Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study
- Geneva University Hospitals, Switzerland
- Imperial College London, United Kingdom
Abstract
Background: There is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings.
Methods: We performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, to determine who infected whom. We evaluated general transmission patterns according to case type (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each case type across all posterior trees and comparing them to random expectations.
Results: During the study period (March 1 to May 7, 2020) we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10-19% for patients, and 21% for HCWs. We estimated that 16 importation events occurred with high confidence (four patients, 12 HCWs) that jointly led to up to 41 secondary cases; in six additional cases (five HCWs, one patient), importation was possible with a posterior between 10-50%. Most patient-to-patient transmission events involved patients having shared a ward (95.2%, 95% credible interval [CrI] 84.2-100%), in contrast to those having shared a room (19.7%, 95%CrI 6.7-33.3%). Transmission events tended to cluster by case type: patientnoso were almost twice as likely to be infected by other patientnoso than expected (observed:expected ratio 2.16, 95%CrI 1.17 - 4.20, p = 0.006); similarly, HCWoutbreak were more than twice as likely to be infected by other HCWoutbreak than expected (2.72, 95%CrI 0.87-9.00, p = 0.06). The proportion of infectors being HCWcovid was as expected as random. We found a trend toward a greater proportion of high transmitters (≥2 secondary cases) among HCWoutbreak than patientnoso in the late phases (28.6% vs. 11.8%) of the outbreak, although this was not statistically significant.
Conclusions: Most importation events were linked to HCW. Unexpectedly, transmission between HCWcovid was more limited than transmission between patients and HCWoutbreak. This finding highlights gaps in infection control and suggests possible areas of improvements to limit the extent of nosocomial transmission.
Funding: This work was supported by a grant from the Swiss National Science Foundation under the NRP78 funding scheme (Grant no. 4078P0_198363).
Data availability
Due to small size of the various clusters, the raw clinical data will not be shared to safeguard anonymity of patients and healthcare workers. Processed data of the output of the model, which will comprise the posterior distribution of infectors, will be made available in an anonymized version. This will allow reproducing the analyses looking at the proportion of healthcare workers among infectors, and the number of secondary infections. This data will not allow reconstruction of the transmission tree, which would require the raw data. The raw data in an anonymized format will be made available upon reasonable and justified request, subject to approval by the project's Senior Investigator. The genomic sequencing data have been submitted to the Genbank repository (GenBank accession numbers: ON209723-ON209871).
Article and author information
Author details
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (4078P0_198363)
- Mohamed Abbas
- Dr Anne Cori
- Samuel Cordey
- Florian Laubscher
- Tomás Robalo Nunes
- Anne Iten
- Stephan Harbarth
National Institute for Health Research Health Protection Research Unit (NIHR200908)
- Mohamed Abbas
- Dr Anne Cori
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
Ethics
Human subjects: The Ethics Committee of the Canton of Geneva (CCER), Switzerland, approved this study (CCER no. 2020-01330 and CCER no. 2020-00827). Written informed consent was obtained from HCWs. Written informed consent was not required for patients as data were generated in a context of mandatory surveillance.
Version history
- Received: January 6, 2022
- Preprint posted: January 10, 2022 (view preprint)
- Accepted: July 3, 2022
- Accepted Manuscript published: July 19, 2022 (version 1)
- Version of Record published: July 27, 2022 (version 2)
Copyright
© 2022, Abbas et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study
eLife 11:e76854.
https://doi.org/10.7554/eLife.76854
Further reading
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- Medicine
- Neuroscience
Background:
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.
Methods:
We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.
Results:
We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.
Conclusions:
These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry.
Funding:
This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1–190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016–0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 – 2056) (FXV).
Clinical trial number:
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