The New Normal: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs

The New Normal: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs, 2023, Jennifer K Frediani et al

Abstract
Background
Early in the COVID-19 pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads.

Methods
We assessed SARS-CoV-2 and influenza A viral loads relative to symptom duration in symptomatic adults (>16y) presenting for testing in Georgia (4/2022-4/2023; Omicron variant predominant). Participants provided symptom duration and recent testing history. Nasal swabs were tested by Xpert Xpress SARS-CoV-2/Flu/RSV assay and Ct values recorded. Nucleoprotein concentrations in SARS-CoV-2 PCR-positive samples were measured by Single Molecule Array. To estimate hypothetical antigen rapid diagnostic test (Ag RDT) sensitivity on each day after symptom onset, percentages of individuals with Ct value <30 or <25 were calculated.

Results
Of 348 newly-diagnosed SARS-CoV-2 PCR-positive individuals (65.5% women, median 39.2y), 317/348 (91.1%) had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, median viral loads rose from the day of symptom onset and peaked on the fourth/fifth day. Ag RDT sensitivity estimates were 30.0-60.0% on the first day, 59.2-74.8% on the third day, and 80.0-93.3% on the fourth day of symptoms.

In 74 influenza A PCR-positive individuals (55.4% women; median 35.0y), median influenza viral loads peaked on the second day of symptoms.

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad582/7285011?rss=1


Conclusions
In a highly immune adult population, median SARS-CoV-2 viral loads peaked around the fourth day of symptoms. Influenza A viral loads peaked soon after symptom onset. These findings have implications for ongoing use of Ag RDTs for COVID-19 and influenza.