Serum cortisol concentration may potentially serve as another marker to help doctors identify which patients with coronavirus disease 2019 (COVID-19) are more likely to need intensive care, a new study finds.
According to results published in The Lancet Diabetes & Endocrinology, cortisol levels in patients with COVID-19 were significantly greater than those without, ranging up to 3241 nmol/L, indicating a cortisol stress response that is “perhaps higher than is observed in patients undergoing major surgery,” reported Tricia Tan, Imperial College London, London, UK, and colleagues.
They also found high cortisol concentrations were linked to increased mortality and reduced median survival, “probably because this is a marker of the severity of illness.” They noted that in their cohort study “cortisol seemed to be a better independent predictor than were other laboratory markers associated with COVID-19, such as C-reactive protein (CRP), D-dimer, and neutrophil-to-leukocyte ratio.”
The study looked at acute cortisol concentrations in patients with a clinical suspicion of COVID-19 admitted to three large hospitals in London, UK, from March 9 to April 22, 2020. Only baseline cortisol measurements made within 48 hours of admission for suspected COVID-19 or diagnosis of COVID-19 during a hospital admission were included. Patients had a standard set of blood samples drawn, including full blood count, creatinine, CRP, D-dimer, and serum total cortisol. Those with pre-existing hypoadrenalism, concurrent systemic glucocorticoid treatment, or who had cortisol measured as part of a diagnostic test (eg, a synacthen test) were excluded.
A total of 535 patients with cortisol measurements were available for analysis, of whom 403 were diagnosed with COVID-19 on the basis of either a positive real-time RT-PCR test of a nasopharyngeal swab (356 [88%]) or a strong clinical and radiological suspicion of COVID-19, despite negative swab testing (47 [12%]).
In the group of patients with COVID-19, the mean age was 66.3 years (SD 15.7) and 240 (59.6%) were men. The most frequent comorbidities in this group were hypertension (191 [47.4%]), diabetes (160 [39.7%]), cardiovascular disease (94 [23.3%]), chronic kidney disease (50 [12.4%]) and a current diagnosis of cancer (38 [9.4%]).
A total of 112 (27.8%) of the patients with COVID-19 died during the study period, compared to 9 (6.8%) in the non-COVID-19 group (p<0.0001). The median cortisol concentration in the COVID-19 group was 619 nmol/L [IQR 456–833] versus 519 nmol/L [378–684] among those without COVID-19 (p<0.0001).
An optimal cut-off for cortisol was selected. Among patients with COVID-19, those with a baseline cortisol level of 744 nmol/L (268 patients [67%]) or less had a median survival of 36 days [95% CI 24–not determined], whereas COVID-19 patients whose cortisol levels were over the 744 nmol/L mark (135 patients [33%]) had a median survival of 15 days [10–36] (log-rank test p<0.0001)).
Multivariable analysis showed that a doubling of cortisol concentration was associated with a significant 42% increase in the hazard of mortality, after adjustment for age, the presence of comorbidities, and laboratory tests.
“Our analyses show for the first time that patients with COVID-19 mount a marked and appropriate acute cortisol stress response and that this response is significantly higher in this patient cohort than in individuals without COVID-19. In other words, our cohort did not obviously exhibit an adrenal insufficiency with SARS-CoV-2 infection in the acute setting,” the authors said, but noted that it is possible patients might exhibit a relative adrenal insufficiency later on in their disease.
They also said the data suggest “it is appropriate for patients with hypoadrenalism — a situation quite commonly encountered in the 3% of the population taking systemic glucocorticoid therapy — to take or be given supplemental glucocorticoids at a high dose to prevent an acute adrenal crisis if they acquire a SARS-CoV-2 infection.”
According to the authors, some caveats in the study include the analysis confining itself to single baseline cortisol concentrations measured within 48 hours of admission, a restriction that does not allow for variations in cortisol stress response dynamics, both within and between individuals, to be considered. Further, they indicated that their cortisol concentration cut-off of more than 744 nmol/L being a predictor for reduced survival “is likely to differ with other cortisol assays.” They said the role for cortisol measurement as a prognostic biomarker for COVID-19 requires validation in a prospective study.