Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator
Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. This was a retrospective, ob...
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| Veröffentlicht in: | Clinical microbiology and infection 2021-08, Vol.27 (8), p.1137-1144 |
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| creator | Mussini, Cristina Cozzi-Lepri, Alessandro Menozzi, Marianna Meschiari, Marianna Franceschini, Erica Rogati, Carlotta Cuomo, Gianluca Bedini, Andrea Iadisernia, Vittorio Volpi, Sara Milic, Jovana Tonelli, Roberto Brugioni, Lucio Pietrangelo, Antonello Girardis, Massimo Cossarizza, Andrea Clini, Enrico Guaraldi, Giovanni Bacca, Erica Bedini, Andrea Borghi, Vanni Burastero, Giulia Carli, Federica Ciusa, Giacomo Corradi, Luca Di Gaetano, Margherita Faltoni, Matteo Franceschi, Giacomo Orlando, Gabriella Pellegrino, Francesco Puzzolante, Cinzia Raimondi, Alessandro Santoro, Antonella Tutone, Marco Yaacoub, Dina Andreotti, Alberto Biagioni, Emanuela Bondi, Filippo Busani, Stefano Chierego, Giovanni Scotti, Marzia Serio, Lucia Bellinazzi, Caterina Borella, Rebecca De Biasi, Sara De Gaetano, Anna Fidanza, Lucia Gibellini, Lara Iannone, Anna Lo Tartaro, Domenico Mattioli, Marco Paolini, Annamaria Fogliani, Rossella Righini, Grazia Lugli, Mario |
| description | Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference.
This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death according to sex. Interaction was formally tested to compare the risk difference by sex in sub-populations. Mediation analysis with a binary endpoint IMV or death (yes/no) by day 28 of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted.
Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54–77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs. 191 mmHg; p 0.023). By 28 days from admission, 49.2% (95% CI 39.6–58.9%) of males vs. 31.7% (17.9–45.4%) of females underwent IMV or death (log-rank p |
| doi_str_mv | 10.1016/j.cmi.2020.12.010 |
| format | Article |
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This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death according to sex. Interaction was formally tested to compare the risk difference by sex in sub-populations. Mediation analysis with a binary endpoint IMV or death (yes/no) by day 28 of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted.
Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54–77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs. 191 mmHg; p 0.023). By 28 days from admission, 49.2% (95% CI 39.6–58.9%) of males vs. 31.7% (17.9–45.4%) of females underwent IMV or death (log-rank p < 0.0001) and this amounted to a difference in terms of HR of 0.40 (0.26–0.63, p 0.0001). The area under the curve in C-reactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex.
Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. Specifically, CRP showed a predominant role to mediate the difference in risk by sex.</description><identifier>ISSN: 1198-743X</identifier><identifier>EISSN: 1469-0691</identifier><identifier>DOI: 10.1016/j.cmi.2020.12.010</identifier><identifier>PMID: 33359539</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>COVID-19 ; COVID-19 pneumonia ; Inflammation ; Mediation ; Original ; Prognosis ; Sex differences</subject><ispartof>Clinical microbiology and infection, 2021-08, Vol.27 (8), p.1137-1144</ispartof><rights>2020 European Society of Clinical Microbiology and Infectious Diseases</rights><rights>Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.</rights><rights>2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. 2020 European Society of Clinical Microbiology and Infectious Diseases</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-bd5b7209e68d011a5dbf33bce7bcc3bc87c97fd0fc6b4ab9fcd712520db693fa3</citedby><cites>FETCH-LOGICAL-c451t-bd5b7209e68d011a5dbf33bce7bcc3bc87c97fd0fc6b4ab9fcd712520db693fa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33359539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mussini, Cristina</creatorcontrib><creatorcontrib>Cozzi-Lepri, Alessandro</creatorcontrib><creatorcontrib>Menozzi, Marianna</creatorcontrib><creatorcontrib>Meschiari, Marianna</creatorcontrib><creatorcontrib>Franceschini, Erica</creatorcontrib><creatorcontrib>Rogati, Carlotta</creatorcontrib><creatorcontrib>Cuomo, Gianluca</creatorcontrib><creatorcontrib>Bedini, Andrea</creatorcontrib><creatorcontrib>Iadisernia, Vittorio</creatorcontrib><creatorcontrib>Volpi, Sara</creatorcontrib><creatorcontrib>Milic, Jovana</creatorcontrib><creatorcontrib>Tonelli, Roberto</creatorcontrib><creatorcontrib>Brugioni, Lucio</creatorcontrib><creatorcontrib>Pietrangelo, Antonello</creatorcontrib><creatorcontrib>Girardis, Massimo</creatorcontrib><creatorcontrib>Cossarizza, Andrea</creatorcontrib><creatorcontrib>Clini, Enrico</creatorcontrib><creatorcontrib>Guaraldi, Giovanni</creatorcontrib><creatorcontrib>Bacca, Erica</creatorcontrib><creatorcontrib>Bedini, Andrea</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Burastero, Giulia</creatorcontrib><creatorcontrib>Carli, Federica</creatorcontrib><creatorcontrib>Ciusa, Giacomo</creatorcontrib><creatorcontrib>Corradi, Luca</creatorcontrib><creatorcontrib>Di Gaetano, Margherita</creatorcontrib><creatorcontrib>Faltoni, Matteo</creatorcontrib><creatorcontrib>Franceschi, Giacomo</creatorcontrib><creatorcontrib>Orlando, Gabriella</creatorcontrib><creatorcontrib>Pellegrino, Francesco</creatorcontrib><creatorcontrib>Puzzolante, Cinzia</creatorcontrib><creatorcontrib>Raimondi, Alessandro</creatorcontrib><creatorcontrib>Santoro, Antonella</creatorcontrib><creatorcontrib>Tutone, Marco</creatorcontrib><creatorcontrib>Yaacoub, Dina</creatorcontrib><creatorcontrib>Andreotti, Alberto</creatorcontrib><creatorcontrib>Biagioni, Emanuela</creatorcontrib><creatorcontrib>Bondi, Filippo</creatorcontrib><creatorcontrib>Busani, Stefano</creatorcontrib><creatorcontrib>Chierego, Giovanni</creatorcontrib><creatorcontrib>Scotti, Marzia</creatorcontrib><creatorcontrib>Serio, Lucia</creatorcontrib><creatorcontrib>Bellinazzi, Caterina</creatorcontrib><creatorcontrib>Borella, Rebecca</creatorcontrib><creatorcontrib>De Biasi, Sara</creatorcontrib><creatorcontrib>De Gaetano, Anna</creatorcontrib><creatorcontrib>Fidanza, Lucia</creatorcontrib><creatorcontrib>Gibellini, Lara</creatorcontrib><creatorcontrib>Iannone, Anna</creatorcontrib><creatorcontrib>Lo Tartaro, Domenico</creatorcontrib><creatorcontrib>Mattioli, Marco</creatorcontrib><creatorcontrib>Paolini, Annamaria</creatorcontrib><creatorcontrib>Fogliani, Rossella</creatorcontrib><creatorcontrib>Righini, Grazia</creatorcontrib><creatorcontrib>Lugli, Mario</creatorcontrib><creatorcontrib>Office of information and communication technologies of Policlinico di Modena</creatorcontrib><creatorcontrib>Modena Covid-19 Working Group (MoCo19)</creatorcontrib><title>Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator</title><title>Clinical microbiology and infection</title><addtitle>Clin Microbiol Infect</addtitle><description>Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference.
This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death according to sex. Interaction was formally tested to compare the risk difference by sex in sub-populations. Mediation analysis with a binary endpoint IMV or death (yes/no) by day 28 of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted.
Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54–77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs. 191 mmHg; p 0.023). By 28 days from admission, 49.2% (95% CI 39.6–58.9%) of males vs. 31.7% (17.9–45.4%) of females underwent IMV or death (log-rank p < 0.0001) and this amounted to a difference in terms of HR of 0.40 (0.26–0.63, p 0.0001). The area under the curve in C-reactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex.
Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. Specifically, CRP showed a predominant role to mediate the difference in risk by sex.</description><subject>COVID-19</subject><subject>COVID-19 pneumonia</subject><subject>Inflammation</subject><subject>Mediation</subject><subject>Original</subject><subject>Prognosis</subject><subject>Sex differences</subject><issn>1198-743X</issn><issn>1469-0691</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9UctuFDEQtBARCYEP4IJ85DKLHzP2GiSksDwSKVIuAXGzbE878WrGHmzvIv4eRxsiuOTS3ZarqltVCL2iZEUJFW-3KzeHFSOsvdmKUPIEndBeqI4IRZ-2map1J3v-4xg9L2VLCGGc98_QMed8UANXJyh9hFoh4yWnm5hKKDhE7GE2ExT8K9RbXGAPGfDm6vvFp44qvETYzSkG8w4vqZRgJ8A5tZJ84_rJzLOpIUVsSgNUiDWYCc8wBlNTfoGOvJkKvLzvp-jbl8_Xm_Pu8urrxebssnP9QGtnx8FKRhSI9UgoNcNoPefWgbTOtb6WTkk_Eu-E7Y1V3o2SsoGR0QrFveGn6MNBd9nZttu1M7KZ9JLDbPJvnUzQ___EcKtv0l7LNRWCiSbw5l4gp587KFXPoTiYJhMh7YpmveQ95UrIBqUHqMvNkAz-YQ0l-i4ovdUtKH0XlKZMt6Aa5_W_9z0w_ibTAO8PAGgu7QNkXVyA6JqPGVzVYwqPyP8Bl1SnUA</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Mussini, Cristina</creator><creator>Cozzi-Lepri, Alessandro</creator><creator>Menozzi, Marianna</creator><creator>Meschiari, Marianna</creator><creator>Franceschini, Erica</creator><creator>Rogati, Carlotta</creator><creator>Cuomo, Gianluca</creator><creator>Bedini, Andrea</creator><creator>Iadisernia, Vittorio</creator><creator>Volpi, Sara</creator><creator>Milic, Jovana</creator><creator>Tonelli, Roberto</creator><creator>Brugioni, Lucio</creator><creator>Pietrangelo, Antonello</creator><creator>Girardis, Massimo</creator><creator>Cossarizza, Andrea</creator><creator>Clini, Enrico</creator><creator>Guaraldi, Giovanni</creator><creator>Bacca, Erica</creator><creator>Bedini, Andrea</creator><creator>Borghi, Vanni</creator><creator>Burastero, Giulia</creator><creator>Carli, Federica</creator><creator>Ciusa, Giacomo</creator><creator>Corradi, Luca</creator><creator>Di Gaetano, Margherita</creator><creator>Faltoni, Matteo</creator><creator>Franceschi, Giacomo</creator><creator>Orlando, Gabriella</creator><creator>Pellegrino, Francesco</creator><creator>Puzzolante, Cinzia</creator><creator>Raimondi, Alessandro</creator><creator>Santoro, Antonella</creator><creator>Tutone, Marco</creator><creator>Yaacoub, Dina</creator><creator>Andreotti, Alberto</creator><creator>Biagioni, Emanuela</creator><creator>Bondi, Filippo</creator><creator>Busani, Stefano</creator><creator>Chierego, Giovanni</creator><creator>Scotti, Marzia</creator><creator>Serio, Lucia</creator><creator>Bellinazzi, Caterina</creator><creator>Borella, Rebecca</creator><creator>De Biasi, Sara</creator><creator>De Gaetano, Anna</creator><creator>Fidanza, Lucia</creator><creator>Gibellini, Lara</creator><creator>Iannone, Anna</creator><creator>Lo Tartaro, Domenico</creator><creator>Mattioli, Marco</creator><creator>Paolini, Annamaria</creator><creator>Fogliani, Rossella</creator><creator>Righini, Grazia</creator><creator>Lugli, Mario</creator><general>Elsevier Ltd</general><general>European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210801</creationdate><title>Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator</title><author>Mussini, Cristina ; Cozzi-Lepri, Alessandro ; Menozzi, Marianna ; Meschiari, Marianna ; Franceschini, Erica ; Rogati, Carlotta ; Cuomo, Gianluca ; Bedini, Andrea ; Iadisernia, Vittorio ; Volpi, Sara ; Milic, Jovana ; Tonelli, Roberto ; Brugioni, Lucio ; Pietrangelo, Antonello ; Girardis, Massimo ; Cossarizza, Andrea ; Clini, Enrico ; Guaraldi, Giovanni ; Bacca, Erica ; Bedini, Andrea ; Borghi, Vanni ; Burastero, Giulia ; Carli, Federica ; Ciusa, Giacomo ; Corradi, Luca ; Di Gaetano, Margherita ; Faltoni, Matteo ; Franceschi, Giacomo ; Orlando, Gabriella ; Pellegrino, Francesco ; Puzzolante, Cinzia ; Raimondi, Alessandro ; Santoro, Antonella ; Tutone, Marco ; Yaacoub, Dina ; Andreotti, Alberto ; Biagioni, Emanuela ; Bondi, Filippo ; Busani, Stefano ; Chierego, Giovanni ; Scotti, Marzia ; Serio, Lucia ; Bellinazzi, Caterina ; Borella, Rebecca ; De Biasi, Sara ; De Gaetano, Anna ; Fidanza, Lucia ; Gibellini, Lara ; Iannone, Anna ; Lo Tartaro, Domenico ; Mattioli, Marco ; Paolini, Annamaria ; Fogliani, Rossella ; Righini, Grazia ; Lugli, Mario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-bd5b7209e68d011a5dbf33bce7bcc3bc87c97fd0fc6b4ab9fcd712520db693fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>COVID-19</topic><topic>COVID-19 pneumonia</topic><topic>Inflammation</topic><topic>Mediation</topic><topic>Original</topic><topic>Prognosis</topic><topic>Sex differences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mussini, Cristina</creatorcontrib><creatorcontrib>Cozzi-Lepri, Alessandro</creatorcontrib><creatorcontrib>Menozzi, Marianna</creatorcontrib><creatorcontrib>Meschiari, Marianna</creatorcontrib><creatorcontrib>Franceschini, Erica</creatorcontrib><creatorcontrib>Rogati, Carlotta</creatorcontrib><creatorcontrib>Cuomo, Gianluca</creatorcontrib><creatorcontrib>Bedini, Andrea</creatorcontrib><creatorcontrib>Iadisernia, Vittorio</creatorcontrib><creatorcontrib>Volpi, Sara</creatorcontrib><creatorcontrib>Milic, Jovana</creatorcontrib><creatorcontrib>Tonelli, Roberto</creatorcontrib><creatorcontrib>Brugioni, Lucio</creatorcontrib><creatorcontrib>Pietrangelo, Antonello</creatorcontrib><creatorcontrib>Girardis, Massimo</creatorcontrib><creatorcontrib>Cossarizza, Andrea</creatorcontrib><creatorcontrib>Clini, Enrico</creatorcontrib><creatorcontrib>Guaraldi, Giovanni</creatorcontrib><creatorcontrib>Bacca, Erica</creatorcontrib><creatorcontrib>Bedini, Andrea</creatorcontrib><creatorcontrib>Borghi, Vanni</creatorcontrib><creatorcontrib>Burastero, Giulia</creatorcontrib><creatorcontrib>Carli, Federica</creatorcontrib><creatorcontrib>Ciusa, Giacomo</creatorcontrib><creatorcontrib>Corradi, Luca</creatorcontrib><creatorcontrib>Di Gaetano, Margherita</creatorcontrib><creatorcontrib>Faltoni, Matteo</creatorcontrib><creatorcontrib>Franceschi, Giacomo</creatorcontrib><creatorcontrib>Orlando, Gabriella</creatorcontrib><creatorcontrib>Pellegrino, Francesco</creatorcontrib><creatorcontrib>Puzzolante, Cinzia</creatorcontrib><creatorcontrib>Raimondi, Alessandro</creatorcontrib><creatorcontrib>Santoro, Antonella</creatorcontrib><creatorcontrib>Tutone, Marco</creatorcontrib><creatorcontrib>Yaacoub, Dina</creatorcontrib><creatorcontrib>Andreotti, Alberto</creatorcontrib><creatorcontrib>Biagioni, Emanuela</creatorcontrib><creatorcontrib>Bondi, Filippo</creatorcontrib><creatorcontrib>Busani, Stefano</creatorcontrib><creatorcontrib>Chierego, Giovanni</creatorcontrib><creatorcontrib>Scotti, Marzia</creatorcontrib><creatorcontrib>Serio, Lucia</creatorcontrib><creatorcontrib>Bellinazzi, Caterina</creatorcontrib><creatorcontrib>Borella, Rebecca</creatorcontrib><creatorcontrib>De Biasi, Sara</creatorcontrib><creatorcontrib>De Gaetano, Anna</creatorcontrib><creatorcontrib>Fidanza, Lucia</creatorcontrib><creatorcontrib>Gibellini, Lara</creatorcontrib><creatorcontrib>Iannone, Anna</creatorcontrib><creatorcontrib>Lo Tartaro, Domenico</creatorcontrib><creatorcontrib>Mattioli, Marco</creatorcontrib><creatorcontrib>Paolini, Annamaria</creatorcontrib><creatorcontrib>Fogliani, Rossella</creatorcontrib><creatorcontrib>Righini, Grazia</creatorcontrib><creatorcontrib>Lugli, Mario</creatorcontrib><creatorcontrib>Office of information and communication technologies of Policlinico di Modena</creatorcontrib><creatorcontrib>Modena Covid-19 Working Group (MoCo19)</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical microbiology and infection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mussini, Cristina</au><au>Cozzi-Lepri, Alessandro</au><au>Menozzi, Marianna</au><au>Meschiari, Marianna</au><au>Franceschini, Erica</au><au>Rogati, Carlotta</au><au>Cuomo, Gianluca</au><au>Bedini, Andrea</au><au>Iadisernia, Vittorio</au><au>Volpi, Sara</au><au>Milic, Jovana</au><au>Tonelli, Roberto</au><au>Brugioni, Lucio</au><au>Pietrangelo, Antonello</au><au>Girardis, Massimo</au><au>Cossarizza, Andrea</au><au>Clini, Enrico</au><au>Guaraldi, Giovanni</au><au>Bacca, Erica</au><au>Bedini, Andrea</au><au>Borghi, Vanni</au><au>Burastero, Giulia</au><au>Carli, Federica</au><au>Ciusa, Giacomo</au><au>Corradi, Luca</au><au>Di Gaetano, Margherita</au><au>Faltoni, Matteo</au><au>Franceschi, Giacomo</au><au>Orlando, Gabriella</au><au>Pellegrino, Francesco</au><au>Puzzolante, Cinzia</au><au>Raimondi, Alessandro</au><au>Santoro, Antonella</au><au>Tutone, Marco</au><au>Yaacoub, Dina</au><au>Andreotti, Alberto</au><au>Biagioni, Emanuela</au><au>Bondi, Filippo</au><au>Busani, Stefano</au><au>Chierego, Giovanni</au><au>Scotti, Marzia</au><au>Serio, Lucia</au><au>Bellinazzi, Caterina</au><au>Borella, Rebecca</au><au>De Biasi, Sara</au><au>De Gaetano, Anna</au><au>Fidanza, Lucia</au><au>Gibellini, Lara</au><au>Iannone, Anna</au><au>Lo Tartaro, Domenico</au><au>Mattioli, Marco</au><au>Paolini, Annamaria</au><au>Fogliani, Rossella</au><au>Righini, Grazia</au><au>Lugli, Mario</au><aucorp>Office of information and communication technologies of Policlinico di Modena</aucorp><aucorp>Modena Covid-19 Working Group (MoCo19)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator</atitle><jtitle>Clinical microbiology and infection</jtitle><addtitle>Clin Microbiol Infect</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>27</volume><issue>8</issue><spage>1137</spage><epage>1144</epage><pages>1137-1144</pages><issn>1198-743X</issn><eissn>1469-0691</eissn><abstract>Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference.
This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death according to sex. Interaction was formally tested to compare the risk difference by sex in sub-populations. Mediation analysis with a binary endpoint IMV or death (yes/no) by day 28 of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted.
Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54–77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs. 191 mmHg; p 0.023). By 28 days from admission, 49.2% (95% CI 39.6–58.9%) of males vs. 31.7% (17.9–45.4%) of females underwent IMV or death (log-rank p < 0.0001) and this amounted to a difference in terms of HR of 0.40 (0.26–0.63, p 0.0001). The area under the curve in C-reactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex.
Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. Specifically, CRP showed a predominant role to mediate the difference in risk by sex.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33359539</pmid><doi>10.1016/j.cmi.2020.12.010</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1198-743X |
| ispartof | Clinical microbiology and infection, 2021-08, Vol.27 (8), p.1137-1144 |
| issn | 1198-743X 1469-0691 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7816626 |
| source | EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | COVID-19 COVID-19 pneumonia Inflammation Mediation Original Prognosis Sex differences |
| title | Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator |
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