Coronavirus ‘spillovers’ more frequent than thought

University of Florida researchers have detected past instances of people becoming infected with a type of coronavirus that was until now thought only to be found in pigs.

The infections occurred between 2014 and 2015 and no known transmission to other people occurred. But the discovery marks the first time that any coronavirus strain from the subgroup that commonly infects pigs, known as deltacoronaviruses, has been found in humans. It also adds to growing evidence that coronaviruses common to animals may switch hosts and “spill over” into people more frequently than once thought.

The findings were published November 17 in Nature.

The good news is that most spillover infections are not serious and rarely lead to person-to-person transmission, says UF Emerging Pathogens Institute Director J. Glenn Morris Jr., M.D., M.P.H. & T.M., who is also the study’s senior author.

“What we’ve shown is that there is likely some movement back and forth with coronaviruses between animals and people,” Morris said. “It’s simply not detected most of the time because we don’t look for it.”

Coronaviruses are a diverse group of viruses known to infect most mammals, some birds and even a few amphibians. The coronavirus family is divided into four major groups, noted by the Greek letters alpha, beta, delta and gamma.

Conventional wisdom holds that only seven viruses from the alpha- and betacoronavirus groups infect people. Four of these cause common colds. The other three emerged in the past few decades from the betacoronavirus group, and they all cause serious and sometimes fatal respiratory diseases — Middle East respiratory syndrome, severe acute respiratory syndrome and COVID-19. Traditionally, it was thought that deltacoronaviruses infected only nonhuman animals.

“Finding a deltacoronavirus in humans challenges the basic concept that there are only a few coronaviruses capable of infecting people,” Morris said. “We don’t think this virus will take over the world, it’s not likely the next pandemic. But this does provide some idea as to the readiness of coronaviruses to gain mutations that let them infect us.”

The newly reported instances of human infection by a deltacoronavirus occurred in three Haitian children under the age of 10 between 2014-2015.

UF Emerging Pathogens Institute researchers have monitored infectious disease in Haiti’s Gressier region since 2013. The ongoing study began in the aftermath of the Haitian earthquakes and subsequent spread of cholera. When participating children come to their school’s clinic with fevers but no other symptoms linked to an obvious known illness, clinicians ask parents to allow their children to give a blood sample. The program has previously uncovered some unexpected pathogens.

In this case, the blood samples were collected from three children with fevers. But at the time the researchers were unable to identify a cause for their illness. All three children recovered.

It was not until the current pandemic that the research team reevaluated the samples and looked for an unknown virus as a possible cause. The samples had already tested negative for Zika, dengue, chikungunya and common respiratory viruses. But using laboratory techniques that inoculate cell culture with human plasma samples, the team observed changes in the cells consistent with a viral infection. Though it was clearly a virus, it was not one picked up by standard tests.

They then used advanced techniques to replicate the virus in the culture. Tests on genetic sequences from this process indicated it was a type of coronavirus. The team then used global databases containing viral genetic sequencing data and determined it was similar to known deltacoronaviruses found in pigs.

The study’s first author, John Lednicky, Ph.D., a research professor in the department of environmental and global health in the UF College of Public Health and Health Professions, said the research team thought outside the box to overcome the challenge of testing for an unknown virus.

“Traditional PCR technology is guided by a dogmatic view that ‘if you look, you find,’” Lednicky said. “But we merged classic virology with molecular approaches. My laboratory does this frequently, and we continually find viruses that are overlooked by standard tests.”

Samples from the children also revealed another twist: The infections were caused by two different genetic porcine (pig) deltacoronavirus strains. One strain, which caused infection in two children at the same school, closely matched sequences known from epidemics of deltacoronavirus in pigs in China. The other, isolated from a child at a different school, matched sequences known from deltacoronavirus epidemics in pigs in the United States. The two strains indicate that the virus was introduced separately on two occasions into Haiti, probably into pig populations, Morris says.

Both strains found in the Haitian children contained identical genetic mutations in areas related to the spike protein that enables coronaviruses to enter human cells. This means that nature figured out the exact same trick, independently, twice.

“It’s a nice example of convergent evolution,” Morris said. “Both strains underwent the necessary evolutionary changes to infect people. This is probably happening all the time. We’ve been lucky in that there have not been many outbreaks until the recent COVID-19 pandemic.”

The team recently reported a second and separate example of an animal coronavirus spillover into a person, this time from a strain known to infect dogs. That study was published in the journal Clinical Infectious Diseases. After isolating an unknown virus from a U.S. medical team member who had fallen ill upon returning from Haiti, the team demonstrated that it was closely related to a canine coronavirus but also contained genetic elements of coronaviruses known from cats and pigs.

The current COVID-19 pandemic shows that coronaviruses are a clear cause for public health concern. But the new research also offers broader context, and good news, of a sort.

“Coronaviruses are very common in the animal world,” Morris said. “What our observations say is that they probably move into human populations periodically, it’s just that most probably lack the critical genes to cause serious illness.”

Media contact: Ken Garcia at kdgarcia@ufl.edu or 352-265-9408