Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data

Abstract

Background: Rapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding potential transmission clusters, but the low mutation rate of SARS-CoV-2 can make interpretation using standard phylogenetic methods difficult. Methods: We developed a novel statistical method and sequence reporting tool (SRT) that combines epidemiological and sequence data in order to provide a rapid assessment of the probability of HCAI among HOCI cases (defined as first positive test >48 hours following admission) and to identify infections that could plausibly constitute outbreak events. The method is designed for prospective use, but was validated using retrospective datasets from hospitals in Glasgow and Sheffield collected February-May 2020. Results: We analysed data from 326 HOCIs. Among HOCIs with time-from-admission >8 days the SRT algorithm identified close sequence matches from the same ward for 160/244 (65.6%) and in the remainder 68/84 (81.0%) had at least one similar sequence elsewhere in the hospital, resulting in high estimated probabilities of within-ward and within-hospital transmission. For HOCIs with time-from-admission 3-7 days, the SRT probability of healthcare acquisition was >0.5 in 33/82 (40.2%). Conclusions: The methodology developed can provide rapid feedback on HOCIs that could be useful for infection prevention and control teams, and warrants further prospective evaluation. The integration of epidemiological and sequence data is important given the low mutation rate of SARS-CoV-2 and its variable incubation period. Funding: COG-UK HOCI funded by COG-UK consortium, supported by funding from UK Research and Innovation, National Institute of Health Research and Wellcome Sanger Institute.

The Alpha variant was not associated with excess nosocomial SARS-CoV-2 infection in a multi-centre UK hospital study

“…The definition of an outbreak was considered carefully. Previous outbreak data suggest that the mutation rate of SARS-CoV-2 is low, with an average of less than one fixed mutation occurring for each transmission 33 . Nonetheless, up to 2 single nucleotide differences have been described in viruses that are known to be part of a single nosocomial outbreak 34 .…”

“…Notably though, sequencing of 694 cases, from three labs not using Ct thresholds with available Ct data, did not find any difference in the distribution of genotypes in samples with Ct values below and above 32 (supplementary figure 1). A second limitation of our work is that towards the end of the study all three trusts outside London were using a sequence reporting tool (SRT), as part of the HOCI study 33 , rather than phylogenetic analysis alone to help determine whether cases were part of linked outbreaks. It is not known whether the SRT may have limited the extent of outbreaks as data processing and analysis for the HOCI study is still ongoing.…”

Combined epidemiological and genomic analysis of nosocomial SARS-CoV-2 infection early in the pandemic and the role of unidentified cases in transmission

“…Previous literature discusses the probability of acquiring SNPs between cases based on the mutation rate of SARS-CoV-2, estimating a 24% chance of one new SNP and 4% of two new SNPs per generation (further in Supplementary Methods) [24]. Assuming all relevant cases were captured, for our 77 sequenced nosocomial cases one expects 0.04*77=3.1 cases to differ by ≥2 SNPs from their infection source.…”

Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals

“…The study will evaluate the contribution of whole-genome sequencing combined with a novel viral sequence report design to IPC investigation and response to cases of hospital-onset COVID-19infection, and whether this can reduce the overall incidence of hospital-acquired infections. 10 …”