RNA loads of severe acute respiratory syndrome coronavirus 2 in patients with breakthrough coronavirus disease 2019 caused by the Delta and Omicron variants

OBJECTIVES: To compare the RNA loads of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal specimens collected from patients with breakthrough coronavirus disease 2019 (COVID-19) caused by the Delta variant with those in specimens collected from patients with breakthrough COVID-19 caused by the Omicron variant. METHODS: A retrospective, observational study was conducted, including 240 consecutive adult out-patients, of whom 121 (74 females; median age, 40 years) had COVID-19 due to the Omicron variant and 119 (65 females; median age, 48 years) had COVID-19 caused by the Delta variant. The viral RNA load was quantitated using the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, MS, USA). The viability platinum chloride reverse transcription-PCR assay was used to discriminate between potentially infectious viral particles and free (encapsidated) viral RNA. RESULTS: Overall, the viral RNA loads were significantly higher (p 0.003) for the Omicron variant (median, 8.1 log(10) copies/mL; range, 4.0–10.9 log(10) copies/mL) than for the Delta variant (median, 7.5 log(10) copies/mL; range, 3.0–11.6 log(10) copies/mL). A trend towards higher viral loads was noticed for Omicron compared with that for Delta across the following time frames since vaccination: 16–90 days (median, 6.83 vs. 5.88 log(10) copies/mL, respectively; range, 3.91–10.68 vs. 3.67–9.66 log(10) copies/mL, respectively; p 0.10), 91–180 days (median, 8.09 vs. 7.46 log(10) copies/mL, respectively; range, 4.30–10.92 vs. 3.03–11.56 log(10) copies/mL, respectively; p 0.003) and 181–330 days (median, 8.56 vs. 8.10 log(10) copies/mL, respectively; range, 6.51–10.29 vs. 3.03–10.61 log(10) copies/mL, respectively; p 0.11). The platinum chloride treated or untreated reverse transcription-PCR cycle threshold ratio for the nucleocapsid gene as the target was slightly higher for Omicron than for Delta (median, 0.62 vs. 0.57, respectively; range, 0.57–0.98 vs. 0.61–0.87, respectively), although statistical significance was not reached (p 0.10). CONCLUSION: The time elapsed since vaccination has a major impact on the RNA loads of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal specimens, particularly for the Omicron variant. The Omicron variant may be better adapted for replication in the upper respiratory tract than the Delta variant, in which this is unlikely given its more efficient generation of viral particles.