MERS outbreak picks up pace in Middle East

Behind the news that the United States has had its first case of the deadly respiratory virus known as Middle East Respiratory Syndrome coronavirus, or MERS coronavirus, is a far more worrisome trend: Case numbers are exploding on the Arabian Peninsula. As doctors struggle to treat patients, scientists are rushing to answer some basic questions about the virus’s biology, whose answers could stop the virus from becoming a pandemic.

As far as anyone knows, the first human victims of MERS were a university student and a nurse, who both got sick and died in Jordan in the spring of 2012. In the two years between then and March 2014, public health officials recorded an average of 14 or 15 cases per month, for a total of 207 cases. Of those cases, 93 people died, making the mortality rate about 45 percent.

“If you do the math on the mortality rate of the virus and the number of people on the planet, it's scary,” says Ralph Baric, a virologist at the University of North Carolina at Chapel Hill who has long studied coronaviruses, including MERS and its cousin SARS.

The situation has only worsened recently. In April 2014 alone the MERS virus infected at least 217 people — more than in the previous two years combined — and killed 38, mostly in Saudi Arabia and the United Arab Emirates. Those countries have been focal points of the disease since early in the outbreak. And the first documented case in the United States was announced on May 2; the patient is a health care worker who had recently traveled from Saudi Arabia (SN Online: 5/2/14).

The World Health Organization has a team in Saudi Arabia attempting to determine why MERS has begun to spread so rapidly, says WHO spokesperson Tarik Jasarevic. Scientists have already ruled out one possibility: “There is absolutely no evidence that the virus has changed,” he said.

Part of the problem in explaining the deluge of cases is that no one is certain how people become infected, Jasarevic says. Both camels and bats have been found to carry related viruses, with camels regarded as the most likely source for human infections.

Now, researchers have discovered that dromedary camels carry live MERS viruses in their noses that can infect primate cells. Thomas Briese, a virologist and molecular geneticist at Columbia University and his colleagues report the finding April 29 in mBio. The evidence strengthens the case that camels may be a reservoir of infection. Previous studies had hinted that the dromedaries could be involved (SN: 4/5/14, p. 8), but fell short of demonstrating that the animals carry live viruses that can transmit to humans.

Even with the incriminating evidence, camels can’t be blamed for all MERS cases. Many people who have fallen ill were city dwellers who had no contact with camels, Briese says. And if camels were the primary source, he says, one might expect camel handlers or people who work at slaughterhouses or otherwise have intense contact with camels and their bodily fluids to be the people who get MERS most often. But that’s not the case, Briese says.

Instead, the virus most often attacks the old and already sick. Scientists are still trying to determine what makes some people more susceptible. Also unclear is exactly how the virus makes the leap from camel to human. Briese and his colleagues are testing camel meat, milk and urine as possible sources of the virus.

The method of transmission is just one of the fundamental questions scientists have yet to answer about MERS nearly a year and a half after its discovery. 

Researchers have learned that MERS uses a protein on its surface, known as the spike protein, to pick a particular lock and gain access to human cells. The lock is a protein known as dipeptidyl peptidase 4, or DPP4, that sits on the surfaces of cells (SN Online, 3/13/13). Many species make a version of DPP4, but the MERS virus can crack a limited number of those, including the versions made by humans, camels and bats. It can’t get past the DPP4 lock on the surfaces of cells from mice, rats or ferrets, says Vincent Munster, a virologist at the National Institutes of Health’s Rocky Mountain National Laboratories in Hamilton, Mont.

That’s a problem because it means those laboratory favorites can’t be experimentally infected with MERS. Munster and his colleagues discovered that the coronavirus can infect rhesus monkeys, however. The researchers can use the primates to test potential therapies. But the monkeys don’t completely mimic the human infection, Munster says, and “not that many labs can handle nonhuman primates.”

Finding a useful animal MERS model may be partially solved thanks to a team led by Stanley Perlman, a virologist and pediatric infectious disease specialist at the University of Iowa in Iowa City. Perlman and his colleagues devised a way to get mice to temporarily produce the human version of DPP4 in their respiratory tracts, the researchers reported in the April 1 Proceedings of the National Academy of Sciences. Mice that make human DPP4 can be infected with MERS coronavirus, enabling the researchers to learn how the immune system handles the virus.

Perlman’s group is genetically engineering mice to permanently replace their DPP4 protein with the human version. If all goes as planned, the mice should be available in November, Perlman says.

Other potentially good news surfaced when two groups of researchers reported April 28 in the Proceedings of the National Academy of Sciences and in the April 30 Science Translational Medicine that they had isolated human antibodies that could prevent the MERS virus from latching on to its target. The discovery raises the possibility that the antibodies could be used to treat MERS infections or to protect health care workers or close contacts of MERS patients from becoming infected with the virus, says Wayne Marasco, an immunologist and infectious disease specialist at Harvard Medical School in Boston, a coauthor of one of the reports.   

The study also suggests that healthy human immune systems can keep the MERS virus in check, Marasco says. During the course of the experiments, sometimes the virus developed mutations in its spike protein that allowed MERS to evade the antibodies’ grasp. “In cases where viruses could escape, they did so at the expense of their own fitness,” says Marasco. The mutated viruses either had a harder time grasping cells, which would make infection harder, or they grew less well in primate cells. Weakened viruses may be easy pickings for a strong immune system.

Unfortunately, many people who have contracted MERS already had other illnesses that may have damaged their ability to fight the virus. Each infected person is like a test tube where the virus can mutate; having more test tubes means an ever-increasing chance that the virus could become better at growing in humans. “A weakened immune system is clearly consistent with an environment where adaptation can occur,” says Marasco.

Many of the new cases in Saudi Arabia and the United Arab Emirates have been spread from a sick person to a health care worker, family member, hospital patient or another contact. People who caught the virus from someone else tend to have mild illnesses or no symptoms at all, Jasarevic says, and the virus rarely, if ever, transmits beyond the second person infected.

That’s an assertion that Trish Perl, an epidemiologist and infectious disease doctor at Johns Hopkins University, challenges. Perl traveled to Saudi Arabia last year to investigate a large MERS outbreak at hospitals. The researchers found evidence for long chains of person-to-person transmission of the virus, especially among dialysis patients (SN Online: 6/19/13). “It’s clear that there is a lot going on in the health care environment,” Perl says.

In the last month, health officials have reported a growing number of milder cases and cases with no symptoms. Some of those cases may have been detected thanks to better surveillance and it is possible that mild cases were missed earlier. The growing number of milder cases is also lowering the virus’s overall mortality rate to somewhere around 30 percent. That’s still a frightening number, Perlman says, but “it’s not as scary as it could be.”

He sees MERS as primarily a camel cold virus that sometimes leaps into susceptible people; proper precautions, he says, may make it disappear. “If you have good infection control measures and people stop getting so close to sick camels, there’s a good chance it will die out.”