EVOLUTION OF CRITICAL IMMUNE PARAMETERS IN HOSPITALIZED COVID-19 PATIENTS

MAZZOCCO, YL; BERGERO, G; DEL ROSSO, S; EBERHARDT, N; CASTELLANO, A; OCHOA, D; SAKA, A; SOLA, C; VILLADA, S; BOCCO, JL; AOKI, MP

Conferencia; Reunión Conjunta SAIC SAI SAFIS. Noviembre 2022; 2022

EVOLUTION OF CRITICAL IMMUNE PARAMETERS IN HOSPITALIZED COVID-19 PATIENTSYanina Luciana Mazzocco1;2, Gastón Bergero1;2, Sebastián Del Rosso1;2, Natalia Eberhardt2, Andrés Castellaro1,2, Denise Ochoa1,2, Alex Saka1,2, Claudia Sola1,2, Sofía Villada3, José Luis Bocco1,2 , Maria Pilar Aoki1,2. 1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina, 2Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET, Córdoba, Argentina, 3Hospital Privado, Córdoba, Argentina. We have reported that IL-6 released early after a systemic infection exerts a potent anti-oxidative effect that regulates the lethal release of nitric oxide (NO). Recently, we demonstrated that monocyte-derived NO causes protein nitration of CD8+ T-cells limiting CD8-cytotoxic effector functions. The present work aims to determine the evolution of the immune response in hospitalized COVID-19 patients focusing on IL-6 and NO production. To this aim, we comparatively study the immune profile of peripheral blood samples from 27 adult patients (18 male and 9 female) obtained at hospital admission and discharge with moderate pneumonia and positive serology for SARS-CoV2 infection. Patients with No-COVID-19 pneumonia (6 male and 5 female) were used as control. Univariate linear models adjusted for potential confounders showed that higher levels of IL-6, TNF-α, IL-8, and IL-10 significant predicted longer hospitalization time. At admission, NO production by CD14+CD16+ monocytes inversely correlated to IL-6 levels while, at discharge, this correlation was reverted for both NO+CD14+CD16+ and NO+CD14++CD16- cell populations. In line with this, principal component analysis showed that NO production properly discriminated COVID patients from controls. Compared to discharge, at admission there was a higher frequency of nitrated (NT) CD8+ T-cells (p=0.008), and the NT rate positively correlated with NO+ monocytes. Interestingly, NO production, and NT label in T-cells were restored at discharge. Our results suggest that in mild COVID-19, the increase in IL-6 levels could be critical to controlling NO production and balancing the oxidative environment. Moreover, the data highlight that NO could have a dual role in acting as a microbicidal metabolite and regulating CD8+ T-cell function. The parameters are restored at the time of discharge and seem related to an effective recovery. These unreported data help to depict the etiopathogenic mechanisms associated with COVID-19 outcome.