The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19

Carvalho, Jonatan C. S. de; Toro, Diana Mota; Fuzo, Carlos Alessandro; Nardini, Viviani; Pimentel, Vinícius E.; Pérez, Malena M.; Fraga-Silva, Thais Fernanda de Campos; Oliveira, Camilla Narjara Simão; Degiovani, Augusto M.; Ostini, Fátima M.; Feitosa, Marley Ribeiro; Parra, Rogério Serafim; Rocha, José Joaquim Ribeiro da; Féres, Omar; Vilar, Fernando Crivelenti; Gaspar, Gilberto Gambero; Santos, Isabel M.; Fernandes, Ana Paula; Maruyama, Sandra Regina; Russo, Elisa Maria de Sousa; Bonato, Vânia Luiza Deperon; Cardoso, Cristina Ribeiro de Barros; Dias‐Baruffi, Marcelo; Faccioli, Lúcia Helena; Sorgi, Carlos Artério

doi:10.3390/v15020573

Cited by 3 publications

(4 citation statements)

References 100 publications

(109 reference statements)

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“…In this line, some interactions have already been described, such as for the steroid dexamethasone that may act to limit pro-inflammatory eicosanoid generation or increase SPM production 35,36 . Other relevant interactions have also been described; for example, relative to the use of glucocorticoids as anti-inflammatory therapy during COVID-19; and also via the synthesis of lipid mediators, such as overexpression of the 2-arachidonoylglycerol or underexpression of the platelet-activating factor (PAF) induced by modification of lipid metabolism-enzyme gene expression 37 . Moreover, antiviral drugs, antibiotics, and immunosuppressants can induce liver injury 38 , which causes an inflammatory response that may influence LM profiles.…”

Section: Discussionmentioning

confidence: 99%

Serum lipid mediator profiles in COVID-19 patients and lung disease severity: a pilot study

Irún

Gracia

Piazuelo

et al. 2023

Sci Rep

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Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is highly heterogeneous, ranging from asymptomatic to severe and fatal cases. COVID-19 has been characterized by an increase of serum pro-inflammatory cytokine levels which seems to be associated with fatal cases. By contrast, the role of pro-resolving lipid mediators (SPMs), involved in the attenuation of inflammatory responses, has been scarcely investigated, so further studies are needed to understand SPMs metabolism in COVID-19 and other infectious diseases. Our aim was to analyse the lipid mediator metabolome, quantifying pro- and anti-inflammatory serum bioactive lipids by LC–MS/MS in 7 non-infected subjects and 24 COVID-19 patients divided into mild, moderate, and severe groups according to the pulmonary involvement, to better understand the disease outcome and the severity of the pulmonary manifestations. Statistical analysis was performed with the R programming language (R Foundation for Statistical Computing, Vienna, Austria). All COVID-19 patients had increased levels of Prostaglandin E2. Severe patients showed a significant increase versus controls, mild- and moderate-affected patients, expressed as median (interquartile range), in resolvin E1 [112.6 (502.7) vs 0.0 (0.0) pg/ml in the other groups], as well as in maresin 2 [14.5 (7.0) vs 8.1 (4.2), 5.5 (4.3), and 3.0 (4.0) pg/ml, respectively]. Moreover, 14-hydroxy docosahexaenoic acid (14-HDHA) levels were also increased in severe vs control and mild-affected patients [24.7 (38.2) vs 2.4 (2.2) and 3.7 (6.4) ng/mL, respectively]. Resolvin D5 was also significantly elevated in both moderate [15.0 (22.4) pg/ml] and severe patients [24.0 (24.1) pg/ml] versus controls [0.0 (0.0) pg/ml]. These results were confirmed by sparse partial least squares discriminant analysis which highlighted the contribution of these mediators to the separation between each of the groups. In conclusion, the potent inflammatory response to SARS-CoV-2 infection involves not only pro- but also anti-inflammatory lipid mediators that can be quantified in easily accessible serum samples, suggesting the need to perform future research on their generation pathways that will help us to discover new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Serum lipid mediator profiles in COVID-19 patients and lung disease severity: a pilot study

Irún

Gracia

Piazuelo

et al. 2023

Sci Rep

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“…PAF is produced by cells involved in host defense, and its biological actions bear similarities with COVID-19 disease manifestations [ 39 ]. Increased levels of PAF have been found in the blood of moderate COVID-19 patients [ 40 ]. In addition to PAF, lysophosphatidic acid has been found to promote thrombus stability by inducing the rapid formation of NETs [ 41 ].…”

Section: Covid-19-associated Coagulopathy (Cac)mentioning

confidence: 99%

“…The latter is then acetylated through the action of acetyl-CoA:lyso-PAF acetyltransferases to produce PAF. Both lyso-PAF and PAF species were found in the plasma of COVID-19 patients [ 40 ]. Levels of PAF are higher in mild/moderate COVID-19 patients compared to healthy controls, but levels decrease in individuals with severe/critical disease [ 40 ] ( Figure 1 and Figure 2 ).…”

Section: Covid-19-associated Changes In Lysophospholipidsmentioning

confidence: 99%

“…Both lyso-PAF and PAF species were found in the plasma of COVID-19 patients [ 40 ]. Levels of PAF are higher in mild/moderate COVID-19 patients compared to healthy controls, but levels decrease in individuals with severe/critical disease [ 40 ] ( Figure 1 and Figure 2 ). The above findings provide additional support for a close relationship between PLA2 activity and thromboses in patients with COVID-19.…”

Section: Covid-19-associated Changes In Lysophospholipidsmentioning

confidence: 99%

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COVID-19, Blood Lipid Changes, and Thrombosis

Farooqui

Sun

et al. 2023

Biomedicines

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Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A2 that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A2 IIA (sPLA2-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA2-IIA levels together with eicosanoids in the sera of COVID patients. sPLA2 could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A2, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA2-IIA in COVID-19-associated coagulopathy (CAC).

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The Role of Platelet Molecules in Risk Stratification of Patients with COVID-19

de Oliveira Sales,

de Oliveira,

da Silva

et al. 2023

Hemato

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The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and is responsible for Coronavirus disease (COVID-19). Despite being well tolerated by most patients, a fraction of cases evolve into a potentially fatal condition requiring intensive care. In addition to respiratory complications, several studies have reported cases of patients who developed intense thrombosis, including acute myocardial infarction and ischemic stroke, as well as the presence of elevated coagulation markers. Evidence has shown that the virus can interact directly with platelets and modulate their thrombotic and inflammatory functions, with significant prognostic implications. It is important to highlight that the emerging literature shows that when hyperactive these cells can act as pro-viral infections both in transporting their particles and in increasing inflammation, leading to a hyperinflammatory state and consequent clinical worsening. In this review, we searched for studies available in public databases and discussed the interaction of platelet biomarkers in the pathogenesis of COVID-19. In this context, understanding the mechanism of SARS-CoV-2 and these cells in different clinical conditions could help us to understand the coagulation and inflammation profiles of critically ill patients with the disease, guiding faster clinical management and enabling the reuse and targeting of more efficient therapies.

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The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19

Cited by 3 publications

References 100 publications

Serum lipid mediator profiles in COVID-19 patients and lung disease severity: a pilot study

Serum lipid mediator profiles in COVID-19 patients and lung disease severity: a pilot study

COVID-19, Blood Lipid Changes, and Thrombosis

The Role of Platelet Molecules in Risk Stratification of Patients with COVID-19

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