Association between Lipid Levels, Anti-SARS-CoV-2 Spike Antibodies and COVID-19 Mortality: A Prospective Cohort Study

Background: Recent studies suggest that both lipid levels and anti-severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) antibody levels are associated with outcome in coronavirus disease 2019 (COVID-19). While both parameters have separately been implicated in the neutralization and clearance of pathogens during severe infections, it is currently unclear whether the interplay of these parameters affects outcome in COVID-19. We therefore aimed to determine whether there was a relationship between lipoproteins, anti-SARS-CoV-2 antibodies, and COVID-19 mortality. Methods: In this prospective, multicenter cohort study, we recruited 1152 hospitalized patients with COVID-19 from five hospitals. Total cholesterol (TC), LDL-C, HDL-C, triglycerides, and anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The investigated endpoint was in-hospital mortality. Results: LDL-C, HDL-C, and TC were significantly lower in non-survivors than in survivors (mg/dL, 95%CI; 56.1, 50.4–61.8 vs. 72.6, 70.2–75.0, p < 0.001; 34.2, 31.7–36.8 vs. 38.1, 37.2–39.1, p = 0.025; 139.3, 130.9–147.7 vs. 157.4, 54.1–160.6, p = 0.002). Mortality risk increased progressively with lower levels of LDL-C, HDL-C, and TC (aOR 1.73, 1.30–2.31, p < 0.001; 1.44, 1.10–1.88, p = 0.008; 1.49, 1.14–1.94, p < 0.001). Mortality rates varied between 2.1% for high levels of both LDL-C and anti-SARS-CoV-2 antibodies and 16.3% for low levels of LDL-C and anti-SARS-CoV-2 antibodies (aOR 9.14, 95%CI 3.17–26.34, p < 0.001). Accordingly, for total cholesterol and anti-SARS-CoV-2 antibodies, mortality rates varied between 2.1% and 15.0% (aOR 8.01, 95%CI 2.77–23.18, p < 0.001). Conclusion: The combination of serum lipid levels and anti-SARS-CoV-2 antibodies is strongly associated with in-hospital mortality of patients with COVID-19. Patients with low levels of LDL-C and total cholesterol combined with low levels of anti-SARS-CoV-2 antibodies exhibited the highest mortality rates.