With the BA.5 omicron subvariant leading to a rise in reinfections, even for those who may have already had omicron, and with rare rebound cases being reported with a popular COVID treatment medication, how can you know which you have?
Questions over rebound infections heightened after President Joe Biden tested positive for a second time in what appears to be in a rare case of “rebound” following treatment with an anti-viral drug.
After initially testing positive on July 21, Biden, 79, was treated with the anti-viral drug Paxlovid. He tested negative for the virus on this past Tuesday and Wednesday, clearing him to leave isolation while wearing a mask indoors.
Research suggests that a minority of those prescribed Paxlovid to experience a rebound case of the virus.
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So what is the difference between a rebound case and reinfection?
White House COVID-19 coordinator Dr. Ashish Jha told reporters on Monday that data "suggests that between 5 and 8 percent of people have rebound” after Paxlovid treatment.
“Acknowledging the potential for so-called ‘rebound’ COVID positivity observed in a small percentage of patients treated with Paxlovid, the President increased his tested cadence, to protect people around him and to assure early detection of any return of viral replication,” O'Connor wrote in his letter.
O'Connor cited negative tests for Biden from Tuesday evening, Wednesday morning, Thursday morning and Friday morning, before Saturday morning's positive result by antigen testing. “This in fact represents ‘rebound' positivity," he wrote.
According to the CDC, those with rebound COVID should isolate for at least five days, ending that if a fever has resolved itself for 24 hours without medication and symptoms have improved. The patient “should wear a mask for a total of 10 days after rebound symptoms started. Some people continue to test positive after day 10 but are considerably less likely to shed infectious virus.”
Both the Food and Drug Administration and Pfizer point out that 1% to 2% of people in Pfizer’s original study on Paxlovid saw their virus levels rebound after 10 days. The rate was about the same among people taking the drug or dummy pills, “so it is unclear at this point that this is related to drug treatment,” according to the FDA.
Paxlovid has been proven to significantly reduce severe disease and death among those most vulnerable to COVID-19. U.S. health officials have encouraged those who test positive to consult their doctors or pharmacists to see if they should be prescribed the treatment, despite the rebound risk.
While many experts say the exact timing for potential reinfection remains unclear, cases are being reported in as early as one month.
"We don't know know exactly how soon, but people have been recorded to get the infection as soon as four weeks after having a previous infection," said Dr. Sharon Welbel, director of hospital epidemiology and infection control at Cook County Health.
Welbel said that current reinfections could be related to either waning immunity from a previous infection or from vaccinations, depending on if a person has had a booster shot and when. For that reason, Welbel said it's possible some could contract the virus again even earlier than one month post-infection.
"It could even be sooner," she said. "I would think, you know, depending on one's immune system, on their level of antibodies - to either the vaccine or a previous infection - but because, you know, we do not become immune to this from our vaccine or from a previous infection to any of the variants that we have already experienced ... I don't see why somebody couldn't even get it as soon as two weeks later. Have I been seeing that? No. Have I been seeing that talked about? No. But definitely have seen people within a month."
Chicago Department of Public Health Commissioner Dr. Allison Arwady said that while reinfection in a matter of weeks is not likely, it is possible.
Chicago's top doctor noted that while the omicron variant itself marked a distinct shift in reinfections, evading natural immunity from infections with previous strains, BA.5 has similarly evaded immunity from even other omicron infections.
"All of the variants prior to this, we were not seeing a lot of reinfection with the current variant," Arwady said. "So we saw people who had alpha or delta in the past be relatively protected, but potentially get infected with omicron. Everything has been omicron since January, to be clear - all of these subvariants are different versions of omicron. BA.4, BA.5 is the first one where we're seeing some reinfection even of people that had a prior version of omicron. So that is different."
Arwady said while it's still not likely someone will be reinfected if you had COVID recently, "we are seeing some more of these infections."
"Especially if you're counting on an omicron infection from six months ago, like don't be counting on that," she said.
While patients who have recovered from earlier variants of COVID-19 have tended to have high levels of immunity to future reinfection for 90 days, Jha said that the BA.5 subvariant that infected Biden has proven to be more “immune-evasive.”
“We have seen lots of people get reinfected within 90 days,” he said, adding that officials don’t yet have data on how long those who have recovered from the BA.5 strain have protection from reinfection.
Aside from being even more contagious than previous variants, scientists have been tracking a mutation in BA.4 and BA.5 that could help it evade some immunity and cause reinfections.
A genetic trait that harkens back to the pandemic's past, similar to what is known as the “delta mutation," appears to allow the subvariants "to escape pre-existing immunity from vaccination and prior infection, especially if you were infected in the omicron wave," said Dr. Wesley Long, a pathologist at Houston Methodist in Texas. That's because the original omicron strain that swept the world didn’t have the mutation.
This genetic change is bad news for people who caught the original omicron and thought it made them unlikely to get COVID-19 again soon. Although most people don't know for sure which variant caused their illness, the original omicron caused a giant wave of cases late last year and early this year.
Long said lab data suggests a prior infection with the original omicron is not very protective against reinfection with the new mutants, though the true risk of being reinfected no matter the variant is unique to every person and situation.
However, COVID-19 vaccinations have continued to prevent severe hospitalization and death, experts said.