Scientists have found the first solid evidence that people can be reinfected with the virus that causes COVID-19. A new study shows a 33-year-old man who was treated at the hospital for a mild case in March harbored the virus again when he was tested at the Hong Kong airport after returning from Europe on 15 August, less than 5 months later. He had no symptoms this time. Researchers had sequenced the virus, SARS-CoV-2, from the first infection; they did so again after the patient's second diagnosis and found numerous differences between the two, bolstering the case that the patient had been infected a second time.
"This case proves that at least some patients do not have life-long immunity," Kelvin To, a clinical microbiologist at the University of Hong Kong (HKU) and one of the authors of a paper on the case, told Science today.
Exactly what that finding means is unclear, however. To and his colleagues make some sweeping statements in their paper, parts of which Science has seen. "It is unlikely that herd immunity can eliminate SARS-CoV-2," the authors write, referring to the idea that the epidemic will peter out once enough people have been infected and become immune. "Second, vaccines may not be able to provide life-long protection against COVID-19."
But it's too early to draw those conclusions, says Columbia University virologist Angela Rasmussen. "I disagree that this has huge implications across the board for vaccines and immunity," she wrote in an email, because the patient described in the study may be a rare example of people not mounting a good immune response to the first infection.
Mark Slifka, a viral immunologist at Oregon Health & Science University, says his takeaway from the paper is the opposite of what the authors write: "Even though [the patient] got infected with a very different strain that's distinct from the first time around, they were protected from disease," he says. "That is good news."
Fueling the debate over the importance of the case is that the paper on it isn't public yet, which means scientists can't scrutinize its data in full. HKU put out a press release about the study today and said the paper had been accepted for publication by the journal Clinical Infectious Diseases. To confirmed that a few pages of the manuscript circulating online were from the paper but said he could not make the full text available. "This is why I loathe data disclosure by press release," Rasmussen wrote. "It seems designed to stoke sensationalism by leaving all these provocative questions unanswered, some of which could probably be answered by just reading the paper and examining the figures."
There have been several reports of COVID-19 patients testing positive for SARS-CoV-2 again after apparently clearing their infection, but in those cases there was less time between the tests and researchers did not have sequences of the viruses to confirm there were two different infections. Many of these cases were likely testing errors, says Jeffrey Barrett, a genomic epidemiologist at the Wellcome Sanger Institute: "I wasn't convinced by any of them."
In the current case, the press release and paper excerpts say, the HKU scientists found 24 differences between the first and second viral genome, including one in the first virus that truncates a gene known as ORF8. "There's sort of no chance that it's the same infection twice," Barrett says. "It is much more convincing than any other anecdotal reports that have come out so far," agrees virologist Charlotte Houldcroft of the University of Cambridge.
Even if the finding settles the question of whether people can be reinfected with the pandemic virus, it raises many additional questions: How often does this happen? Do people have milder infections, or no symptoms at all, the second time around? Can they still infect others? If natural infection does not always confer solid protection, will that be true for vaccines as well?
To says he believes reinfections are not rare—just difficult to find. "This case is very special because he was screened at the airport," he says. "Under normal circumstances, he may not even have been aware that he was infected again." If reinfections are more likely to lead to asymptomatic cases, To notes, they may be tougher to spot.
In a press conference on Monday morning, epidemiologist Maria Van Kerkhove of the World Health Organization warned against jumping to conclusions. "We need to look at this at a population level," she said. Given that there have been more than 24 million reported SARS-CoV-2 infections worldwide, a single reinfection report may signal a very rare event, Barrett says. "Biology is complicated. You always find some strange exceptions." He hopes efforts like the COVID-19 Genomics UK Consortium, which is sequencing viral samples from tens of thousands of patients, will provide data on how often reinfection occurs. Houldcroft says studies in health care workers may be key, because they are most likely to be exposed repeatedly.
There were reasons to expect that SARS-CoV-2 can reinfect at least some recovered COVID-19 patients, Houldcroft says. Experiments in the 1980s in the United Kingdom showed some people who were infected with coronaviruses that cause the common cold could be deliberately reinfected a year later. "I think most virologists were waiting for this to happen and it was more of a question of when rather than if," she says. "It's almost impossible to be protected completely from a reinfection, especially [with] upper respiratory tract viruses and bacteria," Slifka adds. "We get reinfected all the time."
In the 1980s experiments, participants who produced less robust immune responses during the first infection were most likely to be reinfected. Perhaps that happened in the Hong Kong case: The man tested negative for immunoglobulin G antibodies against SARS-CoV-2, an important part of the immune response, 10 days after his mild symptom began in the first infection, the authors write. "People with low neutralizing antibody titers will be expected to be more susceptible to reinfection," Houldcroft says. "We have no idea what it means for everyone else." But the assay used in the paper, which targets the nucleoprotein of the virus, is particularly prone to false negative results, Slifka says.
Whether reinfected people can still spread the virus may turn out to be the crucial question, Houldcroft says. "If they don't shed and they're dead ends, that's fine. If they are still infectious, that's a bit more of a problem." Whether the Hong Kong case was infectious after his second brush with SARS-CoV-2 is not clear; the researchers are trying to culture live virus from the patient, To says. "But viral culture takes some time, so we don't know yet." Given the experience with other respiratory viruses, Slifka says he would expect the patient to be about 10 times less infectious the second time around.
Even if reinfections turn out to be more common and to lead people to shed infectious virus, that does not mean vaccines won't work. "The protection given by the [human papillomavirus] jab, for instance, is more durable and better than natural infection," Houldcroft says. "It's not impossible that we will do the same for the coronavirus."
To says it was important to get the available information out as soon as possible, because recovered COVID-19 patients should keep practicing physical distancing and other measures to avoid infection. "People should not assume that once they get infected, they have life-long immunity," he says. But he stresses that the findings "shouldn't cause panic."
Correction, 25 August 2020, 6:50 p.m.: A previous version of this story incorrectly said that the ORF8 gene was truncated in the patient's second viral genome instead of the first.
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