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Sex Differences in Long-Term Cardiovascular Outcomes and Mortality After COVID-19 Hospitalization During Alpha, Delta
Kristen Kopp1, Lukas J Motloch1,2,3, Michael Lichtenauer1
1University Clinic for Internal Medicine II, Paracelsus Medical University, Muellner Hauptstrasse 48, 5020 Salzburg, Austria.
Insights
Men experienced higher cardiovascular mortality and outcomes during the Delta variant wave of COVID-19 compared to women. No significant sex differences in cardiovascular outcomes were observed with the Alpha or Omicron variants.
Area of Science:
- Cardiology
- Infectious Diseases
- Epidemiology
Background:
- Male sex is linked to increased mortality and cardiovascular (CV) events in moderate to severe SARS-CoV-2 infection.
- Limited data exist on long-term CV outcomes stratified by sex and COVID-19 variant (Alpha, Delta, Omicron).
Purpose of the Study:
- To investigate sex-based differences in long-term cardiovascular outcomes following SARS-CoV-2 pneumonia hospitalization.
- To evaluate these differences across distinct COVID-19 variant waves (Alpha, Delta, Omicron).
Main Methods:
- Prospective study of 4882 patients hospitalized for SARS-CoV-2-associated pneumonia.
- Assessed primary combined CV outcomes and secondary outcomes at 18-month follow-up.
- Analyzed survival rates by sex and variant using Kaplan-Meier and Gehan-Wilcoxon tests; Cox models identified risk factors.
Main Results:
- Men showed significantly higher 18-month CV mortality and combined CV endpoint incidence during the Delta wave compared to women (p=0.017).
- No significant sex differences in CV outcomes were observed during the Alpha and Omicron variant waves.
- Demographic and comorbidity discrepancies were noted between COVID-19 variants.
Conclusions:
- The Delta variant wave was associated with higher male CV mortality and CV outcomes, though not all reached statistical significance.
- The lowest incidence of CV outcomes was observed during the Omicron variant wave.
- Sex-specific long-term cardiovascular risk varies by SARS-CoV-2 variant.
Abstract:
Background: Increased mortality and occurrence of cardiovascular (CV) outcomes during hospitalization and in short-term follow-up for moderate to severe SARS-CoV-2 infection have been associated with male sex, yet data regarding long-term outcomes by sex and COVID-19 variant (Alpha, Delta, and Omicron) are limited. Methods: This prospective study of 4882 patients examines potential differences by sex in the occurrence of primary combined cardiovascular outcomes (CV death, CV hospitalization, myocardial infarction (MI), stroke, pulmonary embolism) as well as secondary outcomes (CV death, cardiovascular hospitalizations, myocardial infarction, stroke, pulmonary embolism) at 18-month follow-up after urgent hospitalization for SARS-CoV-2-associated pneumonia, as well as evaluating for differences during the three COVID-19 waves. Survival rate was analyzed for the entire cohort by sex and SARS-CoV-2 variant and adjusted for age using the multiple Kaplan-Meier method. To compare survival in groups of men and women for each wave, the Gehan-Wilcoxon test was applied with significance p < 0.05. Univariate Cox proportional hazards models were used to search for potential risk factors of CV death at 18-months follow-up separately for men and women in each COVID-19 wave. Results: Men had significantly higher 18-month CV mortality compared to women in the Delta wave (6.13% men vs. 3.62% women, p = 0.017). Although men had higher percentages of all other CV endpoints (excepting pulmonary embolism) at follow-up during the Delta wave, none were significant compared with women, except for the combined CV endpoint (16.87% men vs. 12.61% women, p = 0.017). No significant differences by sex in CV outcomes were seen during the Alpha and Omicron variants. Discrepancies in CV outcomes in demographical data and concomitant disease between the COVID-19 variants of concern existed. Conclusions: Higher male mortality and higher but non-significant incidences of CV outcomes occurred during the Delta wave of the COVID-19 pandemic, with the lowest incidence of CV outcomes observed during the Omicron variant.
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