Phylogeographic and genetic network assessment of COVID-19 mitigation protocols on SARS-CoV-2 transmission in university campus residences

Abstract

Background: Congregate living provides an ideal setting for SARS-CoV-2 transmission in which many outbreaks and superspreading events occurred. To avoid large outbreaks, universities turned to remote operations during the initial COVID-19 pandemic waves in 2020 and 2021. In late-2021, the University of California San Diego (UC San Diego) facilitated the return of students to campus with comprehensive testing, vaccination, masking, wastewater surveillance, and isolation policies.

Methods: We performed molecular epidemiological and phylogeographic analysis of 4418 SARS-CoV-2 genomes sampled from UC San Diego students during the Omicron waves between December 2021 and September 2022, representing 58% of students with confirmed SARS-CoV-2 infection. We overlaid these analyses across on-campus residential information to assess the spread and persistence of SARS-CoV-2 within university residences.

Findings: Within campus residences, SARS-CoV-2 transmission was frequent among students residing in the same room or suite. However, a quarter of pairs of suitemates with concurrent infections had distantly related viruses, suggesting separate sources of infection during periods of high incidence in the surrounding community. Students with concurrent infections residing in the same building were not at substantial increased probability of being members of the same transmission cluster. Genetic network and phylogeographic inference indicated that only between 3.1 and 12.4% of infections among students could be associated with transmission within buildings outside of individual suites. The only super-spreading event we detected was related to a large event outside campus residences.

Interpretation: We found little evidence for sustained SARS-CoV-2 transmission within individual buildings, aside from students who resided in the same suite. Even in the face of heightened community transmission during the 2021-2022 Omicron waves, congregate living did not result in a heightened risk for SARS-CoV-2 transmission in the context of the multi-pronged mitigation strategy.

Funding: SEARCH Alliance: Centers for Disease Control and Prevention (CDC) BAA (75D301-22-R-72097) and the Google Cloud Platform Research Credits Program. J.O.W.: NIH-NIAID (R01 AI135992). T.I.V.: Branco Weiss Fellowship and Newkirk Fellowship. L.L.: University of California San Diego.

Keywords: Mitigation; Phylogeography; SARS-CoV-2; Transmission cluster; University.

Fig. 1

Residential contact network among students with concurrent SARS-CoV-2 infections. The residential connections between students in clusters with ≥10 students. Each student is represented by a black dot. Lines between nodes denote a residential connection. Bold lines indicate genetic linkage between pairs of students. Dashed lines indicate genetically unlinked pairs of students. The type of residential connection is denoted by colour, as shown in the key.

Fig. 2

Genetic links between students in network analysis. The expected and observed number of viral genetic links for students with concurrent SARS-CoV-2 diagnoses by (A) suite, (B) floor, and (C) building are shown: solid bar is the observed number of genetically linked student pairs. The density distribution shows the number of expected genetically linked student pairs in each category based on 10,000 permutations. For building, expected links are shown based on total expectation and expectation conditioned on membership in the same residential college (i.e., group of buildings).

Fig. 3

Pairs of students with concurrent SARS-CoV-2 diagnoses residing in the same building, floor, or suite and the strength of evidence for genetic linkage. Darker colour indicates stronger evidence that the link is supported based on binomial expectation. High support (<5% expectation of coincidental linkage), moderate support (5–50% expectation of coincidental linkage), and low support (>50% expectation of coincidental linkage). Light colouring denotes student pairs with genetically distantly related viruses. The area of the grey circle is proportional to the total number of links represented.

Fig. 4

Suitemates with concurrent SARS-CoV-2 diagnoses. (a) Total number of mutations and (b) number of days separating concurrently diagnosed pairs of suitemates. (c) Genetically linked and unlinked suitemates are shown by week over time relative to the total number of students with a SARS-CoV-2 infection with documentation of on-campus residence and off-campus. Grey bars denote academic quarters. Grey points denotes the total number of weekly SARS-CoV-2 diagnoses in San Diego County, which is shown on a different scale.

Fig. 5

Phylogenetic trees depicting building trees from phylogeographic analysis. Omicron sub-variants are shown separately: (a) BA.1, (b) BA.2, (c) BA.4, (d) BA.5. Bold red lineages indicate virus from students residing in the same building, floor, or suite. Blue bar in BA.2 tree denotes the polytomy defined by the T22054G mutation. Scale bar reflects time in days. The number of genomes in each sub-variant phylogeny is reported at the root.

Fig. 6

Building-level clusters that persisted for at least 7 days. Cases are plotted as the number of days since the diagnosis of the index case. Days on which multiple students were diagnosed within a cluster are placed both above and below the line.