Associations of serum levels of cGAMP in the context of COVID-19 infection, atherosclerosis, sterile inflammation, and functional endothelial biomarkers in patients with coronary heart disease and healthy volunteers.

Objectives: The present study evaluated the relationships of the serum levels of the cyclic dinucleotide 2'3'-cyclic GMP-AMP (cGAMP) marker of activation of pattern-recognition receptors with immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status and endothelial dysfunction.

Methods: Selected groups from two cohorts (cohort 1 of 307 healthy volunteers and cohort 2 of 218 coronary heart disease [CHD] patients). COVID-19 infection was confirmed by detection of IgG-SARS against SARS-CoV-2 S1 protein receptor-binding domain. Cohort 1 was examined for systematic coronary risk evaluation by European Society of Cardiology (SCORE) starting from 2019 before the onset of the COVID-19 pandemic. Cohort 2 was processed starting from 2017 (three years prior to the COVID-19 pandemic) in a hospital setting to undergo coronary angiography to assess coronary lesions as Gensini score. The levels of cGAMP and endothelial markers (nitrate and nitrite combined as NOx and endothelin-1) were assessed in the serum to evaluate the associations with IgG-SARS status, SCORE, and extent of coronary lesions by correlation and receiver operating characteristic analyses.

Results: Serum cGAMP did not discriminate between SARS-positive and SARS-negative healthy subject of cohort 1. Moreover, the level of cGAMP was not associated with endothelial biomarkers in healthy subjects. However, Serum cGAMP was associated with atherosclerosis, with area under the curve 0.69 (95 % CI 0.587-0.806; p=0.001), and with endothelial markers in cohort 2.

Conclusions: Low cGAMP was associated with atherosclerosis in CHD patients, suggesting that cGAMP is a new biomarker in the context of sterile inflammation.