What if immunity to covid-19 doesn’t last?

Further out, though, changes like social distancing or grounding airline flights may not be the biggest factor in our fate. Whether or not people acquire immunity to the virus, and for how long, will be what finally determines the toll of the disease, some researchers say.

Early evidence points to at least temporary protection against reinfection. Since the first cases were described in China in December, there has been no cut-and-dried case of someone being infected twice. While some people, including in South Korea, have tested positive a second time, that could be due to testing errors or persistence of the virus in their bodies.

“There are a lot of people who were infected and survived, and they are walking around, and they don’t seem to be getting reinfected or infecting other people,” says Mark Davis, a researcher at Stanford University. As of April 26, more than 800,000 people had officially recovered from the disease, according to the Johns Hopkins case-tracking dashboard.

Researchers in China also tested directly whether macaque monkeys resisted a second exposure to the new coronavirus. They infected the monkeys with the virus, and then four weeks later, after they recovered, tried again. The second time, the monkeys didn’t develop symptoms, and researchers couldn’t find any virus in their throats.

What’s unknown is how long immunity lasts—and only five months into the outbreak, there is no way to know. If it’s for life, then every survivor will add to a permanent bulwark against the pathogen’s spread. But if immunity is short, as it is for the common coronaviruses, covid-19 could set itself up as a seasonal superflu with a high fatality rate—one that emerges in a nasty wave winter after winter.

The latest computer models of the pandemic find that the duration of immunity will be a key factor, and maybe the critical one. One model, from Harvard University and published in Science, shows the covid-19 virus becoming seasonal—that is, staging a winter resurgence every year or two as immunity in the population builds up and then ebbs away.

After testing different scenarios, the Harvard group concluded that their projections of how many people end up getting covid-19 in the coming years depended “most crucially” on “the extent of population immunity, whether immunity wanes, and at what rate.” In other words, the critical factor in projecting the path of the outbreak is also a total unknown.

Seasonal virus

Because so many other human coronaviruses are mild, they haven’t gotten the same attention as influenza, a shape-shifting virus that is closely followed and genetically analyzed to create a new vaccine each year. But it’s not even known, for instance, whether the common coronaviruses mutate in ways that let them evade the immune system, or whether there are other reasons immunity is so short-lived.

“There is no global surveillance of coronavirus,” says Burtram Fielding, a virologist at the University of the Western Cape, in South Africa, who tracks scientific reports in the field. “Even though the common cold costs the US $20 billion a year, these viruses don’t kill, and anything that does not kill, we don’t have surveillance for.”

The Global Virome Project in Manhattan, led by Shaman with funding from the Defense Department, has been an exception. It set out to detect respiratory viruses with the eventual aim of “nowcasting,” or having a live tracker on common infections circulating in the city.

One finding of the research is that people who got the same coronavirus twice didn’t have fewer symptoms the second time. Instead, some people never got symptoms at all; others had bad colds two or three times. Shaman says the severity of infection tended to run in families, suggesting a genetic basis.  

The big question is what this fizzling, short-lived resistance to common cold viruses means for covid-19. Is there a chance the disease will turn into a killer version of the common cold, constantly out there, infecting 10% or 20% of the population each year, but also continuing to kill one in a hundred? If so, it would amount to a plague capable of shaving the current rate of world population growth by a tenth.

Some scientists find the question too dark to contemplate. Shaman didn’t want to guess at how covid-19 will behave either. “Basically, we have some unresolved questions,” he wrote in an email. “Are people one and done with this virus? If not, how often will we experience repeat infections? Finally, will those repeat infections be milder, just as severe, or even worse?”

Immune surveys

Big studies of immunity are already under way to try to answer those questions. Germany has plans to survey its population for antibodies to the virus, and in North America, 10,000 players and other employees of Major League Baseball are giving pinprick blood samples for study. In April, the US National Institutes of Health launched the COVID-19 Pandemic Serum Sampling Study, which it says will collect blood from 10,000 people, too.

By checking for antibodies in people’s blood, such serosurveys can determine how many people have been exposed to the virus, including those who had no symptoms or only mild ones.

Researchers will also be scavenging through the blood of covid-19 cases in order to measure the nature and intensity of immune responses, and to figure out if there’s a connection to how sick people got. “What we are seeing right now with the coronavirus is the need for immune monitoring, because some people are shrugging this off and others are dying,” Davis says. “The gradient is serious and no one really understands why.”

Our immune system has different mechanisms for responding to germs we’ve never seen before. Antibodies, made by B cells, coat a virus and don’t let it infect cells. T cells, meanwhile, regulate the immune response or destroy infected cells. Once an infection is past, long-term “memory” versions of either type of cell can form.

What sort of immune memory will covid-19 cause? Stephen Elledge, a geneticist at Harvard University says the severity of the disease could put it in a different category from the ordinary cold. “You might have a cold for a week, whereas if you go through three weeks of hell, that may give you more of a memory for longer,” he says.

Other clues come from the 2002-03 outbreak of SARS, a respiratory infection even more deadly than covid-19. Six years after the SARS outbreak, doctors in Beijing went hunting for an immune response among survivors. They found no antibodies or long-lived memory B cells, but they did find memory T cells.

Because doctors managed to stop the SARS outbreak after about 8,000 cases, there’s never been a chance for anyone to get infected a second time, but those T cells could be a sign of ongoing immunity. A later vaccine study in mice found that memory T cells protected the animals from the worst effects when scientists tried infecting them again with SARS.

To Frieman, at the University of Maryland, all this uncertainty about immune response to coronaviruses means there’s still little chance of predicting when, or how, the outbreak ends. “I don’t know when this goes away, and if anyone says they know, they don’t know what they are talking about,” he says.

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