Lipid Profile Features and Their Associations With Disease Severity and Mortality in Patients With COVID-19

Abstract

Background: Emerging studies have described and analyzed epidemiological, clinical, laboratory, and radiological features of COVID-19 patients. Yet, scarce information is available regarding the association of lipid profile features and disease severity and mortality.Methods: We conducted a prospective observational cohort study to investigate lipid profile features in patients with COVID-19. From 9 February to 4 April 2020, a total of 99 patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were included in the study. Dynamic alterations in lipid profiles were recorded and tracked. Outcomes were followed up until 4 April 2020.Results: We found that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apoA-1) levels were significantly lower in the severe disease group, with mortality cases showing the lowest levels (p < 0.0001). Furthermore, HDL-C and apoA-1 levels were independently associated with disease severity (apoA-1: odds ratio (OR): 0.651, 95% confidence interval (CI): 0.456–0.929, p = 0.018; HDL-C: OR: 0.643, 95% CI: 0.456–0.906, p = 0.012). For predicting disease severity, the areas under the receiver operating characteristic curves (AUCs) of HDL-C and apoA-1 levels at admission were 0.78 (95% CI, 0.70–0.85) and 0.85 (95% CI, 0.76–0.91), respectively. For in-hospital deaths, HDL-C and apoA-1 levels demonstrated similar discrimination ability, with AUCs of 0.75 (95% CI, 0.61–0.88) and 0.74 (95% CI, 0.61–0.88), respectively. Moreover, patients with lower serum concentrations of apoA-1 (<0.95 g/L) or HDL-C (<0.84 mmol/l) had higher mortality rates during hospitalization (log-rank p < 0.001). Notably, levels of apoA-1 and HDL-C were inversely proportional to disease severity. The survivors of severe cases showed significant recovery of apoA-1 levels at the end of hospitalization (vs. midterm apoA-1 levels, p = 0.02), whereas the mortality cases demonstrated continuously lower apoA-1 levels throughout hospitalization. Correlation analysis revealed that apoA-1 and HDL-C levels were negatively correlated with both admission levels and highest concentrations of C-reactive protein and interleukin-6.Conclusions: Severely ill COVID-19 patients featured low HDL-C and apoA-1 levels, which were strongly correlated with inflammatory states. Thus, low apoA-1 and HDL-C levels may be promising predictors for severe disease and in-hospital mortality in patients suffering from COVID-19.

The bidirectional link between HDL and COVID-19 infections

“…With recovery from COVID-19 infection the lipid levels return towards levels present prior to infection ( 28 , 29 , 30 , 42 , 43 ). As expected, the greater the severity of the illness the greater the reduction in LDL-C and/or HDL-C levels ( 29 , 31 , 32 , 33 , 34 , 35 , 36 , 38 , 42 , 44 , 45 ). LDL-C and HDL-C levels are inversely correlated with C-reactive protein (CRP) levels i.e., the higher the CRP levels the lower the LDL-C or HDL-C level ( 28 , 29 , 31 , 45 ).…”

“…Low LDL-C and/or HDL-C levels at admission to the hospital predict an increased risk of developing a severe disease. Increased mortality was observed in patients with low total cholesterol, LDL-C, and/or HDL-C levels at admission to the hospital and in these very ill patient’s lipid levels continued to decline during the hospitalization ( 28 , 36 , 38 , 41 , 43 , 44 , 45 ). A single study reported that the time to develop a negative RT-PCR test for SARs-CoV-2 was increased in patients with low HDL-C levels ( 46 ).…”

Triglyceride/High-Density Lipoprotein Cholesterol Ratio is associated with the mortality of COVID-19: An Observational Study

“…Hypertriglyceridemia induces endothelial dysfunctionality, causing COVID-19 patients to become more susceptible to complications related to cardiovascular diseases 14 . It was reported that TG levels signi cantly increased in COVID-19 patients with poor prognoses 15 .…”

“…A marked decrease in HDL-c concentrations during the acute phase response is well documented, however, the mechanisms underlying this decrease are not clearly de ned. Apolipoprotein-1 (ApoA-1), a major structural protein of HDL-c, reportedly decreased together with lower HDL-c when proin ammatory cytokines, such as interleukin-6 (IL-6) and CRP inhibited the activity of apolipoprotein synthesis enzymes 15,17 . Serum amyloid A (SAA)-enriched HDL displaced and decreased ApoA-1 levels and scavenged HDL more rapidly which was signi cantly higher in patients with a severe COVID-19 diagnosis 11,15 .…”

“…Apolipoprotein-1 (ApoA-1), a major structural protein of HDL-c, reportedly decreased together with lower HDL-c when proin ammatory cytokines, such as interleukin-6 (IL-6) and CRP inhibited the activity of apolipoprotein synthesis enzymes 15,17 . Serum amyloid A (SAA)-enriched HDL displaced and decreased ApoA-1 levels and scavenged HDL more rapidly which was signi cantly higher in patients with a severe COVID-19 diagnosis 11,15 . Paraoxonase 1 (PON1), an antioxidant enzyme of HDL, could be inactivated under oxidative stresses and further weaken HDL functions 30 .…”