Coronaviruses Have Been Around For Centuries: What Differentiates COVID-19?

What to know about transmission, who is at risk and how to protect your patients

This article was originally published on Feb. 11, 2020. It has been updated to reflect rapidly evolving information about COVID-19. 

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In late January 2020, the World Health Organization declared the outbreak of the virus SARS-Cov-2 and the disease it causes COVID-19, an international public health emergency. The respiratory disease, first detected in Wuhan City, China, has over 93,100 confirmed cases and 3,199 fatalities across nearly 80 countries (as of March 4, 2020). 1

The surge in cases globally is due to the spread of the SARS-Cov-2 infection outside of China, but also reflected in those numbers is an increase in testing of new patients infected with the virus across the globe. In the U.S., for example, the Centers for Disease Control and Prevention (CDC) recommended more relaxed testing guidelines, compared with previous guidelines that were contingent on two factors: direct contact with someone with documented COVID-19 or recent travel from an area with high transmission rates of the disease.

The recent surge in cases in the U.S. is also associated with an outbreak in a long-term healthcare facility, “demonstrating the infectibility of this disease and also the need to have screening available to prevent exposure to our most vulnerable patient populations,” according to Frank Esper, MD, pediatric infectious disease specialist at Cleveland Clinic.

Access to testing will increase reported cases in the short term

“We should expect that reported cases will likely continue to rise in the short term,” says Dr. Esper. “Now that the Food and Drug Administration is allowing healthcare institutions to develop their own polymerase chain reaction [PCR] assays and the CDC is making these tests more available to state and local health departments, there will be greater capacity to detect infection.”

Testing for SARS-Cov-2 will ultimately help control disease transmission. Many people who present with non-severe symptoms may be unknowingly spreading the disease. COVID-19 has no truly pathognomonic feature that differentiates it from other viral infections like influenza, making access to this test essential to diagnose the disease.

Elderly patients and those with underlying heart or lung disease and diabetes have an elevated risk of severe infection. Additional cases may demonstrate that other patient groups, such as those with cancer, may also be more susceptible to developing the disease.

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. Genetically they are separated into four groups: alpha, beta, gamma and delta coronaviruses; only alpha and beta coronaviruses have been found to infect humans.2

The older human coronaviruses were first identified in the mid-1960s, but have likely circulated in humans for centuries. These include 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus) and HKU1 (beta coronavirus).3  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, SARS-Cov-2. 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.

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“This is what we saw with SARS in 2002-2003 and MERS in 2012 and likely what just happened with SARS-Cov-2,” 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 less-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 SARS-Cov-2, 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.

“Once these virus mutations allow transmission to humans, their survival becomes dependent on optimization of virus infection between 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 spread of the virus, like weather conditions 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. 4 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%.5

The virulence of SARS-Cov-2 remains to be seen, although it has demonstrated significant adaptability to spread from person-to-person in areas of outbreak and outpaced SARS in number of documented cases and fatalities. Dr. Esper cautions that the true number of infected patients will still take some time to confirm.

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 connectivity, for better and for worse.

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“It was a wake-up 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.

“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.”

What’s next?

There is currently no vaccine for COVID-19, 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. “Growing the virus to develop a viable vaccine candidate is an important step, but there are still many others.”

In the U.S, a clinical trial is investigating the use of remdesivir, a broad-spectrum antiviral drug, to treat COVID-19, but so far there are no data to validate its efficacy to treat this particular strain of the disease.

This rapidly evolving situation means clinicians should remain vigilant and up-to-date on public health guidelines, keeping in mind that there is still much more we are going to learn about this virus.

“At this point in time, there is no treatment. There is no vaccine. The best thing we can do is give everyone the information that they need on how to protect themselves, which will also aid in mitigating further spread,” says Dr. Esper.


  1. World Health Organization. Accessed February 7, 2020.
  2. Cui J, Li F, Shi ZL. Nat Rev Microbiol. 2019 Mar;17(3):181-192.
  3. Human Coronavirus Types. Accessed March 5, 2020.
  4. Centers for Disease Control and Prevention. Published December 6, 2017. Accessed February 7, 2020.
  5. Middle East respiratory syndrome coronavirus (MERS-CoV). World Health Organization. Published January 23, 2020. Accessed February 7, 2020.