Outcome predictors in COVID-19: An analysis of emergent systemic inflammation indices in Mexican population.

Introduction: The systemic viral disease caused by the SARS-CoV-2 called coronavirus disease 2019 (COVID-19) continues to be a public health problem worldwide. Objective: This study is aimed to evaluate the association and predictive value of indices of systemic inflammation with severity and non-survival of COVID-19 in Mexican patients. Materials and Methods: A retrospective study was carried out on 807 subjects with a confirmed diagnosis of COVID-19. Clinical characteristics, acute respiratory distress syndrome (ARDS), severity according to PaO2/FiO2 ratio, invasive mechanical ventilation (IMV), and non-survival outcome were considered to assess the predictive value and the association of 11 systemic inflammatory indices derived from hematological parameters analyzed at the hospital admission of patients. The receiver operating characteristics curve was applied to determine the thresholds for 11 biomarkers, and their prognostic values were assessed via the Kaplan-Meier method. Results: 26% of the studied subjects showed COVID-19 severe (PaO2/FiO2 ratio ≤ 100), 82.4% required IMV, and 39.2% were non-survival. The indices NHL, NLR, RDW, dNLR, and SIRI displayed predictive values for severe COVID-19 and non-survival. NHL, SIRI, and NLR showed predictive value for IMV. The cut-off values for RDW (OR = 1.85, p < 0.001), NHL (OR = 1.67, p = 0.004) and NLR (OR = 1.56, p = 0.012) were mainly associated with severe COVID-19. NHL (OR = 3.07, p < 0.001), AISI (OR = 2.64, p < 0.001) and SIRI (OR = 2.51, p < 0.001) were associated with IMV support, while for non-survival the main indices associated were NHL (OR = 2.65, p < 0.001), NLR (OR = 2.26, p < 0.001), dNLR (OR = 1.92, p < 0.001), SIRI (OR = 1.67, p = 0.002) and SII (OR = 1.50, p = 0.010). The patients with an RDW, PLR, NLR, dNLR, MLR, SII, and NHL above the cut-off had a survival probability of COVID-19 50% lower, with an estimated mean survival time of 40 days. Conclusion: The emergent systemic inflammation indices NHL, NLR, RDW, SII, and SIRI have a predictive power of severe COVID-19, IMV support, and low survival probability during hospitalization by COVID-19 in Mexican patients.

IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19.

Interferons (IFNs) are a group of cytokines with antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities. Type I IFNs amplify and propagate the antiviral response by interacting with their receptors, IFNAR1 and IFNAR2. In COVID-19, the IFNAR2 (interferon alpha and beta receptor subunit 2) gene has been associated with the severity of the disease, but the soluble receptor (sIFNAR2) levels have not been investigated. We aimed to evaluate the association of IFNAR2 variants (rs2236757, rs1051393, rs3153, rs2834158, and rs2229207) with COVID-19 mortality and to assess if there was a relation between the genetic variants and/or the clinical outcome, with the levels of sIFNAR2 in plasma samples from hospitalized individuals with severe COVID-19. We included 1,202 subjects with severe COVID-19. The genetic variants were determined by employing Taqman® assays. The levels of sIFNAR2 were determined with ELISA in plasma samples from a subgroup of 351 individuals. The rs2236757, rs3153, rs1051393, and rs2834158 variants were associated with mortality risk among patients with severe COVID-19. Higher levels of sIFNAR2 were observed in survivors of COVID-19 compared to the group of non-survivors, which was not related to the studied IFNAR2 genetic variants. IFNAR2, both gene, and soluble protein, are relevant in the clinical outcome of patients hospitalized with severe COVID-19.

Circulating Levels of PD-L1, TIM-3 and MMP-7 Are Promising Biomarkers to Differentiate COVID-19 Patients That Require Invasive Mechanical Ventilation.

Background: COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Many COVID-19 patients require invasive mechanical ventilation (IMV) while others, even with acute respiratory failure, do not (NIMV). Therefore, we aimed to evaluate serum levels of MMP-7 and molecules related to exhausted T-cells as potential biomarkers to differentiate between IMV and NIMV patients. Methods: 105 patients diagnosed with COVID-19 and confirmed by RT-PCR for SARS-CoV-2 were divided into two groups according to the requirement for IMV. Serum levels of sPD-L1, sPD-L2, sTIM-3, sGal-9 and sMMP-7 were quantified by ELISA and correlated with clinical data. Twelve patients were followed up after eight months to compare the levels of the biomarkers between acute disease and post-COVID-19. Results: IMV patients experienced a lower PaO2/FiO2 (p < 0.0001) and a longer hospital stay (p < 0.0001), and exhibited higher levels of sPD-L1 (p < 0.05), sTIM-3 (p < 0.01) and sMMP-7 (p < 0.0001) when compared with NIMV patients. According to a ROC analysis, sMMP-7 had the highest sensitivity (78%) and specificity (76%) with a cut point of 4.5 ng/mL, followed by sTIM-3 and sPD-L1. Eight months post-COVID-19, IMV patients displayed a significant decrease in the initially high levels of sPD-L1, sTIM-3 and sGal-9, while sPD-L2 was increased, and sMMP-7 was unchanged. Conclusion: Circulating levels of sPD-L1, sTIM-3 and sMMP-7 are potential biomarkers of disease severity to distinguish patients requiring IMV. MMP-7 could also be a marker for the persistence of lung lesions post-COVID-19.