Abstract
BackgroundMale sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19.Patients and MethodsWe studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020.ResultsMen had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E2) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p < 0.001), IL-6 levels (rs = - 0.563, p < 0.001), lower cholesterol levels (rs = 0.407, p < 0.001) and an increased morbidity and mortality. Men with tT levels < 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 – 144.639], p = 0.006) compared to men with tT levels > 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E2 levels at admission, we detected a negative correlation with the tT/E2 ratio upon hospital admission.ConclusionHospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.
Highlights
Coronavirus disease 2019 (COVID-19) is still influencing the daily life of people all over the world
Upon initial hospital admission men presented with significantly lower serum cholesterol (121 vs. 141 mg/dL, p < 0.001), low-density lipoprotein (LDL) (72 vs. 83 mg/dL, p = 0.001) and high-density lipoprotein (HDL) levels (31 vs. 40 mg/dL, p < 0.001) as well as significantly higher immune activation markers, namely C-reactive protein (CRP; 6.01 mg/dL vs. 3.70 mg/dL, p < 0.001), interleukin 6 (IL-6; 44.5 vs. 24.0 ng/L, p < 0.001), procalcitonin (PCT; 0.13 vs. 0.07 ng/mL, p < 0.001), neopterin (51.2 vs. 41.3 nmol/L, p = 0.002), fibrinogen (511 vs. 439 G/L, p = 0.002) and ferritin levels (662 vs. 265 mg/L, p < 0.001) as well as higher leukocytes counts (5.80 vs. 5.00 G/L, p = 0.003) compared to women
In the present study we found that low serum total and free testosterone levels upon hospital admission are associated with disease severity indicated by lower oxygen saturation, higher WHO score and increased risk for intensive care unit (ICU) admission or death during the hospital stay in men with SARS-CoV-2 infection
Summary
Coronavirus disease 2019 (COVID-19) is still influencing the daily life of people all over the world. Most patients infected with the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) have developed mild symptoms, while up to 20% need hospitalization due to severe disease course characterized by shortness of breath and hypoxia [1]. Male sex is related to more severe COVID-19 manifestation, even though there are no sex differences in the absolute number of confirmed COVID-19 cases [6]. Male sex is related to increased COVID-19 severity and fatality confirmed infections are distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19
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