Alteration in the Lipid Profile and the Desaturases Activity in Patients With Severe Pneumonia by SARS-CoV-2

Abstract

The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

Keywords: COVID-19; NEFAs; SARS-CoV-2; fatty acids; phospholipids; pneumonia.

FIGURE 1

Total phospholipids in plasma of HS and COVID-19 patients. The main phospholipids are phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylinositol. A decrease significant is observed in COVID-19 patients vs. HS. Statistical significance was determined by the Mann–Whitney rank sum test followed by the normality test (Shapiro-Wilk). Values expressed represent the median and Min–Max range (n = 42 COVID-19 patients and 22 HS). COVID-19 = coronavirus disease-19, HS = healthy subjects.

FIGURE 2

Total NEFAs in plasma of healthy subjects and COVID-19 patients. A decrease significant is observed in COVID-19 patients vs. HS. Statistical significance was determined by the Mann–Whitney rank sum test followed by the normality test (Shapiro-Wilk). Values expressed represent the median and Min–Max range (n = 42 COVID-19 patients and 22 HS). COVID-19 = coronavirus disease-19, HS = healthy subjects, NEFAS = non-esterified fatty acids.

FIGURE 3

The SARS-CoV-2 can modulate and rearrange the host lipid profile to reach an intricate homeostasis which is optimal for viral replication and propagation. However, any exogenous manipulation that disrupts this the equilibrium might interfere with the replication of the virus such as high EPA and DHA concentration that decrease pro-inflammatory state being precursor of SPMs to and probably the AA however this FA might have two effects; increase inflammatory and thrombotic prostaglandins that would aggravate the infection by SARS-CoV-2 and/or decrease viral replication and propagation. AA = arachidonic acid, ACE2 = angiotensin converting enzyme 2, COX = cyclooxygenase, CT = cholesterol, D-γ-LA = dihomo-γ-linolenic acid, DHA = docosahexaenoic acid, EPA = eicosapentaenoic acid, FA = Fatty Acid, GPx = glutathione peroxidase, GR = glutathione reductase, GSH = glutathione, GSSG = oxidized glutathione, H2O2 = hydrogen peroxide, LA = linoleic acid, LOX = lipoxygenase, O₂ = superoxide anion, PGE2 = prostaglandin E2, PL = phospholipids, PLA2 = phospholipase A₂, PUFA = polyunsaturated fatty acids, SOD = superoxide dismutase, SPMs = specialized pro-resolving mediators, TXA2 = thromboxane A2, γ-LA = γ-linoleic acid.