Comparison of Immune Activation and Gut Barrier Dysfunction Between Long COVID and HIV Infection

BACKGROUND: Human Immunodeficiency Virus (HIV) infection is characterized by persistent immune dysregulation and inflammation, with emerging evidence suggesting overlapping pathophysiological mechanisms with Long COVID. Biomarkers of systemic inflammation and gut integrity may provide insight into shared and distinct pathways underlying these conditions. The status of the anti-inflammatory vitamin K may play a role in sustained inflammation in these conditions. METHODS: This cross-sectional study enrolled participants belonging to one of 3 groups: individuals with Long COVID (Long COVID; n=108) without HIV, participants with HIV (PWH), virologically suppressed with no previous COVID-19 infection (HIV+; n=256), and controls without Long COVID or HIV (controls; n=193). Plasma samples were analyzed for inflammatory, gut integrity biomarkers, and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) as an established marker of vitamin K status. Associations were assessed using multivariable linear and logistic regression models adjusted for demographic, metabolic, and lifestyle covariates. RESULTS: 557 participants were included. Long COVID was independently associated with elevated oxLDL (β=0.39 vs. HIV, β=0.54 vs. controls; P<0.001 for both). PWH had higher odds of worse vitamin K status [OR: 1.5; 95% CIs (1.02-2.2), P=0.04]. Independent of Long COVID or HIV status, worse vitamin K status was strongly associated with higher levels of inflammatory markers. CONCLUSION: Long COVID and HIV share chronic immune dysregulation features but demonstrate distinct inflammatory profiles. Those findings highlight the importance of large longitudinal studies to delineate shared versus unique inflammatory pathways to guide potential Long COVID therapeutic strategies.