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.

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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.”

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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.

A new type of coronavirus is responsible for the outbreak of respiratory illnesses that began in Wuhan, China December 2019. While experts are still unclear how exactly these viruses are transmitted, coronaviruses such as those that caused the SARS and MERS outbreaks in years past offer clues. Alex Hogan and Hyacinth Empinado/STAT

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.

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  • I see in Italy they are closing schools but wouldn’t it be smarter to close aeroports to stop people from contracting the virus?

    • Once the disease is imbedded, you’ve got to reduce transmissibility. That’s what Gabriel Leung suggested China do and that’s what they did outside of Wuhan. That means minimizing contact and educating public on hygiene, etc. No schools, work from home, no public gatherings.

      If you wait to long, you get Wuhan (or Iran). Italians are doing the right thing, but not quarantining China travelers created this problem.

      Michigan and Canada are making the same mistake.

  • Wake up Ron & Bob,

    What would be the ROI on these tansmision limting reducing tech logies compared to a cure or vaccine? How much can you charge for yet another face mask or respirator or IR thermometer? How much can ou charge for an effective antibiotic (e.g., hopefully GIlead’s remdesivir) or a first effect vaccine? Where is the insurance company’s take or a doctor’s take on mere new technological devices? No windfall profit, then why invest?

    • What part of Global Pandemic do you not understand? The releease that clearly identified a bioweapons lab as the source. A vaccine made by fellow Chu’s is the last thing anyone needs from China! BUY A VOWEL or two, f_ck Ch_na and anyone from that, “Sh_t H_le C__ntry!”

  • If the four milder coronaviruses that we already have, that cause cold-like symptoms, are “new”, I mean if they arrived in the last century, does that mean that mankind has seen an increase in the number of upper-respiratory illnesses that we had a century ago. Is it possible that the advances in medicine we have seen in fighting pneumonia and the flu: antibiotics, vaccines, and Tamiflu – are being counterbalanced by more and more common upper respiratory infections that we can catch. I’ve read that the Native Americans had almost no immunity to colds and flus because they hadn’t really existed in the Americas before the European contact. Why? Because there was no animal husbandry in the Americas before Columbus, no cows, swine, chickens or ducks etc..
    Would a new coronavirus, that is more dangerous than influenza, become a recurring Winter burden for people? Does that mean that as we have advanced our medicine and science we haven’t really been paying attention as our numbers and our reach into the natural world has been increasing the number of illnesses we have to contend with. And if that is the case will this continue until the infections we can catch totally counterbalance any advances we have made in medicine. What is the good of vaccines and antibiotics when we are sick most of Winter with something.

    • Well a look back at my own family history, or a walk through any older cemetery, reveals an age where whole families were wiped out by diseases we do have under control now. 150 years ago it was just typical to have 8 kids born but only 4 or 5 survived to adulthood. I can’t imagine how sad it must have been to have an epidemic sweep through town and watch 3 of your kids die, one after another over a matter of days. I’ll happily catch a cold 3 times per winter, thank you.

  • We used to fear lions, tigers, and bears. Now we have pangolins, iguanas and bats. Off to see the Wizards of China, who let out the flying monkeys. Willing to wager a vaccine has your name on it???

  • Bob Green, your thoughts are exactly right on the mark. I have found few people willing to even consider capital investment’s into technologies to slow transmission. This will get much worse, with all the mis-information floating around.

  • How can these professional epidemiologists says this will be become “just another coronavirus” or similar to endemic influenza when the fatality rate is up to 100 times higher? The transmission rate much greater than flu as well.

    The fatality rate could just as well be higher than 2.5% – we won’t know anything until this virus becomes widespread in countries with open governments. No data coming from China can be trusted, and they continue to prevent outside experts from doing any significant work in the country.

    If the fatality rate continues to hold at 1% or higher, with transmission rates higher than influenza, and asymptomatic transmission, then public life in the USA may never be the same. What the experts should be saying is “we haven’t seen a threat this dangerous in 100 years, and we don’t know how bad it’s going to get. Governments and health care corporations should immediately begun increased manufacture of supplies and equipment like ventilators and protective gear” and we’re not hearing that at all.

    • Need local testing badly. The CDC can’t deliver it’s tests to the states, but at least on private company has applied for FDA EUA, and more are coming. The FDA is slow and very bureaucratic, however, so not too hopeful there.

    • Pretty hard to tell the transmission rate at this point I should think. But of course the death rate will be higher when our immune systems are inexperienced with it, than what the death rate would be the 10th time it went around the globe. That is the difference… we have pre-existing resistance, or we don’t.

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