2291. SARS-CoV-2 Viral Kinetics Among Immunologically Naïve Adults: Comparison by Variant and Reinfection Status
Authors: Doll Margaret K , Shakoor Brianna Levenson , Kimball Louise E , Crukley Jeffery , Ozbek Nina , Blazevic Rachel L , Mose Larry , Boonyaratanakornkit Jim , Stevens-Ayers Terry L , Cornell Kevin , Sheppard Benjamin D , Hampson Emma , Sharmin Faria , Goodwin Benjamin , Dan Jennifer M , Archie Tom , O’Connor Terry , Boeckh Michael J , Crotty Shane , Waghmare Alpana 
Published: November 2023

Abstract

Background
SARS-CoV-2 viral dynamics offer insights into clinical trajectories and immune responses. While research has explored SARS-CoV-2 viral kinetics by variant and immune status, changes in population immunity make results difficult to interpret. Here, we examined SARS-CoV-2 viral kinetics in a community-based cohort of immunologically naïve adults.

Methods
Unvaccinated adults 30 to 64 years of age without prior infection were followed for ≤ 72 weeks. Subjects submitted weekly nasal swabs for SARS-CoV-2 RT-PCR; if symptomatic or positive, swabs were collected every other day (up to 14 days). We examined RT-PCR cycle threshold (Ct) results from infections with sufficient data, defined as ≥ 3 swabs collected between ‒10 and 28 days of the peak Ct value with ≥ 1 Ct&lt; 30. Bayesian hierarchical piecewise models were used to estimate viral kinetics by variant (classified by date) or first vs. second infections using data from peak swabs and those collected within ±3 days of another swab; if negative, Ct values were set to the detection limit and only the first of consecutive negatives were included.

Results
Sufficient data were available for 179/187 (96%) first SARS-CoV-2 infections, with 27 (15%) Delta, 132 (74%) Omicron BA.1/BA.2, and 20 (11%) Omicron BA.4/BA.5 infections. Of these, 35 (20%) subjects had a second infection while unvaccinated (32 [91%] sufficient data). Figure 1 shows Ct values and model predictions by variant or infection status. Lower mean peak Ct values were found for first vs. second infections (‒5.7, 95% CI: ‒7.4, ‒4.1 cycles), and suggested for Delta vs. Omicron BA.1/BA.2 infections (‒1.4, 95% CI: ‒3.0, 0.5 cycles). Delta had a shorter mean time to peak (‒2.5, 95% CI: ‒3.8, ‒1.3 days) and longer clearance (2.7, 95% CI: 0.7, 4.9 days) vs. Omicron BA.1/BA.2 infections; first infections had longer clearance (3.5, 95% CI: 1.4, 5.3 days) vs. second infections.Figure 1.Participant RT-PCR cycle threshold (Ct) trajectories with model predictions (black lines) and 95% credible intervals (gray ribbons) by variant or infection status.

Conclusion
Modeled estimates suggest Delta infections experienced higher viral loads, shorter time to peak, and longer clearance times compared with Omicron BA.1/BA.2. First infections had higher viral loads and longer clearance times vs. second infections. As population immunity is dynamic, characterizing viral kinetics among immunologically naïve individuals is valuable to inform SARS-CoV-2 trajectories.

Disclosures
Jim Boonyaratanakornkit, MD, PhD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|IgM Biosciences: Grant/Research Support|IgM Biosciences: Patent on antibodies to respiratory viruses|Vir Biotechnology: Grant/Research Support Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Symbio: Advisor/Consultant Alpana Waghmare, MD, Allovir: Grant/Research Support|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|GlaxoSmithKline/Vir: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Pfizer: Grant/Research Support|Vir Biotechnology: Advisor/Consultant