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

By Rose S. Penfold, Maria Beatrice Zazzara, Marc F Österdahl, GSTT CovidCollaborative, Carly Welch, Mary Ni Lochlainn, Maxim Freidin, Ruth C.E. Bowyer, Ellen E.J. Thompson, Michela Antonelli, Yu Xian Rachel Tan, Carole Sudre, Marc Modat, Benjamin Murray, Jonathan Wolf, Sebastien Ourselin, Tonny Veenith, Janet M Lord, Claire J Steves

Posted 28 Jan 2021
medRxiv DOI: 10.1101/2021.01.26.21250480

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.

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