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

Abstract

Background: Early in the coronavirus disease 2019 (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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A viral loads relative to symptom duration in symptomatic adults (≥16 years) 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 cycle threshold (Ct) values recorded. Nucleoprotein concentrations in SARS-CoV-2 polymerase chain reaction (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 39.2 years), 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 35.0 years), median influenza viral loads peaked on the second day of symptoms.

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.

Keywords: COVID-19; SARS-CoV-2; kinetics; symptom; viral load.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/the-new-normal-delayed-peak-sars-cov-2-viral-loads-relative-to-symptom-onset-and-implications-for-covid-19-testing-programs-a6c0d9ff-2c70-4d88-93fb-2bb9c5c24714/update

Figure 1.

SARS-CoV-2 Ct values (A) and paired log-transformed antigen concentrations (B) measured in anterior nasal swab samples plotted by days since symptom onset for PCR-positive symptomatic adults (day 0 = the first day of symptoms). The blue bar in (A) outlines the window between Ct of 30 and Ct of 25. Abbreviations: Ct, Cycle threshold; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Influenza A Ct values measured in anterior nasal swab samples plotted by days since symptom onset for PCR-positive symptomatic adults (day 0 = the first day of symptoms). A, Ct value for influenza A target 1 (PA, a phosphoprotein subunit of influenza RNA polymerase); B, Ct value for influenza A target 2 (PB2, polymerase basic 2 subunit of influenza RNA polymerase). Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction.