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. 2024 Aug 22;14(1):19558.
doi: 10.1038/s41598-024-70172-5.

Circulating endocannabinoid levels in SARS-CoV-2 infection and their potential role in the inflammatory response

Maria Velasco  1   2   3 , Maria Posada-Ayala  4 , Elia Pérez-Fernández  5 , Frida Loria  5 , Mario Amores  5 , José Miguel Ramos  6 , Elena Jaime  7 , Carlos Guijarro  8   6 , Julián Romero  4 , Maria Ruth Pazos  9   10
Affiliations

Circulating endocannabinoid levels in SARS-CoV-2 infection and their potential role in the inflammatory response

Maria Velasco et al. Sci Rep. .

Abstract

Plasma levels of endocannabinoids (eCBs) are very dynamic and variable in different circumstances and pathologies. The aim of the study was to determine the levels of the main eCBs and N-acylethanolamines (NAEs) in COVID-19 patients during the acute and post-acute phase of SARS-CoV-2 infection. Samples collected before December 31, 2020 were used for the determination of circulating eCB levels by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between plasma eCB measurements and biochemical and hematological parameters, as well as serum IL-6 levels, was evaluated. Samples of 64 individuals were analysed, n = 18 healthy donors, n = 30 acute, and n = 16 post-acute patients. Plasma levels of 2-arachidonoylglycerol (2-AG), were significantly elevated in COVID-19 patients when compared to healthy individuals. Plasma N-palmitoylethanolamide (PEA) and N-arachidonoylethanolamide (AEA) levels were found to be decreased in post-acute patient samples. These results suggest that 2-AG plays an important role in the inflammatory cascade in COVID-19 disease; in addition, eCBs might be involved in the post-acute pathogenesis of COVID-19. This study provides evidence of altered levels of circulating eCBs as a consequence of SARS-CoV-2 infection.

Keywords: Biomarkers; COVID-19; Endocannabinoids; Inflammation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
IL-6 serum concentration in COVID-19 patients (acute n = 30; post-acute n = 16) compared to healthy donors (control n = 16). The Kruskall-Wallis test was conducted for statistical analysis and Dunn test was used to calculate adjusted p-values: *p < 0.05; **p < 0.001.
Figure 2
Figure 2
Circulating eCB levels per milligram of total protein in COVID-19 patients (acute n = 30; post-acute n = 16) compared to healthy donors (control n = 16). Univariate analysis was performed using the Kruskall-Wallis test and Dunn test was used to calculate adjusted p-values: *p < 0.05; **p < 0.001. 2-AG: 2-arachidonoylglycerol, AEA: N-araquidonoylethanolamine, PEA: N-palmitoylethanolamine, OEA: N-oleoylethanolamine.
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