Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection

Abstract

Pathogenic human coronaviruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent MERS 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 to 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 to 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 (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs 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 susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

“…MERSCoV and SARSCoV have also been found to infect more males than females. 19,20 The reduced susceptibility of females to viral infections could be attributed to the protection from X chromosome and sex hormones, which play an important role in innate and adaptive immunity. 21 Additionally, about half of patients infected by 2019nCoV had chronic underlying diseases, mainly cardiovascular and cerebrovascular diseases and diabetes; this is similar to MERSCoV.…”

“…19 Our results suggest that 2019nCoV is more likely to infect older adult males with chronic comorbidities as a result of the weaker immune func tions of these patients. [19][20][21][22] Some patients, especially severely ill ones, had co infections of bacteria and fungi. Common bacterial cultures of patients with secondary infections included A baumannii, K pneumoniae, A flavus, C glabrata, and C albicans.…”

Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis

“…The result we observed more men than women, statistics about 23871:22377 in the COVID-19 infection. MERS-CoV and SARS-CoV have also been found to infect more males than females 11,12 . It is customary to think women are less likely to affect many bacteria and viruses than men, partly because of their more robust innate and adaptive immune responses 13 .…”

Mucin 4 Protects Female Mice from Coronavirus Pathogenesis

“…We chose Muc4 192 as our priority candidate gene for follow up, with the initial hypothesis that Muc4 suppressed 193 apoptosis and possible the interferon response, and that its absence in a Muc4 -/mouse would 194 therefore lead to increased apoptosis and inflammation, thereby inhibiting Our validation utilized a Muc4 -/mouse and confirmed a role for Muc4 in protection from 197 SARS-CoV-and CHIKV-induced disease and pathogenesis. https://doi.org/10.1101/2020.02.19.957118 doi: bioRxiv preprint (Channappanavar et al, 2017). CC-BY-NC-ND 4.0 International license author/funder.…”