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

Abstract

\n Background\n Nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. We performed an outbreak investigation using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission.\n \n Methods\n We investigated a nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic, involving patients and HCWs, with high coverage of pathogen whole genome sequences (WGS). We estimated the time-varying reproduction number from epidemiological data (Rt) and produced a maximum likelihood phylogeny to assess genetic diversity of the pathogen. We combined genomic and epidemiological data into a Bayesian framework to model directionality of transmission. We performed a Case-control study to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients.\n \n Findings\n The outbreak spanned from March 14 to April 12, 2020 and involved 37 patients (31 with WGS) and 39 employees (31 with WGS) of whom 37 are HCWs. We estimated a peak R\n \n t\n between 2.2 – 3.6. The phylogenetic tree showed very limited genetic diversity, with 60/62 (96.7%) isolates forming one large cluster of identical genomes. Despite the resulting uncertainty in reconstructed transmission events, our analyses suggest that HCWs (one of whom was the index Case) played an essential role in cross-transmission, with a significantly larger fraction of infections (p < 2.2e-16) attributable to HCWs (70.7%) than expected given the number of HCWs cases (46.7%). The excess of transmission from HCWs was larger when considering infection of patients (79.0%; 95%CI 78.5% - 79.5%), and especially frail patients (Clinical Frailty Scale >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 OR 6.94; 95%CI 2.13 – 22.57).\n \n Interpretation\n 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, our study shows that despite such uncertainty, significant transmission patterns can be observed.\n