key: cord-354762-3a3a3ku9
authors: Afsar, Cigdem Usul; Afsar, Selim
title: SARS-CoV-2 (COVID-19): INTERFERON-EPSILON MAY BE RESPONSIBLE OF DECREASED MORTALITY IN FEMALES
date: 2020-06-02
journal: J Reprod Immunol
DOI: 10.1016/j.jri.2020.103154
sha: 
doc_id: 354762
cord_uid: 3a3a3ku9

nan

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Pangolins which are unique mammals, are thought to be a natural reservoir of SARS-CoV-2like CoVs (Zhang and others, 2020) . IFN is particularly expressed in epithelial cells and it is essential in skin and mucosal immunity (lung, intestines and reproductive tissues) of all African and Asian pangolin species (Choo and others, 2016) . The production of IFN-I or IFN-α/β is the basic natural immune defense response against viral infections (Ye and others, 2020) . IFN, like the other type I IFNs, might be responsible of decreased mortality in females because of its antiviral effects. The pangolin immune system evolved differently than in other mammals, the single copy intronless IFN gene is pseudogenised in pangolin species (Choo and others, 2016) .

This might play a role in pangolin's symptoms during coronovirus infections and their immun response to viral infections. Furthermore; IFN protects the female reproductive tract from viral and bacterial infections, especially from HIV-1 infection (Fung and others, 2013) . IFNε is constitutively expressed by reproductive tract epithelium and regulated by hormones during the menstruel cycle, reproduction, and menopause and by exogenous hormones (Marks and others, 2019) . IFN-ε regulates mucosal immunity against viral and bacterial infections, and can suppress HIV replication and its expression correlates negatively with progesterone levels (Li and others, J o u r n a l P r e -p r o o f 2018). In females, IFN has limited role in the reproductive tract and it has no role in any other organ. This can be a reason why females has less mortality rather than males. On the other hand, in a new report, higher mortality rates in males was found to be associated with lower ACE2 receptor levels (Sharma and others, 2020) . Other IFNs, such as IFN-λ may be an ideal treatment for covid-19 because it reduces the viral load and improves the clinical symptoms of patients.

However, it has no effect on mortality (Ye and others, 2020) .

Covid-19 patients can have darkness/rash in their skin in severe cases (Estébanez and others, 2020) and there is a report which shows a decrease in spermatogenezis in covid patients (Zhengpin and Xiaojiang, 2020) . IFNε is present in both tissues and there is another report which argues that covid infection is likely to be androgen mediated (Wambier and Goren, 2020) .

It has been shown that IFNε also exerts its biological activity by stimulating immune mediators and activating the JAK-STAT signal pathways in vitro and in vivo (Zwarthoff and others, 1985) . The JAK/STAT pathway responds to type I IFN secreted from neighboring cells and SARS-CoV proteins have been shown to affect this pathway before (Frieman and Baric, 2008) .

Another arguement is about the furin like cleavage of the S protein of the virus. Furin is especially expressed in differentiated Th1 cells in a Stat4-dependent manner. Expression of furin enhances IFN- secretion, whereas inhibition of furin interferes with IFN- production (Pesu and others, 2006) . Transcription through the JAK-STAT signalling pathway activated by IFNs, leads to the upregulation of many IFN-controlled genes that quickly kill viruses in infected cells (Pesu and others, 2006) . JAK-STAT signal blocking by baricitinib (a selective JAK1 and JAK2 inhibitor) produces an impairment of IFN-mediated antiviral response, with a potential facilitating effect on the evolution of SARS-CoV-2 infection.

The initial sensing of coronaviruses by the innate immune machinery might be the critical step in protecting the host from infection, especially in men.

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The authors declare that they have no conflicts of interests.J o u r n a l P r e -p r o o f