Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal (UNIVERSAL) study: a prospective observational cohort study protocol

Abstract

Background: Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies. The Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal Study is an observational study which addresses this need by investigating the heterogeneity of RVIs in hospitalised adults, aiming to identify clinical and biological predictors of adverse outcomes. This study aims to bridge critical knowledge gaps in the clinical course and the economic impact of RVIs by characterising the phenotypic diversity of these infections and their recovery patterns following hospital admission and thus assisting with the optimal design of future interventional studies.

Methods and analysis: This prospective longitudinal observational study (V.6, 20 September 2023) will be conducted across multiple UK secondary care sites from August 2022 onwards, with an aim to enrol 1000 participants testing positive for RVI. Adults admitted with respiratory symptoms who test positive for RVIs via the BioFire® FilmArray® System or other validated diagnostic PCR tests will be enrolled. The data collected include patient demographics, clinical history, comorbidities and symptoms experienced prior to, during and after hospitalisation with follow-up after discharge at weeks 1, 2, 4, 8, 12 and 26. In addition, biological samples are collected at multiple time points during the hospital stay. The primary endpoints are to study the impact of different RVIs and identify predictors of disease progression and length of stay. Secondary endpoints include time to recovery and healthcare cost. Exploratory endpoints focus on biomarker profiles associated with virus type and clinical outcomes.

Ethics and dissemination: The study protocol received ethical approval from the relevant committees (English Ethics Reference Number: 22/WM/0119; Scottish Ethics Reference Number: 22-SS-0101, 20/09/2023). For patients who lack the capacity to consent, the study complies with the Mental Capacity Act 2005, using a consultee process where a family member, carer or an independent clinician may provide assent on behalf of the patient. Data from all the study centres will be analysed together and disseminated through peer-reviewed journals, conference presentations and workshops. The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format.

Trial registration number: ISRCTN49183956.

Keywords: Hospitalization; Observational Study; Patient Reported Outcome Measures; Respiratory infections; SARS-CoV-2 Infection.

Figure 1. UNIVERSAL study recruitment pathway. Potential participants are identified by research staff through detailed review of the clinical records to ensure that eligibility criteria are met. Each participant is then provided with information regarding the study, and a written informed consent form is obtained. *ARI includes acute respiratory symptoms that may be caused by conditions such as acute upper or lower respiratory tract infections or acute exacerbation of chronic respiratory diseases. **Participants who test negative for RVI have baseline clinical data collected, and as per protocol amendment V.6.0 on 20 September 2023, a subset of participants testing negative for RVI have samples collected to act as a comparison cohort. Created with BioRender.com. RVI, respiratory viral infection; UNIVERSAL, Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal.

Figure 2. Data capture and timepoints for participants in the UNIVERSAL study. EQ-5D-5L, EuroQol 5-Dimension 5-Level; FACIT, Functional Assessment of Chronic Illness Therapy—Fatigue Scale; FLU-PRO PLUS, inFLUenza Patient-Reported Outcome Plus; GAD-7, Generalised Anxiety Disorder-7; HRG, Healthcare Resource Group; OSCI, Ordinal Scale for Clinical Improvement; PHQ-9, Patient Health Questionnaire-9; PRO, patient-reported outcome; RALE, Radiographic Assessment of Lung Edema; UNIVERSAL, Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal. Created with BioRender.com.