SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9
(PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels
and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60
patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared
to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive
protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9
regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC)
were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap
mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared
to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with
severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe
COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The
FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival.
The current study suggests that the imbalance between CE and FC levels is associated with disease
severity and mortality in patients with COVID-19.