Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

Abstract

Background: The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron's rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta.

Methods: We analyzed nasal swab PCR tests for samples collected between December 12 and 16, 2021, in Connecticut when the proportion of Delta and Omicron variants was relatively equal. We used the spike gene target failure (SGTF) to classify probable Delta and Omicron infections. We fitted an exponential curve to the estimated infections to determine the doubling times for each variant. We compared the test positivity rates for each variant by vaccination status, number of doses, and vaccine manufacturer. Generalized linear models were used to assess factors associated with odds of infection with each variant among persons testing positive for SARS-CoV-2.

Findings: For infections with high virus copies (Ct < 30) among vaccinated persons, we found higher odds that they were infected with Omicron compared to Delta, and that the odds increased with increased number of vaccine doses. Compared to unvaccinated persons, we found significant reduction in Delta positivity rates after two (43.4%-49.1%) and three vaccine doses (81.1%), while we only found a significant reduction in Omicron positivity rates after three doses (62.3%).

Conclusion: The rapid rise in Omicron infections was likely driven by Omicron's escape from vaccine-induced immunity.

Funding: This work was supported by the Centers for Disease Control and Prevention (CDC).

Keywords: COVID-19 vaccines; Delta; Omicron; SARS-CoV-2; epidemiology; genomic surveillance.

Graphical abstract

Figure 1

Variant case counts, test positivity, and odds of infection by vaccination status (A) Number of persons infected with Delta and Omicron SARS-CoV-2 variants and the proportion of Omicron cases in southern Connecticut. Overlaid on the plot showing the number of positive cases is the proportion of Omicron variants (dots) with a fitted smoothed curve. The growth rate of Omicron compared to Delta during their respective emergence periods is shown in Figure S1. (B) The proportion of positive SARS-CoV-2 PCR tests (Ct ≤ 30) for Delta and Omicron variants (using SGTF to differentiate) by vaccination status. Data shown as means with 95% confidence intervals. The positivity rate values are listed in Table 2. (C) Odds of infection with Omicron relative to Delta variants by age, sex, and vaccination status among individuals who tested positive for SARS-CoV-2. We regressed the binary outcome for the SARS-CoV-2 variant (Delta as the reference group) and specified females and unvaccinated persons as the reference categories for the sex and vaccination status predictor variables in the model. ORs >1 indicate higher odds of detecting Omicron relative to Delta in persons testing positive for SARS-CoV-2 infection. Data shown as means with 95% confidence intervals. The OR values are listed in Table S1. The positivity rates and ORs stratified by vaccine manufacturers are shown in Figure S2 and Table S2.

Figure 2

Effect of sex, age, variant, and vaccination status on the nasal swab PCR cycle threshold (A) Nasal swab PCR cycle threshold (Ct) values for the Delta and Omicron SARS-CoV-2 variants by vaccination status. Data shown as means with 95% confidence intervals. (B) Association of age, sex, and vaccination status with PCR Ct values. The effect sizes >1 indicate a higher CT value (lower virus RNA) for Omicron compared to Delta, males relative to females, and vaccinated relative unvaccinated persons who received different doses. Data shown as means with 95% confidence intervals. The OR values are shown in Table S3. (C) Association of age, sex, vaccination status, and vaccine manufacturer with PCR Ct values. Data shown as means with 95% confidence intervals. The OR values are shown in Table S4.