Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

Ikonomidis, Ignatios; Pavlidis, George; Katsimbri, Pelagia; Lambadiari, Vaia; Parissis, John; Andreadou, Ioanna; Tsoumani, Maria; Boumpas, Dimitrios; Kouretas, Dimitrios; Iliodromitis, Efstathios

We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis(RA). Eighty RA patients were randomized to tocilizumab(n=40) or conventional synthetic disease-modifying antirheumatic drugs(csDMARDs) and glucocorticoids(GC) (n=40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: a)perfused boundary region(PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), b)pulse wave velocity(PWV), c)global LV longitudinal strain(GLS), d)global work index(GWI) using speckle tracking echocardiography and e)C-reactive protein(CRP), malondialdehyde(MDA) and protein carbonyls(PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers(P<0.05). Compared with baseline, tocilizumab reduced PBR(2.14±0.2 versus 1.97±0.2μm; P<0.05) while no significant differences were observed post-csDMARDs+GC(P>0.05). Compared with csDMARDs+GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P<0.05). The percent improvement of glycocalyx thickness(PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P<0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs+GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03288584