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Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19
Journal article   Open access   Peer reviewed

Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19

Sandeep Dhindsa, Nan Zhang, Michael J McPhaul, Zengru Wu, Amit K Ghoshal, Emma C Erlich, Kartik Mani, Gwendalyn J Randolph, John R Edwards, Philip A Mudd, …
JAMA network open, Vol.4(5), pp.e2111398-e2111398
05/03/2021
DOI: 10.1001/jamanetworkopen.2021.11398
PMCID: PMC8150664
PMID: 34032853
url
https://doi.org/10.1001/jamanetworkopen.2021.11398View
Published (Version of record) Open Access

Abstract

Male sex is a risk factor for developing severe COVID-19 illness. It is not known whether sex hormones contribute to this predisposition. To investigate the association of concentrations of serum testosterone, estradiol, and insulinlike growth factor 1 (IGF-1, concentrations of which are regulated by sex hormone signaling) with COVID-19 severity. This prospective cohort study was conducted using serum samples collected from consecutive patients who presented from March through May 2020 to the Barnes Jewish Hospital in St Louis, Missouri, with COVID-19 (diagnosed using nasopharyngeal swabs). Testosterone, estradiol, and IGF-1 concentrations were measured at the time of presentation (ie, day 0) and at days 3, 7, 14, and 28 after admission (if the patient remained hospitalized). Baseline hormone concentrations were compared among patients who had severe COVID-19 vs those with milder COVID-19 illness. RNA sequencing was performed on circulating mononuclear cells to understand the mechanistic association of altered circulating hormone concentrations with cellular signaling pathways. Among 152 patients (90 [59.2%] men; 62 [40.8%] women; mean [SD] age, 63 [16] years), 143 patients (94.1%) were hospitalized. Among 66 men with severe COVID-19, median [interquartile range] testosterone concentrations were lower at day 0 (53 [18 to 114] ng/dL vs 151 [95 to 217] ng/dL; P = .01) and day 3 (19 [6 to 68] ng/dL vs 111 [49 to 274] ng/dL; P = .006) compared with 24 men with milder disease. Testosterone concentrations were inversely associated with concentrations of interleukin 6 (β = -0.43; 95% CI, -0.52 to -0.17; P < .001), C-reactive protein (β = -0.38; 95% CI, -0.78 to -0.16; P = .004), interleukin 1 receptor antagonist (β = -0.29; 95% CI, -0.64 to -0.06; P = .02), hepatocyte growth factor (β = -0.46; 95% CI, -0.69 to -0.25; P < .001), and interferon γ-inducible protein 10 (β = -0.32; 95% CI, -0.62 to -0.10; P = .007). Estradiol and IGF-1 concentrations were not associated with COVID-19 severity in men. Testosterone, estradiol, and IGF-1 concentrations were similar in women with and without severe COVID-19. Gene set enrichment analysis revealed upregulated hormone signaling pathways in CD14+CD16- (ie, classical) monocytes and CD14-CD16+ (ie, nonclassical) monocytes in male patients with COVID-19 who needed intensive care unit treatment vs those who did not. In this single-center cohort study of patients with COVID-19, lower testosterone concentrations during hospitalization were associated with increased disease severity and inflammation in men. Hormone signaling pathways in monocytes did not parallel serum hormone concentrations, and further investigation is required to understand their pathophysiologic association with COVID-19.
 Aged COVID-19 - blood COVID-19 - complications COVID-19 - pathology Estradiol - blood Female Gonadal Steroid Hormones - blood Hospitalization Hospitals Humans Inflammation - blood Inflammation - etiology Insulin-Like Growth Factor I - metabolism Male Middle Aged Missouri SARS-CoV-2 Severity of Illness Index Sex Factors Testosterone - blood

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