Sex differences in determinants of COVID-19 severe outcomes – findings from the National COVID Cohort Collaborative (N3C)

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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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-022-07776-7.

Related collections

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy

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In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited.

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Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

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Author and article information

Contributors

Yilin Yoshida: yyoshida1@tulane.edu

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 12 October 2022

Publication date PMC-release: 12 October 2022

Publication date Collection: 2022

Volume: 22

Electronic Location Identifier: 784

Affiliations

[1 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Section of Endocrinology and Metabolism, Deming Department of Medicine, , Tulane University School of Medicine, ; 1430 Tulane Ave. New Orleans, 70112 New Orleans, LA USA

[2 ]GRID grid.64337.35, ISNI 0000 0001 0662 7451, Pennington Biomedical Research Center, , Louisiana State University, ; Baton Rouge, LA USA

[3 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, School of Science and Engineering, , Tulane University, ; New Orleans, LA USA

[4 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Department of Biostatistics and Data Science, , Tulane University School of Public Health and Tropical Medicine, ; New Orleans, LA USA

[5 ]GRID grid.265219.b, ISNI 0000 0001 2217 8588, Pulmonary and Critical Care, Deming Department of Medicine, , Tulane University School of Medicine, ; New Orleans, LA USA

[6 ]GRID grid.279863.1, ISNI 0000 0000 8954 1233, Department of Genetics, , Louisiana State University Health Sciences Center, ; New Orleans, LA USA

Article

Publisher ID: 7776

DOI: 10.1186/s12879-022-07776-7

PMC ID: 9555705

PubMed ID: 36224551

SO-VID: 0ba3ab31-29a1-44e1-bf78-62ef84bbbd40

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 13 April 2022

Date revision received : 4 October 2022

Date accepted : 10 October 2022

Funding

Funded by: National Institute of General Medical Sciences of the National Institutes of Health

Award ID: U54 GM104940

Funded by: the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Scholar

Award ID: K12HD043451