Endothelial cell biomarkers in critically ill COVID‐19‐patients with encephalitis

Victor Altmayer (1, 2) , Jason Ziveri (3) , Corinne Frère (4, 2) , Joe‐elie Salem (2, 5, 6) , Nicolas Weiss (1, 7, 8) , Albert Cao (1, 2) , Clémence Marois (1, 2, 7) , Benjamin Rohaut (1, 9, 2) , Sophie Demeret (1, 2) , Sandrine Bourdoulous (10) , Loic Le Guennec (1, 3, 2)

1 NeurATRIS - IHU-A-ICM - Institut de neurosciences translationnelles de Paris
2 CHU Pitié-Salpêtrière [AP-HP]
3 IC UM3 (UMR 8104 / U1016) - Institut Cochin
4 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
5 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
6 Vanderbilt University Medical Center [Nashville]
7 GRC 30 - RESPIRE - Groupe de recherche cinique Réanimation et soins intensifs du patient en Insuffisance respiratoire aigüe
8 CRSA - Centre de Recherche Saint-Antoine
9 ICM - Institut du Cerveau = Paris Brain Institute
10 [Institut Cochin] Departement Infection, immunité, inflammation

COVID-19 is associated with encephalitis in critically ill patients and endothelial dysfunction seems to contribute to this life-threatening complication. Our objective was to determine the hallmark of endothelial activation in COVID-19 related encephalitis. In an observational study in intensive care unit (ICU), we compared vascular biomarkers of critically ill COVID-19 patients with or without encephalitis. To be classified in the Encephalitis group, patients had to have new onset of central neurologic symptom, and pathological findings on either brain magnetic resonance imaging (MRI) and/or electroencephalogram (EEG). Among the 32 critically ill COVID-19 consecutive patients, 21 were categorized in the Control group and 11 in the Encephalitis group. Encephalitis patients had a longer ICU-stay than Control patients (median length [25th-75th percentile] of 52[16-79] versus 20.5[11-44] days respectively, p=0.04). Nine-months overall follow-up mortality reached 21% (7/32 patients), with mortality rates in the Encephalitis-group and the Control group of 27% and 19% respectively. Encephalitis was associated with significant higher release of soluble endothelial activation markers (sE-selectin, Tumor-Necrosis-Factor-α (TNF-α), Interleukin-6, Placental Growth Factor and Thrombomodulin), but these increases were correlated with TNF-α plasmatic levels. The hypoxia-inducible protein Angiopoietin-like-4 (ANGPTL4) was at significantly higher levels in Encephalitis patients compared to Control patients (p=0.0099), and in contrary to the other increased factors, was not correlated with TNF-α levels (r=0.2832, p=0.1163). Our findings suggest that COVID-19 related encephalitis is a cytokine-associated acute brain dysfunction. ANGPTL4 was the only elevated marker found in Encephalitis patients, which was not correlated with systemic inflammation, suggesting that ANGPTL4 might be a relevant factor to predict encephalitis in critically ill COVID-19 patients

Mots clés: COVID-19; acute respiratory distress syndrome; Encephalitis; Endothelial cell biomarker; Angiopoietinlike-4

Domaines: Maladies infectieuses; Maladies émergentes; Neurobiologie

Victor Altmayer, Jason Ziveri, Corinne Frère, Joe‐elie Salem, Nicolas Weiss, et al.. Endothelial cell biomarkers in critically ill COVID‐19‐patients with encephalitis. Journal of Neurochemistry, inPress, ⟨10.1111/jnc.15545⟩. ⟨hal-03452050⟩