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      Sex hormones, autoimmunity and gender disparity in COVID-19

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          Abstract

          The Coronavirus disease 2019 (COVID-19) pandemic has majorly contributed to massive and widespread mortality. Epidemiological data strongly indicates a sex-based disparity in COVID-19 clinical outcomes, with women having lower infection and hospitalisation rates, coupled with better prognosis and lesser mortality. This disparity may be explained by several mechanisms including differences in innate and adaptive immune responses, genetic factors, and an interplay between sex hormones and immune effectors, as well as gender-specific behaviour differences. These pathways, particularly the immunological divergence in response to viral infection, could potentially influence not only COVID-19 pathogenesis and disease course, but also the response to antiviral drugs and vaccines. Furthermore, factors that confer a protective advantage against COVID-19 may be exploited to develop therapeutic strategies to improve clinical outcomes in COVID-19.

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          Most cited references67

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

            Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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              Sex differences in immune responses

              Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.
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                Author and article information

                Contributors
                hussain_gorz@outook.com
                parikshit.sen@hotmail.com
                omaimaanisbhatti@gmail.com
                drlatikagupta@gmail.com
                Journal
                Rheumatol Int
                Rheumatol Int
                Rheumatology International
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0172-8172
                1437-160X
                26 April 2021
                : 1-12
                Affiliations
                [1 ]GRID grid.411190.c, ISNI 0000 0004 0606 972X, Medical College, , Aga Khan University Hospital, ; Stadium Road, Karachi, Pakistan
                [2 ]GRID grid.414698.6, ISNI 0000 0004 1767 743X, Maulana Azad Medical College, ; 2-Bahadur Shah Zafar marg, New Delhi, India
                [3 ]GRID grid.263138.d, ISNI 0000 0000 9346 7267, Department of Clinical Immunology and Rheumatology, , Sanjay Gandhi Postgraduate Institute of Medical Sciences, ; Lucknow, 226014 India
                Author information
                http://orcid.org/0000-0002-0346-894X
                http://orcid.org/0000-0002-1630-6026
                http://orcid.org/0000-0003-4005-1104
                http://orcid.org/0000-0003-2753-2990
                Article
                4873
                10.1007/s00296-021-04873-9
                8075025
                33903964
                29dbaf68-8dc7-43f5-8ebe-5cd9061ae80b
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 21 February 2021
                : 19 April 2021
                Categories
                Review

                Rheumatology
                covid-19,coronavirus,gender bias,sex differences,clinical outcomes
                Rheumatology
                covid-19, coronavirus, gender bias, sex differences, clinical outcomes

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