Sex differences and disparities in cardiovascular outcomes of COVID-19

Raffaele Bugiardini; Stefano Nava; Gaetano Caramori; Jinsung Yoon; Lina Badimon; Maria Bergami; Edina Cenko; Antonio David; Ilir Demiri; Maria Dorobantu; Oana Fronea; Radmilo Jankovic; Sasko Kedev; Nebojsa Ladjevic; Ratko Lasica; Goran Loncar; Giuseppe Mancuso; Guiomar Mendieta; Davor Miličić; Petra Mjehović; Marijan Pašalić; Milovan Petrović; Lidija Poposka; Marialuisa Scarpone; Milena Stefanovic; Mihaela van der Schaar; Zorana Vasiljevic; Marija Vavlukis; Maria Laura Vega Pittao; Vladan Vukomanovic; Marija Zdravkovic; Olivia Manfrini

doi:10.1093/cvr/cvad011

Sex differences and disparities in cardiovascular outcomes of COVID-19

Cardiovasc Res. 2023 May 22;119(5):1190-1201. doi: 10.1093/cvr/cvad011.

Authors

Raffaele Bugiardini¹, Stefano Nava^{1

2}, Gaetano Caramori³, Jinsung Yoon⁴, Lina Badimon⁵, Maria Bergami¹, Edina Cenko¹, Antonio David⁶, Ilir Demiri⁷, Maria Dorobantu⁸, Oana Fronea⁸, Radmilo Jankovic⁹, Sasko Kedev^{10

11}, Nebojsa Ladjevic¹², Ratko Lasica¹³, Goran Loncar¹⁴, Giuseppe Mancuso¹⁵, Guiomar Mendieta¹⁶, Davor Miličić¹⁷, Petra Mjehović¹⁷, Marijan Pašalić¹⁷, Milovan Petrović¹⁸, Lidija Poposka^{10

11}, Marialuisa Scarpone¹, Milena Stefanovic⁷, Mihaela van der Schaar^{19

20}, Zorana Vasiljevic²¹, Marija Vavlukis^{10

11}, Maria Laura Vega Pittao^{1

2}, Vladan Vukomanovic²², Marija Zdravkovic²³, Olivia Manfrini^{1

24}

Affiliations

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.

PMID: 36651866
DOI: 10.1093/cvr/cvad011

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.

Keywords: Acute heart failure; Acute kidney injury; Acute respiratory failure; COVID-19; Mortality; Sex; Women.

MeSH terms

Acute Kidney Injury* / diagnosis
Acute Kidney Injury* / epidemiology
Acute Kidney Injury* / therapy
COVID-19* / complications
COVID-19* / therapy
Cross-Sectional Studies
Female
Humans
Male
Retrospective Studies
Risk Factors
SARS-CoV-2
Sex Characteristics

Associated data

ClinicalTrials.gov/NCT05188612