June 18, 2020

expert reaction to research letter looking at cortisol levels and mortality from COVID-19

A peer-reviewed research letter, published in The Lancet Diabetes & Endocrinology, has looked at levels of cortisol and associated mortality in COVID-19 patients.

Prof Kavita Vedhara, Professor of Health Psychology, University of Nottingham, said:

“This study identifies that levels of the stress hormone cortisol are not only significantly higher in people with COVID-19, than those without the infection, but also that survival is halved in people with the highest cortisol levels. The authors rightly question whether this increase in cortisol is related to the pathogenic processes of the disease. However, it is important to acknowledge that cortisol is also influenced by psychological stress, and that stress-related increases in cortisol dysregulate the immune system. As such, the findings raise the intriguing possibility that increased cortisol may not be (or may not only be) a consequence of COVID-19, but may also play a causal role. In theory this could occur at two levels. First, the cortisol mediated dysregulation in immunity could increase our risk of COVID-19 infection i.e., people with higher levels of the hormone due to the experience of greater stress, may be more likely to become infected. Second, this dysregulation in immunity may also influence whether people experience asymptomatic/mild disease versus much more severe disease. At present, the main correlates of severe disease are characteristics that are not amenable to change (e.g. age, gender, ethnicity). Thus, they don’t offer avenues for modifying the progression or severity of the disease. Cortisol, on the other hand, can be modified by both pharmacological and non-pharmacological treatments. Therefore, if cortisol plays a role in disease progression, early intervention to reduce levels of the hormone could stall or slow progression of the disease.

“Of course, these findings also tie in with the recent news that dexamethasone may be an effective treatment in some patients with COVID-19. Dexamethasone is a synthetic version of cortisol and usually results in a reduction in the body’s production of the hormone. Thus, pulling the findings from the two studies together suggests that the reason dexamethasone works in some patients is because it is dampening down the patient’s overproduction of cortisol.

“Regardless of whether elevated cortisol is a cause or consequence of COVID-19, the increased levels seen in this cohort of patients suggest that it is imperative that we rapidly work towards understanding the role of the hormone not only at the most severe end of the disease, but also examine whether it may also play a role in vulnerability to COVID-19, progression from asymptomatic to severe disease and the role of psychological stress and mental health in these processes.”

Prof Stafford Lightman, Professor of Medicine at the University of Bristol, said:

“This is a worthwhile study, but all it tells us is that people with COVID-19 have a healthy adrenal response to their illness – and suggests that the more ill you are the higher your cortisol. The real problem with this study is that they only take a single basal cortisol level. Since cortisol is a VERY pulsatile hormone – even in severely sick patients, it can vary greatly within 30 minutes or so – so the idea that a cut-off of 744 nmols/litre tells you anything significant is not warranted! If you had taken the sample half an hour earlier you might have got quite a different result. (See: Dynamic Pituitary-Adrenal Interactions in the Critically Ill after Cardiac Surgery; Gibbison B, Keenan DM, Roelfsema F, Evans J, Phillips K, Rogers CA, Angelini GD, Lightman SL; J Clin Endocrinol Metab. 2020 May 1;105(5):1327-42. doi: 10.1210/clinem/dgz206).

“Basically if you wanted to know whether there was any way to interpret your cortisol level you would need a study taking multiple timed samples.”

“Association between high serum total cortisol concentrations and mortality from COVID-19” by Tricia Tan et al, was published in The Lancet Diabetes & Endocrinology on Thursday 18 June.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.