Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID‐19

Author:

Devine Kerri12,Russell Clark D.3,Blanco Giovanny R.4,Walker Brian R.12,Homer Natalie Z. M.15,Denham Scott G.5,Simpson Joanna P.5,Leavy Olivia C.6,Elneima Omer7,McAuley Hamish J. C.7,Shikotra Aarti7,Singapuri Amisha7,Sereno Marco7,Saunders Ruth M.7,Harris Victoria C.7,Houchen‐Wolloff Linzy7,Greening Neil J.7,Lone Nazir I.8,Thorpe Mathew8,Greenhalf William9,Chalmers James D.10,Ho Ling‐Pei11,Horsley Alex12,Marks Michael131415,Raman Betty16,Moore Shona C.17,Dunning Jake18,Semple Malcolm G.17,Andrew Ruth15,Wain Louise V.67,Evans Rachael A.7,Brightling Christopher E.7,Kenneth Baillie John19,Reynolds Rebecca M.1ORCID,

Affiliation:

1. BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh Bioquarter University of Edinburgh Edinburgh UK

2. Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK

3. University of Edinburgh Centre for Inflammation Research Queen's Medical Research Institute Edinburgh UK

4. Edinburgh Cancer Research UK Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UK

5. Mass Spectrometry Core, Edinburgh Clinical Research Facility, Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK

6. Department of Population Health Sciences University of Leicester Leicester UK

7. NIHR Leicester Biomedical Research Centre University of Leicester Leicester UK

8. Centre for Medical Informatics, The Usher Institute University of Edinburgh Edinburgh UK

9. University of Liverpool Liverpool UK

10. Ninewells Hospital and Medical School University of Dundee Dundee UK

11. MRC Human Immunology Unit University of Oxford Oxford UK

12. Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health University of Manchester Manchester UK

13. Department of Clinical Research London School of Hygiene and Tropical Medicine London UK

14. Hospital for Tropical Diseases University College London Hospital London UK

15. Division of Infection and Immunity University College London London UK

16. Radcliffe Department of Medicine University of Oxford Oxford UK

17. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences University of Liverpool Liverpool UK

18. Pandemic Sciences Institute University of Oxford Oxford UK

19. Division of Genetics and Genomics, Roslin Institute University of Edinburgh Edinburgh UK

Abstract

AbstractObjectiveEndocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID‐19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID‐19 and with post‐COVID symptoms have glucocorticoid and sex hormone deficiencies.Design/PatientsSamples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID‐19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow‐up 5 months after hospitalisation (Post‐hospitalisation COVID‐19 study).MeasurementsPlasma steroids were quantified by liquid chromatography–mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD).ResultsIn the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow‐up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121–192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in‐hospital severity, perception of recovery, or patient‐reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in‐hospital severity, perception of recovery or symptom scores.ConclusionsCirculating glucocorticoids in patients hospitalised with COVID‐19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post‐COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

Funder

Medical Research Council

Medical Research Scotland

Bill and Melinda Gates Foundation

Publisher

Wiley

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