Seattle-area man the third in US confirmed to have been infected twice with COVID-19

SEATTLE — The Seattle-area nursing home resident first tested positive for the novel coronavirus in early March. He spent more than 40 days in the hospital with fever, pneumonia and difficulty breathing before testing negative multiple times and being discharged.

Then, nearly five months later, he got sick again with COVID-19.

Now, genetic testing by a team of Seattle physicians and scientists has revealed that sexagenarian’s second bout of the illness caused by the coronavirus in July wasn’t a relapse but a new infection with a slightly different variant of the virus.

The patient is only the third person in the United States — and one of about 20 worldwide — confirmed to have experienced such a double whammy.

Since posting a preprint in late September describing their findings, which have not been peerreviewed, the Seattle team has confirmed one additional local reinfection and is examining a handful of other possible cases, said Dr. Jason Goldman, an infectious-disease specialist at Swedish Medical Center.

“It’s not unexpected this would occur, because we know immunity wanes to other respiratory infections, like flu,” Goldman said. “But I was a little surprised to find it in my own hospital.”

Scientists are still trying to figure out the significance of the cases, but it’s reassuring that reinfection seems to be rare, Goldman said. That indicates most people develop a protective immune response after infection, though how long it lasts remains unclear.

“And we still don’t know what level of immunity you need to be protected,” he said.

The local patient wasn’t as sick the second time around and has since recovered, which suggests some level of protection even if it wasn’t strong enough to block infection, Goldman noted. That seems to be the case for most reinfections reported so far, he added.

But for a handful of patients, including a 25-yearold Nevada man whose experience was first made public in August followed by a full report published this week in The Lancet, the second infection was more severe. An 89-year-old woman in the Netherlands, who was also undergoing chemotherapy for lymphoma, is the first person known to have died from a repeat infection.

According to a site that tracks reinfections around the globe, the other U.S. case was a 45-year-old man who works at a military hospital in Virginia and who also was much sicker during his second bout with the virus.

Building on a collaboration between Swedish Health Services and the

Seattle-based Institute for Systems Biology (ISB) to assemble a vast “biobank” of health data from COVID-19 patients, the Seattle team performed the most detailed analysis yet of a patient’s immune response to a second infection.

They found that the patient’s body was slow to produce antibodies, particularly the type most effective at neutralizing the virus.

They also determined through genetic sequencing that the initial infection was caused by the viral variant that hit Washington early in the pandemic and which is closely related to the original strain first discovered in Wuhan, China. The patient’s second infection was caused by a separate variant that triggered major outbreaks on the East Coast and arrived in the U.S. via Europe. That strain now predominates in the U.S.

In laboratory tests, the antibodies the patient eventually produced after his second infection were somewhat more effective at neutralizing the European variant than the first strain.

But the difference isn’t big enough to raise concerns about vaccines based on the original strain, or to suggest that the shift in viral strains was responsible for the patient’s reinfection, said Dr. Bill Messer, an infectious-disease physician and virologist at Oregon Health & Science University who was not involved in the analysis.

“This isn’t a case of the second virus escaping the immune response to the first virus,” Messer said.

What’s more likely is that the patient failed to develop a robust and lasting immune response to the first infection and so fell prey again, Messer said.

Some documented reinfections have occurred in people with compromised immune systems, like the Dutch woman who died. The Seattle-area patient also suffers from emphysema, and was treated with steroids, which can dampen immune response, Messer pointed out.

“There’s probably something about this patient’s immune system that isn’t really functioning well,” Goldman agreed.

But because no blood samples were stored from the man’s first infection, the researchers weren’t able to compare the two immune responses.

However, the Seattle team and their collaborators do have two sets of samples for some of the other possible reinfections they are investigating, said Dr. Jim Heath, president of ISB, a nonprofit biomedical research center known for its expertise in “big data” analysis.

One of the major unknowns about people who get reinfected is whether they are infectious enough to spread the virus to others, said Heath. “We just don’t know that yet,” he said. “I think it’s likely some people will be, but probably most people won’t.”

The local patient’s viral load was so low during his second infection that it’s unlikely he would have been infectious — but that not certain, Heath added.

It’s impossible to draw many conclusions from single case studies like this one, Goldman stressed. That’s why he and his colleague are now reaching out to researchers around the world in hopes of comparing all the data and looking for common features and clues to why some people’s immune systems falter.

He also expects to see more reinfections in the coming months, as transmission rates rise during the fall and winter and more people who recovered from earlier infections are exposed again.

“Our experience has been that once we start looking for it, we find it,” Goldman said.

At a briefing Wednesday, Washington State Health Officer Dr. Kathy Lofy said there have been about 100 people in Washington who tested positive for the virus, appeared to recover, then tested positive again more than 90 days later. It’s not clear if these are cases of reinfection or simply instances of people continuing to shed the virus or viral particles for long periods of time, she said.

The only way to confirm reinfection is to compare viral genomes, but many laboratories have thrown out the initial samples used to detect the virus.