What could be worse than getting the pneumonia-like illness now known as Covid-19? Getting it twice.
That’s what Japanese government officials say may have happened to a female tour bus guide in Osaka. The woman was first diagnosed with Covid-19 in late January, according to a statement released by Osaka’s prefectural government Wednesday. She was discharged shortly after, once her symptoms had improved. A subsequent test came back negative for the virus. Three weeks later she returned with a sore throat and chest pain and tested again. For a second time, she tested positive for Covid-19.
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News reports detailing the case raised the possibility that people may not be developing immunity to the new coronavirus, even after they’ve recovered. But several infectious disease specialists say there’s not enough data to support that conclusion. Another possibility is that the virus subsided and flared up again. (Some viruses tend to do that.) Or the test was simply wrong.
“The question is really: How good is the proof?” says Donald Burke, an international health expert at the University of Pittsburgh. “And we’re a long way away from anything solid. What we need is the sequence of the virus.”
The only way to differentiate between a relapse—meaning the same coronavirus seemed to go away and came back—and reinfection, in which a second strain of coronavirus swooped in just as the first cleared out, is a full viral sequence. The tests currently available for diagnosing Covid-19 are based on a method called RT-PCR, which picks up some pieces of the virus’s genetic code, but not everything. It’s designed to grab only the chunks that are unique to the new coronavirus, but stable enough that they won’t disappear if it mutates. Thanks to some specialized fluorescent dye, the more viral bits there are, the brighter the genetic material glows, creating a pattern of light that signals for the presence of the virus.
In theory, if doctors completely sequenced the virus in a patient’s nose or mouth swab at the time of each positive diagnosis, they could compare each genetic letter using genome-reading software and determine if the person had the same strain of coronavirus or a new one. Without that kind of data, says Burke, there’s no way of knowing for sure.
But others think the more likely scenario is that the virus can just linger in some people’s bodies longer than expected. “I suspect this is in fact a continuation of the original infection,” says Susan Kline, an infectious disease physician and epidemiologist at the University of Minnesota.
For one thing, she says, just not enough time has elapsed for reinfection. In the case of the other coronaviruses people catch, like the ones that cause the common cold, people tend to develop immunity following an infection. But it doesn’t last forever. The body produces antibodies that are protective against subsequent exposures, and then over time that immune response wanes, says Kline. That process usually takes longer than three weeks. “It’s too soon,” says Kline. “This entire outbreak has only been going on for two months. I would be very surprised if people are getting reinfected in that time span.”
So why then, did the Japanese woman test negative? Kline says there are a few potential explanations.
One is that the test wasn’t sensitive enough to pick up traces of the virus. The RT-PCR tests currently in use for diagnosing Covid-19 require a fair amount of genetic material to work well. If the coronavirus is actively making more copies of itself, there will be lots of RNA for the test to detect. But if the viral load goes down, the test can give false negatives. That can happen because the patient’s immune system is mounting a strong response. Or it could be that a treatment is slowing down the coronavirus’s self-replication spree. Another possibility is that the sample was just bad—the swab didn’t pick up much virus in the first place.
Other viruses are known to exhibit similar dynamics. HIV, for example, starts out with a burst of viral replication before the immune system is alerted to its presence. Once the body starts to mount a response, the amount of viral genetic material drops, sometimes below detectable levels. Then as HIV attacks the body’s immune cells and patients get sicker and sicker, it becomes detectable again.
During the SARS epidemic 17 years ago, there were reports of people who were given steroids to clear up their pneumonia. Those treatments caused the SARS virus to drop off, before coming back again later.
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The Osaka case, which was first reported by Reuters, is the first time anyone in Japan has been reported to have—maybe—caught the coronavirus more than once. But similar cases have also been reported in China, which is still the epicenter of an outbreak that has infected more than 83,000 globally and killed 2,858, according to the World Health Organization’s latest numbers.
Last month, a Chinese physician warned that it was possible for recovered patients to contract the virus again. Speaking at a Chinese National Health Commission briefing on January 30, Zhan Quingyuan, director of pneumonia prevention and treatment at the China-Japan Friendship Hospital in Beijing, said that while Covid-19 patients all seem to generate antibodies against the coronavirus, in some individuals the antibodies don’t appear to last for very long. “For those patients who have been cured, there is a likelihood of relapse,” Zhan said.
Burke says he’s keeping an eye on this, and any other data that emerges suggesting people are relapsing from Covid-19 or catching multiple strains. Both could have potentially huge consequences for the public health response to the outbreak. “If there were an appreciable number of genuine relapses, I would be concerned about how you decide when it’s safe to take a person out of containment,” says Burke. Health workers would need to adapt monitoring strategies to make sure people aren’t reactivating and becoming infectious again once they’ve recovered and are back in their communities.
And the spectre of reinfection raises a host of other potential problems. “If the natural infection doesn’t give you solid immunity, then we would start to worry about the effectiveness of a vaccine,” says Burke.
Of course, at this point, all of that is just speculation. For now, the best advice anyone has to offer is the same thing the Japanese government told its own citizens in Osaka: Wash your hands, and practice good cough etiquette.
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