Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19

Crespo-Bermejo, C.; Brochado-Kith, O.; Grande-Garcia, S.; Lara-Aguilar, V.; Llamas-Adan, M.; Arca-Lafuente, S.; Martin-Carbonero, L.; de los Santos, I.; Jimenez Sousa, M. A.; Resino, S.; Berenguer, J.; Madrid, R.; Fernandez-Rodriguez, A.; Briz, V.

doi:10.1101/2024.03.12.584682

bioRxiv · 10.1101/2024.03.12.584682

Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19

Crespo-Bermejo, C.·Brochado-Kith, O.·Grande-Garcia, S.·Lara-Aguilar, V.·Llamas-Adan, M.·Arca-Lafuente, S.·Martin-Carbonero, L.·de los Santos, I.·Jimenez Sousa, M. A.·Resino, S.·Berenguer, J.·Madrid, R.·Fernandez-Rodriguez, A.·Briz, V.

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Abstract

BackgroundBoth SARS-CoV-2 and HIV infection exhibit alterations in the senescence profile and immune checkpoint (IC) molecules. However, the midterm impact of SARS-CoV-2 on these profiles in people with HIV (PWH) remains unclear. This study aimed to evaluate differences in plasma biomarker levels related to ICs, the senescence-associated secretory phenotype (SASP), and pro- and anti-inflammatory cytokines in PWH following recovery from SARS-CoV-2 infection. MethodsWe conducted a cross-sectional study of 95 PWH receiving antiretroviral therapy, stratified by SARS-CoV-2 infection status: a) 48 previously infected (HIV/SARS) and b) 47 controls without previous infection (HIV). Plasma biomarkers (n=44) were assessed using Procartaplex Multiplex Immunoassays. Differences were analyzed using a generalized linear model adjusted for sex and ethnicity and corrected for the false discovery rate. Significant values were defined as an adjusted arithmetic mean ratio [≥]1.2 or [≤]0.8 and a qvalue<0.1. Spearman correlation evaluated relationships between plasma biomarkers (significant correlations, rho[≥]0.3 and q value<0.1). ResultsThe median age of the PWH was 45 years, and 80% were men. All SARS-CoV-2-infected PWH experienced symptomatic infection; 83.3% had mild symptomatic infection, and sample collection occurred at a median of 12 weeks postdiagnosis. The HIV/SARS group showed higher levels of ICs (CD80, PDCD1LG2, CD276, PDCD1, CD47, HAVCR2, TIMD4, TNFRSF9, TNFRSF18, and TNFRSF14), SASP (LTA, CXCL8, and IL13), and inflammatory plasma biomarkers (IL4, IL12B, IL17A, CCL3, CCL4, and INF1A) than did the HIV group. ConclusionsSARS-CoV-2 infection in PWH causes significant midterm disruptions in plasma ICs and inflammatory cytokine levels, highlighting SASP-related factors, which could be risk factors for the emergence of complications in PWH.

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Crespo-Bermejo, C., Brochado-Kith, O., Grande-Garcia, S., Lara-Aguilar, V., Llamas-Adan, M., Arca-Lafuente, S., Martin-Carbonero, L., de los Santos, I., Jimenez Sousa, M. A., Resino, S., Berenguer, J., Madrid, R., Fernandez-Rodriguez, A., Briz, V.. 2024-03-13. Changes in the senescence profile and immune checkpoints in HIV-infected individuals after COVID-19. https://doi.org/10.1101/2024.03.12.584682

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