sick is really important. Don't let the illness spread beyond you. Stay away as much as you can from other people."

The average number of new infections generated by each infected person has been estimated at roughly 2.3. That “reproduction number” is based on data from China when the coronavirus was circulating undetected; when people take protective measures, the number of infections can drop. For any epidemic to begin to subside, the reproduction number needs to fall below 1.

Experts assume there are many more infections than are officially documented. Some people with infections may have mild or no symptoms, and never realize they carried the virus. One of the most urgent questions is whether and to what extent people can spread the disease if they're not symptomatic.

Another uncertainty is the lethality of the virus. About 3.4% of the people with confirmed infections globally have died, the World Health Organization said Tuesday. For the elderly and people with underlying health conditions, the fatality rate is considerably higher - about 14% for people over the age of 80, according to the China data.

The actual fatality rate may be much lower, experts say, because most people with the virus haven't been diagnosed, and the confirmed infections tend to be among people who became severely ill.

The relative mildness of the disease for most people has enhanced the ability of the virus to spread, as infected people continue to move about.

"In just two months, the novel coronavirus spread from a cluster in Wuhan, China to an impending global pandemic with cases in more than 60 countries. This is unprecedented. Never before has a new pathogen emerged and caused a global spread like this. And that's scary. It's new. It has the ability to cause enormous social and economic disruption," said Tom Frieden, a former Centers for Disease Control and Prevention director, in a news briefing Monday in New York, where he is president and CEO of Resolve to Save Lives, part of Vital Strategies, a global health organization.

Infectious disease experts rely on forecasting models that take into account what is known of the viral outbreak so far and how past epidemics have unfolded.

Public health officials need to prepare for “disease burden roughly 10X severe flu season,” according to James Lawler, director of the Global Center for Health Security and a professor for the University of Nebraska Medical Center, in a presentation given to the American Hospital Association and obtained by The Washington Post.

The CDC estimates that, since 2010, between 12,000 and 60,000 people in the U.S. have died each flu season. Since the flu season began on Oct. 1 of last year, between 18,000 and 46,000 people have died, among 32 million to 45 million illnesses, the CDC estimates.

The Lawler estimate, based on data from China, suggests that fatalities from coronavirus could greatly exceed those flu totals, but he cautions that the number can be lowered through aggressive efforts to slow down and mitigate the epidemic.

"We have tools that we can potentially use to impact this curve. This is not a fait accompli by any stretch of the imagination," Lawler told The Post.

The best protection against seasonal flu is the flu vaccine, and many labs around the world are working on vaccines for coronavirus, but one won’t be ready in time to stop the current spread.

"We have been saying, if everything moves as quickly as possible, the soonest it could possibly be would be one and a half to two years," Hilary Marston, medical officer and policy adviser at the National Institute of Allergy and Infectious Disease, said by video link at the Harvard event. "That still could be optimistic."

It's not a certainty that the virus will spread broadly across the U.S., but there is a consensus that the country needs to prepare for exactly that.

"I don't think we're going to be able to control it, the same we're not able to control flu," said Jeffrey Shaman, a Columbia University epidemiologist. "The problem is, this is 10 times or maybe 20 times the burden of a typical seasonal flu. Maybe 40 times. That is daunting."

As the disease continues to spread, “We definitely are looking at models. The problem is we don’t know which one is true,” said Biddinger. “It may be that 20% or more of the population ultimately will get infected before we have enough collective immunity to be through the wave of illness. We don’t now how long it will be before we reach that 20% number.”

If the virus turns out to be seasonal (like most flus and the common cold), it means the U.S. and other northern hemisphere countries may get a respite this spring and summer. That would be precious time to make preparations for a possible second wave in the fall.

But no one knows why flus follow this seasonal pattern. Virologists' best guesses are that it has to do how these viruses are less stable with humidity and temperature.

"Right now there's no reason to think this virus would act differently in different climate settings. We'll have to see what happens as this progresses," said WHO epidemiologist Maria Van Kerkhove.

The CDC calls the 1918 Spanish Flu “the deadliest pandemic flu virus in human history,” because of it infected roughly one third of the world’s population and killed an estimated 50 million people worldwide.

But Florian Krammer, a virologist specializing on influenzas and vaccines at Icahn School of Medicine at Mount Sinai, said the world is vastly different today than 1918.

"We didn't have the tools to diagnose diseases or antibiotics to fight secondary infections. Hospitals back then were places where you went to die, not to get treatment. And in 1918, the world was at war. And a lot of the people infected were soldiers stuck in trenches. Nutrition and health systems were much worse. That is, hopefully, not how this is going to play out."

Howard Markel, a medical historian at the University of Michigan, cautioned that comparing flu to the coronavirus is "the viral equivalent of apples and oranges," because the illnesses are caused by completely different viruses, and it's too early to make clear predictions.

"Nobody can truly predict the path of an epidemic while it's still in midcourse," Markel said. "Anyone who tells you they can is either lying or foolish."

The influenza pandemic of 1957spread rapidly around the world. About 250 million people became sick and 1 million to 1.5 million people died, about 70,000 of them in the United States. The case fatality rate was about 0.2%, about double the seasonal flu. It affected the elderly more than younger people, as is the case with the novel coronavirus.

Some schools, movie theaters and ballparks were closed. Because it began in the summer of 1957 - an unusual time for an outbreak - some summer camps were shuttered. People suspected of having the virus were quarantined in their homes; people who had it were put in hospital isolation rooms.

Ventilators, used to help people breathe in hospitals, were almost unheard of in 1957, and intensive care was not widespread, Markel said.

Some pandemics have only modest impacts. The 2009 H1N1 outbreak, also called swine flu, spread quickly, eventually infecting an estimated 11 to 21% of the global population. The WHO declared it a pandemic and it received massive media attention. But H1N1 caused little more than runny noses and coughs in most people. H1N1 is now part of the seasonal flus that come and go every year and is included in the flu vaccine.

The Ebola outbreak in West Africa in 2014 offers an instructive tale about epidemic modeling.In September 2014, the CDC predicted that Liberia and Sierra Leone could suffer 1.4 million infections by January, if authorities did not intervene and communities did not change their behavior. Hundreds of thousands could die, the CDC predicted.

But people did change their behavior. The crisis changed cultural practices, including burial rituals, and through rigorous efforts at contact tracing and isolation of patients the epidemic was brought under control. When the outbreak ended, those two countries had seen fewer than 25,000 cases and about 8,700 deaths.

One mystery of the novel coronavirus is that it seems to have little effect on children. It's not clear if they're immune somehow or are merely mildly symptomatic or asymptomatic, Harvard epidemiologist Marc Lipsitch said.

That has implications for one of the standard social-distancing strategies, which is school closures, he said. "We don't know if that's an important control measure or if it's just a very expensive, costly and disruptive control measure."

One thing people shouldn't do is rush to the hospital if they feel a little bit sick. That happened in China, according to Harvard professor of global health policy Winnie Chi-Man Yip - actions that were "just crashing the system," she said.

The experts say that, although it may be impossible to contain the virus, slowing its spread remains important, in part to prevent a sudden, debilitating surge of patients in hospitals and the resulting chaos and disruptions to normal medical care.

"Slowing the epidemic is what we have to do if we can't stop it," said Lipsitch.

The Washington Post’s Lena H. Sun contributed to this report.