Individual factors including age, BMI and heritable factors underlie temperature variation in sickness and in health: an observational, multi-cohort study

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

BACKGROUND: Ageing affects immunity, potentially altering fever response to infection. We assess effects of biological variables on basal temperature, and during COVID-19 infection, proposing an updated temperature threshold for older adults ≥65 years. METHODS: Participants were from four cohorts: 1089 unaffected adult TwinsUK volunteers; 520 adults with emergency admission to a London hospital with RT-PCR confirmed SARS-CoV-2 infection; 757 adults with emergency admission to a Birmingham hospital with RT-PCR confirmed SARS-CoV-2 infection and 3972 adult community-based COVID Symptom Study participants self-reporting a positive RT-PCR test. Heritability was assessed using saturated and univariate ACE models; mixed-effect and multivariable linear regression examined associations between temperature, age, sex and BMI; multivariable logistic regression examined associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis was used to identify temperature threshold for adults ≥ 65 years. RESULTS: Among unaffected volunteers, lower BMI (p=0.001), and increasing 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 was associated with lower temperatures in Birmingham and community-based cohorts (p<0.001). For each additional year of age, participants were 1% less likely to demonstrate a fever ≥37.8°C (OR 0.99; p<0.001). Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults <65 years for discriminating infection. CONCLUSIONS: Ageing affects temperature in health and acute infection, with significant heritability, indicating genetic factors contribute to temperature regulation. Our observations suggest a lower threshold (37.4°C/97.3°F) for identifying fever in older adults ≥65 years.