A new JCI Insight study led by the POSITIVES team and the Barczak Lab at the Ragon Institute followed people with mild COVID-19 to see whether newer Omicron subvariants behave differently over time. Despite ongoing viral evolution, the team found core features—how much viral nucleic acid is found in the nose and how long people shed live virus—were broadly similar across the BA.1x, BA.2x, BA.4/5x, XBB.x, and JN.x subvariants.

The study was conceived and led by Ragon faculty member Amy Barczak, MD, with virology performed in the Ragon BSL3 lab. The POSITIVES cohort asked ambulatory, immunocompetent participants who weren’t on antivirals to self-swab six times over 15 days. Researchers measured nasal viral RNA by PCR, attempted to grow live virus from the same samples, and sequenced each virus to identify the subvariant. 

Across these groups, median peak viral load was about one to two million copies per milliliter. The virus typically peaked around days 4–5, PCR tests turned negative in roughly 12–14 days, and samples stopped yielding live virus in about 4–6 days (depending on the lab system used). These measures did not differ meaningfully by subvariant.

One exception was technical, not clinical in that JN.x didn’t grow in a common lab cell line, but did grow in cells outfitted with the human entry proteins ACE2 and TMPRSS2. When tested on those cells, the time to stop shedding live virus looked similar to other variants.

Symptoms did not line up well with infectiousness. Using current CDC symptom-based criteria as a benchmark, an estimated one-third to about two-thirds of participants were still shedding live virus when they would be cleared to end isolation, and a smaller but notable share were still shedding at the end of the recommended masking period. Fewer than 15% reported fever at any point. The researchers noted that alternatives such as incorporating antigen testing may better align guidance with infectiousness.

Together, these results show that while Omicron continues to diversify, the basic virologic timeline for mild infections has remained steady—and that symptom-only rules can miss periods when some people are still shedding live virus particles.