Hospital-based Surveillance of Influenza in Switzerland - a pilot study

Influenza virus infections are, each year, a major cause of morbidity, mortality, and expenses. It is therefore an important disease to monitor to reduce its burden as much as possible.

In Switzerland, two declaration systems for influenza cases are operating:

all diagnostic of Influenza diseases of type A and B in hospitals and private laboratories must be reported to the Federal office of Public Health (FOPH) within a week.
the second system, called Sentinella, is a surveillance system in which primary care practitioners must report within a week all the Influenza-like illnesses (ILI) symptoms/diagnostics they witnessed during consultation. A sub-division of those practitioners also collects respiratory samples from patients who have been diagnosed ILI, in order for the Centre National de Référence de l’Influenza (CNRI) to detect and characterise the virus.

These surveillance systems follow the progression of ILI within an epidemic and can partially characterise the current ILI viruses. However, it does not identify the severe case of influenza infections which require hospitalisation.

It is likely that influenza cases in hospitals are different from community acquired cases, especially with regards to patients’ characteristics (e.g. older population with more underlying medical conditions in hospitals), and potentially to the current viruses strains. With this hospital-based surveillance system, we propose to study the progression of the influenza epidemic and to try to better understand influenza in hospitalised patients, who have a higher risk of complications. This will generate information on high-risk groups for which prevention and treatment must prevail.

Within this pilot study, we test the feasibility of such a national, hospital-based surveillance system for severe influenza cases.

Since the 2020-2021 season, because of the COVID-19 surveillance project, both databases have been merged into one single registry, modified to account for both diseases and easily include other respiratory viruses if needed.

Objectives

The main goal of this project is to evaluate the feasibility of setting a national hospital-based surveillance system in eight participating hospitals. On a longer term, the objective is to fill a gap in the hospital surveillance of influenza in Switzerland. In particular, the pilot study aims to:

Verify the possibility of gathering a minimal amount of high-quality epidemiological, clinical, and viral data about hospital cases of influenza.
Create a central database and set up a normalised questionnaire for data collection on the Web and in the participating centres.
Analyse the number and the characteristics of patients infected with influenza, hospitalised during an epidemic.
Summarise the results in a report and/or a scientific publication

PARTICIPANTS

Currently, 20 Swiss hospitals (including university hospitals and cantonal hospitals) are participating in this surveillance system:

Centre Hospitalier Universitaire Vaudois (CHUV) in Lausanne - VD
Ente Ospedaliero Cantonale (EOC) in Lugano - TI
Hôpital du Valais (HVS) in Sion - VS
Hôpitaux Universitaires de Genève (HUG) in Geneva - GE
Inselspital Bern (INSEL) in Bern - BE
Kinderspital Basel (UKBB) in Basel - BS
Kinderspital Zürich (KISPI USZ) in Zürich - ZH
Kantonsspital Sankt Gallen (KSSG) in Sankt Gallen - SG
Universitätspital Basel (USB) in Basel - BS
Universitätspital Zürich (USZ) in Zürich - ZH
Kantonsspital Graubuenden (KSGR) in Chur - GR
Kindersspital St. Gallen (OKS) in Sankt Gallen - SG
Hôpital de Fribourg (HFR - paediatrics only) in Fribourg - FR
Kantonsspital Aarau (KSA - paediatrics only) in Aarau - AG
Kantonsspital Winterthur (KSW - paediatrics only) in Winterthur - ZH
Spitaeler Schaffhausen (Spitaeler SH) in Schaffhausen - SH
Luzerner Kantonsspital (LUKS) in Luzern - LU
Kantonsspital Münsterlingen (STGAG) in Münsterlingen - TG
Hirslanden AG Zürich (HAGZH) in Zürich - ZH
Hirslanden Clinic St Ana - Luzern in Luzern - LU

Previously participating were:

Kantonsspital Niedwald (KSNW) in Stans - NW - until 28/02/2022

ACCESSING DATA

It is possible to access the data contained within the database with some restriction. The procedure is described in the following document (the document explains how it works for COVID-19 database, but the process is the exact same for Influenza):

Procedure for submitting projects

Concept Sheet

In a nutshell: the applicant must fill a concept sheet detailing the team in charge of the analysis, the analysis plan, and the variables needed for the analysis. The applicant then must send it the Organising Committee (OC) who will forward it to the Scientific Committee (SC). After acceptance by the SC, the concept sheet will be circulated among participating hospital to decide if they want to opt-out of the analysis. Note that we only accept one project per concept-sheet.

Before submitting a concept sheet, please make sure that it is not a duplicate from one of the accepted projects (listed below) and that everything is complete. If you need any additional information, please reach one of the contact person listed on the right.

The CH-SUR study group member list can be found here. This is the official co-author list for each participating hospital.

ACCEPTED PROJECTS

Hospital-based surveillance of influenza in Switzerland: a 3 years pilot study - 2018-2021

Lead: Amaury Thiabaud (ISG) & Anne Iten (HUG)

Status: Submitted to PLoS One

Content: Description of the database, its content, and the project.

COVID-19: More than "a little flu"? Insights from the Swiss hospital-based surveillance of Influenza and COVID-19

Lead: Georg Fröhlich (INSEL) & Rami Sommerstein (INSEL)

Status: Published in Eurosurveillance

Background and study aim
It has been a matter of ongoing debate, whether in-hospital outcomes of infection with SARS-CoV-2 are comparable to outcomes of infection with Influenza A/B virus. Therefore, this study aims to compare adverse outcomes in patients, who were hospitalized with SARS-CoV-2 and/or Influenza A/B virus infection. To the best of our knowledge, only a few small case series were reported to directly compare outcomes for Coronavirus disease 2019 (COVID-19) with Influenza infection.

Methods

Data are derived from the prospective registries “Hospital based surveillance of COVID-19 and Influenza” that are based at the Geneva University Hospitals/Institute of Global Health, University of Geneva. In total, 15 hospitals all over Switzerland collected data on patient characteristics, concomitant medication and outcomes in 2 separate cohorts with similar data collection of various patient-related variables, including a diverse group patients with Covid-19 and Influenza. Data collection included Influenza patients, collected from 7 hospitals. All registered patients ≥ 18 years will be included into the analysis. The study groups consist of hospitalized patients with either laboratory-proven Covid-19 OR Influenza infection. The primary outcome measure is the in-hospital all-cause mortality. Secondary outcome measures are need for ICU care, need for non-invasive or invasive ventilation, need for readmission, and complications like pneumonia, kidney or liver. For the analysis we will use mixed-effects Cox proportional hazards model. To adjust for differences in baseline characteristics and clustering effects, inverse probability weighted propensity score matching and multivariate mixed-effects models with subdistribution analysis of competing outcomes (discharge) will be applied.

Results and Outlook

The results will provide a robust estimate regarding risks in outcomes for hospitalized Covid-19 patients when compared to seasonal influenza patients. These results will provide valuable elements for the ongoing discussion on morbidity and mortality of Covid-19 vs seasonal influenza patients. Moreover, it may help clinicians, scientists, policy makers and the population to make evidence-based decisions on the level of prevention/actions

Patterns of antimicrobial prescribing in patients hospitalized for influenza virus infection or COVID-19

Lead: Dr. Danielle Vuichard-Gysin (STGAG/Swissnoso), Dr. Julia Anna Bielicki (UKBB), Prof. Sarah Tschudin-Sutter(USB), Dr. Catherine Plüss-Suard (IFIK/UniBE), Prof. Stephan Harbarth (HUG), Prof. Olivia Keiser (ISG/UniGE), Prof. Andreas Widmer(USB)

Status: Ongoing

Background and objectives:

Widespread use of antimicrobials drives emergence of antibiotic resistance. Antibiotics are often prescribed for viral respiratory infections without clear indication representing inappropriate use. Designing effective interventions to improve antimicrobial use in patients admitted with viral respiratory infections requires understanding of prescribing practices. So far, antimicrobial prescribing in hospitalized patients with influenza has not been compared to patients with COVID-19. Our main goal is to characterize antimicrobial use in these patients.

Methods

We propose to use data from the prospective national surveillances on influenza and COVID-19, respectively, to investigate and compare antimicrobial use in these two cohorts. We will consider all adults, hospitalized for > 24 hours with either laboratory confirmed influenza virus infection or COVID-19. The primary outcome measure is the proportion of patients prescribed antimicrobial agents in each cohort. Secondary outcomes are the relative proportions of AWaRe group antibiotics among treated patients, the proportion of patients with single or combined antibiotic treatment, distribution of different antimicrobial classes between the two cohorts, proportion of broad-spectrum antibiotic and the proportion of patients with infectious complications.

For our primary analysis, we will use univariable logistic regression to calculate odds ratios for antimicrobial use among influenza and COVID-19 patients. To adjust for potential confounders, we perform multivariable logistic regression analysis. We will use Generalized Estimating Equations to adjust for clustering at the hospital level.

Results and outlook

Results derived from these analyses may eventually help to design new interventions for rational use of antibiotics in patients admitted with respiratory viral infections.

Comparison of clinical characteristics and outcomes of children hospitalized with COVID-19 and seasonal influenza in Switzerland

Lead: Dr Julia Bielicki (UKBB)

Status: Ongoing

Background and objectives

Seasonal influenza and acute SARS-CoV-2 infection in childhood can both result in admission to hospital. However, it is unclear whether there is a difference in the clinical spectrum, severity and outcomes between the two diseases.

The objectives of this project are

To describe the spectrum of clinical disease and outcomes of children hospitalized with COVID-19 related disease (either acute or post-infectious, such as PIMS-TS) in Switzerland
To compare the clinical characteristics of children hospitalized with seasonal influenza and those hospitalized with acute COVID-19.
To compare undesirable clinical outcomes between children hospitalized with seasonal influenza and those hospitalized with acute COVID-19.
To investigate and compare risk factors for undesirable clinical outcomes in children hospitalized with seasonal influenza and those hospitalized with acute COVID-19.

Methods

This will be a retrospective cohort study using data from the hospital-based surveillance of COVID-19 and influenza in Switzerland. Patients of any age hospitalized with either laboratory confirmed influenza virus infection or COVID-19 on a neonatal or paediatric ward and patients

The clinical characteristics and outcomes of the children hospitalized with seasonal influenza and those hospitalized with acute COVID-19 will be analysed descriptively. Categorical variables will be described as percentages, and continuous variables will be described using mean, median, and interquartile ranges (IQR). We will compare characteristics using Chi-square tests for categorical variables and Mann-Whitney U tests for continuous variables.

The primary outcome measure of interest will be a composite of in-hospital death, need for intensive care and readmission within fourteen days after discharge from the index episode. Secondary outcomes will be in-hospital mortality, admission to intermediate or intensive care, readmission within 14 and 28 days of discharge from the index episode, requirements for and duration of ventilation and inotropic support and length of stay in hospital and in ICU.

We will further use univariable and multivariable logistic regression analysis to investigate the risk factors associated with the primary outcome of interest. The analysis will be adjusted for important confounders, such as age, sex, pre-existing chronic comorbidities. Missing explanatory variables will be imputed by multiple imputation.

Relevance

Results may inform planning of acute paediatric inpatient services and support targeting of preventive measures for both seasonal influenza and COVID-19 in this population, including vaccination.

Hospital outcomes of community acquired Sars-CoV-2 Omicron variant versus Influenza

Lead: Lea Portmann (Uni Luzern), Prof. Rami Sommerstein (Hirsl LUZ), PD Dr. Georg Fröhlich (Hirsl)

Status: Ongoing

Background and objectives

Previous studies have shown that COVID-19 is associated with an adverse outcome compared with seasonal influenza A/B infections. However, the virus has emerged in different types and the variant B.1.1.529 (Omicron) is less virulent than earlier variants. Therefore, this study aims to compare adverse outcomes in patients hospitalized with COVID-19 between 15.01.22 and 15.03.22 in Switzerland and Influenza A/B virus infection. This will provide an important information for public health authorities and may enable some planning for the 2022/2023 Covid-Influenza season.

Methods

Data are from the prospective registry “Hospital based surveillance of COVID-19 and Influenza” based at the Geneva University Hospitals/Institute of Global Health. 17 hospitals all over Switzerland collected data on patient characteristics, concomitant medication and outcomes in patients hospitalized because of/with COVID-19. 7 hospitals collected corresponding data in patients hospitalized because of/with Influenza A/B. All registered patients ≥ 18 years will be included into the analysis. Study groups consist of patients with laboratory-proven Covid-19 hospitalized between 15.01.22 and 15.03.22 and hospitalized patients with an Influenza infection. We expect to include ~2000 patients with Covid and ~1500 patients with influenza. The primary outcome measure is in-hospital all-cause mortality. Secondary outcome measures are need for ICU care, need for non-invasive or invasive ventilation, 28-day readmission, and complications like pneumonia, kidney, or liver failure. One limitation will be that information on the vaccination status for influenza cases is largely missing.

Results and Outlook

The results will show if the outcomes for hospitalized COVID-19 patients with Omicron variant are comparable to seasonal influenza patients. These results may help clinicians, scientists, policy makers and the population to make evidence-based decisions on the level of prevention/actions to protect the population as well as HCWs in the post pandemic phase.