Explosive nosocomial outbreak of SARS-CoV-2 in a rehabilitation clinic: the limits of genomics for outbreak reconstruction

Abstract

Background: Nosocomial outbreaks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. An outbreak investigation was undertaken using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission.

Methods: A nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic was investigated, involving patients and HCWs, with high coverage of pathogen whole-genome sequences (WGS). The time-varying reproduction number from epidemiological data (R_t) was estimated, and maximum likelihood phylogeny was used to assess genetic diversity of the pathogen. Genomic and epidemiological data were combined into a Bayesian framework to model the directionality of transmission, and a case-control study was performed to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients.

Findings: The outbreak lasted from 14^th March to 12^th April 2020, and involved 37 patients (31 with WGS) and 39 employees (31 with WGS), 37 of whom were HCWs. Peak R_t was estimated to be between 2.2 and 3.6. The phylogenetic tree showed very limited genetic diversity, with 60 of 62 (96.7%) isolates forming one large cluster of identical genomes. Despite the resulting uncertainty in reconstructed transmission events, the analyses suggest that HCWs (one of whom was the index case) played an essential role in cross-transmission, with a significantly greater fraction of infections (P<2.2e-16) attributable to HCWs (70.7%) than expected given the number of HCW cases (46.7%). The excess of transmission from HCWs was higher when considering infection of patients [79.0%; 95% confidence interval (CI) 78.5-79.5%] and frail patients (Clinical Frailty Scale score >5; 82.3%; 95% CI 81.8-83.4%). Furthermore, frail patients were found to be at greater risk for nosocomial COVID-19 than other patients (adjusted odds ratio 6.94, 95% CI 2.13-22.57).

Interpretation: This outbreak report highlights the essential role of HCWs in SARS-CoV-2 transmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, this study shows that despite such uncertainty, significant transmission patterns can be observed.

Keywords: COVID-19; Healthcare-associated infection; Infection prevention and control; Long-term care facilities; Nosocomial outbreaks; SARS-CoV-2.

Figure 1

(A) Epidemic curve of the nosocomial outbreak of coronavirus disease 2019 (COVID-19) in a rehabilitation clinic involving healthcare workers (HCWs) and patients. (B) Estimated time-varying reproduction number (R_t) across the duration of the outbreak. (C) Timeline of infection prevention and control interventions implemented hospital-wide (Geneva University Hospitals), and specifically in the rehabilitation clinic. I, group activities with patients suspended; II, cafeterias only open to employees; III, universal masking (HCWs); IV, visitors banned; V, physical distancing in cafeterias; a, meals in rooms for patients; b, room confinement for patients on second floor; c, single bed rooms only (second floor); d, ward closure on second floor; e, ward attribution to physical therapists; f, daily meetings with infection prevention and control (IPC) nurse; g, pre-emptive contact and droplet precautions in wards with at least one patient with COVID-19; h, reminder of IPC measures; i, universal masking outside room (patients); j, systematic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) screening of all patients on second floor; k, systematic SARS-CoV-2 screening of all patients on first floor; l, ward closure on first floor; m, systematic SARS-CoV-2 screening of all admissions; n, ward closure ground floor. PPE, personal protective equipment; CrI, credible interval.

Figure 2

Phylogenetic tree of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genome sequences. The tree includes 62 sequences related to the outbreak (patient and employee sequences are named C2xx and H20xx, respectively), alongside all the community cases in the canton of Geneva that were sequenced in March–April 2020 and submitted to GISAID [virus names and accession ID (i.e. EPI_ISL_) are indicated] in the context of an epidemiological surveillance. For each sequence, the date of the sample collection is mentioned (yyyy-mm-dd).

Figure 3

Selected output of the outbreaker2 model. (A) Ancestry reconstruction. (B) Transmission tree from Markov-Chain Monte-Carlo iteration with highest likelihood. Patients and employees are named C2xx and H20xx, respectively. HCW, healthcare worker.

Figure 4

Proportions of transmissions attributed to healthcare workers (HCWs) (f_HCW). The blue histograms indicate the expected binomial distributions of f_HCW given the proportion of HCWs amongst cases. The red histograms show the distribution of f_HCW across 999 transmission trees reconstructed by outbreaker2. Dotted lines indicate the mean estimate of the proportion. (A) All cases. (B) Transmission to HCWs alone. (C) Transmission to patients alone. (D) Transmission to frail patients alone.