Individual factors underlie temperature variation in sickness and in health: influence of age, BMI and genetic factors in a multi-cohort study

Penfold, R. S.; Zazzara, M. B.; Österdahl, M. F.; GSTT CovidCollaborative,; Welch, C.; Ni Lochlainn, M.; Freidin, M.; Bowyer, R. C. E.; Thompson, E. E. J.; Antonelli, M.; Tan, Y. X. R.; Sudre, C.; Modat, M.; Murray, B.; Wolf, J.; Ourselin, S.; Veenith, T.; Lord, J. M.; Steves, C. J.

Introduction: Ageing affects immune function resulting in aberrant fever response to infection. We assess the effects of biological variables on basal temperature and temperature in COVID-19 infection, proposing an updated temperature threshold for older adults. Methods: Participants: a) Unaffected twin volunteers: 1089 adult TwinsUK participants. b) London hospitalised COVID-19+: 520 adults with emergency admission. c) Birmingham hospitalised COVID-19+: 757 adults with emergency admission. d) Community-based COVID-19+: 3972 adults self-reporting a positive test using the COVID Symptom Study mobile application. Analysis: Heritability assessed using saturated and univariate ACE models: Linear mixed-effect and multivariable linear regression analysing associations between temperature, age, sex and BMI; multivariable logistic regression analysing associations between fever (>=37.8degC) and age; receiver operating characteristic (ROC) analysis to identify temperature threshold for adults >=65 years. Results: Among unaffected volunteers, lower BMI (p=0.001), and older age (p<0.001) associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% Confidence Interval 18-57%). In COVID-19+ participants, increasing age associated with lower temperatures in cohorts (c) and (d) (p<0.001). For each additional year of age, participants were 1% less likely to demonstrate a fever (OR 0.99; p<0.001). Combining healthy and COVID-19+ participants, a temperature of 37.4degC in adults >=65 years had similar sensitivity and specificity to 37.8degC in adults <65 years for discriminating fever in COVID-19. Conclusions: Ageing affects temperature in health and acute infection. Significant heritability indicates biological factors contribute to temperature regulation. Our observations indicate a lower threshold (37.4degC) should be considered for assessing fever in older adults.