The Global Battle to Force the Coronavirus Below Its Tipping Point
(Bloomberg Businessweek) -- The difference between a global pandemic and a short-lived outbreak is the number 1. That’s the tipping point of epidemiology. If each case of the novel coronavirus from Wuhan, China, leads to more than one additional infection, the disease will continue to spread. If each case leads to less than one additional infection, it will stop spreading and then slowly but surely fade away. It’s that simple.
Almost everything being done to fight the new virus—the face masks, quarantines, travel limitations, crash development of a vaccine—can be thought of as part of an effort to push the “reproductive number” of the virus from above 1 to below that tipping point.
The one exception is the necessary effort to save the lives of people already infected, which exposes health-care workers to great risk of infection. But even there, treating the sick rather than simply isolating them may help reduce the reproductive number by persuading more sick people that it’s safe to come forward and seek help.
Will the effort to slow the new virus succeed? Probably. However, success depends not only on what people do, but also on the characteristics of the virus itself, which are still not fully understood. “It’s all about the virus,” says Dr. Mark Denison, director of the division of pediatric infectious diseases at Vanderbilt University School of Medicine. “It’s all about the bug. We’re along for the ride and responding as best we can.”
Viruses are simultaneously dumb—so dumb that they can’t reproduce on their own, instead hijacking the reproductive machinery of the cells they attack—and wicked smart. They evolve to thwart every weapon against them. “It’s our ingenuity vs. their biological ingenuity,” says C. Brandon Ogbunu, a professor of ecology and evolutionary biology at Brown University. “They are unquestionably the greatest threat to Homo sapiens, except for other people, and probably will continue to be for the duration of our existence.”
The reproduction number of a virus is highest when it attacks a population that has no immunity because it has never been exposed to the virus or anything resembling it, and nothing is done to control the spread. This is the basic reproduction number, also called “R-nought,” spelled R₀. For measles, which is highly contagious, R-nought is a shocking 12 to 18. Severe acute respiratory syndrome, or SARS, which broke out in 2003, infecting more than 8,000 people and killing 774, had a basic reproduction number of 2 to 5. The novel coronavirus is probably in that range because it’s structurally similar to SARS, scientists say.
Something always happens to lower the reproduction number from its basic starting point, which is why every pandemic in history has come to an end. Public-health safeguards such as face masks and hand-washing can reduce transmissibility. A vaccine can give protection. Even if there’s no vaccine, some percentage of the people who are exposed will survive and acquire immunity. As long as a big enough share of people have some immunity, the susceptible people in their midst will be shielded. But a lot of people have to die before herd immunity kicks in, as in the Spanish flu pandemic of 1918, which is why it’s far better to nip an outbreak in the bud, before most people are exposed, says Dr. Peter Palese, chairman of the microbiology department at Icahn School of Medicine in New York.
One reason the coronavirus’s reproductive number remains above 1 so far is that it has a long incubation period, averaging about 10 days and ranging up to 14 days, according to Chinese health authorities. That makes it hard to contain its spread: People who are infected can travel while asymptomatic and then get sick and begin spreading the disease in new locations.
Also scary is that the new coronavirus, while killing some people, makes others only mildly ill. They can spread the disease widely while going about their daily business, possibly not even realizing they harbor the virus. That would make the new virus like influenza—which each year kills about half a million people, according to the World Health Organization.
Whether people can be contagious while showing no symptoms at all is a separate issue. That, of course, would make the reproduction number even higher. Ma Xiaowei, director of China’s National Health Commission, said on Jan. 26 that, “from our observations, the virus can be contagious during the incubation period.” But U.S. authorities haven’t seen the data on that. Even if there are rare instances of asymptomatic transmission, they’re unlikely to become a major factor in the spread, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told reporters on Jan. 28. “Asymptomatic transmission has never been the driver of outbreaks” for any respiratory virus, he said.
Transmission of respiratory viruses occurs mainly from coughing, sneezing, and contact with hands and infected surfaces, so it makes sense that the respiratory viruses are less contagious before the patient is coughing, sneezing, and wiping the nose, says Dr. Thomas Birch, an infectious diseases specialist who is medical director of the Institute for Clinical Research at Holy Name Medical Center in Teaneck, N.J. On the other hand, influenza is somewhat contagious before symptoms show. Simply speaking can project viral particles.
Driving a disease’s reproduction number below the tipping point of 1 isn’t always a permanent victory. Influenza, for one, comes back every year in a different guise. One reason is that there’s a reservoir of the virus in livestock and other animals that live close to human beings in large numbers, making it easy for new strains to make the interspecies leap, says Brown’s Ogbunu.
Some scientists say that the novel coronavirus has its natural home in bats, which aren’t as much in contact with people as, say, cattle. That’s the good news, Ogbunu says. The bad news is that the virus may have passed from bats to people, possibly via other animals, in live-animal markets in Wuhan. In such markets, exotic species that would never come in contact in the wild are exposed to one another.
While viruses are dumb, evolution is smart. As Charles Darwin taught, mutations are random and thoughtless. Some by chance make an organism fitter. Those survive, while the rest perish. RNA viruses, of which the coronavirus is one type, are notoriously sloppy at reproducing, which means they mutate rapidly. The fact that the vast majority of mutations are failures doesn’t matter—the few that make the virus more successful quickly take over.
Coronaviruses mutate less rapidly than other RNA viruses because they have a genome that’s two to three times bigger than other RNA viruses and thus more complex, so accuracy in reproduction is more important for them. They are the only RNA virus family with a “proofreading” capability, says Vanderbilt’s Denison. But he and others demonstrated that the proofreading function seems to switch off if coronaviruses are under evolutionary pressure—as they would be, say, from an antiviral drug—which allows for more mutations and more rapid adaptation.
One promising way to attack the new coronavirus is to interfere with its proofreading. Locking in the proofreading function could make the virus unadaptable and thus easier to attack. Getting rid of the proofreading altogether could cause it to mutate so much that it essentially falls apart. That’s the angle Denison’s team is investigating.
It takes more than a village to fight a dangerous new virus. Ogbunu, for one, says he got interested in viruses after witnessing the cataclysm of the AIDS epidemic. He earned a bachelor’s degree at Howard University and then went on for a doctorate at Yale and postdoctoral training at Harvard before moving to Brown. On his website he relates some of his previous jobs: “bouncer, usher, statistics tutor, nanny, data scientist, personal trainer and light heavyweight boxer.” All that time, the vast power of tiny viruses never ceased to amaze him.
“The great paradox of this thing,” he says, “is that they are really just a vanishingly small fraction of the biomass on earth.”
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