Genomic epidemiology of SARS-CoV-2 in a university outbreak setting and implications for public health planning

Abstract

Whole genome sequencing of SARS-CoV-2 has occurred at an unprecedented scale, and can be exploited for characterising outbreak risks at the fine-scale needed to inform control strategies. One setting at continued risk of COVID-19 outbreaks are higher education institutions, associated with student movements at the start of term, close living conditions within residential halls, and high social contact rates. Here we analysed SARS-CoV-2 whole genome sequences in combination with epidemiological data to investigate a large cluster of student cases associated with University of Glasgow accommodation in autumn 2020, Scotland. We identified 519 student cases of SARS-CoV-2 infection associated with this large cluster through contact tracing data, with 30% sequencing coverage for further analysis. We estimated at least 11 independent introductions of SARS-CoV-2 into the student population, with four comprising the majority of detected cases and consistent with separate outbreaks. These four outbreaks were curtailed within a week following implementation of control measures. The impact of student infections on the local community was short-term despite an underlying increase in community infections. Our study highlights the need for context-specific information in the formation of public health policy for higher educational settings.

Figure 1

(a) Numbers of University of Glasgow student cases identified from contact tracing information over time, and (b) for the subset with sequenced samples, according to university residential halls or private accommodation. (c) Frequency distributions of SARS-CoV-2 lineages and (d) unique sequences identified among the student cases.

Figure 2

Phylogenetic tree of high quality genome sequences collected from University of Glasgow students. The reference sequence Wuhan Hu-1 (GenBank accession MN90894) was included as an outgroup. Four notable clades of sequences were identified, corresponding to cases that were putatively linked via direct transmission, as identified by the A2B-COVID software package. Shades of gray indicate three other sets of putatively linked cases. The phylogenetic analysis was conducted using iQ-Tree2, while the figure was made with iTOL. The tree scale indicates the fraction of sites in the genome at which substitutions were observed. The tree scale bar denotes nucleotide substitutions per site.

Figure 3

Potential origins of major SARS-CoV-2 clades identified in the University of Glasgow (UoG) student population. Numbers of UoG student sequences associated with each major clade (left column) are shown alongside data describing the associated UK-wide clades. Figures show the proportion of SARS-CoV-2 sequences collected each week in Scotland (middle column) and in the rest of the UK (right column) that were associated with each student clade, coloured by the regions in which the clade-associated sequences were collected. Total numbers of sequences informing this analysis were as follows: Clade 1 n = 412; Clade 2 n = 255; Clade 3 n = 541; Clade 4 n = 4006.

Figure 4

Dates of sequenced PCR-confirmed cases of SARS-CoV-2 infection identified in University of Glasgow students resident in halls or private accommodation, coloured by transmission clade. Data is shown for residential halls in which a minimum of four cases were observed. The identification of viruses from multiple transmission clusters in many of the residential halls suggests that there were multiple introductions of SARS-CoV-2 into each hall.

Figure 5

Phylogenetic relationship between student (red) and community (blue) sequences associated with transmission clade 1. Shades indicate the week in which sequences were collected, the lightest colour indicating dates before and including the week of 14th September, and the darkest colour indicating dates from the 5th October onwards. Community sequences describe those identified in NHS Greater Glasgow and Clyde sharing a common ancestor with the student sequences. Student and community cases were observed in multiple subclades of the tree, indicating ongoing transmission between the students and local community. Phylogenetic analysis was conducted using iQ-Tree2, while the figure was made with iTOL.

Figure 6

Age-stratified 7-day rolling proportions of PCR-confirmed cases of SARS-CoV-2 infection (test positivity) among all tested individuals in the City of Glasgow community [excluding University of Glasgow (UoG) students], and in comparison with the rest of Scotland, excluding the City of Glasgow. The vertical lines indicate the start of the UoG student halls cluster around 19th September 2020.

Figure 7

Age distribution of SARS-CoV-2 cases among residents of NHS Greater Glasgow and Clyde with sequences that phylogenetically clustered with each University of Glasgow (UoG) student transmission clade. UoG student cases were excluded. Numbers of sequences informing this analysis were as follows: Clade 1 n = 163, Clade 2 n = 27, Clade 3 n = 362, Clade 4 n = 106.