Nosocomial transmission clusters and lineage diversity characterized by SARS-CoV-2 genomes from two large hospitals in Paris, France, in 2020

Abstract

France went through three deadly epidemic waves due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing major public health and socioeconomic issues. We proposed to study the course of the pandemic along 2020 from the outlook of two major Parisian hospitals earliest involved in the fight against COVID-19. Genome sequencing and phylogenetic analysis were performed on samples from patients and health care workers (HCWs) from Bichat (BCB) and Pitié-Salpêtrière (PSL) hospitals. A tree-based phylogenetic clustering method and epidemiological data were used to investigate suspected nosocomial transmission clusters. Clades 20A, 20B and 20C were prevalent during the spring wave and, following summer, clades 20A.EU2 and 20E.EU1 emerged and took over. Phylogenetic clustering identified 57 potential transmission clusters. Epidemiological connections between participants were found for 17 of these, with a higher proportion of HCWs. The joint presence of HCWs and patients suggest viral contaminations between these two groups. We provide an enhanced overview of SARS-CoV-2 phylogenetic changes over 2020 in the Paris area, one of the regions with highest incidence in France. Despite the low genetic diversity displayed by the SARS-CoV-2, we showed that phylogenetic analysis, along with comprehensive epidemiological data, helps to identify and investigate healthcare associated clusters.

Figure 1

Overall distribution of PANGO lineages identified during year 2020 within Pitié-Salpêtrière hospital (a) and Bichat Claude-Bernard hospital (b), two French hospitals located in the Parisian urban area. The x-axis represents each month, the left y-axis the percentage of each lineage and the right y-axis the number of SARS-CoV-2 genomes sequenced per month within our study (grey zone).

Figure 2

Phylogenetic tree showing 736 SARS-CoV-2 completes genomes from health care workers and patients from Bichat Claude-Bernard and Pitié-Salpêtrière hospitals, Paris, France, over the year 2020. The maximum likelihood phylogenetic tree was inferred from the alignment of the 736 reconstructed full SARS-CoV-2 genomes and 2932 worldwide sequences extracted from GISAID database, with IQTREE v2.0 with a GTR + G nucleotide substitution model, 1000 ultrafast bootstrap replicates and using Wuhan Hu-1 genome (NC_045512.2) as an outgroup. For greater clarity, 2932 worldwide representative sequences extracted from GISAID database were masked from the phylogenetic tree representation.

Figure 3

Large clusters (4 to 11 participants) identified by phylogenetic clustering and validated by epidemiological investigations. Overview of 8 large clusters from Bichat Claude-Bernard (blue squares) and Pitié-Salpêtrière (red circles) hospitals identified by phylogenetic clustering and confirmed by epidemiological investigations. Health care workers (HCWs) and patients were identified by stars or triangles symbols, respectively. Wards of participants from clusters were indicated by a color code.