Tracking Inflammation in Real Time Following Vaccination: Validation of a Novel Individualized Digital Inflammatory Biomarker Relative to Serum Biomarkers

BackgroundInflammatory changes underly many diseases and therapeutic interventions, making accurate tracking of inflammation critical for clinical evaluation of disease course and therapy response. Traditional methods like fever detection and serum biomarkers are limited by imprecision and invasiveness. Collection of self-reported symptoms after vaccination is a common vaccine trial endpoint, but prone to bias. Wearable sensors offer a promising alternative by detecting subtle physiological changes over time. Prior studies show they identify transient post-vaccine inflammation but lack validation relative to serum biomarkers. MethodsThis study included 61 volunteers who were administered one of four mRNA vaccines (1 or 2 doses) for a total of 80 doses. Participants wore a torso sensor patch for 14 days beginning seven days before vaccination, whose data was used to derive an individualized digital biomarker of inflammation - inflammatory multivariate change index (iMCI). The reference outcome was a serum biomarker panel collected at baseline and five post-vaccination timepoints. Self-reported reactogenicity symptoms were tracked daily for 7 days starting the day of vaccination. The correlation between total iMCI response within 48 hours following vaccination and maximal change in select serum biomarkers was determined, along with their relationship to reactogenicity. FindingsThere was a moderate to strong positive Spearman correlation between total iMCI and change in C-reactive protein (CRP) (0.59, p < 0.01) and interferon gamma (IFN-Y)(0.56, p < 0.01) across vaccine types and vaccine doses, similar to the correlation between CRP and IFN-Y (0.60, p < 0.01). The associations with self-reported systemic reactogenicity was only moderate for all: 0.48, p < 0.01 for iMCI, 0.34, p = 0.01 for interferon gamma, 0.36, p <. 0.01 for C-reactive protein. InterpretationThe personalized multivariate inflammatory digital biomarker derived from wearable sensor data can quantify an individuals inflammatory response to vaccination as an alternative to serial serum biomarker testing. This scalable, non-invasive approach can enable real-time monitoring of the onset, duration, and severity of inflammation. FundingModerna, Inc