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An Interplay between Oxidative Stress (Lactate Dehydrogenase) and Inflammation (Anisocytosis) Mediates COVID-19 Severity Defined by Routine Clinical Markers.

ABSTRACT: Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO₂) and the putative interaction with inflammation. The investigation enrolled 1808 patients (mean age of 68 and 60% male) with COVID-19 from the HM Hospitals database. To explore interactions, a regression model and mediation analyses were performed. The patients with lower SaO₂ presented lymphopenia and higher values of neutrophils-to-lymphocytes ratio and on the anisocytosis coefficient. The regression model showed an interaction between LDH and anisocytosis, suggesting that high levels of LDH (>544 U/L) and an anisocytosis coefficient higher than 10% can impact SaO₂ in COVID-19 patients. Moreover, analysis revealed that LDH mediated 41% (p value = 0.001) of the effect of anisocytosis on SaO₂ in this cohort. This investigation revealed that the oxidative stress marker LDH and the interaction with anisocytosis have an important role in the severity of COVID-19 infection and should be considered for the management and treatment of the oxidative phenomena concerning this within a precision medicine strategy.

SUBMITTER: Alonso-Bernaldez M

PROVIDER: S-EPMC9951932 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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An Interplay between Oxidative Stress (Lactate Dehydrogenase) and Inflammation (Anisocytosis) Mediates COVID-19 Severity Defined by Routine Clinical Markers.

Alonso-Bernáldez Marta M Cuevas-Sierra Amanda A Micó Víctor V Higuera-Gómez Andrea A Ramos-Lopez Omar O Daimiel Lidia L Dávalos Alberto A Martínez-Urbistondo María M Moreno-Torres Víctor V Ramirez de Molina Ana A Vargas Juan Antonio JA Martinez J Alfredo JA

Antioxidants (Basel, Switzerland) 20230120 2

Viral infections activate the innate immune response and the secretion of inflammatory cytokines. They also alter oxidative stress markers, which potentially can have an involvement in the pathogenesis of the disease. The aim of this research was to study the role of the oxidative stress process assessed through lactate dehydrogenase (LDH) on the severity of COVID-19 measured by oxygen saturation (SaO<sub>2</sub>) and the putative interaction with inflammation. The investigation enrolled 1808 pa ...[more]

PMID: 36829793

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Project description:BackgroundTreated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy.MethodsWe performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL < 130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy. A complete blood count and biomarkers of inflammation and immune activation/exhaustion were measured in peripheral blood at entry and after 24 and 48 weeks. Associations with RDW were estimated using linear regression and linear mixed models.ResultsThe median age (IQR) for the cohort at enrollment was 46 (40-53) years; 78% were male and 68% were African American. The median RDW for the cohort was 13.4% (12.9-14.0). Compared with the lowest RDW tertile, patients in the highest tertile were less likely to be male, and more likely to be African American, have lower hemoglobin, lower mean corpuscular volume, and higher platelet counts (all P < 0.05). At baseline, RDW weakly correlated with C-reactive protein (r = 0.196), d-dimer (r = 0.214), fibrinogen (r = 0.192), IL-6 (r = 0.257), CD4+DR+38+ T cells (r = 0.195), and CD4+PD1+ T cells (r = 0.227), all P < 0.05. Only IL-6, CD4+38+DR+ T cells, and CD4+PD1+ T_cells remained associated after adjustment for clinical factors known to affect RDW in the general population. Over 48 weeks, RDW did not change and there was no significant effect of statin (P = 0.45). After adjustment for clinical parameters, RDW remained positively associated with CD4+38+DR+ and CD4+PD1+ T cells across all time points (P = 0.05).ConclusionIn this population of treated HIV+ subjects, anisocytosis was associated with biomarkers of inflammation and T-cell activation/exhaustion over time and independent of clinical confounders. Therefore, RDW may be a useful prognostic biomarker of cardiovascular risk that partially reflects chronic inflammation and immune exhaustion in PLHIV receiving antiretroviral therapy.

Dataset Information

An Interplay between Oxidative Stress (Lactate Dehydrogenase) and Inflammation (Anisocytosis) Mediates COVID-19 Severity Defined by Routine Clinical Markers.

Publications

An Interplay between Oxidative Stress (Lactate Dehydrogenase) and Inflammation (Anisocytosis) Mediates COVID-19 Severity Defined by Routine Clinical Markers.

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