Genomic surveillance of SARS-CoV-2 Omicron variants on a university campus

The SARS-CoV-2 pandemic has been characterized by the continuous emergence of new variants of concern (VOCs), posing significant challenges to public health efforts. The Omicron variant (B.1.1.529), designated a VOC by the World Health Organization on November 26, 2021, rapidly spread globally, demonstrating enhanced transmissibility despite widespread vaccination and pre-existing immunity. Omicron's increased transmissibility and the observed decrease in vaccine effectiveness against it compared to the Delta variant resulted in substantial numbers of breakthrough infections. Studies have yielded mixed results regarding differences in viral load between Omicron and Delta. Understanding Omicron's transmission dynamics, particularly within households, is crucial for effective public health interventions. University settings, with their established testing programs, offer valuable opportunities for real-time epidemiologic and genomic surveillance. This study leverages data collected from a university campus testing program to characterize the emergence and transmission dynamics of the Omicron variant compared to the Delta variant in a highly vaccinated population.

Prior research has highlighted the importance of genomic surveillance in tracking the evolution and spread of SARS-CoV-2 variants. Several studies have investigated the transmission characteristics of Omicron, reporting higher attack rates and shorter serial intervals within households compared to Delta. However, the majority of these studies lacked genomic data to precisely assess serial intervals, potentially leading to biases. Differences in viral load between Omicron and Delta have also been inconsistently reported across studies. Existing research underscores the need for longitudinal genomic data to fully understand Omicron's unique transmission dynamics and its impact on vaccinated populations.

This study utilized data from the Husky Coronavirus Testing (HCT) research study at the University of Washington, which provided free SARS-CoV-2 testing to students, faculty, and staff. Between September 10, 2021 and February 14, 2022, 74,955 samples were collected from 24,393 participants, with 3,630 (4.8%) testing positive. Genomic sequencing was performed on 2,101 samples from 1,939 individuals, identifying Delta and Omicron infections. Data on demographic characteristics, symptoms, vaccination status, and household exposure were collected through electronic questionnaires. The serial interval between genetically identical symptomatic infections within households was determined. Phylogenetic analyses were conducted to trace the spread of variants on campus and estimate the number of introduction events. Statistical analyses included Pearson's chi-squared tests, Mann-Whitney U tests, and multiple linear regression models. Swab types used were US Cotton #3 swabs and RHINOstic™ Automated Nasal Swabs. Cycle threshold (Ct) values were analyzed to assess viral load. Phylogenetic trees were constructed using Nextstrain software, incorporating both study genomes and publicly available Washington state genomes from GISAID.

A total of 1,939 individuals had their SARS-CoV-2 infections sequenced, revealing 209 Delta and 1,730 Omicron cases. Omicron had a significantly shorter median serial interval between genetically identical, symptomatic infections within households (2 days compared to 6 days for Delta, P=0.021). Omicron also demonstrated a greater basic reproductive number (R) of 2.4 compared to 1.8 for Delta. The mean cycle threshold (Ct) value for Omicron was 1.07 lower than Delta (95% CI: 0.58, 1.57; P<0.0001), suggesting a potentially higher viral load for Omicron. Despite near-universal vaccination and stringent mitigation measures, Omicron rapidly replaced Delta as the predominant strain on campus. Phylogenetic analysis indicated that the Delta cases resulted from 83 separate introductions, with an average of 2.5 sequenced cases per introduction. In contrast, the Omicron variant showed a more dispersed distribution on the phylogenetic tree, suggesting multiple introduction events and rapid diversification within the campus community. Analysis of symptom profiles revealed that fever, myalgia, and chills were more common in Omicron cases, while loss of taste and smell was more prevalent in Delta cases.

The rapid displacement of the Delta variant by Omicron on a highly vaccinated university campus, despite stringent mitigation measures, highlights Omicron's exceptional transmissibility. The shorter serial interval observed for Omicron underscores its capacity for rapid spread within households. The difference in symptom profiles may aid in distinguishing between Delta and Omicron infections, although the overlap warrants caution. The phylogenetic analysis revealed distinct transmission patterns for Delta and Omicron, with Delta showing concentrated clusters suggestive of fewer introduction events and Omicron demonstrating a more dispersed pattern reflecting multiple introductions and rapid diversification. These findings emphasize the importance of integrating genomic surveillance into university testing programs to enhance understanding of VOC spread and to facilitate timely public health interventions.

This study demonstrates the rapid replacement of Delta by Omicron in a highly vaccinated university population, emphasizing the importance of ongoing genomic surveillance. The shorter serial interval, higher R value, and potentially higher viral load of Omicron underscore its increased transmissibility. Future research could explore the impact of Omicron sublineages on transmission dynamics and the effectiveness of vaccination strategies against these variants in various settings.

The study's limitations include the focus on a single university campus, potentially limiting the generalizability of the findings. The reliance on self-reported symptom and vaccination data may introduce biases. Changes in swab types during the study could have affected viral load assessments. The study also did not include repeat infections, which may have influenced the results.