Alterations in the lipid profile associate with a dysregulated inflammatory, prothrombotic, anti-fibrinolytic state and development of severe acute kidney injury in coronavirus disease 2019 (COVID-19): A study from Cincinnati, USA

Abstract

Background and aims Reduction of atherogenic lipoproteins is often the ultimate goal of nutritional interventions, however this is complicated given that hypolipidemia is frequently observed in coronavirus disease 2019 (COVID-19) patients. We aimed to explore the association of hypolipidemia with patient outcomes in terms of immunothrombosis and multiorgan injury, focusing on specialized apolipoproteins apo A1 and apo B. Methods Lipid profiles of 50 COVID-19 patients and 30 sick controls presenting to the Emergency Department (ED) were measured in this prospective observational study. The primary outcome was development of severe acute kidney injury (AKI). Need for hospitalization and ICU admission were secondary outcomes. Lipoproteins were analyzed for independent association with serum creatinine (SCr) increase ratio and correlated with a wide panel of biomarkers. Results COVID-19 cohort had significantly lower apo A1 (p = 0.006), and higher apo B/apo A1 ratio (p = 0.041). Patients developing severe AKI had significantly lower LDL-C (p = 0.021). Apo B/apo A1 was associated with 2.25-fold decrease in serum SCr increase ratio, while LDL-C with a 1.5% decrease. Hypolipidemia correlated with low plasminogen, ADAMTS13 activity/VWF:Ag, and high inflammatory biomarkers (CRP, IL-6, IL-8, IL-10), plasminogen activator inhibitor-1 (PAI-1), ED creatinine, and SCr increase ratio. Conclusion Although favored in dietetics, findings of a low LDL-C in COVID-19 patients should be alarming in light of our observations. Low apo B/apo A1 ratio and LDL-C are predictive of renal deterioration in COVID-19 patients, and low LDL-C in particular may potentially serve to indicate COVID-19 related AKI driven by disrupted fibrinolysis and a secondary thrombotic microangiopathy-like process.

Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients

“…For example, increased lipid accumulation was reported in SARS-CoV-2 infected cells and in the lungs of COVID-19 patients, suggesting a role for lipids in SARS-CoV-2 pathogenesis 57 . Also, low apo B/apo A1 ratio and low density lipoprotein-C (LDL-C) are observed to be predictive of renal deterioration in COVID-19 patients 58 , supporting the roles of alterations of lipid metabolism in the pathogenesis of COVID-19.…”

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

“…The protective effects of carnosine are widely attributed to its antioxidant, anti-glycation, and anti-inflammatory properties 11 . For instance, reduced circulating levels of low-density lipoprotein (LDL) has been associated with increased risk of acute kidney injury in COVID-19 patients 17 , and carnosine, known to block lipid peroxynitrite-mediated modification of human LDL at physiological levels 18 , may protect against LDL degradation. Intriguingly, recent studies suggest that carnosine may also protect against SARS-CoV-2 infection through more specific mechanisms.…”

Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework

“…ApoA1 prevented thrombosis in mice by upregulating nitric oxide availability [ 286 ], while in vitro studies have demonstrated its potential at fostering the anticoagulant protein C pathway [ 287 ]. In correlation with other biomarkers, observational studies have shown that low levels of ApoA1 and low levels in ApoB/ApoA1 in COVID-19 patients would potentially be associated with an “anti-fibrinolytic state” [ 288 ], as ApoA1 negatively correlated with PAI-1 while ApoB/ApoA1 were positively associated with plasminogen, resulting in reduced fibrinolytic capacity. Thus, the low HDL precondition associated with atherogenic dyslipidemia observed in severe COVID-19 may contribute to coagulopathy via the loss of the antithrombotic effect provided by these lipoproteins.…”

“…Lipids impact innate and adaptive immune responses. The lipoprotein dyslipidemia associated with COVID-19 severity (high TG and low total, LDL and HDL cholesterol) was inversely correlated with inflammatory biomarkers such as increased levels of serum CRP, IL-6, IL-8, and IL-10 [ 288 , 371 ]. In obesity, immune cells interact with various classes of lipids, which can control the plasticity of macrophages and T lymphocytes.…”