High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study

Emerg Microbes Infect. 2021 Dec;10(1):1807-1818. doi: 10.1080/22221751.2021.1969869.

Abstract

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; critical illness; cytokines; sex differences; sex hormones.

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / blood
  • COVID-19 / mortality*
  • COVID-19 / pathology*
  • Critical Care
  • Critical Illness
  • Estradiol / blood*
  • Extracorporeal Membrane Oxygenation
  • Female
  • Humans
  • Hypogonadism / pathology
  • Intensive Care Units
  • Interferon-gamma / blood
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • SARS-CoV-2
  • Severity of Illness Index
  • Sex Distribution
  • Testosterone / blood*

Substances

  • IFNG protein, human
  • Testosterone
  • Estradiol
  • Interferon-gamma

Grants and funding

This study was supported by a rapid response grant from the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG) to GG. MS receives funding from the Medical Faculty of the University of Hamburg for clinical leave. The study funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.