H7N9 avian influenza virus infection in men is associated with testosterone depletion

Tian Bai, Yongkun Chen, Sebastian Beck, Stephanie Stanelle-Bertram, Nancy Kouassi Mounogou, Tao Chen, Jie Dong, Bettina Schneider, Tingting Jia, Jing Yang, Lijie Wang, Andreas Meinhardt, Antonia Zapf, Lothar Kreienbrock, Dayan Wang, Yuelong Shu () and Gülsah Gabriel ()
Additional contact information
Tian Bai: Viral Zoonoses-One Health, Leibniz Institute for Virology (LIV)
Yongkun Chen: Sun Yat-sen University
Sebastian Beck: Viral Zoonoses-One Health, Leibniz Institute for Virology (LIV)
Stephanie Stanelle-Bertram: Viral Zoonoses-One Health, Leibniz Institute for Virology (LIV)
Nancy Kouassi Mounogou: Viral Zoonoses-One Health, Leibniz Institute for Virology (LIV)
Tao Chen: Chinese Center for Disease Control and Prevention
Jie Dong: Chinese Center for Disease Control and Prevention
Bettina Schneider: University of Veterinary Medicine Hannover
Tingting Jia: Sun Yat-sen University
Jing Yang: Chinese Center for Disease Control and Prevention
Lijie Wang: Chinese Center for Disease Control and Prevention
Andreas Meinhardt: Justus-Liebig University of Gießen
Antonia Zapf: University Medical Center Hamburg-Eppendorf
Lothar Kreienbrock: University of Veterinary Medicine Hannover
Dayan Wang: Chinese Center for Disease Control and Prevention
Yuelong Shu: Chinese Center for Disease Control and Prevention
Gülsah Gabriel: Viral Zoonoses-One Health, Leibniz Institute for Virology (LIV)

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Human infections with H7N9 avian influenza A virus that emerged in East China in 2013 and caused high morbidity rates were more frequently detected in men than in women over the last five epidemic waves. However, molecular markers associated with poor disease outcomes in men are still unknown. In this study, we systematically analysed sex hormone and cytokine levels in males and females with laboratory-confirmed H7N9 influenza in comparison to H7N9-negative control groups as well as laboratory-confirmed seasonal H1N1/H3N2 influenza cases (n = 369). Multivariable analyses reveal that H7N9-infected men present with considerably reduced testosterone levels associated with a poor outcome compared to non-infected controls. Regression analyses reveal that testosterone levels in H7N9-infected men are negatively associated with the levels of several pro-inflammatory cytokines, such as IL-6 and IL-15. To assess whether there is a causal relationship between low testosterone levels and avian H7N9 influenza infection, we used a mouse model. In male mice, we show that respiratory H7N9 infection leads to a high viral load and inflammatory cytokine response in the testes as well as a reduction in pre-infection plasma testosterone levels. Collectively, these findings suggest that monitoring sex hormone levels may support individualized management for patients with avian influenza infections.

Date: 2022
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DOI: 10.1038/s41467-022-34500-5

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