Observational Digital Biomarker Discovery in Respiratory Virus Challenge Studies

Study Description:

Wearable and sensor digital devices have the potential to be important tools in infectious diseases surveillance. In this study, digital devices will be used to evaluate responses before and after respiratory virus challenge on a separate NIH protocol. Participants recently enrolled, currently enrolled, or planned for enrollment in a challenge study are eligible. Devices will be worn and/or used during the inpatient hospitalization and at outpatient follow-up visits. Participants may be sent smartwatches at home to collect additional baseline or healthy data. Devices may collect data on coughing, speech, heart rate, heart rhythm, sweating, and temperature to identify digital biomarkers associated with respiratory virus infection. The correlation between digital device measurement data and clinical data, particularly on cough, will be determined. We hypothesize that sensor-collected data will correlate with symptom severity obtained by clinician assessment and participant report. We also hypothesize that digital biomarkers can predict influenza infection and can be used to develop a predictive model.

Objectives:

• Primary:

• To correlate continuous cough sensor data to cough severity after challenge.
• To develop a predictive model for mild-moderate influenza disease (MMID) and influenza infection using digital biomarkers
• Secondary: To correlate continuous and noncontinuous vital sign sensor data to routine vital signs obtained by clinical staff.
• Exploratory:

• To evaluate body sensor data after challenge.
• To correlate digital biomarker data to biological biomarker data.

Endpoints:

Primary:

• Cough quantity:

-Continuous cough measurements

• Infection

• Defined as:

• MMID (positive PCR for influenza and >=1 symptoms)
• Flu (positive PCR for influenza or convalescent four-fold increase in serum antibodies to the hemagglutinin (HA) or neuraminidase (NA) of the challenge virus and >=1 symptoms)
• Influenza infection (positive PCR for influenza)
• Using predictor variables such as:

• Smartwatch photoplethysmography (PPG) determined heart rate
• Smartwatch electrodermal activity (EDA) determined sweating
• Smartwatch determined temperature
• Smartwatch Electrocardiogram (ECG) monitoring
• Audio voice recording

Secondary: Vital signs:

• Heart rate
• Respiratory rate
• Temperature

Exploratory:

Correlations between digital biomarker data and biological biomarker data (e.g. antibody titers)

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Able to provide informed consent.
• Current, recent, or planned enrollment in a respiratory virus challenge study at the NIH Clinical Center.
• Willing to wear devices as instructed.
• Willing to participate in monitoring activities as instructed.
• Willing to have monitoring data stored.
• Willing to have monitoring data shared with protocol investigators at NIH, University of Washington, and University of Toronto.
• Willing to have select clinical data from the challenge study such as vital signs, viral shedding, pulmonary function test and/or spirometry results, and clinical symptoms data shared with investigators at University of Washington and University of Toronto.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Co-enrollment guidelines: Participants must be co-enrolled, planned for co-enrollment, or recently enrolled in a challenge study. Co-enrollment in other studies is restricted but may take place after study staff notification and only with approval of the principal investigator or designee.