Finalist: Helen Branswell, Andrew Joseph and the late Sharon Begley of STAT, Boston, Mass.

By Helen Branswell

The mysterious and growing cluster of unexplained pneumonia cases in the Chinese city of Wuhan has infectious disease experts parsing limited public statements from Chinese authorities for clues to what is happening.

With machine-translated reports that the outbreak might be caused by a new virus, and perhaps even a new coronavirus — the family of viruses that produced both SARS and MERS — watchers are hoping that Chinese authorities will provide additional information soon.

“I think we need to give them a couple of days but I want to hear something from a credible source on the investigations that are ongoing,” said Marion Koopmans, director of the department of virology at Erasmus Medical Center in Rotterdam, the Netherlands.

As of Friday, health authorities in Wuhan reported 44 cases, a big jump from the 27 reported on Tuesday. Eleven of the 44 were seriously ill, the Wuhan Municipal Health Commission said, though there were no reported deaths to date. The health of 121 close contacts of the cases was being monitored. The infections are linked to a large seafood market where it is believed some exotic animals were also sold for consumption.

The World Health Organization has said little about the outbreak beyond that it is in close contact with China authorities on the issue.

“We’re closely monitoring the situation in Wuhan and are in active communication with our counterparts in China,” WHO’s regional office for the Western Pacific Region, which includes China, said on Twitter. “We’ve activated our incident management system across the three levels of WHO (country office, regional office, HQ) and can launch a broader response, if needed.”

The agency noted that China “has extensive capacity to respond to public health events and is responding proactively and rapidly to the current incident in Wuhan — isolating patients, tracing close contacts, cleaning up the market, and searching for the cause and for additional cases.”

Ralph Baric, a coronavirus expert at the University of North Carolina, agreed that China has deep expertise in virology. Baric has a collaborative grant with some researchers in Wuhan to study emerging coronaviruses, and has visited the facilities there.

“Wuhan is the epicenter for a lot of virology research in China. They have state of the art BSL3 and BSL4 facilities and world-class facilities to do anything that you would want to do on new emerging infectious diseases. So it’s occurring in the right spot,” he said.

BSL is shorthand for the bio-safety level designation of a laboratory; level 3 and level 4 are the labs in which the most dangerous pathogens are worked on.

Social media platforms — both in China and outside it — have been abuzz with discussion of the Wuhan outbreak, with some commentators arguing the lack of a clear answer by now is reminiscent of China’s behavior during the 2002-2003 SARS outbreak.

But Baric disagreed, saying China’s approach to infectious disease outbreaks has evolved considerably since SARS, an event for which it was harshly criticized globally.

“The situation in China between 2003 and 2020 is night and day,” he said. “They have many of the best virologists in the world there that are working on this. And my gut feeling is we’re going to see a showcase of what they’ve accomplished in 20 years.”

Koopmans and Baric have a number of questions they’d like answered — “very soon,” Koopmans said — to help assess the severity of the situation.

Knowing whether Chinese scientists have identified the cause of the illness is top of the list. Whether it is indeed a new virus — and what viral family it belongs to — is right up there too.

During the SARS outbreak, it took a full month from when the WHO tasked a global network of 11 laboratories to find the cause of the outbreak before confirmation was received that a new coronavirus was the culprit. The SARS coronavirus probably originated in bats, but civet cats — wild animals eaten as a delicacy in southern China — were the virus’ route to people.

Technology has improved a lot since then, said Baric, who said multiplexing PCR — polymerase chain reaction testing — and RNA-Seq, which looks for evidence of the RNA of pathogens in clinical samples, could make finding the culprit a much quicker job this time round.

But even with the new technology, finding the cause of pneumonia can be tricky. With some infections, by the time a person is evidently ill, their immune system has cleared away most of the causative agent. The symptoms of illness are actually the effect the cascade of immune system weapons unleashed on tissues that had been infected.

“There’s a window there of viral detection of the viral nucleic acid,” Baric said.

“If most of these initial patients were caught late in infection, when the more severe disease symptoms came on, they may not have any acute cases and it may be very difficult. Very low levels of nucleic acid to chase to discover the disease.”

Koopmans noted finding the cause may be complicated by the fact that pneumonia is common and can be caused by many pathogens. If authorities started looking for pneumonia cases after realizing there was a problem in Wuhan, some of the cases they found might have been unrelated to the actual event.

Both are keen to know if there is any spread of the illness between people, which would be worrying. Wuhan health authorities have said there was no human-to-human transmission. But unless they know what is causing the illness, how long the illness takes to develop, and have developed a test that can detect mild cases, it is not clear that can be ruled out at this point.

“I don’t find the comments [about human transmission] that I see spread throughout the internet as credible — unless they know what it is,” Baric said.

The fact that health officials in Wuhan closed and decontaminated the seafood market — there is video of this happening on social media — is suggestive that an animal virus had spilled over into people, he added.

The statement from the Wuhan health board said that influenza, avian influenza, and adenovirus infections — the latter can cause serious respiratory illness — have been ruled out.

Because of SARS, attention is focusing on coronaviruses, though both Koopmans and Baric noted a number of different virus families could cause respiratory outbreaks.

But coronaviruses have shown themselves to be adept at jumping from animal hosts to people, sometimes establishing themselves as human pathogens. There are four human coronaviruses that are common causes of cold-like illness. Those viruses were formerly animal viruses — experts can tell by comparing their genetic sequences to animal coronaviruses. When the four started infecting humans is not clear in most cases.

Some coronaviruses have jumped from animals to people on multiple occasions — the MERS virus in the Arabian Peninsula is an example — but haven’t acquired the ability to spread easily from person to person.

Sometimes the damage can be significant.

In late November of 2002, people in the southern Chinese province of Guangdong started to become ill from unexplained pneumonias. The WHO began hearing rumors of the illness, but Chinese authorities played it down.

But in late February, travelers from a number of countries — Vietnam, Singapore, Canada among them — stayed on the same floor in a Hong Kong hotel as a doctor from China who had been looking after some of the pneumonia cases. He was ill, and he infected multiple other hotel guests, seeding the new infection across Southeast Asia and to Toronto.

Transmission of the new disease was stopped by the summer of 2003, but in its short history SARS — short for severe acute respiratory syndrome — infected more than 8,000 people and killed nearly 800.

Baric said he’s hopeful Chinese scientists will have figured out what is going on in Wuhan and will report on it soon.

“If the number of cases keeps increasing, then it becomes more and more of a global public health threat,” he said. “The chance of [infected] people slipping through the screening platforms for international travel or travel elsewhere in China become greater as long as they don’t know what the pathogen is.”

By Andrew Joseph and Helen Branswell 

It’s been only three weeks since Chinese authorities alerted the World Health Organization that it had an outbreak of unusual pneumonia cases. An astonishing amount of information has been learned in the days since about the outbreak, caused by a new virus that jumped from animals into people. But a frustrating amount of information remains still beyond our grasp.

Scientists and public health officials in China and beyond are scrambling to try to learn more about the virus, which has already spread out from the Chinese city of Wuhan, where the outbreak appears to have started, to other parts of China and several other countries, including the United States. 

We all have more questions than answers. But here’s some of what we’ve learned about this new disease threat. 

Where did the virus come from? 

Health officials in China tracked many of the initial cases to a large seafood market in Wuhan, a city in central China, that also sold wild animals as meat. The leader of an expert committee working on the outbreak has said some type of game is the most likely source.

The virus, provisionally called 2019-nCoV, is a coronavirus — from the same family as the viruses that caused SARS and MERS. These viruses are generally believed to originate in bats, but they can spread to other animals before making the leap to people. The 2002-2003 SARS outbreak, for example, was traced back to palm civets and other small mammals, while MERS jumps from camels to people. Once people are infected with a virus, it’s possible they can transmit it to other people — though how easily it can spread among people depends on a number of factors. 

So how easily can this virus spread?

Experts don’t yet know the mode of transmission — or how easily transmission can happen. Many of the cases detected initially were tied directly to the market in Wuhan. But some of the subsequent infections were clearly examples of person-to-person spread.

Health officials are confident that there is at least limited person-to-person spread. But the World Health Organization has also raised the possibility that there could be ongoing, sustained transmission — meaning that the virus could transmit easily from one person to the next and then onward, like the flu.

What are the symptoms of this viral infection? How dangerous is it? 

China alerted the WHO on Dec. 31 to an unusual burst of cases of pneumonia — an inflammation of the lungs, accompanied by cough and phlegm, that can be caused by a variety of pathogens. As health officials have learned more, they’ve seen a broader array of symptoms, according to the WHO. Overall, health authorities say, symptoms include fever, cough, and shortness of breath. 

A number of patients have been treated at hospitals and released within a few days. For others, the complications have been much more severe. As of Wednesday, 17 people with the infection in China had died.

It’s possible that some people have such mild symptoms they’re not seeking medical care or that health authorities have missed some of these mild cases. That makes it hard to know how dangerous the virus is to most people, and it remains very early in the outbreak. 

The WHO said this week that of 278 confirmed cases in China, 51 people are severely ill, with 12 in critical condition. 

“A major concern is the range of severity of symptoms this virus is causing,” Jeremy Farrar, the director of the Wellcome Trust, said in a statement Tuesday. “It is clear some people are being affected and are infectious while experiencing only very mild symptoms or possibly without experiencing symptoms at all (asymptomatic). This may be masking the true numbers infected and the extent of person to person transmission. It is a matter of urgency to work this out.”

One common thread among most of the fatal cases is that the patients had other health problems. The first death was a 61-year-old man who also had abdominal tumors and chronic liver disease. Two deaths reported Tuesday — the fifth and sixth of the outbreak — were a 66-year-old man with COPD, hypertension, and other conditions, and a 48-year-old woman who had diabetes and who had had a stroke. 

Why has the number of cases spiked so quickly? 

There’s no disputing the case count has risen sharply. As of Friday, local health officials in Wuhan had confirmed 45 cases, with three identified “exported” cases in Thailand and Japan. By Wednesday, there were nearly 450 confirmed cases in China. 

There are a few possible explanations for the spike. One is that the virus is simply spreading quickly on its own. But when you’re looking for something, you’re also more likely to spot it. As awareness about the virus increased, and health authorities throughout China and in other countries started keeping an eye out, they started investigating cases of respiratory infections more rigorously. People with symptoms may have been more likely to seek out medical care. Plus, researchers have publicly released the genetic sequences of virus they’ve collected, which allows for conclusive diagnosis. 

There’s also the political factor. Chinese President Xi Jinping said Monday that the outbreak “must be taken seriously” and that “party committees, governments, and relevant departments at all levels should put people’s lives and health first.” This was seen as a signal from the country’s leader that officials should be transparent about the scope of the outbreak as opposed to restricting information. 

How likely is it that the numbers we’re seeing reflect the actual number of infections?
 
Not very. With most infectious diseases, there’s a spectrum of illness. With some diseases, some infections are so mild the person may have no discernible symptoms or may feel just a little off. With some diseases, the other end of the spectrum can be critical illness and death.

Infectious disease experts sometimes use the analogy of an iceberg, with the really sick cases represented by the part of the iceberg that’s above the water. The people who are asymptomatic or so mildly sick they don’t seek medical attention are the part of the iceberg that doesn’t come into view. It’s not yet clear with this new disease how much of the disease we’re seeing. Until that picture comes into focus, it’s hard to put the number of deaths being reported into any useful context.

Seventeen deaths out of nearly 450 cases is a fairly concerning number. If there are actually 10 times or 100 times more cases the decimal on any rough calculation of a fatality rate slides to a less alarming position. While it’s impossible to know with any degree of certainty how big this outbreak is at the moment, infectious disease epidemiologists are using mathematical models to try to come up with estimates. One group, led by Neil Ferguson of Imperial College London, estimated Friday there had been at least 1,723 cases in Wuhan alone by Jan. 12. Ferguson’s team has re-run the model, plugging in the latest available data. The new estimate, published Wednesday, suggests there were 4,000 cases in Wuhan by Jan. 18.

How is this like SARS? How is it different? 

There are obvious similarities and sharp distinctions. Let’s start with the former.

This outbreak is being caused by a coronavirus, from the same family as the virus that caused SARS. In fact, genetically this virus is similar-ish to SARS — its genetic sequence varies from the SARS epidemic virus by about 20%.

Both outbreaks started in China. SARS jumped to people from small wild mammals sold as a delicacy in what are known as wet markets, where live animals can be bought and butchered on the spot. It will surprise exactly no one if this virus jumped to people in the same way.

Another similarity: This outbreak is evolving super quickly, just as SARS did 17 years ago. 

But the differences between this outbreak and SARS are profound. Chinese authorities tried to cover up SARS for months before exported cases finally alerted the world to what was going on. 

This time they have been far more forthcoming, alerting the WHO, isolating a virus from a patient, sharing genetic sequences so that laboratories could design tests for the new virus, sharing information on case increases daily. This is night and day, experts say.

They also appear to have discovered that a new virus had emerged really rapidly — the result, likely, of the major investment the country made in infectious diseases science after SARS.

They discovered it fast? How fast?

There’s no way to be certain when this coronavirus started infecting people. But by studying the available genetic sequences — 14 have been placed into international databases to date — some informed guesses can be made. 

Andrew Rambaut, a professor of molecular evolution at the University of Edinburgh’s Institute of Evolutionary Biology, has compared the sequences. Rambaut told STAT there is very little variation in them, suggesting they haven’t been spreading in people for very long.

By looking at the rate at which coronaviruses mutate — their evolutionary clock — Rambaut has estimated when these viruses started infecting people. 

The sequences suggest China caught this outbreak almost immediately.

“The sequence evidence suggests that the virus first cropped up in humans very, very shortly before the outbreak was identified,” Rambaut said, pointing to early December. The Chinese reported the outbreak to the WHO on Dec. 31.

That suggests a remarkably finely tuned surveillance system, he said — all the more impressive because these unusual pneumonia cases were occurring during cold and flu season, when pneumonia is pretty common.

What does it mean there’s now a case in the U.S.?

Health authorities suggested it was only a matter of time before a case would appear in the U.S., and on Tuesday, they announced that a man in his 30s in Washington state who had traveled from Wuhan had the virus. Wuhan is a travel hub, with about 10% of the 60,000 people who travel from the city to the U.S. every year come in January because of the Lunar New Year celebrations, according to the CDC. 

But health authorities say that, for now, the risk to the broader American public is low. That’s based on what’s known now — but the situation is evolving very rapidly. It’s important for everyone to remember that in outbreaks, information evolves.

CDC officials said they were anticipating additional cases in the U.S., likely from other travelers. All passengers coming to the country from Wuhan will now land at one of five airports — San Francisco, Los Angeles, New York’s JFK, Atlanta, and Chicago’s O’Hare — where officials are surveying passengers about their health and screening them for symptoms. The screening at the airports is meant not only to try to spot possible cases, but also serve as a reminder that people coming from Wuhan who may develop symptoms later should seek medical care.

By Helen Branswell

Some infectious disease experts are warning that it may no longer be feasible to contain the new coronavirus circulating in China. Failure to stop it there could see the virus spread in a sustained way around the world and even perhaps join the ranks of respiratory viruses that regularly infect people.

“The more we learn about it, the greater the possibility is that transmission will not be able to be controlled with public health measures,” said Dr. Allison McGeer, a Toronto-based infectious disease specialist who contracted SARS in 2003 and who helped Saudi Arabia control several hospital-based outbreaks of MERS.

If that’s the case, she said, “we’re living with a new human virus, and we’re going to find out if it will spread around the globe.” McGeer cautioned that because the true severity of the outbreak isn’t yet known, it’s impossible to predict what the impact of that spread would be, though she noted it would likely pose significant challenges to health care facilities. 

The pessimistic assessment comes from both researchers studying the dynamics of the outbreak — the rate at which cases are rising in and emerging from China — and infectious diseases experts who are parsing the first published studies describing cases to see if public health tools such as isolation and quarantine could as effective in this outbreak as they were in the 2003 SARS epidemic.

And the warnings come as the United States reported over the weekend finding three more cases, the country’s third, fourth, and fifth. Two were diagnosed in California. One is a traveler from Wuhan, where the outbreak is believed to have started, who was diagnosed in Orange County. The other is someone who visited Wuhan who was diagnosed in Los Angeles County. The fifth case was diagnosed in Arizona and is a student at Arizona State University; the person had also traveled to Wuhan.

Confirmed infections within China climbed to nearly 2,750 and the death toll rose to 80.

China’s health minister, Ma Xiaowei, warned Sunday that the virus seems to be becoming more transmissible and the country — which has taken unprecedentedly draconian steps to control the virus — was entering a “crucial stage.”

China’s actions — which include shutting off flights and trains from some affected cities and effectively putting tens of millions of people into quarantine — may not be enough to stop the virus, experts said.

“Despite the enormous and admirable efforts in China and around the world, we need to plan for the possibility containment of this epidemic isn’t possible,” said Neil Ferguson, an infectious diseases epidemiology at Imperial College London who has issued a series of modeling studies on the outbreak.

There may be as many as 100,000 cases already in China, Ferguson told The Guardian newspaper on Sunday, adding the model suggests the number could be between 30,000 and 200,000 cases. “Almost certainly many tens of thousands of people are infected,” he told the British newspaper.

The Bill and Melinda Gates Foundation announced Sunday it is donating $10 million to the response to the virus. Half the money will be given to Chinese groups to help them in containment efforts. The other half will be given to the African Center for Disease Control to fund its efforts to help African countries prepare to have to cope with the new infection.

Also on Sunday, World Health Organization Director-General Tedros Adhanom Ghebreyesus tweeted that he is traveling to Beijing to meet with Chinese authorities to offer support and to learn more about the outbreak.

The WHO so far has not declared the outbreak a global health emergency, though Tedros, as he is known, has said the spread of the new virus is a crisis for China and a risk to countries beyond it. The WHO declined to label the outbreak a global health emergency of international concern on the advice of a panel of experts who met Wednesday and Thursday, though those experts were split on whether a PHEIC should be declared.

This outbreak is caused by a virus — currently known as 2019-nCoV — that belongs to the same family as the viruses that caused the SARS outbreak and which cause sporadic flare-ups of cases of MERS on the Arabian Peninsula.

The SARS virus caused an explosive outbreak in late 2002 and early 2003, infecting more than 8,000 people around the globe and killing nearly 800 before it was contained. MERS has never caused a sustain global outbreak, though a number of large hospital-based outbreaks — including one in South Korea sparked by a businessman who contracted the virus in the Middle East — have been recorded.

One of the luckiest breaks the world got with the SARS outbreak was the fact that the virus did not transmit before people developed symptoms.

With some diseases, like influenza and measles, people who are infected but who are not yet feeling sick — people who are still going to work or school, taking public transit, shopping in malls, or going to movies — can pass the viruses to others.

Tools like quarantine and isolation — which were key to controlling SARS — are unlikely stop spread of a virus that can transmit during the period from infection to symptoms, experts say.

Dr. Nancy Messonnier, director of National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said the agency knows transmission of the virus within the United States may be on the horizon.

“We’re leaning far forward. And we have been every step of the way with an aggressive stance to everything we can do in the U.S.,” she told STAT. “And yet those of us who have been around long enough know that everything we do might not be enough to stop this from spreading in the U.S.”

To date, at least 14 countries and territories outside of mainland China have reported nearly 60 cases. There have been no reports yet of unchecked spreading from those imported cases to others.

“In hours where I’m feeling optimistic I think about the fact that none of the other countries, including the U.S., have seen significant sustained chains of transmission,” Messonnier said. “But that doesn’t mean that it’s not coming.”

It also appears that the incubation time — the time from infection to the development of symptoms — may be a bit shorter than that of SARS, McGeer said, citing a paper published Friday that described transmission within a family in Hong Kong. With SARS, most people developed symptoms about four or five days after infection, she said.

A short incubation period gives health authorities less time to track down and quarantine people who have been exposed to the virus and who are en route to becoming infectious.

Scientists who have been studying the genetic sequences of viruses from China and a few other of the countries that have recorded cases have calculated what is known as the reproductive rate of this outbreak — the number of people, on average, that each case will infect.

An outbreak with a reproductive number of below 1 will peter out. But a number of groups have calculated a reproductive rate for this current outbreak — known by the term R-naught or R0 — in the range of 2 to 3 or beyond.

Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, suggested the estimates are sobering and point to continued spread.

“If it’s not contained shortly, I think we are looking at a pandemic,” Bedford said, though he cautioned that it’s impossible to know at this point how severe that type of event would be.

Dr. Tom Inglesby, director of the Center for Health Security at Johns Hopkins School of Public Health, urged countries to start planning to deal with global spread of the new virus. Such plans need to include far more aggressive efforts to develop a vaccine than have already been announced, he suggested.

“I’m not making a prediction that it’s going to happen,” Inglesby said, though he noted the mathematical modeling, the statements from Chinese authorities, and the sharply rising infection numbers make a case for this possible outcome. “I think just based on those pieces of limited information, it’s important for us to begin some planning around the possibility that this won’t be contained.”

By Sharon Begley

With the new coronavirus spreading from person to person (possibly including from people without symptoms), reaching four continents, and traveling faster than SARS, driving it out of existence is looking increasingly unlikely.

It’s still possible that quarantines and travel bans will first halt the outbreak and then eradicate the microbe, and the world will never see 2019-nCoV again, as epidemiologist Dr. Mike Ryan, head of health emergencies at the World Health Organization, told STAT on Saturday. That’s what happened with SARS in 2003.

Many experts, however, view that happy outcome as increasingly unlikely. “Independent self-sustaining outbreaks [of 2019-nCoV] in major cities globally could become inevitable because of substantial exportation of pre-symptomatic cases,” scientists at the University of Hong Kong concluded in a paper published in The Lancet last week.

Researchers are therefore asking what seems like a defeatist question but whose answer has huge implications for public policy: What will a world with endemic 2019-nCoV — circulating permanently in the human population — be like?

“It’s not too soon to talk about this,” said Dr. Amesh Adalja, an infectious disease specialist at the Johns Hopkins Center for Health Security. “We know that respiratory viruses are especially difficult to control, so I think it’s very possible that the current outbreak ends with the virus becoming endemic.”

Experts see two possibilities, each with unique consequences:

Just another coronavirus

2019-nCoV joins the four coronaviruses now circulating in people. “I can imagine a scenario where this becomes a fifth endemic human coronavirus,” said Stephen Morse of Columbia University’s Mailman School of Public Health, an epidemiologist and expert on emerging infectious diseases. “We don’t pay much attention to them because they’re so mundane,” especially compared to seasonal flu.

Although little-known outside health care and virology circles, the current four “are already part of the winter-spring seasonal landscape of respiratory disease,” Adalja said. Two of them, OC43 and 229E, were discovered in the 1960s but had circulated in cows and bats, respectively, for centuries. The others, HKU1 and NL63, were discovered after the 2003-2004 SARS outbreak, also after circulating in animals. It’s not known how long they’d existed in people before scientists noticed, but since they jumped from animals to people before the era of virology, it isn’t known whether that initial jump triggered widespread disease.

OC43 and 229E are more prevalent than other endemic human coronaviruses, especially in children and the elderly. Together, the four are responsible for an estimated one-quarter of all colds. “For the most part they cause common-cold-type symptoms,” said Richard Webby, an influenza expert at St. Jude Children’s Research Hospital. “Maybe that is the most likely end scenario if this thing becomes entrenched.”

All four, in particular HKU1, can cause pneumonia, and sometimes death. It is rare enough that researchers do not have good estimates of its prevalence or virulence, but two of the others have been better studied. In one of the few close looks at OC43 and 229E, researchers measured their infection rates during four winters (1999-2003) in Rochester, N.Y., among 2,897 healthy outpatients, adults with cardiopulmonary disease, and patients hospitalized with acute respiratory illnesses.

They identified 398 coronavirus infections (four people had both OC43 or 229E). Infection rates ran from 0.5% among healthy elderly adults to 15% among healthy young adults (where “healthy” means they had no viral symptoms), with the highest rates coming in the winter of 2000-2001, for no obvious reason — suggesting that coronavirus infection rates will rise and fall unpredictably, much like seasonal flu, and that its consequences will also be similar: some serious illness, some mild, and a lot of asymptomatic infections.

The most common symptoms were runny nose, cough, and congestion, for about 10 days; no one even ran a fever. All told, 35% of infections with 229E and 18% with OC43 were asymptomatic. “Asymptomatic infection … [meaning] without respiratory symptoms was fairly common,” the authors concluded.

But sometimes symptoms were nothing to sneeze at. There were 96 coronavirus infections among the 1,388 hospitalized patients. OC43 caused more severe disease than 229E, requiring intensive care for 15% of those infected. About one-third of the patients admitted to the hospital with either coronavirus developed pneumonia; one of the 229E patients and two of the OC43 patients died.

On the bright side, if a coronavirus infects enough people regularly there will be greater business incentive to develop a vaccine and other countermeasures. That never happened with SARS because it died out, leaving no market for such products.

On the decidedly darker side, a fifth endemic coronavirus means more sickness and death from respiratory infections.

Odds: Moderate. “I think there is a reasonable probability that this becomes the fifth community-acquired coronavirus,” Adalja said, something he expanded on in his blog. Webby agreed: “I have a little bit of hope that, OK, we’ll put up with a couple of years of heightened [2019-nCoV] activity before settling down to something like the other four coronaviruses.”

2019-nCoV returns repeatedly like a bad seasonal flu

The “seasonal” reflects the fact that viruses can’t tolerate high heat and humidity, preferring the cool and dry conditions of winter and spring, Webby said. That’s why flu, as well as the four coronaviruses, are less prevalent in warm, humid months. If the new coronavirus follows suit, then containment efforts plus the arrival of summer should drive infections to near zero.

But also like flu viruses, that doesn’t mean it’s gone.

The “bad” reflects the fact that the number of 2019-nCoV cases and deaths so far suggests that the new coronavirus has a fatality rate around 2%. That’s almost certainly an overestimate, since mild cases aren’t all being counted. But even 2% is less than SARS’ 10% and nowhere near the 37%  of MERS (Middle East respiratory syndrome coronavirus). On the other hand, seasonal flu kills fewer than 0.1% of those it infects, though that’s still tens of thousands of deaths a year just in the U.S. The global disaster that was the 1917 “Spanish flu” pandemic killed 2.5% (though some estimates exceed 10%).

“One scenario is that we go through a pandemic,” as the current outbreak may become, said Columbia’s Morse. “Then, depending what the virus does, it could quite possibly settle down into a respiratory illness that comes back seasonally.”

The toll that would take depends on how many people it infects and how virulent it is. Virulence reflects the viruses’ genetics.

The genome of the novel coronavirus consists of a single strand of RNA. Microbes with that kind of genome mutate “notoriously quickly,” said biologist Michael Farzan of Scripps Research, who in 2005 was part of the team that identified the structure of the “spike protein” by which SARS enters human cells.

But SARS has a molecular proofreading system that reduces its mutation rate, and the new coronavirus’s similarity to SARS at the genomic level suggests it does, too. “That makes the mutation rate much, much lower than for flu or HIV,” Farzan said. That lowers the chance that the virus will evolve in some catastrophic way to, say, become significantly more lethal.

The coronavirus “may not change [genetically] at all” in a way that alters function, said biologist Andrew Rambaut of the University of Edinburgh, who has been analyzing the genomes of the 2019-nCoV’s from dozens of patients. “It is transmitting quite well already so it may not have to ‘evolve’ to be endemic.”

Any evolution that does take place in an endemic coronavirus, including one that spikes seasonally, might well be toward less virulence. “It doesn’t want to kill you before you transmit it,” Farzan said. “One would therefore expect a slow attenuation” of virulence if the virus becomes like seasonal flu. Dead people don’t transmit viruses, “and even people sitting in their beds and shivering” because they are seriously ill “don’t transmit that well,” he said.

The toll of a seasonal-flu-like coronavirus also depends on immunity — which is also scientifically uncertain. Exposure to the four endemic coronaviruses produces immunity that lasts longer than that to influenza, Webby said, but not permanent immunity. Like respiratory syncytial virus, which can re-infect adults who had it in childhood, coronavirus immunity wanes.

“Everyone, by the time they reach adulthood, should have some immunity to some coronavirus,” said Tim Sheahan, a coronavirus researcher at University of North Carolina’s Gillings School of Global Public Health. But because it doesn’t last, older people can get reinfected. The elderly also have a higher death rate from coronaviruses such as SARS and MERS, a pattern 2019-nCoV is following.

“There is some evidence that people can be reinfected with the four coronaviruses and that there is no long-lasting immunity,” Dr. Susan Kline, an infectious disease specialist at of the University of Minnesota. “Like rhinoviruses [which cause the common cold], you could be infected multiple times over your life. You can mount an antibody response, but it wanes, so on subsequent exposure you don’t have protection.” Subsequent infections often produce milder illness, however.

The common-cold-causing coronaviruses are different enough that an infection from one won’t produce immunity to another. But the novel coronavirus overlaps enough with SARS that survivors of the 2002-3003 outbreak might have some immunity to the new arrival,  Sheahan said: “Is it enough to prevent infection? I don’t know.”

How widespread even limited immunity would be, and therefore how many people would become ill from the next go-round of 2019-nCoV, also “depends on how many people get infected the first time around,” Webby said. That number is certainly higher than the more than 20,000 identified cases, since people with no or mild symptoms escape the attention of health care systems.

Since 2019-nCoV is new, “this first wave will be particularly bad because we have an immunologically naïve population,” Adalja said. Future waves should pass by people who were exposed (but not necessarily sickened) this time around, Morse said, “but that assumes this virus doesn’t develop the tricks of flu,” which famously tweaks the surface molecules that the immune system can see, making itself invisible to antibodies from previous exposures.

Odds: Pretty good. What we may be seeing “is the emergence of a new coronavirus … that could very well become another seasonal pathogen that causes pneumonia,” said infectious disease expert Michael Osterholm of the University of Minnesota. It would be “more than a cold” and less than SARS: “The only other pathogen I can compare it to is seasonal influenza.”

Helen Branswell and Andrew Joseph contributed reporting.

By Sharon Begley

“Could cause panic.” “Will not help end the crisis.” “Could backfire.”

When the Chinese government blocked most travel into and out of the city at the center of the Covid-19 outbreak in late January, many public health experts took to social media and op-ed pages to decry the measure as not only draconian and a violation of individual rights but also as ineffective: This largest quarantine in history — the city, Wuhan, has a population of 11 million, and the lockdown has been expanded — would have little effect on the course of the epidemic, they argued.

As the U.S. and other countries imposed travel restrictions, even the World Health Organization questioned whether they were a good idea. But early evidence is causing some disease fighters to reconsider.

The last few days have seen a perceptible flattening in growth of Covid-19 cases in China, raising hopes that the epidemic has peaked. (Though there are doubts about the accuracy of China’s count.) That supports the emerging consensus on the Wuhan quarantine in particular: that, at minimum, it bought China and the world time to prepare. Crucially, the time lag allowed public health agencies to devise and distribute a diagnostic test that hospitals can use to identify patients ill with the novel coronavirus.

“Measures on movement restriction have delayed the dissemination of the outbreak two or three days within China and a few weeks outside China,” Sylvie Briand, director of Infectious Hazard Management at the WHO, told reporters this week. “Those measures, if well implemented, could have an impact on the propagation of the outbreak.”

Scientists are still gathering data on the effect of travel restrictions and the historic quarantine — and, in particular, whether they reduced total cases and deaths or just postponed many of them without lowering the eventual cumulative toll. The answer will have broad consequences for future outbreaks, perhaps putting large-scale quarantines back on the list of health officials’ epidemic countermeasures, including in countries that value individual liberties more than China does.

“We should do what we can to understand their effectiveness, because [quarantines and travel restrictions] may be considered again in this epidemic and in future epidemics,” said preparedness expert Tom Inglesby, director of the Center for Health Security of the Johns Hopkins Bloomberg School of Public Health. “It’s important to know not only if they worked in some way but also to gauge if they did harm.”

There have, in fact, been numerous, and in some cases fatal, unintended knock-on effects of the quarantine, as critics warned. People were unable to reach sick, elderly parents in Wuhan, let alone take them out of the city for treatment of heart disease, cancer, diabetes, and other illnesses. This week, UNAIDS announced that one-third of people in China who are living with HIV reported that because of lockdowns and travel restrictions they were at risk of running out of their HIV medications within days. And China’s economy has slowed to a crawl.

The impact of the movement restrictions extends beyond Wuhan, to other areas in China as well as other countries getting a trickle of cases early this month rather than the flood they likely would have if Wuhan residents and visitors had been able to leave the city. As a result, they have been able to deploy countermeasures with deliberation and not in a rushed panic.

The quarantine “let countries field the fly balls coming at them one by one by one and not drop them,” said David Fisman of the University of Toronto, a leading epidemic modeler. “The fact that Wuhan got sealed off made the numbers something other countries could handle. They’ve been able to figure out things like how to identify cases and what to do with them. I think that made a huge difference.”

If thousands of infected people had traveled from Wuhan starting in late January, Fisman said, “every place new cases landed would have had the potential to be another Wuhan,” whose Hubei province is approaching 2,000 deaths.

Instead, health care systems in countries that have had cases (1,073 and counting outside China, according to WHO) had time to prepare, said Alexandra Phelan of Georgetown University’s Center for Global Health Science and Security: “Delays can be a really useful tool, and maybe one of the only tools you have, to implement screening and training for health care workers, and essentially get your house in order.”

Hospitals could have used the time to give their staffs refresher courses in infection control and practice using respiratory gear, said Inglesby (though it’s not clear how many in which countries did so). Agencies such as the U.S. Centers for Disease Control and Prevention had time to update and disseminate technical information, including the use of diagnostic kits.

“The ability to test for the virus has been distributed pretty widely,” including by the CDC to U.S. states and cities, Inglesby said. Testing capacity grew outside the U.S., too, he said: “Certainly more countries can test for the virus now than three weeks ago,” when without the Wuhan quarantine they might have faced a flood of cases, both suspected and real.

With the breathing room the quarantine provided, China has been able to plan or begin about 120 clinical trials of potential Covid-19 treatments, Inglesby added: “There has been time to acquire data on what medications might work,” including those currently in use for other diseases and therefore relatively available.

U.S. travel restrictions (barring most foreign nationals who have been in China recently from entering, requiring Americans returning from China to be quarantined or self-isolate) were, like the Wuhan quarantine, “really meant to slow down the spread” of the coronavirus, Health and Human Services Secretary Alex Azar, told reporters this month. “It’s not meant to hermetically seal the United States from the virus, but rather to allow us to focus our resources,” including by setting up the quarantine centers. “It’s about slowing spread.”

“I think most health officials agree that at best [quarantine or travel restriction] delays and … kind of pauses things,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told reporters. “What we needed was a delay to essentially prepare better.”

Experts are divided, however, on whether the Wuhan quarantine not only resulted in what the WHO’s Briand called “postponing the peak” of the epidemic — the time when the number of new cases tops out — but also in reducing the total number of cases and deaths.

“I haven’t seen anything that says the overall number of people infected in the world will be less” than without the Wuhan quarantine, Inglesby said.

The reason for pessimism is that although the quarantine reduced the rate of transmission and therefore the number of cases in any given time period, normal commercial activity and travel in China “has to resume at some point, so it’s hard to argue that the disease wouldn’t resume its trajectory,” Inglesby said. “No one has put forth the case that what China has done will eliminate this virus from Earth.” Sustained transmission, however, might look more like bad colds (as other coronaviruses cause) than like severe seasonal flu.

Experts who take a more sanguine view believe that slowing the spread and buying time for countermeasures did have a permanent effect on the epidemic, not only postponing what would have been today’s cases into next week but preventing some of those cases forever. If so, then the eventual toll would be less than without the Wuhan quarantine.

That and other control measures changed how many cases each infected person causes “big time,” Fisman said. The lower this “reproductive number,” the lower the total case count. The Wuhan quarantine, he said, “reduced the likelihood of people in Wuhan coming into contact with people not in Wuhan. The rate of transmission is now pretty flat. This is coming under control in other cities [outside Hubei] in China.”

Fisman’s and other mathematical models of the epidemic’s trajectory, however, are undermined by the fact that key numbers in the equations describing disease transmission (a “model” is essentially a group of equations solved by computers) are uncertain.

For instance, the time between when one infected person becomes ill and when someone he infects does was thought to be five to seven days. But an analysis led by Hiroshi Nishiura of Japan’s Hokkaido University suggests this “serial interval” is only four days.

That could be bad news because half the people who get sick do so less than four days after exposure to the virus that causes Covid-19. “A substantial proportion” of transmission may therefore occur before people show symptoms, Nishiura and his colleagues warned. “Pre-symptomatic transmission … may even occur more frequently than symptomatic transmission,” confounding control measures: If people can spread disease before they’re sick, then isolating only sick people won’t stop transmission.

In fact, physicians in China reported this week in the New England Journal of Medicine that a symptom-free individual had just as much virus (according to nose and throat swabs) as patients with symptoms — all set to be sneezed or coughed onto other people.

Although diseases that can be spread by people who aren’t sick are harder to control, there are hints that the worst of the Covid-19 outbreak in China is nevertheless past. Like several other models, three by researchers at Georgia State University School of Public Health projecting Covid-19 cases suggest that the outbreak is losing steam. Total cases in China outside Hubei should stay below 15,000 through the end of February, with little increase after that, the models say. (Projections for Hubei got scrambled when China changed the case definition for Covid-19, producing a sharp one-time uptick in case totals last week.)

As of Thursday, there were 12,644 Covid-19 cases in China outside Hubei.

“For all other provinces, the models are on track,” said mathematical epidemiologist Gerardo Chowell of Georgia State. “The containment strategies implemented in China are successfully reducing transmission,” he and his colleagues wrote in a paper published last week in Infectious Disease Modeling. “The epidemic growth has slowed.”

Chowell inclines toward optimism, he said: “I think that we’ll control this,” especially if the Covid-19 virus (like influenza and other viruses) doesn’t survive or spread as well in warm, humid conditions.

Barring secondary outbreaks (as happened with SARS, a coronavirus that spread around the globe in 2003), Chowell said, the Covid-19 epidemic in China might be over in three weeks. This pathogen might join the other four coronaviruses that give millions of people colds and, in some cases, pneumonia every year.

If it falls well short of an uncontrollable pandemic, quarantines and other measures widely viewed as ineffective and even counterproductive could well join the bag of tools used in future viral outbreaks.

Andrew Joseph contributed reporting.

By Sharon Begley

The new coronavirus is not an equal-opportunity killer: Being elderly and having other illnesses, for instance, greatly increases the risk of dying from the disease the virus causes, Covid-19. It’s also possible being male could put you at increased risk.

For both medical and public health reasons, researchers want to figure out who’s most at risk of being infected and who’s most at risk of developing severe or even lethal illness. With that kind of information, clinicians would know whom to treat more aggressively, government officials would have a better idea of steps to take, and everyone would know whether they need to take special, additional precautions.

Here’s what research has shown three months into the outbreak:

Old and young

The vast majority of cases in China — 87% — were in people ages 30 to 79, the China Center for Disease Control reported last month based on data from all 72,314 of those diagnosed with Covid-19 as of Feb. 11. That probably reflects something about biology more than lifestyle, such as being in frequent contact with other people. Teens and people in their 20s also encounter many others, at school and work and on public transit, yet they don’t seem to be contracting the disease at significant rates: Only 8.1% of cases were 20-somethings, 1.2% were teens, and 0.9% were 9 or younger. The World Health Organization mission to China found that 78% of the cases reported as of Feb. 20 were in people ages 30 to 69.

The death toll skews old even more strongly. Overall, China CDC found, 2.3% of confirmed cases died. But the fatality rate was 14.8% in people 80 or older, likely reflecting the presence of other diseases, a weaker immune system, or simply worse overall health. By contrast, the fatality rate was 1.3% in 50-somethings, 0.4% in 40-somethings, and 0.2% in people 10 to 39.

The age-related death risk probably reflects the strength, or weakness, of the respiratory system. About half of the 109 Covid-19 patients (ages 22 to 94) treated at Central Hospital of Wuhan, researchers there reported, developed acute respiratory distress syndrome (ARDS), in which fluid builds up in the small air sacs of the lungs. That restricts how much air the lungs can take in, reducing the oxygen supply to vital organs, sometimes fatally; half of the ARDS patients died, compared to 9% of patients who did not develop the syndrome.

The ARDS patients had an average age of 61, compared to an average age of 49 for those who did not develop ARDS. Elderly patients “were more likely to develop ARDS,” the researchers wrote, suggesting how age can make Covid-19 more severe and even fatal: age increases the risk that the respiratory system will basically shut down under viral assault.

Youth, in contrast, seems to be protective. The WHO mission reported a relatively low incidence in people under 18, who made up only 2.4% of all reported cases. In fact, through mid-January, zero children in Wuhan, the epicenter of the outbreak, had contracted Covid-19. It’s not clear whether that’s because children do not show signs of illness even if infected.

Even cases among children and teens aged 10 to 19 are rare. As of Feb. 11 there were 549 cases in that age group, 1.2% of the total, China CDC found. Only one had died.

One intriguing explanation for the apparent resilience of youth: in regions near Hubei province, young children seem especially likely to be exposed to other coronaviruses, scientists in China reported in 2018. That might have given them at least partial immunity to this one.

Men and women

The effect of sex on susceptibility to Covid-19 is less clear than the age effect, but preliminary data suggest men might be more susceptible. China CDC found that 106 men had the disease for every 100 women, while the WHO mission found that men make up 51% of cases. A study of 1,099 Covid-19 patients in Wuhan through Jan. 29 found a greater imbalance: 58% were male, the China Medical Treatment Expert Group for Covid-19 reported last week in the New England Journal of Medicine.

It’s possible the apparent sex imbalance reflects patterns of travel and contacts that make men more likely to be exposed to carriers of the virus, not any inherent biological differences. It’s also possible the apparent worse disease severity in men could skew the data. Among hospitalized patients, there is “a slight predominance of men,” U.S. researchers wrote last week in JAMA. If the virus hits men harder than women, health care systems will see, test, and count more men.

To determine if there are sex differences in susceptibility to infection would require an unethical experiment: expose 1,000 otherwise similar men and women to the virus and see who gets sick.

The difference is fatality rates, however, is real: 1.7% for women and 2.8% for men, China CDC reported.

Sick or healthy

The male-female difference in fatality rates, and perhaps in reported incidence, may arise from differences in underlying health. People with pre-existing illness are more likely to get seriously ill from Covid-19, and men have a higher incidence of such chronic illnesses as cardiovascular disease.

In the first large study of the effect of underlying illness, researchers in China analyzed 1,590 patients from throughout the country with laboratory-confirmed disease. They calculated how “co-morbidities” — existing illnesses — affected the risk of being admitted to intensive care, being put on a ventilator, or dying.

After taking into account the patients’ ages and smoking status, the researchers found that the 399 patients with at least one additional disease (including cardiovascular diseases, diabetes, hepatitis B, chronic obstructive pulmonary disease, chronic kidney diseases, and cancer) had a 79% greater chance of requiring intensive care or a respirator or both, or of dying, they reported last week in a paper posted to medRxiv, a preprint site that posts research before it has been peer-reviewed. The 130 with two or more additional diseases had 2.5 times the risk of any of those outcomes.

That fits with what’s known about other respiratory viruses. People with a single co-morbidity who catch avian flu (H7N9) are 3.4 times more likely than otherwise-healthy flu patients to require ventilators and other intensive care. SARS and MERS, which are also caused by coronaviruses, are more severe in patients with underlying illnesses, too.

Breaking down the Covid-19 risk with the most common co-morbidities, the scientists found that cancer raises the risk 3.5-fold, COPD 2.6-fold, and diabetes and hypertension by about 60%. Because it isn’t unusual for someone to have an underlying disease (especially diabetes and hypertension) but not know it, the last figure is likely an underestimate.

Co-morbidities also raise the risk of dying from Covid-19. China CDC’s analysis of 44,672 patients found that the fatality rate in patients who reported no other health conditions was 0.9%. It was 10.5% for those with cardiovascular disease, 7.3% for those with diabetes, 6.3% for people with chronic respiratory diseases such as COPD, 6.0% for people with hypertension, and 5.6% for those with cancer.

Underlying disease might change the course of Covid-19. During the height of the epidemic in Wuhan, 37 of 230 patients receiving dialysis for kidney failure at Renmin Hospital developed the disease. Even though none were sick enough to require intensive care or a mechanical ventilator, six of them died, for a very high fatality rate of 16%. Oddly, however, none of the six died of pneumonia, Renmin researchers reported. Instead, the causes of death were heart disease, stroke, and high blood levels of potassium (a result of kidney failure). The high fatality rate of Covid-19 in already-sick people might result not from the virus but from an exacerbation of existing disease.

About 60% of U.S. adults have at least one underlying health condition, Tom Frieden, former director of the U.S. Centers for Disease Control and Prevention, told reporters on Monday.

Pregnancy

In early February, Chinese state media reported that a woman infected with the virus gave birth to a baby who later tested positive for it. Newborns might become infected because of close proximity to a patient, like anyone else, but the case raised fears that a pregnant woman can transmit the virus to her fetus via the placenta.

Only one small study has investigated such “vertical transmission.” Scientists at Wuhan University found that, of nine pregnant patients infected with the virus (all had a caesarean section) in their third trimester, none seemed to pass the virus to their babies, all of whom scored at the top of the Apgar scale of newborn health.

As for the mothers, “Covid-19 seems not to be especially severe in pregnant women, at least based on the small number in this study,” the scientists wrote. That was somewhat surprising because pregnancy suppresses the immune system (so it doesn’t attack the fetus); pregnant women are more susceptible to respiratory pathogens than non-pregnant women. Nevertheless, none of the nine women developed severe Covid-19 pneumonia.

It may be that immuno-suppression is actually helpful. Some of the most serious symptoms of Covid-19 result from an immune system on the rampage rather than a lethargic one, Chinese scientists found: An extreme immune response called cytokine storm, a flood of immune cells and the biochemicals they produce, tears through lung tissue.