In this study, Blood lipid profile in the patients with COVID-19 patients was abnormal from healthy subjects. Specifically, baseline TC, HDL-C, LDL-C, and ApoA1 gradually decreased across healthy controls, non-severe group, and severe group, whereas ApoB and lipoprotein (a) exhibited no significant differences among the three groups. Although TG was higher in the non-severe group when compared with healthy controls, no significant differences were found between the severe and non-severe group, and the severe group and healthy controls. Additionally, ApoA1 was recognized as an independent risk factor of disease severity using multivariate logistic analysis, and had the highest AUC, sensitivity and specificity among all the single markers for COVID-19 severity. Moreover, the combination of ApoA1 and IL-6 yielded a higher prediction efficiency.
Previous studies have reported that lipid metabolism impairment may be involved in the pathogenesis of sepsis secondary to pneumonia and influenza [8–10]. Similarly, recent studies observed dyslipidemia in patients infected with SARS-CoV-2, using MS analysis [6, 7] and routine laboratory lipid tests , indicating that blood lipid might involve in the pathogenesis of COVID-19. In the study of Wei et al. , a serum hypolipidemia was found in the COVID-19 patients, which showed that the serum level of TC, HDL-C and LDL-C in the patients with COVID-19 were significantly lower than healthy subjects, especially in the severe and critical cases. The above phenomenon was revealed again in the present. However, the former study did not analyse other blood lipid component, such as ApoA1, ApoB and lipoprotein (a), which were also routine tested, and their predictive values for COVID-19 severity were not fully understood. Among the altered lipids in this study, ApoA1 was significantly decreased, and serve as an independent risk factor for the COVID-19 severity.
ApoA1, a major protein component of the HDL complex, is involved in “reverse cholesterol transport” by transporting excess cholesterol from peripheral cells back to the liver for excretion. Besides, ApoA1 has an anti-inflammatory characteristic , suggest its role in the inflammatory diseases. Previous studies have revealed that serum ApoA1 was associated with the outcome of patients with sepsis and acute respiratory distress syndrome induced by pneumonia, as well as critically ill patients [13–16]. In acute inflammatory disease, serum amyloid A (SAA), an acute phase protein, displaces ApoA1 from the HDL complex; then, free ApoA1 is easily eliminated by the kidney, resulting in low levels in the peripheral blood . On the other hand, liver is susceptible to attack by SARS-CoV-2, especially in severe cases ; therefore, reduced synthesis by the injured liver may also play a role.
IL-6 plays a key role in the development of COVID-19, and its predictive value has been revealed previously by us and others [4, 19]. In this study, IL-6 and ApoA1 were identified as independent risk factors. The risk model established by these two markers exhibited the highest predictive value, with an AUC of 0.977 (95% CI: 0.932–0.995).
ApoA1 and its mimetic peptide D-amino acids (D-4F) exhibit therapeutic potential in treating cancer, influenza, sepsis and a variety of lung diseases, such as acute respiratory distress syndrome (ARDS), mainly due to its anti-inflammatory, anti-oxidant and anti-apoptotic properties [12, 20–23]. In addition, it is noteworthy that ApoA1 inhibits IL-6 release and reduces macrophage activation . IL-6 is the main participant in the cytokine storm, and macrophages are the primary source of IL-6. Therefore, ApoA1 may exhibit therapeutic potential in treating patients with COVID-19. It might be worthwhile to test the efficacy and safety of ApoA1 in these patients.
The main strength of this study was that the patients included in this study were treated without delay when infected by SARS-CoV-2, which may represent the early stage of the disease. Second, it enrolled healthy controls to analysis the trends of blood lipid among healthy subjects, non-severe cases and severe cases. Third, the predictive values of verified clinical characteristics and laboratory parameters were selected to compared with blood lipid, which made the results more credible. Last, blood lipids were routinely tested by automatic biochemical analyser, with clinical application value.
The weakness of this study was that it was a single-centre retrospective study with relatively small sample size, and not validated with internal and external cohorts. Therefore, a prospective study with a large sample size is strongly encouraged.