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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320952

ABSTRACT

BACKGROUND 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. We sought to characterize sex differences in hormone levels and cytokine responses in critically ill COVID-19 patients. METHODS We performed a retrospective cohort study of critically ill COVID-19 patients. Males and females were compared. Multivariate regression was performed to assess the association between sex hormones, cytokine responses and the requirement for extracorporeal membrane oxygenation (ECMO) treatment. RESULTS We analyzed sex hormone levels (estradiol and testosterone) of n =181 male and female individuals. These consisted of n =50 critically ill COVID-19 patients ( n =39 males, n =11 females), n =42 critically ill non-COVID-19 patients ( n =27 males, n =15 females), n =39 non-COVID-19 patients with coronary heart diseases (CHD) ( n =25 males, n =14 females) and n =50 healthy individuals ( n =30 males, n =20 females). We detected highest estradiol levels in critically ill male COVID-19 patients compared to non-COVID-19 patients ( p =0.0123), patients with CHD ( p =0.0002) or healthy individuals ( p =0.0007). Lowest testosterone levels were detected in critically ill male COVID-19 patients compared to non-COVID-19 patients ( p =0.0094), patients with CHD ( p =0.0068) or healthy individuals ( p <0.0001). No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends in estradiol levels were observed. In critically ill male COVID-19 patients, cytokine and chemokine responses (IFN-γ, p =0.0301;IL-1RA, p =0.0160;IL-6, p =0.0145;MCP-1, p =0.0052;MIP-1α, p =0.0134) were significantly elevated in those with higher Sequential Organ Failure Assessment (SOFA) scores (8-11). Linear regression analysis revealed that herein IFN-γ levels correlate with estradiol levels in male and female COVID-19 patients (R 2 =0.216, =0.0009). Male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment in the course of their ICU stay ( p =0.0009). CONCLUSIONS We identified high estradiol and low testosterone levels as a hallmark of critically ill male COVID-19 patients. Elevated estradiol levels in critically ill male COVID-19 patients were positively associated with IFN-γ levels and increased risk for ECMO requirement.

2.
Emerg Microbes Infect ; 10(1): 1807-1818, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1360311

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.


Subject(s)
COVID-19/mortality , COVID-19/pathology , Estradiol/blood , Testosterone/blood , Aged , Aged, 80 and over , COVID-19/blood , Critical Care , Critical Illness , 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
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