Coronaviruses Have Been Around For Centuries: What Differentiates 2019-nCoV?

What to look for, what to know about transmission and what’s ahead

In late January 2020, the World Health Organization declared the outbreak of the 2019 novel coronavirus (2019-nCoV) an international public health emergency. Wuhan City, China, is at the epicenter of the pandemic, with over 40,400 cases and 900 fatalities confirmed worldwide (as of Feb. 10, 2020).1

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“The situation continues to evolve, but from what we know so far, community-wide transmission of this virus outside China, and mainly within the disease epicenter of Wuhan, has not been detected,” says Frank Esper, MD, pediatric infectious disease specialist at Cleveland Clinic. “Outside of China, transmission has been largely familial, or between individuals with very close and prolonged contact as evidenced by the spread of this virus on a cruise ship.”

It’s prudent, however, for clinicians to remain updated with guidelines from the Centers for Disease Control and Prevention and the World Health Organization. When screening patients, Dr. Esper says that providers should be aware of the following: “Are they symptomatic for fever and lower respiratory tract illness? Have they had recent travel to China or had close contact with someone who has been infected within the preceding 14 days? If the answer is yes to both of these questions, then we need to consider the possibility that they have been infected with 2019-nCoV,” he says.

A closer look at old and new coronaviruses

To better understand this coronavirus, Dr. Esper urges that we take a closer look at other strains, viewing them categorically as “old” and “new” in terms of how long they have been infecting humans. The older human coronaviruses were first identified in the mid-1960s, although they have likely circulated in humans for centuries. These include 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus) and HKU1 (beta coronavirus).2 For the most part, these older iterations present with a mild respiratory infection, except for HKU1, which can also cause gastrointestinal infection, he notes.

Dr. Esper refers to the newer coronaviruses as “true emerging infectious diseases.” These include SARS-CoV (SARS), MERS-CoV (MERS) and, of course, 2019-nCoV. He explains, “These are strains that have undergone recent animal-to-human transition.” This can happen when a virus either mutates directly to humans, or through a second (intermediary) species that then further mutates into a human pathogen.

“This is what we saw with SARS in 2002-2003 and MERS in 2012 and likely what is happening with 2019-nCoV,” he says.

For the most part, these viral mutations occur in animals — and predominantly stay in animals — but when the rare mutation allows transmission into humans, our immune systems are ill-equipped to manage the disease. “This is the case with these larger epidemics we have seen; although, it’s important to remember, just because a mutation is demonstrating human transmission, doesn’t mean it’s reproducing well,” he says.

In cases of MERS, SARS and 2019-nCoV, reproduction was successful enough to jump from animal-to-human and then from human-to-human, but that doesn’t mean it has evolved enough to become a persistent human pathogen.

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“Once these virus mutations allow transmission to humans, their survival becomes dependent on optimization of virus infection in humans.” A swift public health response can mitigate the likelihood of this, by limiting the spread of infection in humans and thus reducing the chance of new, more efficient viruses from emerging. In some cases, unpredictable variables may also work to suppress the mutation’s level of infectiousness, like weather or other circulating pathogens, as examples.

“We are still speculating why exactly SARS disappeared. One hypothesis is that while SARS was able to cause human-to-human transmission, the virus wasn’t able to go from one season to the next. It basically got its one winter transmission season then largely disappeared and never came back.”

To put the more modern coronaviruses in perspective, the case-fatality rate for SARS was 9.6%; the virus infected a total of 8,098 individuals during the 2003 outbreak and 774 of these cases were fatal. Unlike SARS, the MERS outbreak of 2012 continues to infect several dozen patients each year. The World Health Organization reports that since Sept. 2012, there have been a total of 2,494 confirmed cases and 858 fatalities, a case-fatality rate of 34.4%.3

The virulency of 2019-nCoV remains to be seen, although it has demonstrated significant adaptability to spread from person-to-person in areas of outbreak and recently outpaced SARS in number of documented cases and fatalities. Early reports estimate that it may have a basic reproduction number (R0) of 2.5,4 meaning that for every infected patient, at least two others on average are contracting the disease. Dr. Esper cautions that the true number of infected patients will still take some time to confirm.

“Until seroepidemiologic investigations are performed, which use an immunoassay to identify antibodies to specific antigens, we won’t have a firm understanding of how many people were infected or who was at the highest risk for infection,” he says. “I suspect we will start seeing that kind of information coming out over the next few months.”

Globalization and the ‘new’ coronaviruses

The “new” coronaviruses have also taught us a lot about infectious disease in an era of globalization.

It’s been almost 20 years since the SARS outbreak occurred. Dr. Esper stresses that this was a moment in infectious disease history that highlighted the implications of a pandemic in an era of increased global connectively, for better and for worse.

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“It was a wakeup call. We saw the virus’s ability to circulate very quickly across countries and into new global regions. On the other hand, we also saw a substantial collaborative response among countries and regions to halt and prevent the spread.”

The World Health Organization developed a global outbreak alert and response network shortly after the SARS outbreak. They have continued to strengthen these efforts to equip clinicians with tools and resources to manage patient care and provide real-time data and safety alerts to the public.

On the 2019 n-CoV Dr. Esper says, “Remember, the first infection was in early December 2019, and it was really only recognized as a problem later that month. We just got into February, we already know so much about it. We already have the genome. We already have tests to diagnose it. We already have an alert on what to do and how to prevent the spread.”

What’s next?

There is currently no therapy for the 2019 n-CoV, although development efforts are underway. Dr. Esper notes that making a vaccine is only a fraction of the job. “You have to make sure that the vaccine is safe, effective and can be stably transported to people who need it, not just in one country but across the world,” he says. “Making the protein and a viable vaccine candidate is an important step, but there are still many others.”

In the meantime, he cautions that clinicians in the U.S. stay vigilant and up-to-date on public health guidelines, keeping in mind that there’s still a lot more that we’re going to learn about this virus — and its genome could change again.

“It does stand to reason, however, that we are not playing catch-up as much with this virus as we were with the previous SARS and MERS coronaviruses or pandemic influenza, where by the time we recognized there was a new strain of the virus, it already spread elsewhere in the world.”

References

  1. World Health Organization. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed February 7, 2020.
  2. Centers for Disease Control and Prevention. https://www.cdc.gov/sars/about/fs-sars.html. Published December 6, 2017. Accessed February 7, 2020.
  3. Middle East respiratory syndrome coronavirus (MERS-CoV). World Health Organization. https://www.who.int/emergencies/mers-cov/en/. Published January 23, 2020. Accessed February 7, 2020.
  4. Burki TK. Lancet Respir Med. 2020 Feb 3. pii: S2213-2600(20): 30056-4.