August 25, 2020

A 33-year-old man caught the new coronavirus—twice. What does that mean for immunity?

Daily Briefing

    Researchers at the University of Hong Kong on Monday reported the first documented and confirmed case of novel coronavirus reinfection, raising questions about whether patients who become infected with the virus can develop long-term immunity to the pathogen.

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    US new coronavirus cases near 5.8M, deaths top 177K

    The announcement comes as U.S. officials as of Tuesday morning reported a total of 5,754,100 cases of the novel coronavirus virus since the country's epidemic began—up from 5,713,700 cases reported as of Monday morning.

    Data from the New York Times shows that Guam, the U.S. Virgin Islands, and nine states—Connecticut, Hawaii, Illinois, Iowa, Kansas, Maine, North Dakota, South Dakota, and Wyoming—saw their average daily numbers of newly reported coronavirus cases rise over the past 14 days.

    The Times' data also shows that the average daily numbers of newly reported coronavirus cases over the past two weeks remained mostly stable in Puerto Rico and 18 states: Alaska, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, New Jersey, New York, North Carolina, Oklahoma, Pennsylvania, Rhode Island, Utah, Vermont, and West Virginia.

    In addition, the Times' data shows that Washington, D.C., and 23 states saw their average daily numbers of newly confirmed coronavirus cases decrease over the past 14 days: Alabama, Arizona, Arkansas, California, Colorado, Delaware, Florida, Georgia, Idaho, Louisiana, Maryland, Massachusetts, Nevada, New Hampshire, New Mexico, Ohio, Oregon, South Carolina, Tennessee, Texas, Virginia, Washington, and Wisconsin.

    U.S. officials as of Tuesday morning also reported a total of 177,198 deaths linked to the coronavirus since the country's epidemic began—up from 176,694 deaths reported as of Monday.

    According to the Times' data, 11 states saw their average daily numbers of newly reported deaths linked to the coronavirus rise over the past 14 days: Arkansas, Delaware, Indiana, Iowa, Kentucky, Minnesota, North Dakota, Oklahoma, Oregon, Pennsylvania, and Tennessee.

    Hong Kong researchers report first documented, confirmed case of coronavirus reinfection

    As the coronavirus continues to spread throughout the United States and other countries, researchers have been working to understand whether exposure to the virus could protect people from future infection—a factor that could have implications for developing a vaccine against the virus and treatments for Covid-19, the disease caused by the pathogen.

    Questions regarding immunity to the novel coronavirus haven't yet been answered definitively, and some health care providers have reported cases in which patients appeared to become reinfected with the virus. But to date, researchers had not conducted rigorous testing to confirm that any of those cases had been instances of reinfection. In addition, researchers have pointed to some preliminary evidence suggesting that people infected with the new coronavirus develop antibodies and other immune responses to the pathogen that could protect them against reinfection for at least several months to potentially a few years.

    However, on Monday, researchers in Hong Kong reported that they've confirmed the first documented case of novel coronavirus reinfection. According to the researchers, a 33-year-old man with symptoms of Covid-19 was first diagnosed with a novel coronavirus infection on March 26. The man's symptoms at that point were mild, but he was hospitalized on March 29 in accordance with Hong Kong regulations. On April 14, he was released from the hospital after he twice tested negative for the coronavirus.

    Although he'd been infected with the novel coronavirus, the man did not develop any detectable antibodies to the pathogen, researchers said. And although he recovered from his first bout with the coronavirus and had twice tested negative in April, the man once again tested positive for the virus on a saliva test that was conducted at an airport on Aug. 15, after he had traveled from the United Kingdom to Spain.

    The researchers said they discovered that the man had become infected with a different strain of the novel coronavirus that had been spreading throughout Europe in July and August. However, the man did not experience any symptoms of Covid-19 with this new infection, the researchers said.

    The researchers said that the sequences they performed on the coronavirus strains from the man's first and second infections—which revealed significant differences between the viral strains from each instance of infection—confirmed that the man had been reinfected with the novel coronavirus.

    Kelvin Kai-Wang To, a clinical microbiologist at the University of Hong Kong, said the man's two infections had clearly been caused by different strains of the novel coronavirus. "I believe this is the first reported case that is confirmed by genome sequencing," To said. "Our results prove that his second infection is caused by a new [strain of the] virus that he acquired recently, rather than prolonged viral shedding."

    The researchers' findings have been accepted by the journal Clinical Infectious Diseases for publication, but they have not yet been published.

    What do the findings mean for immunity against the coronavirus?

    The researchers said the man's previous infection from one strain of the novel coronavirus did not prevent him from becoming infected with a different strain of the pathogen, but it appears to have helped his immune system suppress the virus, which resulted in him not experiencing symptoms of Covid-19 when he was reinfected.

    According to the Times, some researchers believe that people with mild coronavirus infections could develop so-called immune "memory" through their immune system's B and T cells, which may help to prevent them from developing symptoms of Covid-19 during subsequent infections from the virus.

    Akiko Iwasaki—an immunologist at Yale University, who was not involved with the Hong Kong research but who has reviewed a manuscript of the research obtained by the Times—said that, in this particular case, "natural infection created immunity that prevented disease but not reinfection." She explained, "The second infection was completely asymptomatic—his immune response prevented the disease from getting worse. It's kind of a textbook example of how immunity should work."

    Iwasaki also noted that the man developed antibodies to the novel coronavirus after his second infection from the virus. "Again, it's what the textbook says should happen," Iwasaki said. "When you have second exposure to the same pathogen, you should elevate the antibody, and that's what's happening."

    Similarly, Brian Wasik, a virologist at Cornell University, said, "The majority of patients likely have a cocktail of immune responses that activate on second exposure. This Hong Kong patient also seems to have been asymptomatic on second infection, perhaps due to some immune response."

    Michael Mina, an immunologist at the Harvard T.H. Chan School of Public Health, explained that it's possible a person's first coronavirus infection will result in "non-sterilizing immunity," but their immune response will increase with each exposure to the virus. "It is often these second and third exposures that help to solidify the memory response for the long term."

    Further, Malik Peiris—a virologist at the University of Hong Kong who was not involved with the latest research, but who is familiar with the case—indicated that it might not be common for patients to become reinfected with the novel coronavirus.

    "The fact that somebody may get reinfected is not surprising. But the reinfection didn't cause disease, so that's the first point," Peiris said. Peiris continued, "And the second thing is that it is important to know whether the patient mounted a neutralizing antibody response to the first infection or not. Because the vast majority of patients in our experience do mount a good neutralizing antibody response. So is this person an outlier or is he likely to be the average person infected?"

    Separately, Jeffrey Shaman, an epidemiologist at Columbia University, said, "We've had, what, 23 million cases documented thus far, but the fact that one out of them at this point has been reinfected should not cause undue alarm as of yet."

    However, Shaman said the findings still are disquieting. "[I]t remains very, very concerning—and this does nothing to dispel that—that we may be subject to repeat infection with this virus," he said.

    Jesse Goodman—a former FDA chief scientist who now directs Georgetown University's Center on Medical Product Access, Safety and Stewardship—explained, "If immunity wanes from natural infection, it could be a challenge for vaccines" and may mean people will need to receive multiple doses of a coronavirus vaccine to help boost their immunity after a certain period of time.

    But many experts noted that it's too early to draw definitive conclusions about immunity to the novel coronavirus based on the Hong Kong researchers' report, because a lot remains unclear, such as how often people can become reinfected and when they're likely to become susceptible to reinfection.

    "Those remain open questions, because one person exhibiting a mild reinfection, clearly documented as a distinct strain of the virus, does not provide enough evidence one way or another," Shaman said.

    Also because of the remaining unknowns, To said, "Covid patients should not be complacent about prevention measures." To added that people should continue to practice physical distancing, wear face coverings, and follow other strategies intended to prevent coronavirus transmission (Mandavilli, New York Times, 8/24; Taylor/Cha, Washington Post, 8/24; Marchione, Associated Press, 8/24; Joseph, STAT News, 8/24; Resnick, Vox, 8/24; New York Times, 8/25).

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