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A healthy 25-year-old Nevada man is the first American to be confirmed to have contracted COVID-19 twice, with the second infection worse than the first.

He has recovered, but his case raises questions about how long people are protected after they are infected with the coronavirus that causes the disease and potentially how protective a vaccine could be.

“It’s a yellow warning light,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, Tennessee, who was not involved in the research.

Respiratory infections like COVID-19 do not provide lifelong immunity like a measles infection. So, Dr. Paul Offit, an infectious disease expert at Children’s Hospital of Philadelphia, said he is not at all surprised that people can be twice infected with the coronavirus, SARS-CoV-2.

It is too early to know if the man from Washoe County, Nevada, who had no known health problems other than his double infection, was highly unusual or if many people could easily be infected more than once with SARS-CoV. -2, Schaffner said.

“There is hardly an infectious disease doctor in the country who hasn’t met a patient who thinks they’ve had a second infection,” he said. “Whether that’s true or not, we don’t know. There are a lot of respiratory infections out there.”

How rare is it?

There have been at least 22 documented cases of reinfection around the world since the start of the pandemic, but it is unclear how many cases there have actually been and how common it can be among people who don’t even know they are infected.

“It could be one in a million event, we don’t know,” said Akiko Iwasaki, a Yale University immunologist and Howard Hughes Medical Institute researcher, who wrote a comment on the study.

With millions of people infected, it’s hard to know whether case studies like the new one represent very rare events or the tip of the iceberg, he said. “It is possible that the vast majority of people are completely protected from reinfection, but we are not measuring them, because they do not come to the hospital.”

Also, many people don’t know they got infected the first time, so it’s hard to tell if they are reinfected.

In one of the recent cases, a Hong Kong man knew he was reinfected only because he was caught during a routine screening on his return from abroad months after he cleared an infection and tested negative.

One of the reasons why there may not be more documented cases of reinfection: It’s hard to prove, said Mark Pandori, a pathologist at the University of Nevada, Reno School of Medicine and senior author of the new study.

His team coordinated early in the pandemic with members of the Washoe County Health District to look for repeat infections. They had the advantage of on-campus sequencing equipment, as did the microbiologists, he said. And they were lucky enough to find someone who had been tested both times that had been infected and eliminated in the meantime.

Why her infection got worse the second time around is unclear, said Pandori, director of the Nevada State Public Health Laboratory. “I can’t tell you if it tells us anything in particular about the biology of this virus.”

The man caught a slightly different version of the virus the second time around, according to a genetic analysis of the man’s infections. It’s possible that the second version was more dangerous, although there is no evidence of this, or that it was different enough not to be recognized by her body, the paper said.

Implications for vaccination

Iwasaki said the study raises questions about how long immunity lasts after a natural infection. Protection with a vaccine is likely to be very different, he said.

“Vaccines can be designed to induce much higher levels of antibodies and much longer-lasting immunity,” he said. Just because natural infection doesn’t give you protection doesn’t mean vaccines can’t. It’s a separate issue. “

Offit, also a vaccine expert at the University of Pennsylvania’s Perelman School of Medicine, said he expects vaccine protection to likely last at least a year or two.

The protection provided by infection or vaccination isn’t 100 percent perfect until the day it goes away completely, he said. Instead, protection fades away gradually, so someone exposed to a huge dose of the virus could be reinfected within months, while others could be protected for years, Offit said.

It is also possible that the Nevada man has an undiagnosed problem with his immune system. “It should probably be seen by an immunologist,” Offit said.

The length of time an infection will be protective remains a major open question about the virus.

Twice infected, two months apart

The Nevada man, considered an indispensable worker, began feeling ill in late March, with a sore throat, cough, headache, nausea and diarrhea. Her workplace had been hit by an epidemic early in the pandemic, before safety measures such as masks could be put in place, said Heather Kerwin, senior epidemiologist at the Washoe County Health District and co-author of the article.

He went for tests on April 18 and his coronavirus infection was confirmed.

On April 27, he reported that his symptoms had all resolved and he was feeling fine, but at the time, employees had to have tested negative for COVID-19 twice before they could return to work, Kerwin said. So he remained isolated at home.

A month later, he started feeling sick again. At the same time, there was an outbreak where one of his parents, also an essential worker, was employed, Kerwin said.

On May 31, he went to an urgent care center, reporting fever, headache, dizziness, cough, nausea and diarrhea. On June 5, he went to see a doctor who found his oxygen levels dangerously low and had him hospitalized. Again, the man tested positive for the virus, although he still had antibodies to the virus in his blood, Kerwin said.

The genetic differences between the viruses responsible for each of his infections suggested that he had been infected twice separate. The researchers found that the virus does not mutate quickly enough within a single person to explain the differences between the two infections.

A parent living with the man also caught COVID-19 and was diagnosed on June 5.

The newspaper reports that it is possible that the man was reinfected because he was exposed to a higher dose of the virus the second time, possibly from the family member.

His cough persisted and he suffered from shortness of breath and mental fog, and he was on oxygen for six weeks after the second infection, Kerwin said. He has now fully recovered.

Reinfections imply that so-called herd immunity cannot be achieved through natural infection alone. If the natural infection only protects for a few months, it will be impossible to simultaneously protect enough people to achieve herd immunity.

The moral of the case study, co-author Pandori said, is that even people who have already been sick with COVID-19 must protect themselves by wearing a mask, avoiding large gatherings, washing their hands often, and keeping social distances.

“You are not invulnerable to this,” said Pandori. “In fact, you might make things worse the second time around.”

Contact Karen Weintraub at kweintraub@usatoday.com and Elizabeth Weise at eweise@usatoday.com

Patient health and safety coverage in USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not make editorial contributions.

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