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Viral load in COVID-19 infection peaks later now than in the early days of the pandemic, driving implications for rapid testing, researchers say.

A paper has been generating discussion among experts, who say high levels of population immunity are responsible for the shift.

That paper, by Nira Pollock, MD, PhD, of Boston Children's Hospital, and colleagues, found that viral loads in the Omicron era peak about 4 days after the onset of symptoms, compared with a peak at symptom onset early in the pandemic.

"Early in the pandemic, before we had much in the way of immunity, it was observed that the viral load peaked either the first day of symptoms or even the day just before, so it was postulated that this is a lot of the reason why there was so much asymptomatic spread," Paul Sax, MD, editor-in-chief of Clinical Infectious Diseases and director of the Infectious Disease Clinic at Brigham and Women's Hospital in Boston, told MedPage Today.

"What's happened more recently ... is that the immune response kicks in much sooner," Sax said. "So you start having symptoms as the virus is getting going, and then you have symptoms for even a few days before the viral load peaks."

Pollock and colleagues wrote that the findings have "major implications for testing practice going forward."

They studied a cohort of 348 people newly diagnosed with COVID on PCR testing from April 2022 to April 2023, when Omicron was the predominant variant. The vast majority (91%) had a history of infection, vaccination, or both.

They found that on PCR testing, median cycle threshold (Ct) values hit their lowest point -- which is consistent with peak viral load -- on the fourth day of symptoms.

Using Ct values to predict rapid antigen results, the researchers estimated a sensitivity of 30% to 60% on the first day of symptoms, rising to 80% to 93% on the fourth day of symptoms.

Early in the pandemic, they wrote, a single negative antigen test had "reasonable negative predictive value," with studies reporting 90% to 95% sensitivity in the first week of symptoms. Now, overall predicted sensitivity in the first week is about 60% to 80%, they said.

"Our data in combination with others' suggest that symptomatic individuals testing positive for SARS-CoV-2 by PCR currently may not reliably test positive on a rapid antigen test until the 3rd, 4th, or even 5th day of symptoms," they wrote.

"Though testing negative on an antigen test suggests that the person is less likely to be viral culture-positive (and presumably infectious) at that moment than someone who tests positive, we note that our data indicate that viral load would be expected to be rising, and not falling in the window after that early false negative test."

Sax said the findings suggest people may want to isolate and avoid going to work or socializing when they start feeling symptoms, before they reach the height of their viral load, and possibly, infectiousness.

It also calls into question whether 5-day isolation guidelines are appropriate, he said, as people may continue to be infectious after day 4 or 5.

Michael Mina, MD, a public health expert and the chief science officer for eMed, told MedPage Today that the findings of a shift in peak viral load shouldn't come as a surprise.

"[I]f you look at it through the lens of what would you expect if a coronavirus -- even a seasonal coronavirus -- were to hit a human population that has no pre-existing immunity to it, well, we would expect exactly what happened," he said. Vaccines and infections have resulted in our immune systems responding faster to this virus, he said.

"We're finding that -- as we expected -- the virus isn't doing anything crazy to evade our immune defenses," Mina said. "Sure we have breakthrough infections, it's able to mutate and get around antibodies, but in general our immune system is activating. It's doing exactly what it's supposed to do."

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