{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:35:33Z","timestamp":1793831733191,"version":"4.6.1"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, before containment strategies and without vaccines or targeted therapies, clinical outcomes among hospitalized patients were heterogeneous. Preliminary reports suggested possible sex-related differences in susceptibility and disease severity. This study examined sex-based differences in clinical presentation, radiological involvement, laboratory findings, and in-hospital outcomes among patients admitted during the pre-lockdown phase of the outbreak in Italy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective observational study of 689 consecutive adults hospitalized at Parma University Hospital between 28 February and 22 March 2020, with chest CT findings consistent with COVID-19\u2013related interstitial pneumonia, regardless of RT-PCR results. Demographics, comorbidities, symptoms, laboratory parameters, and outcomes were compared between males and females. Lung involvement was quantified using a CT visual score. Multivariable logistic regression identified predictors of in-hospital mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Females accounted for 39% of the cohort and were significantly older and frailer than males, with a higher prevalence of Rockwood \u22657 (15 vs. 5%). Despite this, females demonstrated a lower CT visual score (25 vs. 30%), higher oxygenation parameters, and a less pronounced inflammatory and tissue-damage profile, including lower CRP, LDH, and CPK. Females had shorter hospital stays (5 vs. 6 days) and lower age-adjusted mortality. Multivariable analysis confirmed female sex as independently protective (OR 0.597), an effect largely mediated by reduced radiological lung involvement and attenuated inflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Females showed milder radiological and biochemical profiles and reduced mortality despite being older and frailer. These findings highlight intrinsic sex-related biological differences in host response. These early patterns remain relevant today, as sex-specific vulnerability may inform precision medicine and risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1764966","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:35:27Z","timestamp":1770788127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Enduring insights from sex differences in COVID-19: a retrospective post hoc analysis from a large Italian patient cohort"],"prefix":"10.3389","volume":"13","author":[{"given":"Carmine","family":"Siniscalchi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Cerundolo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Di Micco","sequence":"additional","affiliation":[{"name":"Internal Medicine Ward \u201cP.O. Santa Maria delle Grazie\u201d Pozzuoli","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Tana","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Eastern Hospital","place":["Asl Taranto, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Prati","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Parise","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Nouvenne","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital","place":["Parma, 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