Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C)
Abstract Objective The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19. Design Thi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-022-07776-7 |
| _version_ | 1828343140833034240 |
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| author | Yilin Yoshida San Chu Sarah Fox Yuanhao Zu Dragana Lovre Joshua L. Denson Lucio Miele Franck Mauvais-Jarvis |
| author_facet | Yilin Yoshida San Chu Sarah Fox Yuanhao Zu Dragana Lovre Joshua L. Denson Lucio Miele Franck Mauvais-Jarvis |
| author_sort | Yilin Yoshida |
| collection | DOAJ |
| description | Abstract Objective The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19. Design This is a retrospective cohort analysis based on the National COVID Cohort Collaborative (N3C). We included 574,391 adult patients admitted for COVID-19 at hospitals or emergency rooms between 01/01/2020 and 12/31/2021. Methods We defined comorbidities at or before the first admission for COVID-19 by Charlson Comorbidity Index (CCI) and CCI components. We used the averaged lab values taken within 15 days before or after the admission date to measure biomarkers including c-reactive protein (CRP), ferritin, procalcitonin, N-terminal pro b-type natriuretic peptide (NT proBNP), d-dimer, absolute lymphocyte counts, absolute neutrophil counts, and platelets. Our primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation (IMV) and hospital length of stay (LOS). We used logistic regression adjusted for age, race, ethnicity, visit type, and medications to assess the association of comorbidities, biomarkers, and mortality disaggregating by sex. Results Moderate to severe liver disease, renal disease, metastatic solid tumor, and myocardial infarction were the top four fatal comorbidities among patients who were hospitalized for COVID-19 (adjusted odds ratio [aOR] > 2). These four comorbid conditions remained the most lethal in both sexes, with a higher magnitude of risk in women than in men (p-interaction < 0.05). Abnormal elevations of CRP, ferritin, procalcitonin, NT proBNP, neutrophil, and platelet counts, and lymphocytopenia were significantly associated with the risk of death, with procalcitonin and NT proBNP as the strongest predictors (aOR > 2). The association between the abnormal biomarkers and death was stronger in women than in men (p-interaction < 0.05). Conclusion There are sex differences in inpatient mortality associated with comorbidities and biomarkers. The significant impact of these clinical determinants in women with COVID-19 may be underappreciated as previous studies stressed the increased death rate in male patients that is related to comorbidities or inflammation. Our study highlights the importance and the need for sex-disaggregated research to understand the risk factors of poor outcomes and health disparities in COVID-19. |
| first_indexed | 2024-04-13T23:39:00Z |
| format | Article |
| id | doaj.art-6a3d3e1304d04383a793c2757657e862 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-04-13T23:39:00Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-6a3d3e1304d04383a793c2757657e8622022-12-22T02:24:37ZengBMCBMC Infectious Diseases1471-23342022-10-012211910.1186/s12879-022-07776-7Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C)Yilin Yoshida0San Chu1Sarah Fox2Yuanhao Zu3Dragana Lovre4Joshua L. Denson5Lucio Miele6Franck Mauvais-Jarvis7Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of MedicinePennington Biomedical Research Center, Louisiana State UniversitySchool of Science and Engineering, Tulane UniversityDepartment of Biostatistics and Data Science, Tulane University School of Public Health and Tropical MedicineSection of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of MedicinePulmonary and Critical Care, Deming Department of Medicine, Tulane University School of MedicineDepartment of Genetics, Louisiana State University Health Sciences CenterSection of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of MedicineAbstract Objective The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19. Design This is a retrospective cohort analysis based on the National COVID Cohort Collaborative (N3C). We included 574,391 adult patients admitted for COVID-19 at hospitals or emergency rooms between 01/01/2020 and 12/31/2021. Methods We defined comorbidities at or before the first admission for COVID-19 by Charlson Comorbidity Index (CCI) and CCI components. We used the averaged lab values taken within 15 days before or after the admission date to measure biomarkers including c-reactive protein (CRP), ferritin, procalcitonin, N-terminal pro b-type natriuretic peptide (NT proBNP), d-dimer, absolute lymphocyte counts, absolute neutrophil counts, and platelets. Our primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation (IMV) and hospital length of stay (LOS). We used logistic regression adjusted for age, race, ethnicity, visit type, and medications to assess the association of comorbidities, biomarkers, and mortality disaggregating by sex. Results Moderate to severe liver disease, renal disease, metastatic solid tumor, and myocardial infarction were the top four fatal comorbidities among patients who were hospitalized for COVID-19 (adjusted odds ratio [aOR] > 2). These four comorbid conditions remained the most lethal in both sexes, with a higher magnitude of risk in women than in men (p-interaction < 0.05). Abnormal elevations of CRP, ferritin, procalcitonin, NT proBNP, neutrophil, and platelet counts, and lymphocytopenia were significantly associated with the risk of death, with procalcitonin and NT proBNP as the strongest predictors (aOR > 2). The association between the abnormal biomarkers and death was stronger in women than in men (p-interaction < 0.05). Conclusion There are sex differences in inpatient mortality associated with comorbidities and biomarkers. The significant impact of these clinical determinants in women with COVID-19 may be underappreciated as previous studies stressed the increased death rate in male patients that is related to comorbidities or inflammation. Our study highlights the importance and the need for sex-disaggregated research to understand the risk factors of poor outcomes and health disparities in COVID-19.https://doi.org/10.1186/s12879-022-07776-7COVID-19 severitySex differencesComorbiditiesBiomarkers |
| spellingShingle | Yilin Yoshida San Chu Sarah Fox Yuanhao Zu Dragana Lovre Joshua L. Denson Lucio Miele Franck Mauvais-Jarvis Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C) BMC Infectious Diseases COVID-19 severity Sex differences Comorbidities Biomarkers |
| title | Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C) |
| title_full | Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C) |
| title_fullStr | Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C) |
| title_full_unstemmed | Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C) |
| title_short | Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C) |
| title_sort | sex differences in determinants of covid 19 severe outcomes findings from the national covid cohort collaborative n3c |
| topic | COVID-19 severity Sex differences Comorbidities Biomarkers |
| url | https://doi.org/10.1186/s12879-022-07776-7 |
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