Plasma Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) as a Possible Biomarker for Severe COVID-19

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces low density lipoprotein (LDL) uptake, leading to increased plasma levels of LDL. In addition, PCSK9 has been implicated in inflammation independently of the effects on cholesterol metabolism. The current analysis showed that our 156 patients with systemic inflammatory response syndrome (SIRS) or sepsis had higher plasma PCSK9 levels in contrast with the 68 healthy controls. COVID-19 sepsis patients had increased plasma PCSK9 levels in comparison to sepsis patients not infected by SARS-CoV-2. For further analysis, patients were divided in two groups based on COVID-19. In both sub-cohorts, plasma PCSK9 levels did not correlate with C-reactive protein, leukocyte count, and procalcitonin. Plasma PCSK9 levels of both patient groups did not significantly differ among SIRS/sepsis patients with and without dialysis and patients with and without ventilation. Furthermore, vasopressor therapy was not significantly associated with altered plasma PCSK9 levels. In the non-COVID-19 SIRS/sepsis group, patients with Gram-negative and Gram-positive infections had similar plasma PCSK9 levels as patients without a detectable pathogen in their blood. In conclusion, the current study suggests PCSK9 as a possible biomarker for COVID-19, but this needs to be validated in larger cohorts.

Keywords: COVID-19; procalcitonin; survival; ventilation.

Figure 1

PCSK9 in the plasma of the controls, SIRS/sepsis patients, and SIRS/sepsis patients with and without liver cirrhosis. (a) Plasma PCSK9 levels of the 68 controls and the 156 SIRS/sepsis patients; (b) Plasma PCSK9 of the 109 male and 47 female SIRS/sepsis patients. Plasma PCSK9 levels across males and females were similar; (c) Plasma PCSK9 of 32 SIRS/sepsis patients with (Yes) and 124 SIRS/sepsis patients without liver cirrhosis (No). Outliers are plotted as individual circles or asterisks.

Figure 2

PCSK9 in the plasma of patients with SIRS/sepsis stratified for underlying diseases and causes of inflammation and sepsis (patients with liver cirrhosis were excluded). (a) Plasma PCSK9 levels of SIRS/sepsis patients with different underlying diseases. Pancreatitis (31 patients), cholangiosepsis (9 patients), and others (29 patients); (b) Plasma PCSK9 levels of SIRS/sepsis patients with different causes of inflammation. Pneumonia (41 patients) and urinary tract infections (14 patients); (c) Plasma PCSK9 of 103 SIRS/sepsis patients without and 21 patients with SARS-CoV-2 infection; (d) Plasma PCSK9 of patients categorized according to the SIRS criteria and to the Sepsis-3 definition as SIRS (27 patients), sepsis (33 patients), and septic shock (64 patients); (e) Plasma PCSK9 of 76 sepsis patients without and 21 sepsis patients with SARS-CoV-2 infection (patients with SIRS were excluded). The p-values are shown in the figures when significant differences between the groups were observed. Outliers are plotted as individual circles or asterisks.

Figure 3

PCSK9 in the plasma of patients with SIRS/sepsis (patients with COVID-19 and patients with liver cirrhosis were excluded) stratified for the type of bacterial infection and the association of plasma PCSK9 with survival. (a) Plasma PCSK9 levels stratified for the type of bacterial infection (thirty-four patients had no detectable bacterial pathogen, forty-nine patients had Gram-negative infection, nine patients had Gram-positive infection, and nine patients had both Gram-negative and Gram-positive bacteria). (b) Plasma PCSK9 levels of the 84 SIRS/sepsis patients who survived and the 18 patients who did not survive. There were no significant differences observed between these groups. Outliers are plotted as individual circles or asterisks.