Renin–Angiotensin System Components and Arachidonic Acid Metabolites as Biomarkers of COVID-19

Abstract

Through the ACE2, a main enzyme of the renin–angiotensin system (RAS), SARS-CoV-2 gains access into the cell, resulting in different complications which may extend beyond the RAS and impact the Arachidonic Acid (ArA) pathway. The contribution of the RAS through ArA pathways metabolites in the pathogenesis of COVID-19 is unknown. We investigated whether RAS components and ArA metabolites can be considered biomarkers of COVID-19. We measured the plasma levels of RAS and ArA metabolites using an LC-MS/MS. Results indicate that Ang 1–7 levels were significantly lower, whereas Ang II levels were higher in the COVID-19 patients than in healthy control individuals. The ratio of Ang 1–7/Ang II as an indicator of the RAS classical and protective arms balance was dramatically lower in COVID-19 patients. There was no significant increase in inflammatory 19-HETE and 20-HETE levels. The concentration of EETs was significantly increased in COVID-19 patients, whereas the DHETs concentration was repressed. Their plasma levels were correlated with Ang II concentration in COVID-19 patients. In conclusion, evaluating the RAS and ArA pathway biomarkers could provide helpful information for the early detection of high-risk groups, avoid delayed medical attention, facilitate resource allocation, and improve patient clinical outcomes to prevent long COVID incidence.

Contributing to the management of viral infections through simple immunosensing of the arachidonic acid serum level

“…The obtained results show significantly lower ARA concentration in serum of patients diagnosed with SARS-CoV-2 and RSV compared to healthy individuals. This agrees with numerous reports on the relationship between ARA metabolism and COVID-19 infection and lower serum ARA levels in infected patients [ 9 – 11 , 13 , 14 , 17 – 20 , 22 ]. Although lower ARA concentrations in serum have been reported also in SARS and MERS and other similar enveloped viruses [ 11 , 16 – 20 ], these are the first results for ARA concentration levels in RSV-infected patients.…”

“…This agrees with numerous reports on the relationship between ARA metabolism and COVID-19 infection and lower serum ARA levels in infected patients [ 9 – 11 , 13 , 14 , 17 – 20 , 22 ]. Although lower ARA concentrations in serum have been reported also in SARS and MERS and other similar enveloped viruses [ 11 , 16 – 20 ], these are the first results for ARA concentration levels in RSV-infected patients. It is important to remark that the ARA concentrations measured for healthy individuals agree well with that reported previously (mean level of 46.4 µg mL −1 ) [ 36 ], thus confirming the accuracy of the bioplatform for the analysis of serum samples.…”

“…It is important to note that many studies correlate the serum levels of ARA with the susceptibility and severity of certain individuals to respond to viral infections [ 8 , 11 , 16 – 20 ]. Therefore, the developed bioplatform may be applied, in addition to the management of viral infections, to the implementation of personalized vaccination strategies.…”

“…It has been reported that ARA, other unsaturated fatty acids, and some of their metabolites can serve as endogenous antimicrobial compounds and their deficiency can make humans susceptible to infections with SARS-CoV-2, SARS, MERS, and other similar enveloped viruses [ 11 , 16 – 20 ]. Recent research also shows that ARA activates human voltage-gated proton channels in infected, injured, or inflamed cells [ 21 ].…”