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ABSTRACT
SARS-CoV-2 infection is associated with increased morbidities in men compared to women. Androgens are believed to play an important role in SARS-CoV-2 pathogenesis in men due to the postulated androgen-dependency of ACE2 and TMPRSS2. However, it is yet unclear whether the sex bias is mediated by SARS-CoV-2 infection itself or by other confounding factors. Here, using the golden hamster model, we show that SARS-CoV-2 infection attacks reproductive organs, causes massive dysregulation of sex hormones and induces elevated transcription of the androgen-to-estrogen converting enzyme aromatase CYP19A1 in the lung. In male hamsters, SARS-CoV-2 infection causes severely depleted testosterone and highly elevated estradiol levels. In female hamsters, SARS-CoV-2 infection causes reduced estradiol levels. Hormonal dysregulation in infected animals is followed by severe weight loss compared to control groups treated with poly(IC) or PBS. Lungs of SARS-CoV-2 infected animals present abundant CYP19A1 expression in the endothelium and in macrophages, particularly in males. Prominent CYP19A1 expression in endothelial cells and macrophages was verified in lung sections of deceased Covid-19 males compared to females. Our results demonstrate that SARS-CoV-2 infection leads to massive dysregulation of sex hormones, which may increase the risk for sex-specific disease outcome particularly in combination with comorbidities. These findings provide insights into the complex metabolic cross talk between SARS-CoV-2 infection and sex hormones.

Full text: Available Collection: Preprints Database: EuropePMC Type of study: Observational study / Prognostic study / Randomized controlled trials Language: English Year: 2020 Document Type: Preprint

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Full text: Available Collection: Preprints Database: EuropePMC Type of study: Observational study / Prognostic study / Randomized controlled trials Language: English Year: 2020 Document Type: Preprint