A Brief History of Human Coronaviruses
A Brief History of Human Coronaviruses

A Brief History of Human Coronaviruses

Milder, cold-causing members of this pathogenic viral family long remained under the radar, although they aren’t entirely harmless.

Shawna Williams
Shawna Williams
Jun 2, 2020

ABOVE: MERS virus particles on the surface of an infected cell
FLICKR.COM, NIAID

On January 9 of this year, Chinese state media reported that a team of researchers led by Xu Jianguo had identified the pathogen behind a mysterious outbreak of pneumonia in Wuhan as a novel coronavirus. Although the virus was soon after named 2019-nCoV, and then renamed SARS-CoV-2, it remains commonly known simply as the coronavirus. While that moniker has been catapulted into the stratosphere of public attention, it’s somewhat misleading: Not only is it one of many coronaviruses out there, but you’ve almost certainly been infected with members of the family long before SARS-CoV-2’s emergence in late 2019. 

Coronaviruses take their name from the distinctive spikes with rounded tips that decorate their surface, which reminded virologists of the appearance of the sun’s atmosphere, known as its corona. Various coronaviruses infect numerous species, but the first human coronaviruses weren’t discovered until the mid-1960s. “That was sort of the golden days, if you will, of virology, because at that time the technology became available to grow viruses in the laboratory, and to study viruses in the laboratory,” says University of Texas Southwestern Medical Center pediatrician Jeffrey Kahn, who studies respiratory viruses. But the two coronaviruses that were identified at the time, OC43 and 229E, didn’t elicit much research interest, says Kahn, who wrote a review on coronaviruses a few years after the SARS outbreak of 2003. “I don't believe there was a big effort to make vaccines against these because these were thought to be more of a nuisance than anything else.” 

The viruses cause typical cold symptoms such as a sore throat, cough, and stuffy nose, and they seemed to be very common; one early study estimated that 3 percent of respiratory illnesses in a children’s home in Georgia over seven years in the 1960s had been caused by OC43, and a 1986 study of children and adults in northern Italy found that it was rare to come across a subject who did not have antibodies to that virus (an indicator of past infection).

Coronaviruses’ mild-mannered reputation changed with the SARS outbreak. Although related to OC43 and 229E, SARS-CoV was far deadlier, killing about 10 percent of people it infected—a total of 774 worldwide, according to the United Kingdom’s National Health Service. While it’s still unclear exactly where SARS-CoV came from, similar viruses were later found in bats, and some studies suggested the virus could have jumped to humans via an intermediary such as civets

See “Where Coronaviruses Come From

While SARS was a wake-up call that coronaviruses posed a greater risk to humans than had been thought, it’s unsurprising that a virus that’s newly spilled over to humans would be more deadly than its human-adapted cousins, says Rachel Roper, a virologist and immunologist at East Carolina University. “When a species is co-evolving with its pathogen . . . they tend to come to a detente, where the virus will be surviving in the population, and the population is surviving without that much illness,” she explains. “But when a virus jumps species, then you’ve got a real problem.”

In the wake of the SARS epidemic, some researchers went looking for other human coronaviruses—and found them. In 2004, researchers in the Netherlands reported they’d found a novel coronavirus, related to 229E, in a child with pneumonia and in four other people with respiratory disease. That virus came to be known as NL63, and Kahn and his colleagues found it at around the same time in hospitalized children in New Haven, Connecticut (Kahn worked at Yale University School of Medicine at the time). 

Although first identified in people with severe infections, NL63 is, much like 229E and OC43, a widespread virus that causes colds in most people it infects. But there were hints that its effects could extend beyond the respiratory tract. In their 2005 paper on the newly-discovered virus, Kahn and his colleagues reported finding it in 8 of 11 patients they tested who had Kawasaki disease, an inflammation of the blood vessels that occurs primarily in young children. But most follow-up studies failed to find such an association. 

“It could be that it was just chance,” Kahn says of his finding, or “there may be a signal there.” His 15-year-old study has acquired new salience in light of reports that COVID-19 is associated with Kawasaki-like symptoms in some children, but he cautions that this inflammatory syndrome has been defined slightly differently by different groups reporting on it, and isn’t identical to Kawasaki disease.

Close on the heels of NL63’s discovery came a report from Hong Kong on yet another common, cold-causing coronavirus, this one called HKU1. As with NL63, researchers in other parts of the world went looking for HKU1, finding it in Australia, France, and the United States, among other places. 

The cold-causing coronaviruses each carry a similar array of symptoms, says Kahn, and it’s not clear how long any of them have been hosted by humans, or where they came from originally. As ubiquitous as they are, other basic questions about these viruses also remain open, such as whether infection with one of them confers lasting immunity. Studies reported in two recent preprints found that it’s not uncommon for a person to be infected with the same coronavirus twice. But Roper suspects that our bodies do learn to fend off coronaviruses they’ve encountered. “There are literally thousands of respiratory viruses, so probably every time you get a cold, you’re getting a new virus that you’ve never seen before,” she says. “Plus, they’re always mutating.”

Until the emergence of SARS-CoV-2, human coronaviruses that have made the news have been both far more deadly and far more contained than their cold-causing counterparts. No cases of SARS have been detected since 2004, and Middle East respiratory syndrome coronavirus (MERS-CoV), first found in a patient in Saudi Arabia in 2012, has caused fewer than 2,500 confirmed cases worldwide, according to the World Health Organization—but it kills about 35 percent of people with confirmed diagnoses. SARS-CoV-2, which, as its name suggests, is closely related to SARS-CoV, appears to be far more transmissible, and its mortality rate has so far proven difficult to nail down, but many estimates land at around 1 percent

At this point, SARS-CoV-2 may not be containable, Roper says. “I’m a little worried that . . . it’s like closing the barn door after the horses are out.” If that’s the case, she says, the virus’s coexistence with humans will be less analogous to that of other coronaviruses than to illnesses like measles and polio: we’ll be stuck with it indefinitely, but will eventually have vaccines and treatments to mitigate its effects.

THE SCIENTIST STAFF

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Correction (June 4): The original version of this article incorrectly attributed the finding that SARS-CoV-2 is a coronavirus to a single person, and misidentified the affiliation of those who made the finding. The Scientist regrets the error.