Utilizing Genomic Epidemiology to Explore SARS CoV-2 Transmission Patterns and Support Outbreak Investigations in Long Term Care Facilities, Washington State, April-October 2021

ABSTRACT

Background. In Washington State, COVID-19 cases in long-term care facilities (LTCF) have accounted for less than 3% of all cases, yet 30% of all COVID-19 deaths. Understanding transmission patterns and outbreak epidemiology informs outbreak management. From April to October 2021, two large LTCFs experienced COVID-19 outbreaks. Whole genome sequencing and phylogenetic analysis were leveraged to explore transmission patterns and complement outbreak epidemiology. Methods. Epidemiologic data was exported from the Washington Disease Reporting System. Sequences, retrieved from GISAID, were aligned to the Wuhan-1 reference genome using Nextalign version 1.11.0. Pairwise single nucleotide polymorphism (SNP) distance matrices were calculated using SNP-Dists version 0.8.2. Phylogenetic trees for each outbreak were generated using IQ-Tree multicore version 2.2.0-beta COVID-edition using the GTR+F+G4 nucleotide substitution model with 1000 bootstrap replicates. MicrobeTrace was used to visualize the phylogeny, SNP heatmap, and identify clusters among sequences. Results. Weekly, LTCF A tested 162 residents and 800 staff, and LTCF B tested 60 residents and 144 staff. Of all cases in LTCF A (n= 119), 23% (n =27) were residents and 77% (n = 92) were staff, compared to 78% (n =28) residents and 22% (n =7) staff among total LTCF B cases (n=36). In LTCF A, 34% (n=40) of the cases had highquality sequences available. Seven clusters of two or more genetically related sequences and thirteen genetically unrelated sequences were identified. Five of the clusters involved resident and staff cases, linked by unit. Two clusters and remaining unrelated sequences were among staff. In LTCF B, 40% (n=14) of the cases had high-quality sequences available. One cluster of genetically related sequences was identified, all from residents of two floors. The SNP differences between sequences from LTCF A ranged from 0 to 70, whereas SNP differences between LTCF B sequences ranged from 0 to 6. Conclusion. Phylogenetic analysis of the two outbreaks confirms differences in disease transmission patterns. Multiple independent introductions of SARS-CoV-2 were identified in LTCF A, compared to a single introduction in LTCF B. Genomic epidemiology is a valuable resource for outbreak investigation and management.