Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle

Purpose: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). Methods: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. Results: Subjects low Tvalues (< 8 nmol/L; 176 cases) were significantly older (P= 0.001) and had higher serum interleukin-6 (P= 0.001), C-reactive protein (P< 0.001), lactate dehydrogenase (P< 0.001), ferritin (P= 0.012), lower P/Fratio (P= 0.001), increased prevalence of low T3 syndrome (P= 0.041), acute respiratory insufficiency (P< 0.001), more frequently need of ventilation (P< 0.001) and higher mortality rate (P= 0.009) compared to subjects with higher T values. In the multivariable regression analyses, Tvalues maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79–0.94; P< 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69–0.95; P= 0.009), independently of age, comorbidities, thyroid function and inflammation. Conclusion: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.