2291. SARS-CoV-2 Viral Kinetics Among Immunologically Naïve Adults: Comparison by Variant and Reinfection Status

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< 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: see text] 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