Background and aims Low HDL-cholesterol (HDLc) concentration is associated with a greater risk of infection-related mortality. We wanted to evaluate the relationship between pre-infection HDLc levels and mortality among older patients infected with SARS-Cov-2. Methods This is a population-based, cohort study, comprising all individuals residing in Madrid (Spain) born before 1 January 1945, and alive on 31 December 2019. Demographic, clinical, and analytical data were obtained from the primary care electronic clinical records. Confirmed SARS-CoV-2 infection was defined as a positive result in the RT-qPCR or in the antigen test. A death from COVID-19 was defined as that registered in the hospital chart, or as any death occurring in the 15 days following a confirmed SARS-CoV-2 infection. Data on infection, hospitalization, or death due to SAR-CoV-2 were collected from 1 March 2020 through 31 December 2020. Results Of the 593,342 individuals comprising the cohort, 36,966 had a SARS-CoV-2 infection during 2020, and at least one HDLc measurement in the previous five years. Among them, 9689 (26.2%) died from COVID-19. After adjustment for age and sex, the relative risk (95% confidence interval) of COVID-19 death across increasing quintiles of HDLc was 1.000, 0.896 (0.855–0.940), 0.816 (0.776–0.860), 0.758 (0.719–0.799), and 0.747 (0.708–0.787). The association was maintained after further adjustment for comorbidities, statin treatment and markers of malnutrition. While in females this association was linear, in males it showed a U-shaped curve. Conclusions In older subjects, a higher HDLc measured before SARS-CoV-2 infection was associated with a lower risk of death.

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