Sex-based differences in susceptibility to SARS-CoV infection
By Rudragouda Channappanavar, Craig A. Fett, M. Mack, P. T. Ten Eyck, D. Meyerholz, S. Perlman. Journal of Immunology, 2017
845 citations recorded by the source corpus.
Pathogenic human coronaviruses (CoVs), such as the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome–CoV, cause acute respiratory illness. Epidemiological data from the 2002–2003 SARS epidemic and recent Middle East respiratory syndrome outbreak indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared with age-matched females. The degree of sex bias to SARS-CoV infection increased with advancing age, such that middle-aged mice showed much more pronounced differences compared with young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage, and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages and neutrophils in the lungs of male mice, and depletion of inflammatory monocyte macrophages partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality, indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in the susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.
Subfields: Infectious Diseases, Obstetrics and Gynecology
View Paper: https://www.semanticscholar.org/paper/0cfb1a9ade576006c60c6406e93648707c0ca688
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Citations in the corpus
- Drug treatment options for the 2019-new coronavirus (2019-nCoV). (2020, methodology): “The second method involves the screening of a chemical library containing many existing compounds or databases, including information about transcription characteristics in different cell lines (5).”
- COVID‐19 patients' clinical characteristics, discharge rate, and fatality rate of meta‐analysis (2020, result): “There are some studies that showed MERS‐COV and SARS‐COV have also been found to infect more males than females.(22,23) The reduced susceptibility of females to viral infections could be attributed to the protection from X chromosome and sex hormones, which play an essential role in innate and adapt”
- Potential interventions for novel coronavirus in China: A systematic review (2020, background): “However, the mortality was increased in female mice when the ovariectomy was done or the estrogen receptor antagonist was given.(126) Wei et al(127) also found that serum levels of prolactin, follicle‐stimulating hormone, and luteinizing hormone of ZHANG AND LIU | 485”
- Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis (2020, background): “MERS-CoV and SARS-CoV have also been found to infect more males than females 11, 12 .”