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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?

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“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.”

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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.

  • Lets say there would be a treatment or some kind of a cure for it …how will it reach other countries that fast ? other countries that are even playing dumb all of this time and never tell their people if there is actually any cases or not ? or if they are taking good measures ..like in Turkey , they never like NEVER said a word in the news or anything about corona virus till now .

    • Sasha,

      Remember Avian and Swine flu? Heard about Tamiflu (invented by GIlead nd manufactured and sold by Roche)?

      Once available widely, it would be up to each country and its government to “stockpile”.

      Heard or read about Remdesevir? Gilead file for and has the patent globally. China filed for it in China recently. Fully cognizant of the fa that China has hundred of generic firms able to rapidly and cheaply synthesize and scale up any API (active pharmaceutical ingredient). Know anything about compulsory license to manufacture? I am, sure Gilead would voluntarily or would be compelled by the Chinese government to do so (with revenue royalties, at X% of the sal,e from the generic firms to GIlead).

      That’s the way it goes in the global pharmacuetical industry!

  • Most domesticated cats are exposed to coronaviruses shortly after they’re born. The only kittens that are killed by it are the ones who don’t get enough colostrum, such as kittens that are orphaned or abandoned by their mothers. If the immune system is unable to combat the infection quickly, the coronavirus can mutate into a deadly strain that causes feline infectious peritonitis, which is almost always fatal.

    • William,

      I certainly hope you are not hypothesizing or speculating that te current Coronavirus in China did not :mutate” from domesticated feral kittens. If that is the case, we got a huge problem globally! Did you alert the SPCA in the US?

    • I am not implying anything other than we might learn more about coronavirus infection by studying it in other species. Since viruses are nothing more than bundles of DNA looking for host cells, I doubt that cats and humans can be infected by the same strains of coronavirus due to the fact that our genomes are so different.

  • I’m not in your field but understand the basics.

    There is a lot of speculation and a degree of assumprions both science based and social commentary on this issue, but I have some questions.

    If a person in one hospital bed has one strain of a mutating corona virus and on either side of this patient are two patients with different strains ( mutated ) strains of the virus, could the patients all just simply reinfect each other and if so with this particular virus what would be the likely rate of severe complications and or likely RO rate?

    If the answer is in the affirmative on each question, what would be the likely survival rate be for 1000 people in lines of beds in a gymnasium be?

    Current WHO advice states it’s ok for travel and commerce to continue between China and other countries provided key infected regions are avoided. The more recent WHO advice seems to contradict that position as talk of a pandemic gains traction. I note in Articles in relation to the virus from India 2 very important factors affecting their capacity to contain the virus. One is identifying the virus itself. Karel I understand has a modern hospital system equal to world standards and they have 3 cases. With only a handfull of hospitals in India at this standard and the rest sitting 112 in the global standard how will the global community feel confident that the virus ( and mutations) will be adequately addressed, let alone adequately recorded?

    On that issue the Indian Government has actively encouraged it’s citizens to treat infections with traditional remedies in absence of an effective means to dispense the yet to be found treatments. The scientists have already debunked Chinese traditional medicines. With the RO rating claim of 2 derived from the Chinese data ( which is widely questioned in scientific circles) what will be the likely RO rate of deaths be in India and indeed countries of equally poor health services?

    Science since the SARS outbreak has taken giant leaps in virology. SARS by all accounts was a very different coronavirus and at a time China’s specialist skills were in their infancy where a higher death toll was inevitable. Why do people continue to refer to SARS or is it simply a case that to some this obscure benchmark has a feel good nature about it at the same time creating media interest from an industry notorious for fueling unqualified specilation, assumptions and drama and very few facts?

    Answrs or comments would be appreciated.

  • Oh my God, this is scary. I was hoping come summer and thos nightmare ends. With a family member who is on immunosuppression drugs, I feel petrified of the scenario where this monster lurks.

  • David,

    These numbers are well established globally and are thus simple and true facts, regardless of how they may sound:

    National Health Commission (China) Update on February 08, 2020

    From 00:00 to 23:59, February 07, 2020, the National Health Commission (NHC) received confirmed reports from 31 provincial-level administrative divisions (PLADs) and Xinjiang Production and Construction Corp (XPCC) of novel coronavirus-infected pneumonia (NCIP). A total of 34,546 cases were confirmed in China (of which Heilongjiang Province have reexamined and reduced the number of reports by 14), including 6,101 severe cases and 722 deaths. A total of 2,050 patients have recovered and have been discharged. An additional total of 27,657 suspected cases were reported.

    Thus, we all know that the average incubation period is 14 days. So with any doubt, go see a doctor and be careful and monitor your initial symptoms (fever, cough, running nose, body ache, muscle ache, diarrhea, etc.) Do not travel to China. Do not come in close contact with any Chinese or any other person who returned from China in the last two months.

    No from the latest official numbers, if you are diagnosed, then you have about 9 % chance (3,101 out of 34,546) of progressing into severe. Once you have become one of the severe cases, then the mortality rate is 23.3%% (722 out of 3,101). Yes, that number sucks. But You have 66% (2,050 out of 3.101) chance of discharge & recovery. So the key is get diagnosed early, get hospitalized get all the supportive treatment you need there, then pray you don’t progress to severe. Once at severe, then beg, bribe, and appeal to be treated by GIlead’s remdisivir and hope for the best.

    • Only fools believe the PRC and the lies they are spouting. Because the numbers are lies, any analysis done from them is worthless. I hope you didn’t waste too much time on it.

    • “Do not come in close contact with any Chinese or any other person who returned from China in the last two months.”

      You need to be very careful with your words here, as it seems like you are stigmatizing Chinese people. It would be fine to say to avoid contact with any person who was recently in China. There is no reason to avoid people just because they are Chinese. I realize you are Chinese yourself, and my experience has been that some of the most stigmatizing and harmful statements have come from Chinese expats and American-born Chinese. I am close to the Chinese community in my American city and sadly many important community events have been canceled indefinitely because Chinese are irrationally afraid of associating with each other, regardless of the fact that they have not been in China for months or years.

  • Tokyo Rose Adam? Why do you assume I am Japanese? I am pure breed Chinese but I speak fluently both Japanese an Chinese. My graduate degree is in Microbiology minoring in virology and molecular biology. I also have >30 years stint spanning across three major biopharmceutial firms with the last one being Gilead before I retired. So I would like to think I know a lot about the drug industry, Gilead, virology, and remdesivir! How about you? Anything? I am ready to be impressed!

    • Thanks For the nice insight ..
      My opinion would be that with the heat increase towards late march and April beginning the transmission of the virus would stop as its heat sensitive..further the flu shot may provide some antiviral protection due to cross protection against virus ..

  • IMO unless any mutations result n the following, it is not much of a cocern.

    1. Virulence – thus making it more lethal.

    2. Transmissiblity – if it now enables transmission via fecal matter (already being hyhpothezied) or maternal to baby (also being intensely questioned due to one newborm in CHina Wuhan hospital with positive Coronavirus diagnosis).

    4. Resistance to remdesevir, the only drug that is being tested in two clinical studies in China.
    3. Species e.g., umping to pet animals such as cats or dogs.

    • Many trials in China at the moment. Some are struggling to operate given the absolute chaos.

      Gilead pumping out the remdesivir. They know it works. Cocktail it with what drugs, though.

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