Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study
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).
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
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.
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.
- Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States
- 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)
© 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.
- Page views
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.
Social touch constitutes a key component of human social relationships, although in some conditions with social dysfunction, such as autism, it can be perceived as unpleasant. We have previously shown that intranasal administration of oxytocin facilitates the pleasantness of social touch and activation of brain reward and social processing regions, although it is unclear if it influences responses to gentle stroking touch mediated by cutaneous C-touch fibers or pressure touch mediated by other types of fibers. Additionally, it is unclear whether endogenous oxytocin acts via direct entry into the brain or by increased peripheral blood concentrations.
In a randomized controlled design, we compared effects of intranasal (direct entry into the brain and increased peripheral concentrations) and oral (only peripheral increases) oxytocin on behavioral and neural responses to social touch targeting C-touch (gentle-stroking) or other (medium pressure without stroking) cutaneous receptors.
Although both types of touch were perceived as pleasant, intranasal and oral oxytocin equivalently enhanced pleasantness ratings and responses of reward, orbitofrontal cortex, and social processing, superior temporal sulcus, regions only to gentle-stroking not medium pressure touch. Furthermore, increased blood oxytocin concentrations predicted the pleasantness of gentle stroking touch. The specificity of neural effects of oxytocin on C-touch targeted gentle stroking touch were confirmed by time-course extraction and classification analysis.
Increased peripheral concentrations of oxytocin primarily modulate its behavioral and neural responses to gentle social touch mediated by C-touch fibers. Findings have potential implications for using oxytocin therapeutically in conditions where social touch is unpleasant.
Key Technological Projects of Guangdong Province grant 2018B030335001.
Clinical trial number: