Effect of Serum Total Testosterone and Its Relationship with Other Laboratory Parameters on the Prognosis of Coronavirus Disease 2019 (COVID-19) in SARS-CoV-2 Infected Male Patients: A Cohort Study

Background: Higher mortality rate related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led clinicians to investigate newer parameters that might predict prognosis of coronavirus disease 2019 (COVID-19). Our hypothesis was whether serum testosterone and other gonadal hormones might play an important role on the prognosis of COVID-19 in male patients. Therefore, in this cohort study, we aimed to investigate effect of serum testosterone and its relationship with other laboratory parameters on the prognosis of COVID-19 in SARS-CoV-2 infected male patients. Methods: The study included 221 consecutive male patients (>18 years old) with laboratory confirmed SARS-CoV-2 who had been hospitalized due to COVID-19. The patients were divided into 3 groups: Asymptomatic patients (n: 46), symptomatic patients who were hospitalized in the internal medicine unit (IMU) (n: 129), and patients who were hospitalized in the intensive care unit (ICU) (n: 46). Demographic characteristics, co-morbidities, laboratory results, computer tomographic (CT) scan findings, admission to the ICU, days in the ICU and duration of hospital stay were prospectively recorded in every patient. In the patients who had pre-COVID-19 serum gonadal hormones test (n: 24), the hormone levels were compared from pre-COVID-19 to the time of COVID-19. Findings: At the beginning of COVID-19, hypogonadism (serum total testosterone level of <300 ng/dl) was observed in 113 (51.1%) of the male patients. The mortality was observed in 11 (4.97%) of the patients. Of the 46 patients in the ICU group, 35 (76%) had serum total testosterone level of <300 ng/dl, while 21 (45.6%) had serum total testosterone level of <200 ng/dl. As serum total testosterone level at baseline decreases, probability (%) to be in the ICU during hospitalization significantly increases (p=0.001 for linear equation and 0.000 for logarithmic equation). Of the 11 deaths, 10 (90.9%) had serum total testosterone level of <300 ng/dl, while 8 (72.7%) had serum total testosterone level of <200 ng/dl at baseline. As serum total testosterone level at baseline decreases, probability (%) of mortality significantly increases (p=0.002 for linear equation and 0.000 for logarithmic equation). Logistic regression analysis showed that older age (OR: 1.046), longer hospitalization (OR: 1.225), lower albumin level (OR: 1.628), lower total testosterone level (OR: 1.004), presence of fever (OR: 2.236), positive chest CT findings (OR: 3.005), presence of D-dimer ≥1 mg/l (OR: 14.065) and presence of CCI ≥2 (OR: 2.318) were the highly significant predictors for the ICU. In addition, longer hospitalization (OR: 1.118), lower albumin level (OR: 2.188), lower total testosterone level (OR: 1.008), presence of fever (OR: 6.488), presence of D-dimer ≥1 mg/l (OR: 15.750) were the highly significant predictors for the mortality. In the patients who had pre-COVID-19 serum gonadal hormones test (n: 24), serum total testosterone level significantly decreased from pre-COVID-19 level of 458±198 ng/dl to 315±120 ng/ml at the time of COVID-19 in the patients (p=0.003). Interpretation: For the first time, our data suggest that COVID-19 might deteriorate serum testosterone level in SARS-CoV-2 infected male patients. Low serum total testosterone level at baseline has a significant increased risk for the ICU and mortality in patients with COVID-19. Future studies related to testosterone treatment in this population would discover possible improvement in clinical outcomes with the testosterone treatment in SARSCoV-2 infected hypogonadal male patients. Funding Statement: None.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the local ethics committee, consisting of the members from the Turkish Ministry of Health and University of Mersin School of Medicine (2020/#378). An informed consent was taken from all patients, included in the study.