Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection

Abstract

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery–validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines’ quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933–0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127–80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846–0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover–validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.

Lipid peroxidation as a hallmark of severity in COVID-19 patients

“…A total of 136 patients were registered in the study. Clinical characteristics of patients are shown in Discovery cohort panel of Table 1 in Tamayo-Velasco et al [ 21 ]. In terms of age, there were no differences.…”

“…Differences between groups were assessed as described in Tamayo-Velasco A et al [ 21 ]. Differences in oxidative stress molecules' levels between groups were assessed using the Mann Whitney U test.…”

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…Other critical hub-high traffic genes in the blue module included EP300 ( 146 , 147 ), CDK1 ( 4 , 148 ), VEGFA ( 149 – 151 ), CTNNB1 ( 151 , 152 ), IL10 ( 9 , 153 – 155 ), SOCS1 , SOCS3 ( 156 ), SIRT1 ( 157 , 158 ), TFRC ( 159 – 161 ), HSP90AB1 ( 162 ), CYCS ( 163 ), EZR ( 164 ), TNFAIP3 , ICAM1 ( 10 ), and PIK3R1 ( 139 ) as well as TFs such as ATF4 ( 165 ), ATF3 ( 166 , 167 ), and BCL6 ( 152 ) which have important roles in pathogenesis of SARS-CoV-2, and some of which are potential therapeutic targets. For instance, SOCS1 / 3 antagonists may be prophylactic or therapeutic against the COVID-19 pandemic ( 156 ).…”

Children’s Privilege in COVID-19: The Protective Role of the Juvenile Lung Morphometry and Ventilatory Pattern on Airborne SARS-CoV-2 Transmission to Respiratory Epithelial Barriers and Disease Severity

“…Alveolar macrophage activation and neutrophil recruitment are first key events of innate immune activation in response to SARS-CoV-2 and the presence of alveolar damage-associated molecular patterns. A very recent study identified IP-10 (CXCL10) as key predictive cytokine for disease progression to severe courses of illness [45] with LRT involvement. Of note, IP-10 is a chemokine for recruitment of macrophages in response to viral invasion and tissue damage, but also acts as regulator of cell growth and proliferation [46].…”