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Combined epidemiological and molecular investigation of 3 nosocomial outbreaks of SARS-CoV-2 cross-infection

English title Combined epidemiological and molecular investigation of 3 nosocomial outbreaks of SARS-CoV-2 cross-infection
Applicant Harbarth Stephan Jürgen
Number 198363
Funding scheme NRP 78 Covid-19
Research institution Infection Control Program Hôpitaux Universitaires de Genève Faculté de Médecine, Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Methods of Epidemiology and Preventive Medicine
Start/End 01.08.2020 - 30.04.2022
Approved amount 251'700.00
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All Disciplines (2)

Discipline
Methods of Epidemiology and Preventive Medicine
Infectious Diseases

Keywords (6)

Infection prevention; SARS-CoV-2; COVID-19; Healthcare-associated infection; Outbreaks; Healthcare workers

Lay Summary (German)

Lead
Ziel dieses Projekts ist eine bessere Kenntnis der Übertragung von SARS-CoV-2 bei Spitalinfektionen, unter besonderer Berücksichtigung der Rolle des medizinischen Fachpersonals. Bei der Rückverfolgung der Ausbreitung werden epidemiologische und genetische Daten berücksichtigt.
Lay summary

Hintergrund

Im Verlauf der COVID-19-Pandemie ereigneten sich drei (sogenannte nosokomiale) Ausbrüche in drei Abteilungen des Genfer Universitätsspitals. Die Ausbrüche wurden durch verbesserte Prävention und Kontrollen erfolgreich eingedämmt. Neben der Versorgung der mit SARS-CoV-2 infizierten Patienten hat der Schutz des medizinischen Fachpersonals (MFP) höchste Priorität. Auch der Schutz der nicht mit COVID-19 infizierten Patienten ist zentral. Gefährdete Patienten in Geriatrie- und Langzeitpflegeeinrichtungen müssen besonders geschützt werden.

Forschungsziele

Zentrales Anliegen dieser Studie ist die Rekonstruktion von Infektionsketten mithilfe epidemiologischer und genetischer Daten, um die Infektionsdynamik verstehen und zusätzliche Präventivmassnahmen ergreifen zu können. Insbesondere wollen wir:

  • bei den Ausbrüchen die Übertragungswege ermitteln und Infektionsketten nachvollziehen.

  • die Infektionsrichtung erkennen: MFP zu MFP, MFP zu Patient, Patient zu MFP oder Allgemeinheit zu MFP.

Erwartete Ergebnisse und Produkte

Dies ist eine retrospektive Kohortenstudie über COVID-19-Cluster mit 104 Patienten und 185 MFP in drei verschiedenen Abteilungen des Genfer Universitätsspitals. Wir erheben klinische und epidemiologische Daten aller von den Ausbrüchen betroffenen SARS-CoV-2-Patienten und MFP, erstellen Epidemie-Kurven für Patienten und Personal der einzelnen Stationen und berechnen die Neuinfektionen sowie die Verdopplungszeiten. Anhand dieser Daten rekonstruieren wir die vermutliche Infektionskette. Dank DNA-Sequenzierung können wir noch genauere Aussagen treffen als mit einer rein epidemiologischen Analyse und einzelne Cluster sowie eingeschleppte Infektionen erkennen.

Beitrag zur Bewältigung der aktuellen Pandemie

Die Analyse dieser Spitalinfektionen liefert uns wichtige Erkenntnisse über die Infektionsdynamik von SARS-CoV-2 im Gesundheitsbereich, die zum Schutz des medizinischen Fachpersonals und der Patienten in die Leitlinien für die Prävention und Kontrolle von Pandemiewellen übernommen werden. Die Studie belegt auch den Mehrwert der DNA-Sequenzierung für die Ermittlung der komplexen Verbreitung von SARS-CoV-2 in Spitälern. Um die Präventivmassnahmen der MFP in Hochrisiko-Bereichen zu verbessern, wurde mithilfe der epidemiologischen Erkenntnisse ein eLearning-Tool entwickelt.

Direct link to Lay Summary Last update: 22.12.2020

Lay Summary (French)

Lead
Le but de ce projet est de mieux comprendre la dynamique de transmission du SARS-CoV-2 dans les flambées nosocomiales et, en particulier, le rôle des soignants. Nous voulons combiner des données épidémiologiques et génétiques afin de reconstituer les mécanismes de transmission.
Lay summary

Contexte

Au cours de la pandémie de COVID-19, trois flambées nosocomiales sont apparues sur des sites distincts des Hôpitaux Universitaires de Genève. Elles ont été maîtrisées avec succès en renforçant les mesures de prévention et de contrôle des infections. La protection des professionnels de la santé est une priorité essentielle lors de la prise en charge des patients infectés par le SARS-CoV-2. De même, la prévention du COVID-19 associé aux soins chez les patients ne souffrant pas du COVID-19 est primordiale. Une attention particulière doit être accordée aux patients vulnérables dans les établissements de soins de longue durée et en gériatrie.

Objectifs de recherche

L’objectif principal de cette étude est de reconstituer les flambées en combinant des données épidémiologiques et génétiques afin de comprendre la dynamique de transmission du SARS-CoV-2 et d’améliorer les pratiques de contrôle des infections ainsi que d’envisager des stratégies préventives supplémentaires. Les buts spécifiques comprennent :

  • la détermination des voies de transmission du virus lors des flambées épidémiques et la reconstitution du mécanisme de transmission

  • l’identification du sens de la transmission, par exemple de soignant à soignant, de soignant à patient, de patient à soignant ou de la population générale à un soignant.

Résultats et produits envisagés

Il s’agit d’une étude de cohorte rétrospective de foyers épidémiques de COVID-19 comprenant 104 patients et 185 soignants sur trois sites distincts des Hôpitaux Universitaires de Genève. Nous voulons recueillir les données cliniques et épidémiologiques de tous les patients et soignants infectés par le SARS-CoV-2 au cours de ces flambées nosocomiales. Nous construirons des courbes épidémiques par service pour les patients et les soignants et calculerons les taux d’attaque et les temps de doublement. Ces données nous aideront à construire le mécanisme présumé de transmission. Les données de séquençage génétique permettront d’affiner la résolution de cette analyse et d’identifier les foyers épidémiques et les cas importés qui n’auraient pas pu être reconnus par la seule analyse épidémiologique.

Contribution à la lutte contre la pandémie actuelle

L’analyse de ces flambées nosocomiales apportera un éclairage essentiel sur la dynamique de transmission du SARS-CoV-2 dans le secteur de la santé et sera à la base des directives de prévention et de contrôle contre l’infection au cours des vagues successives de la pandémie, afin de mieux protéger les soignants et les patients. En outre, cette étude démontrera la valeur ajoutée du séquençage du génome pour élucider les liens complexes participant à la diffusion du SARS-CoV-2 dans les hôpitaux. Les données fournies par les analyses épidémiologiques ont permis le développement d’un outil d’e-learning destiné à améliorer les pratiques de prévention des soignants dans les secteurs à haut risque.

Direct link to Lay Summary Last update: 22.12.2020

Lay Summary (English)

Lead
The aim of this project is to gain a better understanding of the transmission dynamics of SARS-CoV-2 in healthcare-associated outbreaks, in particular the role of healthcare workers. We will combine epidemiological and genetic data to reconstruct transmission trees.
Lay summary

Background

During the COVID-19 pandemic, three healthcare-associated (known as nosocomial) outbreaks occurred in distinct sites of the Geneva University Hospitals. After improvements in infection prevention and control, the outbreaks were successfully controlled. Protection of healthcare workers (HCWs) is a key priority whilst caring for SARS-CoV-2 patients. Similarly, preventing healthcare-associated COVID-19 among COVID-19 negative patients is key. Particular attention should be paid to vulnerable patients in long-term care facilities and geriatrics.

Research aims

The main objective of this study is to reconstruct the outbreaks, combining epidemiological with genetic data, in order to understand transmission dynamics and improve infection control practices and consider additional preventive strategies. Specific aims include:

  • Establish viral transmission pathways of the outbreak and reconstruct a transmission tree

  • Identify the direction of transmission, for example from HCW to HCW, from HCW to patient, from patient to HCW, or from community to HCW.

Expected results and envisaged products

This is a retrospective cohort study of COVID-19 clusters involving 104 patients and 185 HCWs in three distinct hospital sites of the Geneva University Hospitals. We will obtain clinical and epidemiological data for all SARS-CoV-2 positive patients and HCWs involved in these nosocomial outbreaks. We will construct epidemic curves by ward for patients and HCWs, and compute attack rates and doubling times. These data will be used to construct a putative transmission tree. Genetic sequencing data will provide greater resolution and identify specific clusters and imported cases that could not have been determined by epidemiological analysis alone.

Specific contribution to tackle the current pandemic

Analysing these nosocomial outbreaks will provide key insights into transmission dynamics of SARS-CoV-2 in the healthcare setting and will inform infection prevention guidelines and control guidelines in successive waves of the pandemic in order to enhance protection of HCWs and patients. Furthermore, this study will demonstrate the added value of genome sequencing in elucidating the complex connectivity of SARS-CoV-2 dissemination in hospitals. Insights from the epidemiological investigations have led to the development of an e-learning tool to improve preventive practices of HCWs in high-risk areas.

Direct link to Lay Summary Last update: 22.12.2020

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Occupational and community risk of SARS-CoV-2 infection among employees of a long-term care facility: an observational study
Lenggenhager Lauriane, Martischang Romain, Sauser Julien, Perez Monica, Vieux Laure, Graf Christophe, Cordey Samuel, Laubscher Florian, Nunes Tomás Robalo, Zingg Walter, Cori Anne, Harbarth Stephan, Abbas Mohamed (2022), Occupational and community risk of SARS-CoV-2 infection among employees of a long-term care facility: an observational study, in Antimicrobial Resistance & Infection Control, 11(1), 51-51.
Can long-term care facilities remain a coronavirus disease 2019 (COVID-19)–free bubble? An outbreak report
Robalo Nunes Tomás, Lebowitz Dan, Fraccaro Marlène, Perez Monique, Vieux Laure, Abbas Mohamed, Graf Christophe, Harbarth Stephan (2022), Can long-term care facilities remain a coronavirus disease 2019 (COVID-19)–free bubble? An outbreak report, in Infection Control & Hospital Epidemiology, 43(3), 410-411.
Reconstructing transmission chains of SARS-CoV-2 amid multiple outbreaks in a geriatric acute-care hospital
AbbasMohamed, CoriAnne, CordeySamuel, LaubscherFlorian, Robalo NunesTomás, MyallAshleigh, SalamunJulien, HuberPhilippe, ZekryDina, PrendkiVirginie, ItenAnne, VieuxLaure, SauvanValérie, GrafChristophe, HarbarthStephan (2022), Reconstructing transmission chains of SARS-CoV-2 amid multiple outbreaks in a geriatric acute-care hospital, 2022.01.07.
Nosocomial transmission and outbreaks of coronavirus disease 2019: the need to protect both patients and healthcare workers
Abbas Mohamed, Robalo Nunes Tomás, Martischang Romain, Zingg Walter, Iten Anne, Pittet Didier, Harbarth Stephan (2021), Nosocomial transmission and outbreaks of coronavirus disease 2019: the need to protect both patients and healthcare workers, in Antimicrobial Resistance & Infection Control, 10(1), 7-7.
In-hospital COVID-19 outbreak investigation: A practical approach to root cause analysis
Vuichard-Gysin Danielle, Abbas Mohamed, Harbarth Stephan (2021), In-hospital COVID-19 outbreak investigation: A practical approach to root cause analysis, in Intensive and Critical Care Nursing, 67, 103132-103132.
Nationwide Deployment of a Serious Game Designed to Improve COVID-19 Infection Prevention Practices in Switzerland: Prospective Web-Based Study
Suppan Melanie, Stuby Loric, Harbarth Stephan, Fehlmann Christophe A, Achab Sophia, Abbas Mohamed, Suppan Laurent (2021), Nationwide Deployment of a Serious Game Designed to Improve COVID-19 Infection Prevention Practices in Switzerland: Prospective Web-Based Study, in JMIR Serious Games, 9(4), e33003-e33003.
Explosive nosocomial outbreak of SARS-CoV-2 in a rehabilitation clinic: the limits of genomics for outbreak reconstruction
Abbas Mohamed, Nunes Tomás Robalo, Cori Anne, Cordey Samuel, Laubscher Florian, Baggio Stephanie, Jombart Thibaut, Iten Anne, Vieux Laure, Teixeira Daniel, Perez Monica, Pittet Didier, Frangos Emilia, Graf Christophe E., Zingg Walter, Harbarth Stephan (2021), Explosive nosocomial outbreak of SARS-CoV-2 in a rehabilitation clinic: the limits of genomics for outbreak reconstruction, in Journal of Hospital Infection, 118.
Impact of a Serious Game (Escape COVID-19) on the Intention to Change COVID-19 Control Practices Among Employees of Long-term Care Facilities: Web-Based Randomized Controlled Trial
Suppan Mélanie, Abbas Mohamed, Catho Gaud, Stuby Loric, Regard Simon, Achab Sophia, Harbarth Stephan, Suppan Laurent (2021), Impact of a Serious Game (Escape COVID-19) on the Intention to Change COVID-19 Control Practices Among Employees of Long-term Care Facilities: Web-Based Randomized Controlled Trial, in Journal of Medical Internet Research, 23(3), e27443-e27443.
Impact of a Serious Game on the Intention to Change Infection Prevention and Control Practices in Nursing Homes During the COVID-19 Pandemic: Protocol for a Web-Based Randomized Controlled Trial
Suppan Laurent, Abbas Mohamed, Catho Gaud, Stuby Loric, Regard Simon, Harbarth Stephan, Achab Sophia, Suppan Mélanie (2020), Impact of a Serious Game on the Intention to Change Infection Prevention and Control Practices in Nursing Homes During the COVID-19 Pandemic: Protocol for a Web-Based Randomized Controlled Trial, in JMIR Research Protocols, 9(12), e25595-e25595.
Impact of an e-learning module on personal protective equipment knowledge in student paramedics: a randomized controlled trial
Suppan Laurent, Stuby Loric, Gartner Birgit, Larribau Robert, Iten Anne, Abbas Mohamed, Harbarth Stephan, Suppan Mélanie (2020), Impact of an e-learning module on personal protective equipment knowledge in student paramedics: a randomized controlled trial, in Antimicrobial Resistance & Infection Control, 9(1), 185-185.
A Serious Game Designed to Promote Safe Behaviors Among Health Care Workers During the COVID-19 Pandemic: Development of “Escape COVID-19”
Suppan Mélanie, Catho Gaud, Robalo Nunes Tomás, Sauvan Valérie, Perez Monique, Graf Christophe, Pittet Didier, Harbarth Stephan, Abbas Mohamed, Suppan Laurent (2020), A Serious Game Designed to Promote Safe Behaviors Among Health Care Workers During the COVID-19 Pandemic: Development of “Escape COVID-19”, in JMIR Serious Games, 8(4), e24986-e24986.
Effect of an E-Learning Module on Personal Protective Equipment Proficiency Among Prehospital Personnel: Web-Based Randomized Controlled Trial
Suppan Laurent, Abbas Mohamed, Stuby Loric, Cottet Philippe, Larribau Robert, Golay Eric, Iten Anne, Harbarth Stephan, Gartner Birgit, Suppan Mélanie (2020), Effect of an E-Learning Module on Personal Protective Equipment Proficiency Among Prehospital Personnel: Web-Based Randomized Controlled Trial, in Journal of Medical Internet Research, 22(8), e21265-e21265.
Teaching Adequate Prehospital Use of Personal Protective Equipment During the COVID-19 Pandemic: Development of a Gamified e-Learning Module
Suppan Mélanie, Gartner Birgit, Golay Eric, Stuby Loric, White Marion, Cottet Philippe, Abbas Mohamed, Iten Anne, Harbarth Stephan, Suppan Laurent (2020), Teaching Adequate Prehospital Use of Personal Protective Equipment During the COVID-19 Pandemic: Development of a Gamified e-Learning Module, in JMIR Serious Games, 8(2), e20173-e20173.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Colloque médical Covid-19 Individual talk SARS-COV2 : les défis du contrôle de l’infection 05.11.2021 Geneva, Switzerland Abbas Mohamed;
6th International Conference on Prevention & Infection Control Talk given at a conference Explosive nosocomial outbreak of SARS-COV-2 in a rehabilitation clinic: The limits of genomics for outbreak reconstruction 14.09.2021 Geneva, Switzerland Harbarth Stephan Jürgen; Abbas Mohamed;
International Conference on Prevention & Infection Control (ICPIC) Talk given at a conference Is COVID-19 in hospital employees automatically an occupational disease? SARS-COV-2 acquisition modes and rates among employees in a long-term care facility (LTCF) during the first pandemic wave 14.09.2021 Geneva, Switzerland Harbarth Stephan Jürgen; Abbas Mohamed;
Joint Annual Meeting 2021: SSI | SSHH | SSTMP | SSTTM Talk given at a conference COVID-19 in long-term care facilities – the role of healthcare workers 03.09.2021 Montreux, Switzerland Zingg Walter; Abbas Mohamed; Harbarth Stephan Jürgen;


Knowledge transfer events



Self-organised

Title Date Place
Escape Covid Serious Game 01.01.2021 Geneva, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Computer game helps health workers combat Covid spread France24 International 2021
Media relations: print media, online media Health workers in Switzerland are using videogames to beat COVID-19 Euronews International 2021
Media relations: print media, online media Mieux prévenir les infections au Covid: un jeu très, très sérieux Sciences & Avenir Rhaeto-Romanic Switzerland 2021
Media relations: radio, television Le personnel des EHPAD devrait être dépisté au minimum deux fois par semaine RCF Radio Rhaeto-Romanic Switzerland International 2020

Abstract

Background and rationaleDuring the Coronavirus disease 2019 (COVID-19) pandemic, 3 nosocomial outbreaks occurred in distinct sites in the Department of Rehabilitation and Geriatrics of Geneva University Hospitals. After enhancing infection prevention and control, the outbreaks were successfully controlled. Protection of healthcare workers (HCWs) is a key priority whilst caring for severe acute respiratory syndrome (SARS-CoV-2) infected patients. Similarly, preventing healthcare-associated COVID-19 among COVID-19 negative patients is key. Particular attention should be placed on vulnerable patients in long-term care facilities and geriatrics. In the outbreaks we describe, the complex interplay between and respective role of HCWs and patients in transmission remains unclear. Aim and objectives The overarching objective of this study is to reconstruct the outbreaks in each hospital site (A, B, C) combining epidemiological with genetic data, in order to understand transmission dynamics and improve infection control practices and consider additional preventive strategies.Specific aimsSpecific aims of the study include:•Compute the attack rate in the institution among patients and HCWs•Establish viral transmission pathways of the outbreak and reconstructing a transmission tree•Identify the directionality of transmission (i.e. HCW to HCW, HCW to patient, patient to HCW, community to HCW)•Identify risk factors for healthcare-associated SARS-CoV-2 infection and mortality among patients •Identify risk factors for HCW SARS-CoV-2 infection •Describe and analyse variation among infection control practices across the 3 sites•Identify and develop new strategies to prevent healthcare-associated COVID infection Study design and expected resultsThis is a retrospective cohort study of COVID-19 clusters involving 104 patients and 185 HCWs in 3 distinct hospital sites of the Geneva University Hospitals. We will obtain clinical and epidemiological data of all SARS-CoV-2 positive patients and HCWs. We will construct epidemic curves by ward for patients and HCWs, and compute attack rates and doubling times. These data will help to construct a putative transmission tree. We will perform a nested case-control study in one of the sites that will seek to establish risk factors of HCW infection by SARS-CoV-2. Exposure to COVID-19 patients and other HCWs is assessed, as well as potential community exposure. A nested case-control study will be performed in order to identify risk factors for healthcare-associated SARS-CoV-2 infection among patients, and a case-case-control study to identify risk factors for mortality among these patients.SARS-CoV-2 complete genome sequences will be generated using an amplicon-based next generation sequencing protocol. Complete viral genomes will be obtained after mapping reads to a SARS-CoV-2 reference sequence. We will combine epidemiologic and genetic data using the “outbreaker” package in R software. We will use a Bayesian framework, which will combine the distribution of the generation time, from which a probabilistic transmission tree is constructed, as well as a model of sequence evolution along the transmission chain. We will impute generation times from estimates available from the literature. The output from the model will allow us to estimate the dates of infection, mutation rates, multiple importation events, missed cases, as well as to reconstruct the transmission tree. Expected impactAnalysis of these nosocomial outbreaks will provide key insights into transmission dynamics of SARS-CoV-2 in the healthcare setting and will inform infection prevention guidelines in order to enhance protection of HCWs and patients. Furthermore, this study will demonstrate the added value of genome sequencing in elucidating the complex connectivity of SARS-CoV-2 dissemination in hospitals.
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