A Systems Approach to Predict the Outcome of SARS-CoV-2 in the Population of a City; COVID-19

A Systems Approach to Predict the Outcome of SARS-CoV-2 in the Population of a City

This study is to gain critical knowledge to understand the factors influencing the outcome of a pandemic virus within the city of Basel.

Study Overview

• Status: Recruiting
• Conditions: SARS Coronavirus (SARS-CoV-2) Infection
• Intervention / Treatment: Other: Study A; Other: Study B; Other: Study C; Other: Study D

Detailed Description

In order to evaluate the impact of the new SARS-CoV-2 this study analyzes the clinical outcomes of patients with a confirmed SARS-CoV-2 infection using a systems approach. The objective is to integrate various datasets covering clinical and non-clinical variables. Beside host factors such as age, gender, comorbidities and treatments, microbiological factors, such as SARS-CoV-2 viral loads using a (semi)-quantitative nucleic acid test (QNAT), genome sequences, and virus-specific immune responses are included. In addition, epidemiological aspects within the city, such as case numbers in specific areas and resulting saturation of the healthcare system (e.g. patients being hospitalized, and ICU occupancy), will be analyzed. Further epidemiological data will be generated from biological measurements from all available serum and respiratory samples (leftover material) collected from February 2020 to November 2021 over two seasons as it is likely that a second wave will be circulating in the following winter 2020/2021.

In this project, three retrospective studies will be conducted:

Study A: retrospective observational case-control study to predict the clinical outcomes and features of SARS-CoV-2 infection. The clinical outcomes of SARSCoV-2 infected patients (cases) and non-SARS-CoV-2 infected patients with or without other respiratory viruses (control) will be explored.

Study B: retrospective observational epidemiological surveillance study to describe the epidemiology of the SARS-CoV-2 outbreak; description of the epidemiological spread of the new SARS-CoV-2 virus in people living in Basel.

Study C: retrospective observational viral evolution study whereby respiratory materials and matching blood and tissue materials will be used to perform whole genome sequencing to study pathogen evolution between hosts as well as in-host evolution. No additional material will be collected. Virus genomes obtained during the expanding, peak, and contracting phase of the pandemic will be compared to identify predictors of viral evolution, viral loads, majority species, immune escape variants, and the implications for clinical outcome, diagnostic detection, treatment, and vaccine design. Correlating specifically the occurrence and rate and variants of SARS-CoV-2 re-infections in city blocks of high activity and exposure risk will be of interest.

Study D: retrospective observational treatment outcome study whereby clinical outcome, laboratory, radiological, pulmonary function and virological data as well as data on immune responses will be used to study safety and efficacy of different treatment modalities. All data and material will be collected on a routine basis during hospitalization and in the outpatient setting to assess the safety and effect of different treatment modalities on outcome.

• Study Type: Observational
• Enrollment (Anticipated): 10000

Contacts and Locations

• Study Contact: Name: Adrian Egli, Prof. Dr. med.; Phone Number: +41 61 556 57 49; Email: adrian.egli@usb.ch

Study Locations

• Switzerland
  • Allschwil, Switzerland, 4123
    • Recruiting
    • Viollier AG
    • Contact: Diana Ciardo, Dr. med; Phone Number: +41 61 486 11 11; Email: diana.ciardo@viollier.ch
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Adrian Egli, Prof. Dr. med; Phone Number: +41 61 556 57 49; Email: adrian.egli@usb.ch
    • Sub-Investigator: Roland Bingisser, Prof. Dr. med
    • Sub-Investigator: Andreas Buser, Prof. Dr. med
    • Sub-Investigator: Hans Hirsch, Prof. Dr. med.
    • Sub-Investigator: Hans Pargger, Prof. Dr. med
    • Sub-Investigator: Bram Stieltjes, Dr. med
    • Sub-Investigator: Sarah Tschudin- Sutter, Prof. Dr. med.
  • Basel, Switzerland, 4056
    • Recruiting
    • Biozentrum University of Basel
    • Contact: Richard Neher, Prof. Dr. med; Phone Number: +41 61 207 58 34; Email: richard.neher@unibas.ch
  • Basel, Switzerland, 4056
    • Recruiting
    • sciCore University of Basel
    • Contact: Thierry Sengstag, Dr.; Phone Number: +41 61 207 18 53; Email: thierry.sengstag@unibas.ch
  • Basel, Switzerland, 4058
    • Recruiting
    • Department of Biosystems Science and Engineering ETH Zurich
    • Contact: Karsten Borgwardt, Prof.Dr. med; Phone Number: +41 61 387 34 20; Email: karsten.borgwardt@bsse.ethz.ch
  • Geneva, Switzerland, 1202
    • Recruiting
    • Swiss Institute of Bioinformatics
    • Contact: Valérie Barbié, Dr. med; Phone Number: +41 22 379 02 65; Email: valerie.barbie@sib.swiss
    • Contact: Aitana Lebrand, Dr. med.; Phone Number: +41 22 379 02 67; Email: aitana.lebrand@sib.swiss
    • Sub-Investigator: Aitana Lebrand, Dr. med.
    • Sub-Investigator: Valérie Barbié, Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

SARSCoV- 2 infected patients and non-SARS-CoV-2 infected patients with or without other respiratory viruses with residency in Basel (Basel-Stadt, Riehen, and Bettingen)

Description

Inclusion Criteria:

• Study A: All patients being tested for SARS-CoV-2 at the University Hospital Basel (USB) and with residency in Basel (Basel-Stadt, Riehen, and Bettingen) will be included for clinical outcome evaluation. All age groups will be included. In addition, non-clinical data such as epidemiological and hospital associated data of all people living in Basel but not necessarily tested at the University Hospital Basel will be included
• Study B: Epidemiological data and serum and respiratory samples across all Age groups from people with residency in Basel (Basel-Stadt, Riehen, and Bettingen) with and without confirmed SARS-CoV-2 infection will be included
• Study C: SARS-CoV-2 viral genome analysis will be conducted from all patients tested positive for SARS-CoV-2 genome by NAT at the University Hospital Basel and living in Basel (Basel-Stadt, Riehen, and Bettingen). In addition, viral genome analysis will be conducted from all people tested positive for SARS-CoV-2 genome by NAT living in Basel by the mentioned study partners. All Age groups will be included.
• Patients with cleared SARS-CoV-2 infection coming for plasma donation will be included to describe immunological response after successfully cleared infection.

Exclusion Criteria:

• documented refusal of the general consent or an available/known written or oral statement against Research
• People, who are tested at the USB, with residency outside of Basel (Basel-Stadt, Riehen, and Bettingen)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SARSCoV-infected patients (cases)	Other: Study A; Study A: collection of data of clinical outcomes and features of SARS-CoV-2 infection. Demographical, clinical, microbiological, laboratory, epidemiological and hospital-associated data will be analyzed. For this study part, only patients with a visit at the University Hospital Basel will be included in order to access patient charts.; Other: Study B; Study B: collection of epidemiological surveillance data to describe the epidemiology of the SARS-CoV-2 outbreak. The epidemic transmission of Influenza viruses in the City of Basel serves as an important reference to identify similarities and differences to the pandemic SARS-CoV-2 situation. In addition data collected during the Influenza projects - in particular data on statistical blocks of the city, e.g. population density, income and living space will be re-used. Already collected and stored samples such as serum and respiratory material (leftover material) will be (re-) used.; Other: Study C; Study C: data collection for viral evolution. Respiratory materials and matching blood and tissue materials will be used to perform whole genome sequencing to study pathogen evolution between hosts as well as in-host evolution. No additional material will be collected.; Other: Study D; Study D: collection of safety and efficacy data of different treatment modalities. Currently the following treatments are considered as part of the treatment: Lopinavir/Ritonavir; Hydroxychloroquine; Tocilizumab; Eculizumab; Ruxolitinib; Remdesivir; Treatment with convalescent plasma blood count, blood chemistry and pulmonary function test (collected on a routine basis during hospitalization and in the outpatient setting).
non-SARS-CoV-2 infected patients (control); non-SARS-CoV-2 infected patients with or without other respiratory viruses (control).	Other: Study A; Study A: collection of data of clinical outcomes and features of SARS-CoV-2 infection. Demographical, clinical, microbiological, laboratory, epidemiological and hospital-associated data will be analyzed. For this study part, only patients with a visit at the University Hospital Basel will be included in order to access patient charts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of factors associated with (i) infection (binary, yes/no), (ii) hospitalization (binary, yes/no), (iii) requirement for ICU treatment (binary, yes/no)	Identification of factors associated with (i) infection (binary, yes/no), (ii) hospitalization (binary, yes/no), (iii) requirement for ICU treatment (binary, yes/no)	at baseline
duration of hospitalization (in days)	duration of hospitalization (in days)	at baseline
duration of Intensive Care Unit (ICU) stay (in days)	duration of ICU stay (in days)	at baseline
in-hospital mortality (binary, yes/no)	in-hospital mortality (binary, yes/no)	at baseline
Number of infected cases within the city of Basel	Number of infected cases confirmed either by nucleic acid test (NAT) or by positive serology within the city of Basel expressed as incidence per statistical block	at baseline
whole genome sequencing to study pathogen evolution (number, type, and complexity of viral genome)	Number, type, and complexity of viral genome variants and quasispecies identified by deep-sequencing during rise, peak, and contraction of the pandemic in patients and geographic areas.	at baseline
Identification which treatment modality is associated with adverse events (binary, yes/no)	Identification which treatment modality is associated with adverse events (binary, yes/no)	at baseline
Identification which treatment modality is associated with pulmonary recovery (binary, yes/no)	Identification which treatment modality is associated with pulmonary recovery(binary, yes/no)	after 30 and 90 days

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: sciCORE University of Basel; Leonhard Med IT ETH Zurich; Swiss Institute of Bioinformatics
• Investigators: Principal Investigator: Adrian Egli, Prof. Dr. med., Division of Clinical Bacteriology & Mycology, University Hospital Basel

Publications and helpful links

General Publications

• Sava M, Sommer G, Daikeler T, Woischnig AK, Martinez AE, Leuzinger K, Hirsch HH, Erlanger T, Wiencierz A, Bassetti S, Tamm M, Tschudin-Sutter S, Stoeckle M, Pargger H, Siegemund M, Boss R, Zimmer G, Vu DL, Kaiser L, Dell-Kuster S, Weisser M, Battegay M, Hostettler K, Khanna N. Ninety-day outcome of patients with severe COVID-19 treated with tocilizumab - a single centre cohort study. Swiss Med Wkly. 2021 Aug 10;151:w20550. doi: 10.4414/smw.2021.20550. eCollection 2021 Aug 2.
• Stange M, Mari A, Roloff T, Seth-Smith HM, Schweitzer M, Brunner M, Leuzinger K, Sogaard KK, Gensch A, Tschudin-Sutter S, Fuchs S, Bielicki J, Pargger H, Siegemund M, Nickel CH, Bingisser R, Osthoff M, Bassetti S, Schneider-Sliwa R, Battegay M, Hirsch HH, Egli A. SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event. PLoS Pathog. 2021 Mar 19;17(3):e1009374. doi: 10.1371/journal.ppat.1009374. eCollection 2021 Mar.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 9, 2020
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (ACTUAL): April 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Coronavirus Disease 2019 (COVID19); SARS-CoV-2 re-infection
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections
• Other Study ID Numbers: 2020-00769; qu20Egli2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No