Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia

• Published in: International journal of infectious diseases Vol. 108; pp. 244 - 251
• Main Authors: Camici, Marta, Zuppi, Paolo, Lorenzini, Patrizia, Scarnecchia, Liliana, Pinnetti, Carmela, Cicalini, Stefania, Nicastri, Emanuele, Petrosillo, Nicola, Palmieri, Fabrizio, D’Offizi, Gianpiero, Marchioni, Luisa, Gagliardini, Roberta, Baldelli, Roberto, Schininà, Vincenzo, Pianura, Elisa, Di Stefano, Federica, Curcio, Stefano, Ciavarella, Lucia, Ippolito, Giuseppe, Girardi, Enrico, Vaia, Francesco, Antinori, Andrea
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-07-2021; The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases; Elsevier
• Subjects: Androgen sensitivity; Gender imbalance; SARS-CoV-2; Severity markers; Sex hormones; Testosterone; Androgen sensitivity; Sex hormones; Testosterone; SARS-CoV-2; Severity markers; Gender imbalance
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2021.05.042

•The prognosis of coronavirus diseases 2019 (COVID-19) is gender-related.•TMPRSS2 plays a key role in COVID-19; androgen receptor regulates its expression.•Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can damage the testes.•Low serum testosterone at diagnosis is predictive of severe COVID-19.•Low serum testosterone predicts for longer hospitalization and hyperinflammation.
To investigate the association between sex hormones and the severity of coronavirus disease 2019 (COVID-19). Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied.
This case–control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO2/FiO2 <250 mmHg and who needed ventilatory support during hospitalization (severe COVID-19). The 24 controls were selected in a 1:1 ratio, matched by age, from patients who maintained PaO2/FiO2 >300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission.
Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate.
A low level of testosterone was found to be a marker of clinical severity of COVID-19.