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Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic\/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.<\/jats:p>","DOI":"10.1017\/erm.2021.9","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T06:40:26Z","timestamp":1627972826000},"source":"Crossref","is-referenced-by-count":17,"title":["COVID-19 pandemic: insights into molecular mechanisms leading to sex-based differences in patient outcomes"],"prefix":"10.1017","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1589-9568","authenticated-orcid":false,"given":"Ashutosh","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi K.","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maheswari","family":"Kulandhasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav","family":"Prasoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiman","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujeet","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Pareek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore","family":"Sesham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash S.","family":"Shekhawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamla","family":"Kant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"S1462399421000090_ref61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02740"},{"key":"S1462399421000090_ref56","doi-asserted-by":"publisher","DOI":"10.1080\/08830185.2020.1840566"},{"key":"S1462399421000090_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.08.003"},{"key":"S1462399421000090_ref11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19741-6"},{"key":"S1462399421000090_ref43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700730"},{"key":"S1462399421000090_ref44","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13538"},{"key":"S1462399421000090_ref62","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.05.046"},{"key":"S1462399421000090_ref71","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104811"},{"key":"S1462399421000090_ref38","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0451"},{"key":"S1462399421000090_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.035"},{"key":"S1462399421000090_ref24","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2020-206995"},{"key":"S1462399421000090_ref65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01224"},{"key":"S1462399421000090_ref83","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0201-4"},{"key":"S1462399421000090_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.04.479"},{"key":"S1462399421000090_ref19","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01248-09"},{"key":"S1462399421000090_ref66","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501684"},{"key":"S1462399421000090_ref14","unstructured":"14. 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