№ 572. The Endgame: How Will the Pandemic End?

This is a long read, written in March 2020 at the beginning of the pandemic just after the borders were closed. Quite prophetic.

Three endgames:

1. One that’s very unlikely;

2. One that’s very dangerous; and, 

3. One that’s very long.

 

Even a perfect response won’t end the pandemic. As long as the virus persists somewhere, there’s a chance that one infected traveler will reignite fresh sparks in countries that have already extinguished their fires. This is already happening in China, Singapore, and other Asian countries that briefly seemed to have the virus under control. Under these conditions, there are three possible endgames: one that’s very unlikely, one that’s very dangerous, and one that’s very long.

The first is that every nation manages to simultaneously bring the virus to heel, as with the original SARS in 2003. Given how widespread the coronavirus pandemic is, and how badly many countries are faring, the odds of worldwide synchronous control seem vanishingly small.

The second is that the virus does what past flu pandemics have done: It burns through the world and leaves behind enough immune survivors that it eventually struggles to find viable hosts. This “herd immunity” scenario would be quick, and thus tempting. But it would also come at a terrible cost: SARS-CoV-2 is more transmissible and fatal than the flu, and it would likely leave behind many millions of corpses and a trail of devastated health systems. The United Kingdom initially seemed to consider this herd-immunity strategy, before backtracking when models revealed the dire consequences. The U.S. now seems to be considering it too.

The third scenario is that the world plays a protracted game of whack-a-mole with the virus, stamping out outbreaks here and there until a vaccine can be produced. This is the best option, but also the longest and most complicated.

It depends, for a start, on making a vaccine. If this were a flu pandemic, that would be easier. The world is experienced at making flu vaccines and does so every year. But there are no existing vaccines for coronaviruses—until now, these viruses seemed to cause diseases that were mild or rare—so researchers must start from scratch. The first steps have been impressively quick. Last Monday, a possible vaccine created by Moderna and the National Institutes of Health went into early clinical testing. That marks a 63-day gap between scientists sequencing the virus’s genes for the first time and doctors injecting a vaccine candidate into a person’s arm. “It’s overwhelmingly the world record,” Fauci said.

But it’s also the fastest step among many subsequent slow ones. The initial trial will simply tell researchers if the vaccine seems safe, and if it can actually mobilize the immune system. Researchers will then need to check that it actually prevents infection from SARS-CoV-2. They’ll need to do animal tests and large-scale trials to ensure that the vaccine doesn’t cause severe side effects. They’ll need to work out what dose is required, how many shots people need, if the vaccine works in elderly people, and if it requires other chemicals to boost its effectiveness.

“Even if it works, they don’t have an easy way to manufacture it at a massive scale,” said Seth Berkley of Gavi. That’s because Moderna is using a new approach to vaccination. Existing vaccines work by providing the body with inactivated or fragmented viruses, allowing the immune system to prep its defenses ahead of time. By contrast, Moderna’s vaccine comprises a sliver of SARS-CoV-2’s genetic material—its RNA. The idea is that the body can use this sliver to build its own viral fragments, which would then form the basis of the immune system’s preparations. This approach works in animals, but is unproven in humans. By contrast, French scientists are trying to modify the existing measles vaccine using fragments of the new coronavirus. “The advantage of that is that if we needed hundreds of doses tomorrow, a lot of plants in the world know how to do it,” Berkley said. No matter which strategy is faster, Berkley and others estimate that it will take 12 to 18 months to develop a proven vaccine, and then longer still to make it, ship it, and inject it into people’s arms.

It’s likely, then, that the new coronavirus will be a lingering part of American life for at least a year, if not much longer. If the current round of social-distancing measures works, the pandemic may ebb enough for things to return to a semblance of normalcy. Offices could fill and bars could bustle. Schools could reopen and friends could reunite. But as the status quo returns, so too will the virus. This doesn’t mean that society must be on continuous lockdown until 2022. But “we need to be prepared to do multiple periods of social distancing,” says Stephen Kissler of Harvard.

Much about the coming years, including the frequency, duration, and timing of social upheavals, depends on two properties of the virus, both of which are currently unknown. First: seasonality. Coronaviruses tend to be winter infections that wane or disappear in the summer. That may also be true for SARS-CoV-2, but seasonal variations might not sufficiently slow the virus when it has so many immunologically naive hosts to infect. “Much of the world is waiting anxiously to see what—if anything—the summer does to transmission in the Northern Hemisphere,” says Maia Majumder of Harvard Medical School and Boston Children’s Hospital.

Second: duration of immunity. When people are infected by the milder human coronaviruses that cause cold-like symptoms, they remain immune for less than a year. By contrast, the few who were infected by the original SARS virus, which was far more severe, stayed immune for much longer. Assuming that SARS-CoV-2 lies somewhere in the middle, people who recover from their encounters might be protected for a couple of years. To confirm that, scientists will need to develop accurate serological tests, which look for the antibodies that confer immunity. They’ll also need to confirm that such antibodies actually stop people from catching or spreading the virus. If so, immune citizens can return to work, care for the vulnerable, and anchor the economy during bouts of social distancing.

Scientists can use the periods between those bouts to develop antiviral drugs—although such drugs are rarely panaceas, and come with possible side effects and the risk of resistance. Hospitals can stockpile the necessary supplies. Testing kits can be widely distributed to catch the virus’s return as quickly as possible. There’s no reason that the U.S. should let SARS-CoV-2 catch it unawares again, and thus no reason that social-distancing measures need to be deployed as broadly and heavy-handedly as they now must be. As Aaron E. Carroll and Ashish Jha recently wrote, “We can keep schools and businesses open as much as possible, closing them quickly when suppression fails, then opening them back up again once the infected are identified and isolated. Instead of playing defense, we could play more offense.”

Whether through accumulating herd immunity or the long-awaited arrival of a vaccine, the virus will find spreading explosively more and more difficult. It’s unlikely to disappear entirely. The vaccine may need to be updated as the virus changes, and people may need to get revaccinated on a regular basis, as they currently do for the flu. Models suggest that the virus might simmer around the world, triggering epidemics every few years or so. “But my hope and expectation is that the severity would decline, and there would be less societal upheaval,” Kissler says. In this future, COVID-19 may become like the flu is today—a recurring scourge of winter. Perhaps it will eventually become so mundane that even though a vaccine exists, large swaths of Gen C won’t bother getting it, forgetting how dramatically their world was molded by its absence.

 

Whittier Daily News