Sex differences and disparities in cardiovascular outcomes of COVID-19

Author:

Bugiardini Raffaele1ORCID,Nava Stefano12,Caramori Gaetano3ORCID,Yoon Jinsung4ORCID,Badimon Lina5ORCID,Bergami Maria1ORCID,Cenko Edina1ORCID,David Antonio6,Demiri Ilir7,Dorobantu Maria8ORCID,Fronea Oana8,Jankovic Radmilo9,Kedev Sasko1011,Ladjevic Nebojsa12,Lasica Ratko13,Loncar Goran14,Mancuso Giuseppe15,Mendieta Guiomar16ORCID,Miličić Davor17,Mjehović Petra17,Pašalić Marijan17,Petrović Milovan18,Poposka Lidija1011,Scarpone Marialuisa1,Stefanovic Milena7,van der Schaar Mihaela1920,Vasiljevic Zorana21,Vavlukis Marija1011ORCID,Vega Pittao Maria Laura12,Vukomanovic Vladan22,Zdravkovic Marija23,Manfrini Olivia124ORCID

Affiliation:

1. Department of Medical and Surgical Sciences, University of Bologna , Padiglione 11, Via Massarenti 9, 40138 Bologna , Italy

2. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Respiratory and Critical Care Unit , Bologna , Italy

3. Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), University of Messina , Messina , Italy

4. Google Cloud AI , Sunnyvale, CA , USA

5. Cardiovascular Research Program ICCC, IR-IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, CiberCV-Institute Carlos III , Barcelona , Spain

6. Department of Human Pathology of the Adult and Evolutive Age “Gaetano Barresi”, Division of Anesthesia and Critical Care, University of Messina , Messina , Italy

7. University Clinic of Infectious Diseases, University ‘Ss. Cyril and Methodius’ , Skopje , North Macedonia

8. Emergency Clinical Hospital of Bucharest, ‘Carol Davila’ University of Medicine and Pharmacy , Bucharest , Romania

9. Clinic for Anesthesiology and Intensive Therapy, University Clinical Center Nis, School of Medicine, University of Nis , Nis , Serbia

10. University Clinic for Cardiology , 1000 Skopje , Republic of North Macedonia

11. Faculty of Medicine, Ss. Cyril and Methodius University in Skopje , 1000 Skopje , Republic of North Macedonia

12. Faculty of Medicine, University of Belgrade, University Clinical Centre of Serbia , Belgrade , Serbia

13. Clinical Center of Serbia, University of Belgrade , Belgrade , Serbia

14. Institute for Cardiovascular Diseases Dedinje , Belgrade , Serbia

15. Medical Microbiology, Department of Human Pathology, University of Messina , Messina , Italy

16. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) , Madrid , Spain

17. Department for Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb , Zagreb , Croatia

18. Institute of Cardiovascular Diseases of Vojvodina, Sremska Kamenica, Faculty of Medicine Novi Sad, University of Novi Sad , Novi Sad , Serbia

19. Department of Electrical and Computer Engineering, University of California , Los Angeles, CA , USA

20. Cambridge Centre for Artificial Intelligence in Medicine, Department of Applied Mathematics and Theoretical Physics and Department of Population Health, University of Cambridge , Cambridge , UK

21. Medical Faculty, University of Belgrade , Belgrade , Serbia

22. Clinical Hospital Center Dragiša Mišković , Belgrade , Serbia

23. Faculty of Medicine, University of Belgrade, Clinical Hospital Center Bezanijska kosa , Belgrade , Serbia

24. IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola Hospital, Bologna, Italy

Abstract

Abstract Aims Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. Methods and results This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71–0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90–1.42) and 0.86 (95% CI: 0.70–1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73–2.98; 3.85, 95% CI: 3.21–4.63; and 3.95, 95% CI: 3.04–5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94–1.67 vs. 0.83; 95% CI: 0.59–1.16, pinteraction = 0.04). Conclusions Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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