Biomarker signature discovery study to determine acute bacterial respiratory tract infection.

Often it is difficult to immediately diagnose the cause of an infection as
being bacterial or viral. Laboratory tests available in primary care settings
like C-Reactive Protein (CRP) do not reach the discriminatory power to
accurately distinguish a bacterial from a viral respiratory tract infection
since there are many circumstances in which CRP can be elevated while there is
no bacterial infection present. (Landry et al., 2017)

It is therefore necessary to investigate novel biomarkers with the capacity to
accurately differentiate between viral and bacterial respiratory tract
infections at the time the patient first presents with a suspected infection at
the emergency room or in the clinic. By doing so, the overuse of antibiotics
can be prevented. In addition, growing resistance of microorganisms, increasing
health-care costs and adverse reactions to antibiotics can be averted.

The overall aim of Levels Diagnostics is to develop a rapid diagnostic tool
that can detect a bacterial respiratory tract infection by using a plasma
protein algorithm that is specific to bacterial infections. The studies leading
towards this goal are performed in collaboration with the Leiden University
Medical Center (LUMC), Center for Human Drug Research (CHDR), UMCG and Spaarne
Gasthuis.
By offering a reliable diagnostic tool it will become possible to implement a
policy restricting the use of antibiotic medication without risks for the
patients. It guides the need for infection prevention measures, also in the
out-patient setting. The need for infection control measures with high impact
are unlikely in case of bacterial infection vs viral infections. This study
will build upon data previously found in studies by Levels Diagnostics to
further explore the optimal biomarker signatures in a clinical setting.

Objective: Identification of host biomarker signatures that have discriminatory
difference in patients with a bacterial respiratory tract infection.

Secondary objectives
Identification of host biomarker signatures that have discriminatory difference
within subgroups of patients with a bacterial respiratory tract infection (e.g.
pre-treated patients or with underlying disease).

Study method and participants: Non-interventional cohort study of 300
participants with acute bacterial infections (N=100), acute viral infections
(non-SARS-CoV-2 (N=100)), acute SARS-CoV-2 (N=50) and non-infected patients as
a control group (N=50).

The aim of the study is to identify novel biomarker signatures that are
specifically associated with bacterial infections and hence could allow a
reliable diagnosis. The outcome of this study could contribute to the
development of next generation biomarker tests, which in turn enable better
targeted antibiotic prescriptions, greatly benefiting patients.
At the time of clinical presentation, viral respiratory infections are hard to
distinguish from bacterial infections due to similar symptoms. As a result,
antibiotics are often prescribed to patients with a viral infection, fueling
antibiotic resistance, increasing public health costs and unnecessary side
effects.
The proposed biomarker signature search will be performed with the use of
proteomics (e.g. ELISA assay) with the use of the plasma obtained from one 10
mL EDTA blood tube drawn from participants. For this study the routine
laboratory diagnostics for participants in the RTI cohorts will be more
extensive in order to identify a causative pathogen. To this end one additional
3 mL blood serum tube will be drawn. Participating in the study will not add
discomfort to the patients in the RTI cohorts as routine diagnostics already
includes blood sampling through venipuncture and having culture and molecular
testing done by nasopharyngeal swab. For the patients in the control cohort the
burden of participating in this study will be minimal. Blood collection will
only take place once by venipuncture and only 10 mL will be collected. The
potential risks associated with venipuncture are limited to (minimal) skin
bruising (WHO guidelines on drawing blood: best practices in phlebotomy; World
Health Organization 2010).