AUTHOR=Ryan Jacob M. , Navaneethan Shreenithi , Damaso Natalie , Dilchert Stephan , Hartogensis Wendy , Natale Joseph L. , Hecht Frederick M. , Mason Ashley E. , Smarr Benjamin L. TITLE=Information theory reveals physiological manifestations of COVID-19 that correlate with symptom density of illness JOURNAL=Frontiers in Network Physiology VOLUME=4 YEAR=2024 URL=https://www.frontiersin.org/journals/network-physiology/articles/10.3389/fnetp.2024.1211413 DOI=10.3389/fnetp.2024.1211413 ISSN=2674-0109 ABSTRACT=

Algorithms for the detection of COVID-19 illness from wearable sensor devices tend to implicitly treat the disease as causing a stereotyped (and therefore recognizable) deviation from healthy physiology. In contrast, a substantial diversity of bodily responses to SARS-CoV-2 infection have been reported in the clinical milieu. This raises the question of how to characterize the diversity of illness manifestations, and whether such characterization could reveal meaningful relationships across different illness manifestations. Here, we present a framework motivated by information theory to generate quantified maps of illness presentation, which we term “manifestations,” as resolved by continuous physiological data from a wearable device (Oura Ring). We test this framework on five physiological data streams (heart rate, heart rate variability, respiratory rate, metabolic activity, and sleep temperature) assessed at the time of reported illness onset in a previously reported COVID-19-positive cohort (N = 73). We find that the number of distinct manifestations are few in this cohort, compared to the space of all possible manifestations. In addition, manifestation frequency correlates with the rough number of symptoms reported by a given individual, over a several-day period prior to their imputed onset of illness. These findings suggest that information-theoretic approaches can be used to sort COVID-19 illness manifestations into types with real-world value. This proof of concept supports the use of information-theoretic approaches to map illness manifestations from continuous physiological data. Such approaches could likely inform algorithm design and real-time treatment decisions if developed on large, diverse samples.