PREDICT-ILI: Predicting Severity and Disease Progression in Influenza-like Illness (Including COVID-19)

Sponsor

Imperial College London (Other)

Overall Status

Suspended

CT.gov ID

NCT04664075

Collaborator

(none)

100

Enrollment

Location

23.1

Anticipated Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Respiratory infections such as colds, flu and pneumonia affect millions of people around the world every year. Most cases are mild, but some people become very unwell. Influenza ('flu') is one of the most common causes of lung infection. Seasonal flu affects between 10% and 46% of the population each year and causes around 12 deaths in every 100,000 people infected. In addition, both influenza and coronaviruses have caused pandemics in recent years, leading to severe disease in many people. Although flu vaccines are available, these need to change every year to overcome rapid changes in the virus and are not completely protective.

This study aims to find and develop predictive tests to better understand how and when flu-like illness progresses to more severe disease. This may help to decide which people need to be admitted to hospital, and how their treatment needs to be increased or decreased during infection.

The aim is to recruit 100 patients admitted to hospital due to a respiratory infection. It is voluntary to take part and participants can choose to withdraw at any time. The study will involve some blood and nose samples. This will be done on Day 0, Day 2 and Discharge from hospital, and an out-patient follow-up visit on Day 28. The data will be used to develop novel diagnostic tools to assist in rational treatment decisions that will benefit both individual patients and resource allocation. It will also establish research preparedness for upcoming pandemics.

Condition or Disease	Intervention/Treatment	Phase
Influenza SARS (Severe Acute Respiratory Syndrome) Respiratory Viral Infection Respiratory Tract Infections Infection, Bacterial Infection Viral Covid19 RNA Virus Infections	Biological: Respiratory infections

Detailed Description

Despite clinical advances and decades of research, the ability to reliably predict the course of respiratory viral diseases such as influenza and coronavirus infections remains poor. The aim of this project is to develop a platform for identifying and developing predictive tests by combining physiological data and correlates of severity in influenza-like infections so that progression to severe pulmonary involvement can be anticipated during respiratory viral infection. This would then permit safe discharge of patients with self-limiting disease or more rapid intensification of treatment as appropriate.

Respiratory infections are among the most important causes of severe disease worldwide, with the major respiratory viruses responsible for overwhelming pressure on health services each winter due to annual surges in incidence. The two most common viral causes of severe lung disease, influenza and respiratory syncytial virus (RSV), are responsible for ~50% of hospital admissions in children and 22% in adults, with mortality greatest in older people. As the population ages, this burden of disease is steadily increasing. Furthermore, the continual risk of newly emergent pandemic influenza strains that arise unpredictably is universally considered one of the most critical threats to global health and socioeconomic stability. This has been demonstrated by the recent COVID-19 pandemic.

Risk factors for severe influenza have been investigated extensively in clinical cohorts, with older age, co-morbidities, obesity and pregnancy all increasing the likelihood of severe disease. However, accurate prognostic markers remain elusive and the dynamics of the response to respiratory viral infection has not been explored in naturally-infected patients. Furthermore, biomarker discovery has been limited by heterogeneity in virus strain and dose; delays in timing of presentation; and patient-level confounders. To address these issues, the investigators have conducted controlled human infections with influenza and RSV since 2010, to investigate mechanisms of immunopathogenesis with a particular focus on disease in the human respiratory tract. Recent preliminary data from a cohort of volunteers infected with the influenza A(H1N1)2009 strain showed that rapid changes in the transcriptome of whole blood occurred within 2 days of virus exposure. During the 2009 influenza pandemic, similar studies were also performed with hospitalised patients. There, transcriptomic analysis of blood showed similar antiviral signatures in less severely unwell individuals but divergent signatures associated with poor clinical outcomes.

The aim of this project is to identify and test predictors of disease progression and clinical deterioration in patients with influenza-like illness, in order to develop novel methods to more accurately determine the need for hospital admission and treatment intensification during respiratory viral infection. To further develop and test these biomarkers in an independent cohort of naturally-infected patients, hospitalised adults with influenza-like illness will be recruited within 24 hours of admission and samples obtained from blood and nose at 3 subsequent time-points.

Using these data, predictive transcriptomic signatures will be identified. Longitudinal samples and clinical data will then be used to test, validate and refine them in affected local populations. These findings will then be translated into novel diagnostic tools and a biobank established for further investigation of the virology and immunopathogenesis of severe respiratory viral infections.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Case-Only

Time Perspective:

Cross-Sectional

Official Title:

Predicting Severity and Disease Progression in Influenza-like Illness

Actual Study Start Date :

Jan 25, 2021

Actual Primary Completion Date :

Apr 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Outcome Measures

Primary Outcome Measures

Describe the aetiology of influenza-like illness in hospitalised adults [Day 0 to Day 28]
The identity of pathological organisms associated with influenza-like illness (including respiratory viruses and bacteria) will be obtained from the patient's medical record
Describe the clinical outcomes of influenza-like illness in hospitalised adults [Day 0 to Day 28]
The following data will be collected from the patient's medical record. At enrolment, data will consist of: past medical history, clinical signs and symptoms relating to this admission, vital signs (pulse rate, blood pressure, temperature, oxygen saturation), demographics, drug history, laboratory results including diagnostic microbiological tests and interventions. Data collection on Day 28 will consist of clinical diagnosis at discharge, any febrile illness in the 7 days preceding the visit, mortality and complications between Day 0 and 28.

Secondary Outcome Measures

Identify changes in cytokine levels during influenza-like illness in hospitalised adults [Day 0 to Day 28]
Cytokine levels (in pg/mL) will be measured in plasma and nasal lining fluid samples by MesoScale Discovery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Healthy persons aged ≥ 18, and able to give informed consent
Patient is admitted to hospital
Primary reason for hospital admission is clinical suspicion of a new episode of ARI
Onset of the following symptoms within the last 7 days: i. Sudden onset of self-reported fever OR temperature of ≥ 38°C at presentation AND ii. At least one respiratory symptom (cough, sore throat, runny or congested nose, dyspnoea) AND iii. At least one systemic symptom (headache, muscle ache, sweats or chills or tiredness).