Individual Factors Including Age, BMI, and Heritable Factors Underlie Temperature Variation in Sickness and in Health: An Observational, Multi-cohort Study
Authors: 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 ,   GSTT Covid Collaborative, Iyer Rishi , Anders Rachael , Hennah Lindsay , Amaratunga Gitanjali , Hobill Abigail , Fairhead Cassandra , Taylor Amybel , Maynard Henry , Osterdahl Marc , Dias Maria , Amir Taha , Yeo Natalie , Mawhinney Jamie , Morrin Hamilton , Kok Li , Scott Luca , Haslam Aiden , Levinson Gavriella , Mulhern Stephanie , Worrall Stephanie , Rajeswaran Thurkka , Stamboullouian Katherine , McLachlan Sophie , Griffith Karla , Muller Daniel , O’ Doherty Alice , Mandane Baguiasri , Islek Irem , Emery Alexander , Millwood-Hargrave John , Caracostea Andra , Bremner Laura , Desai Arjun , Kuzeva Aneliya , Akladious Carolyn , Wimalasundera Mettha , Kelly Mairead , Aziz Sally , O’Dwyer Sinead , Perinpanathan Rupini , Barnard Anna , Hrouda Nicole , Panayotidis Ismini , Desai Nirali , Gerretson Hannah , Lau Rebecca , Ghufoor Zaynub , Nguyen Hanna , Heinsohn Torben , Cullen Jack , Watkins Eleanor , Vyas Vaishali , Curley Daniel , Cunningham Niamh , Vergani Vittoria , Miu Kelvin , Stewart Jack , Kelly Nicola , Howells Lara , Deldar Benyamin , Sayers Ross , Fisk Gracie , Sivarajan Sri , Razzak Tahmina , Ye Helen , Dost Samiullah , Dattani Nikhita , Wilcock Catherine , Lee Gabriel , Acott Jodie , Bridgwater Hannah , Fernandez Antia , Khalid Hesham , Hopkinson Katherine , Green Deirdre , Butt Hejab , Gupta Ayushi , Garner Madeleine , Sanghvi Hazel , Daly Madeleine , Ross-Skinner Emily , Patel Shefali , Lis Danielle 
Published: October 2021

Abstract

Background
Aging 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 4 cohorts: 1 089 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 3 972 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 body mass index (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 = .001), and increasing age (p &lt; .001) was 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 &lt; .001). For each additional year of age, participants were 1% less likely to demonstrate a fever ≥37.8°C (OR 0.99; p &lt; .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 &lt;65 years for discriminating infection.

Conclusions
Aging 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.