Metrics from Wearable Devices as Candidate Predictors of Antibody Response Following Vaccination against COVID-19: Data from the Second TemPredict Study

Abstract

There is significant variability in neutralizing antibody responses (which correlate with immune protection) after COVID-19 vaccination, but only limited information is available about predictors of these responses. We investigated whether device-generated summaries of physiological metrics collected by a wearable device correlated with post-vaccination levels of antibodies to the SARS-CoV-2 receptor-binding domain (RBD), the target of neutralizing antibodies generated by existing COVID-19 vaccines. One thousand, one hundred and seventy-nine participants wore an off-the-shelf wearable device (Oura Ring), reported dates of COVID-19 vaccinations, and completed testing for antibodies to the SARS-CoV-2 RBD during the U.S. COVID-19 vaccination rollout. We found that on the night immediately following the second mRNA injection (Moderna-NIAID and Pfizer-BioNTech) increases in dermal temperature deviation and resting heart rate, and decreases in heart rate variability (a measure of sympathetic nervous system activation) and deep sleep were each statistically significantly correlated with greater RBD antibody responses. These associations were stronger in models using metrics adjusted for the pre-vaccination baseline period. Greater temperature deviation emerged as the strongest independent predictor of greater RBD antibody responses in multivariable models. In contrast to data on certain other vaccines, we did not find clear associations between increased sleep surrounding vaccination and antibody responses.

Inter-individual variation in objective measure of reactogenicity following COVID-19 vaccination via smartwatches and fitness bands

“…While the absolute changes are small and would be unrecognizable in a standard healthcare setting, these findings, and their consistency with reported subjective reactogenicity, highlight the value of wearable sensors to detect subtle deviations from an individual’s “normal.” With knowledge of an individual’s pre-vaccine “normal” 22 – 26 , we were able to identify changes in RHR of at least one standard deviation above an individual’s usual, pre-vaccine RHR pattern in ~half of individuals following their second vaccine dose. As there are currently no non-invasive, objective means of detecting a response to vaccines in a scalable manner, these findings, along with other recent work 17 , provide a potential novel mechanism to identify individuals with either a suboptimal or exaggerated immune response to a vaccine.…”

“…The relationship between reactogenicity symptoms after vaccination and immune response is controversial 15 , although one study of a COVID-19 vaccine identified a direct correlation between the duration of time between a first and second vaccine dose, reactogenicity and eventual humoral immune response 16 . In addition, a recent study found a significant relationship between individual changes in physiologic parameters measured using a smart ring and ~30 day antibody levels 17 .…”

The digital phenotype of vaccination

“…Early proof-of-concept data from the DETECT 6 study and from other studies 7 – 9 confirm that consumer wearable sensors can detect the individual physiological and behavioral changes associated with the vaccination and the consequent inflammation. All three studies 7 – 9 identified significant post-vaccine changes in daily summary values of physiological and behavioral parameters relative to their pre-vaccine individual baselines. The level of deviation from normal was moderate.…”

“…The potential value in identifying these small, individual changes was demonstrated by Mason et al 9 in their study of over 1,000 individuals with wearable data from a smart ring and with post-vaccination SARS-CoV-2 receptor-binding domain antibody levels. They identified a significant and direct correlation between the change in several physiological parameters and immunogenicity, with the strongest independent predictor being temperature deviation.…”

The need for more holistic immune profiling in next-generation SARS-CoV-2 vaccine trials

“…Alternate solutions are also in development, such as wearable sensors capable of correlating vaccine-induced physiological changes to antibody and cell-mediated responses ( 47 ), Interferon release assays ( 48 ), TCR sequencing systems ( 49 ), and skin tests ( 50 ). Innovations link these could greatly reduce the cost and complication of evaluating the cell-mediated immune response, rendering these assessments more accessible for clinical trials.…”