An otherwise healthy 25-year-old Nevada man is the first American confirmed to have caught 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 being infected with the coronavirus that causes the disease, and potentially how protective a vaccine might be.
“It’s a yellow caution light,” said Dr. William Schaffner, an infectious disease expert at the Vanderbilt University School of Medicine in Nashville, Tennessee, who was not involved in the research.
Respiratory infections like COVID-19 don’t provide lifelong immunity like a measles infection. So, Dr. Paul Offit, an infectious disease expert at Children’s Hospital of Philadelphia, said he’s not at all surprised people could get infected twice with the coronavirus, SARS-CoV-2.
It’s too soon to know whether 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 get infected more than once with SARS-CoV-2, Schaffner said.
“There’s hardly an infectious disease doctor in the country who hasn’t encountered a patient who thinks they’ve had a second infection,” he said. “Whether that’s true or not, we don’t know. There are lots of respiratory infections out there.”
How rare is he?
There have been at least 22 documented cases of reinfection worldwide since the start of the pandemic, but it’s unclear how many cases there have actually been, and how common it may be among people who don’t even know they’re infected.
“It could be a one in a million event, we don’t know,” said Akiko Iwasaki, an immunologist at Yale University and an investigator with the Howard Hughes Medical Institute, who wrote a commentary with the study.
With millions of people infected, it’s hard to know if case studies like the new one represent very rare events or the tip of an iceberg, she said. “It’s possible that the vast majority of people are completely protected from reinfection, but we’re not measuring them, because they’re not coming to the hospital.”
Also, many people don’t know they are infected the first time, so it’s hard to say whether they’re getting re-infected.
In one of the recent cases, a Hong Kong man only knew he was reinfected because it was caught during a routine screening when he returned from outside the country, months after he had cleared an infection and tested negative.
One reason there may not be more documented cases of reinfection: It’s tough to prove, said Mark Pandori, a pathologist at the University of Nevada, Reno School of Medicine, and senior author on 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 benefit of sequencing equipment on campus, as well as microbiologists, he said. And they got lucky finding someone who had been tested both times he was infected and cleared in between.
Why his infection was worse the second time remains 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, according a genetic analysis of the man’s infections. It’s possible the second version was more dangerous, though there is no evidence of that, or that it was just different enough that his body didn’t recognize it, 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 quite different, she said.
“Vaccines can be designed to induce much higher levels of antibody and much longer lasting immunity,” she said. Just because the natural infection doesn’t give you protection doesn’t mean the vaccines cannot. It’s a separate issue.”
Offit, also a vaccine expert at the Perelman School of Medicine at the University of Pennsylvania, said he expects protection from vaccines will likely last at least a year or two.
The protection provided by infection or vaccination isn’t 100% perfect until the day it disappears completely, he said. Instead, protection fades gradually, so someone exposed to a huge dose of the virus might get re-infected within months, while others could be protected for years, Offit said.
It’s also possible the Nevada man has an undiagnosed problem with his immune system. “He probably should be seen by an immunologist,” Offit said.
The length of time an infection will be protective remains one of the key open questions about the virus.
Infected twice, two months apart
The Nevada man, considered an essential worker, started feeling ill in late March, with a sore throat, cough, headache, nausea and diarrhea. His workplace had been hit with an outbreak early in the pandemic, before safety measures like masks could be put in place, said Heather Kerwin, senior epidemiologist at the Washoe County Health District and a co-author on the paper.
He went for testing on April 18 and his infection with the coronavirus was confirmed.
On April 27, he reported his symptoms had all resolved and he felt fine, but at the time, employees were required to test negative for COVID-19 twice before they would be allowed back to work, Kerwin said. So he remained isolated at home.
A month later, he began feeling poorly again. At the same time, there was an outbreak where one of his parent’s, 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, even though he still had antibodies to the virus in his bloodstream, Kerwin said.
Genetic differences between the viruses responsible for each of his infections suggested he was infected two separate times. The virus doesn’t mutate quickly enough within a single person to explain the differences between the two infections, the researchers found.
A parent living with the man also caught COVID-19 and was diagnosed on June 5.
The paper reports it’s possible the man was reinfected because he was exposed to a higher dose of the virus the second time, perhaps from the family member.
His cough lingered and he suffered from shortness of breath and mental fog, and was on oxygen for six weeks after the second infection, Kerwin said. He has now fully recovered.
Reinfections imply so-called herd immunity cannot be obtained just through natural infection. If natural infection protects for only a few months, then it will be impossible for enough people to be protected simultaneously to reach herd immunity.
The moral of the case study, said co-author Pandori, is even people who already have been sick with COVID-19 need to protect themselves by wearing a mask, avoiding large gatherings, washing hands frequently and maintaining social distance.
“You’re not invulnerable to this,” Pandori said. “In fact, you could get it worse the second time.”
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