https://www.sciencedirect.com/science/article/pii/S1477893921002416?via%3Dihub
Prognostic value of apolipoproteins in COVID-19 patients: A systematic review and meta-analysis
4. Discussion
Exchangeable Apolipoproteins, including Apo As, Apo E, and ApoCs, are constituents of HDL and triglyceride-rich lipoproteins such as VLDL. The best-studied family members are Apo A-I, the most significant HDL protein, in which an anti-atherogenic effect has been documented [32]. In contrast, non-exchangeable Apolipoproteins, such as Apo B, share a similar sequence and structure and can be reversibly associated with lipid surfaces [33]. Apo A is primarily bound to low-density lipoprotein (LDL) in subjects with average triglyceride values. However, Apo A can also bind to APOB100 or triglyceride particles in dyslipidemic states, called very low and intermediate-density lipoproteins [33].
Due to their potential effects and prominence in different pathologies, apolipoproteins have been studied as predictors of clinical outcomes in some diseases. For example, various systematic reviews associated the Apo E with ischemic and hemorrhagic stroke and a higher risk of worse outcomes in patients with traumatic brain disease [[34], [35], [36], [37], [38]]. Similarly, Apo C was associated with the risk of ischemic stroke, although a systematic review found no evidence of this association [39].
In the case of Apo A1, probably due to its anti-atherogenic effect, some systematic reviews and meta-analyses sought its association with cardiovascular outcomes. Haji Aghajani M et al., in a review of seventeen case-control studies, found an association between Apo A 1 levels and premature coronary artery disease. However, the authors note the lack of good quality prospective cohort studies [40]. Erqou S et al., in a systematic review of thirty-six studies, found that people with smaller Apo A isoforms have an approximately 2-fold higher risk of coronary heart disease or ischemic stroke than those with larger proteins [41]. As with cardiovascular outcomes, other systematic reviews found evidence of Apo A1 as a diagnostic marker for bladder cancer [42], a poor prognosis of multiple cancers [43,44], and it was found at lower levels in patients with Alzheimer's disease [45].
To the best of our knowledge, no systematic reviews have been published on the association between Apolipoprotein values as a prognostic factor in patients with COVID-19 or some other infectious disease; however, our results are not surprising. Apo-I's presence characterizes High-density lipoproteins (HDL), and their ability to transport cholesterol from peripheral tissues back to the liver gives it a cardioprotective function [46]. Similarly, it has antioxidant, anti-apoptotic, anti-thrombotic, anti-inflammatory or anti-infectious functions and decreases rapidly in patients with sepsis, which could explain our findings [46]. A study in pediatric patients in intensive care for sepsis found that Apo A5 serum levels were significantly lower in patients who died than survivors. Similarly, Apo A5 serum levels were significantly correlated with multiple organ failure, shock, acute kidney injury, acute liver injury, and gastrointestinal dysfunction, although not respiratory failure [47]. In adults, an association was also found between low levels of Apolipoproteins and a poor prognosis in patients with sepsis. Although the mechanisms are not well understood, it is suggested that the association is explained due to increased platelet activation and monocyte activation [48,49]. In addition, the low levels of Apo A are related to high levels of inflammation [50], and this being a prognostic marker in patients infected by COVID-19 [51], its role in the binding and neutralization of lipopolysaccharides in bacterial infections is known [52].
In patients with virus infections, changes in plasma HDL-C levels were reported during infections, where the viruses would take advantage of the HDL lipid transfer activity in host cells [53]. Although the best evidence is in patients with hepatitis C virus and acquired immunodeficiency virus, in the case of patients with COVID-19 infection, a similar theory is suggested [54]. Therefore, the HDL lipid transfer activity mechanism could explain our results as the relationship between viral load and worse prognosis in patients with COVID-19 is known [55]. Similarly, the hypothesis of the relationship between lipoproteins and inflammation and thrombosis was raised. In this way, our findings could explain since the association between thrombosis and the prognosis are known [56].
Finally, due to its known association with brain and cardiovascular disease, it is possible that in patients with COVID-19, the prognostic value of ApoA1 is mediated by the occurrence of these diseases. Indeed, complications including myocarditis, acute myocardial infarction, heart failure, arrhythmias and venous thromboembolic events are described in these patients [57,58]. Similarly, concerning cerebrovascular complications, episodes of stroke, necrotizing hemorrhagic encephalitis, among others, were reported [59,60].
Our study is the first systematic review to evaluate the prognostic value of Apo A1, ApoB and the ratio of both in patients with an infectious disease. In addition, our study used the NOS to assess the risk of bias of the included articles, which allowed sensitivity analyses when the association between Apo A1 and Apo B with the severity of the disease of patients hospitalized for COVID-19 was analyzed. Our findings allow us to suggest a potential low-cost prognostic marker in patients hospitalized for COVID-19 that will allow health personnel to prioritize or individualize management strategies in patients with low values of these markers.
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