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Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C 2 HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C 2 HEST score result. The measured outcomes included: in-hospital -mortality, three-month- and six-month- all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C 2 HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C 2 HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C 2 HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C 2 HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes. more...