Condition category
Infections and Infestations
Date applied
19/07/2020
Date assigned
22/07/2020
Last edited
22/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
The ongoing pandemic with the novel coronavirus (SARS-CoV-2) is an unprecedented global challenge with an enormous impact on public health, economies and societies worldwide. Despite intensive research efforts, more information about is needed about the effects of an infection with the coronavirus and on its transmission in the population, in order to make well-informed policy decisions to control the spread of the coronavirus and prevent further waves of infection.

It is unclear how the coronavirus infection affects health-related quality of life and what its complications are in the longer term. Furthermore, more knowledge is needed on the spectrum and durability of immune responses and how these relate to immunity against the coronavirus. Moreover, the relation between virus genetics and the severity of disease courses, immune responses and the transmission of the virus in the population are not known. And last, more knowledge is needed about the transmission pathways in the current stage of the pandemic and about what factors are most related to increased transmission.

The aim of this study is to study the long-term clinical outcomes, immune responses, transmission pathways and viral genetics in a representative, population-based cohort of persons infected with the coronavirus and their close contacts in the Canton of Zurich, Switzerland. The findings of this study will be highly important to guide future public health strategies for controlling the spread of the Coronavirus both in Switzerland and worldwide.

Who can participate?
Persons that are infected with the Coronavirus in the Canton of Zurich (so called index cases), as well as their close contacts will be invited to participate in this study.

What does the study involve?
Index cases will be followed up with electronic questionnaires over 1 year. Participants will receive the first questionnaire at enrollment and then again after 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months. Questions will be related to the acute illness (COVID-19), quality of life and mental health, clinical outcomes, medical history, details on the contact that lead to the infection, protective and risk behaviors, as well as experiences and issues with isolation. A selection of the index cases will additionally be invited for the collection of blood and saliva samples to examine their immune responses, e.g. through antibody testing. Blood and saliva collection will take place on five occasions (after 2 weeks, 1 month, 3 months, 6 months and 12 months).

Close contacts will be followed up with electronic questionnaires over approximately two weeks. Participants will receive the first questionnaire at enrollment and then again at the end of quarantine. The questions will be related to COVID-19 symptoms, details on their contact with the index case, protective and risk behaviors, as well as experiences and issues with quarantine. All close contacts will receive a coronavirus test as early as possible and a selection of close contacts that are tested negative in the first test will be tested again at the end of quarantine. Close contacts that are tested positive for the coronavirus will be invited to participate in the study as index cases.

The study additionally involves an analysis of the virus genes from samples obtained through coronavirus testing together with information from contact tracing, to analyze the transmission networks of the coronavirus in the Canton of Zurich and to study the association of virus genetics with disease severity, immune responses and transmissibility.

What are the possible benefits and risks of participating?
This research project will help to better understand the effects of the coronavirus infection and its spread in the population. This information will be highly relevant for public health decision-makers and patients both locally in Switzerland and internationally. The risks of participating in this study are minimal.

Where is the study run from?
The study is run from the Epidemiology, Biostatistics and Prevention Institute (EBPI) at the University of Zurich, Switzerland.

When is the study starting and how long is it expected to run for?
The study will last from May 2020 until September 2022.

Who is funding the study?
The study is funded by the Health Directorate of the Canton of Zurich, Switzerland, and the University of Zurich (UZH) Foundation

Who is the main contact?
Dr Dominik Menges, MPH
dominik.menges@uzh.ch

Trial website

https://www.ebpi.uzh.ch/en/translational_research/community_and_health/zurich_coronavirus_cohort.html

Contact information

Type

Scientific

Primary contact

Prof Milo A. Puhan

ORCID ID

https://orcid.org/0000-0003-4721-1879

Contact details

Epidemiology
Biostatistics and Prevention Institute (EBPI)
University of Zurich
Hirschengraben 84
Zurich
CH-8001
Switzerland
+41 44 634 46 10
miloalan.puhan@uzh.ch

Type

Scientific

Additional contact

Prof Jan Fehr

ORCID ID

https://orcid.org/0000-0003-1113-9895

Contact details

Epidemiology
Biostatistics and Prevention Institute (EBPI)
University of Zurich
Hirschengraben 84
Zurich
CH-8001
Switzerland
+41 44 634 46 79
jan.fehr@uzh.ch

Type

Scientific

Additional contact

Dr Tala Ballouz

ORCID ID

https://orcid.org/0000-0003-2334-8600

Contact details

Epidemiology
Biostatistics and Prevention Institute (EBPI)
University of Zurich
Hirschengraben 84
Zurich
CH-8001
Switzerland
+41 44 634 46 15
tala.ballouz@uzh.ch

Type

Public

Additional contact

Dr Dominik Menges

ORCID ID

https://orcid.org/0000-0001-5970-1846

Contact details

Epidemiology
Biostatistics and Prevention Institute (EBPI)
University of Zurich
Hirschengraben 84
Zurich
CH-8001
Switzerland
+41 44 634 46 15
dominik.menges@uzh.ch

Type

Scientific

Additional contact

Prof Roger Kouyos

ORCID ID

http://orcid.org/0000-0002-9220-8348

Contact details

Department of Infectious Diseases and Hospital Epidemiology
University Hospital Zurich
Rämistrasse 100
Zurich
CH-8091
Switzerland
+41 (0)44 255 36 10
roger.kouyos@usz.ch

Type

Scientific

Additional contact

Prof Alexandra Trkola

ORCID ID

https://orcid.org/0000-0003-1013-876X

Contact details

Institute of Medical Virology (IMV)
University of Zurich
Winterthurerstrasse 190
Zurich
CH-8057
Switzerland
+41 (0)44 634 26 53
trkola.alexandra@virology.uzh.ch

Type

Scientific

Additional contact

Prof Christian Münz

ORCID ID

https://orcid.org/0000-0001-6419-1940

Contact details

Institute of Experimental Immunology
University of Zurich
Winterthurerstrasse 190
Zurich
CH-8057
Switzerland
+41 (0)44 635 37 16
christian.muenz@uzh.ch

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Zurich SARS-CoV-2 Cohort: Towards a long-term control of SARS-CoV-2 transmission - Identifying the epidemiological, immunological and viral genetic drivers of SARS-CoV-2 transmission and pathogenesis in a representative population-based cohort

Acronym

ZSAC

Study hypothesis

The overall aim of this study is to establish a representative, population-based cohort of individuals infected with SARS-CoV-2 in the Canton of Zurich to characterize clinical outcomes and immunological responses and examine transmission patterns among index cases and their close contacts by combining routine contact tracing and viral genetic analyses.

The project is structured in five work packages (WP) with the following objectives:
WP1. Determine long-term clinical outcomes among SARS-CoV-2 positive individuals
WP2. Examine patterns of SARS-CoV-2 infection and transmission among infected index cases and their close contacts in the context of contact tracing
WP3. Infer the transmission network by combining information from routine contact tracing and genetic sequences of SARS-CoV-2
WP4. Characterize immune responses and the development of immunity among SARS-CoV-2 positive individuals
WP5. Determine and identify the impact of SARS-CoV-2 viral genetics on pathogenicity, transmissibility and immune responses

Ethics approval

Approved 09/07/2020, Cantonal Ethics Committee Zurich (Stampfenbachstrasse 121, CH-8090 Zurich, Switzerland; +41 43 259 79 70; Info.KEK@kek.zh.ch), ref: 2020-01739.

Study design

Single-centre combined retrospective and prospective longitudinal cohort study and complementary prospective case-ascertained study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Community

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

COVID-19 (SARS-CoV-2 infection)

Intervention

Individuals diagnosed with SARS-CoV-2 infection (index cases) and their close contacts identified via the contact tracing activities of the Health Directorate of the Canton of Zurich will be asked to provide informed consent for study participation. The study procedures are different for index cases and close contacts and include the following:

Index cases will be followed up over one year using self-administered electronic questionnaires. Evaluations will take place at the time of enrollment (baseline; i.e., as early as possible after identification as an index case), as well as after 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months after identification as an index case. Collected data will include information related to the acute COVID-19 episode (e.g. symptoms, severity, treatment), health-related quality of life and mental health, clinical outcomes (e.g. complications and sequelae of the infection, further healthcare contacts, SARS-CoV-2 reinfection and infection by/reactivation of other pathogens), medical history, details on the relevant contact leading to infection (e.g. setting, timing, factors potentially influencing transmission), protective and risk behaviors, use of digital proximity tracing apps, experiences and issues with isolation, and sociodemographic information. Additional information on relevant medical events, such as potential complications of SARS-CoV-2 or reinfection, may be collected from the treating physicians.

A subsample of index cases (total 500 planned) will additionally be invited for the collection of blood and saliva samples for the determination of immune responses. Evaluations will take place 2 weeks, 1 month, 3 months, 6 months and 12 months after identification as an index case. Blood samples will undergo a detailed analysis for humoral (antibody) and cellular (T cell) immune responses. This will include the measurement of IgM/IgA/IgG antibodies specific for SARS-CoV-2 (N, S1, RBD, S2 antigens) using the ABCORA test developed by the Institute for Medical Virology at the University of Zurich, SARS-CoV-2 neutralizing antibodies using a neutralization assay, T cell subsets and activation using flow cytometry, SARS-CoV-2 specific T cells using interferon (IFN)-gamma ELISpot assays, and immunodominant SARS-CoV-2 proteins/epitopes using T cell incubation. Saliva samples will be analyzed for saliva antibody responses and additionally be evaluated for SARS-CoV-2 persistence (i.e., shedding) and viral viability (if still present) after the end of the isolation period.

Close contacts will be followed up over approximately two weeks using self-administered electronic questionnaires. Evaluations will take place at the time of enrollment (baseline; i.e., as early as possible after identification as a close contact), as well as at the end of quarantine. Collected data will include information related to the presence of COVID-19 related symptoms, details on the relevant contact with the index case (e.g. setting, timing, factors potentially influencing transmission), protective and risk behaviors, use of digital proximity tracing apps, experiences and issues with quarantine, and sociodemographic information.

All close contacts will receive SARS-CoV-2 PCR testing as early as possible after identification as a close contact. A subsample of close contacts tested negative on the first test (total 300 planned) will be retested at the end of quarantine. Close contacts that are tested positive for SARS-CoV-2 during study follow-up will be invited to participate in the study as index cases.

To construct the transmission networks of SARS-CoV-2 in the Canton of Zurich, the available samples from SARS-CoV-2 PCR testing from index cases will be sequenced using full genome sequencing for phylogenetic analyses and to examine the association of viral genetics with disease severity, immune responses and transmissibility. Furthermore, pseudonymized information on the transmission networks from contact tracing will be retrieved and compared with the network constructed through phylogenetic analyses.

Intervention type

Other

Phase

Drug names

Primary outcome measure

WP1. Proportion of SARS-CoV-2 infected individuals developing long-term complications related to COVID-19, measured through participant questionnaires and clinical file review at 12 months
WP2. Secondary infection rate and secondary clinical attack rate among close contacts of SARS-CoV-2 infected index cases, measured through participant questionnaires and SARS-CoV-2 PCR testing at enrollment and at the end of quarantine
WP3. Transmission network constructed via routine contact tracing data and via phylogenetic analyses of SARS-CoV-2 sequences as determined at the end of follow-up
WP4.1. Proportion of SARS-CoV-2 infected individuals with measurable anti-SARS-CoV-2 IgM, IgA and IgG antibodies, measured using ABCORA testing at 2 weeks, 1 month, 3 months, 6 months and 12 months after laboratory confirmation of SARS-CoV-2 infection
WP4.2. Proportion of SARS-CoV-2 infected individuals with SARS-CoV-2 antigen-specific T cells, measured using IFN-gamma assays at 2 weeks, 1 month, 3 months, 6 months and 12 months after laboratory confirmation of SARS-CoV-2 infection
WP5. Extent of association of viral genetics with pathogenicity or transmissibility of SARS-CoV-2, or immune responses against SARS-CoV-2, measured using phylogenetic mixed-effects models and/or other phylogenetic comparative approaches as determined at the end of follow-up

Secondary outcome measures

WP1.1. General and COVID-19 specific health-related quality of life, measured using the EQ-5D, DASS-21, Fatigue Assessment Scale and MRC dyspnoe scale at 2 weeks, 1 month, 3 months, 6 months, 9 months and 12 months after laboratory confirmation of SARS-CoV-2 infection
WP1.2. Proportion of individuals with severe disease courses, defined as requiring hospitalization or leading to death within 28 days of confirmation of SARS-CoV-2 infection, measured through participant questionnaires and clinical file review
WP1.3. Proportion of individuals diagnosed with SARS-CoV-2 reinfection within 12 months of confirmation of SARS-CoV-2 infection, measured using participant questionnaires and contact tracing data
WP1.4. Proportion of individuals diagnosed with a new infection or reactivation of a chronic infection by any pathogen within 12 months of laboratory confirmation of SARS-CoV-2 infection, measured through participant questionnaires and clinical file review
WP1.5. Proportion of individuals requiring hospitalization, ICU admission, mechanical ventilation or death (all cause and COVID-19 related) within 12 months after confirmation of SARS-CoV-2 infection, measured through participant questionnaires and clinical file review
WP1.6. Proportion of individuals with self-reported symptoms and/or known risk factors at time of SARS-CoV-2 testing, measured using participant questionnaires
WP1.7. Proportion of individuals that received treatment against SARS-CoV-2, measured through participant questionnaires and clinical file review at enrollment

WP2.1. Proportion of symptomatic and asymptomatic SARS-CoV-2 infected individuals among close contacts of index cases, measured using participant questionnaires and contact tracing data at enrollment and at the end of quarantine
WP2.2. Serial interval of SARS-CoV-2 infection, calculated based on data from participant questionnaires
WP2.3. Factors potentially influencing SARS-CoV-2 transmission between SARS-CoV-2 infected index cases and their close contacts, measured using participant questionnaires at enrollment
WP2.4. Barriers and facilitators, worries and personal burden related to adhering to quarantine measures among close contacts of SARS-CoV-2 infected index cases, measured using participant questionnaires at enrollment and at the end of quarantine


WP3.1. The proportion of SARS-CoV-2 infected index cases with missing links in routine contact tracing that were identified via phylogenetic analyses as determined at the end of follow-up
WP3.2. The proportion of imported cases among SARS-CoV-2 infected index cases in the Canton of Zurich, as determined by phylogenetic analyses as determined at the end of follow-up

WP4.1. Proportion of individuals with neutralizing anti-SARS-CoV-2 antibodies, measured using neutralization assays at 2 weeks, 1 month, 3 months, 6 months and 12 months after laboratory confirmation of SARS-CoV-2 infection
WP4.2. Proportion of individuals with non-severe and severe COVID-19 that develop anti-SARS-CoV-2 antibody and/or T cell responses, based on the aforementioned measurements at 2 weeks, 1 month, 3 months, 6 months and 12 months
WP4.3. Level and durability of anti-SARS-CoV-2 antibody and/or T cell responses among SARS-CoV-2 infected individuals with non-severe and severe COVID-19, based on the aforementioned measurements at 2 weeks, 1 month, 3 months, 6 months and 12 months
WP4.4. Proportion of SARS-CoV-2 infected individuals with long-term virus persistence (shedding) and viral viability of virus specimen in such individuals, measured by using SARS-CoV-2 PCR testing of saliva samples and virus cultures at 2 weeks and thereafter in 2 weekly intervals until tested negative, stratified by different levels of immune responses

WP5.1. Viral strains associated with pathogenicity or transmissibility of SARS-CoV-2, or immune responses against SARS-CoV-2, identified using viral imprinting approaches based on phylogenetic viral clusters as determined at the end of follow-up
WP5.2. Viral genetic mutations associated with pathogenicity or transmissibility of SARS-CoV-2, or immune responses against SARS-CoV-2, identified using a viral genome wide association study (GWAS) methodology as determined at the end of follow-up

Overall trial start date

01/05/2020

Overall trial end date

30/09/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Index cases:
1. Individuals newly diagnosed with SARS-CoV-2 infection in the Canton of Zurich from the start of the study (prospective index cases)
2. Individuals previously diagnosed with SARS-CoV-2 infection in the Canton of Zurich between February 2020 and the start of the study (retrospective index cases)

Close contacts:
1. Symptomatic and asymptomatic close contacts of prospective index cases as identified by routine contact tracing by the Health Directorate of the Canton of Zurich

Participant type

All

Age group

Adult

Gender

Both

Target number of participants

2,000 index cases (1200 prospective, 800 retrospective sample), 1,200 close contacts

Participant exclusion criteria

1. Children and adolescents aged <18 years
2. Insufficient knowledge of the German language
3. Individuals with primary residence outside of the Canton of Zurich, Switzerland
4. Individuals that are unable to follow study procedures
5. Individuals that cannot be reached on maximum of 5 attempts
6. Individuals that do not provide informed consent

Recruitment start date

27/07/2020

Recruitment end date

30/04/2021

Locations

Countries of recruitment

Switzerland

Trial participating centre

Epidemiology, Biostatistics and Prevention Institute (EBPI)
University of Zurich Hirschengraben 84
Zurich
CH-8001
Switzerland

Sponsor information

Organisation

University of Zurich

Sponsor details

Epidemiology
Biostatistics and Prevention Institute (EBPI)
Hirschengraben 84
Zurich
CH-8001
Switzerland
+41 44 634 46 79
jan.fehr@uzh.ch

Sponsor type

University/education

Website

https://www.ebpi.uzh.ch/en.html

Funders

Funder type

Government

Funder name

Health Directorate of the Canton of Zurich (Gesundheitsdirektion des Kantons Zürich), Switzerland

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University of Zurich (UZH) Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in high-impact, peer-reviewed scientific journals.

IPD sharing statement:
Individual participant level data underlying the results reported in the publications will be made available at a later date directly from the authors or via an openly accessible repository.

Intention to publish date

31/12/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

21/07/2020: Trial's existence confirmed by Cantonal Ethics Committee Zurich.