Storm of soluble immune checkpoints associated with disease severity of COVID-19

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

“…The continuous expression of inhibitory markers such as programmed cell death protein-1 (PD-1) and T-cell immunoglobulin domain and mucin domain protein-3 (TIM-3) by T-cells and NK cells as well as their overall reduced polyfunctionality and cytotoxicity argue in favor for their exhaustion during the infection course [ 41 , 42 ]. Kong et al assessed levels of soluble forms of checkpoint molecules in patients with COVID-19 [ 43 ]. According to the current knowledge, soluble forms may reflect the degree of membrane expression of the corresponding checkpoint proteins [ 44 ].…”

“…According to the current knowledge, soluble forms may reflect the degree of membrane expression of the corresponding checkpoint proteins [ 44 ]. Kong et al found that levels of 13 out of 14 tested molecules were significantly higher in patients with severe COVID-19 than in those with mild, moderate, or asymptomatic infection [ 43 ]. Levels of 8 soluble checkpoint molecules including PD-1 and TIM-3 were negatively correlated with absolute counts of total, CD4, and CD8 T cells but not neutrophil counts, and TIM-3 was identified to have good predictive value for COVID-19 progression.…”

Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report

“…According to several authors, TIM-3 and Gal-9 have shown the ability to induce T-cell exhaustion and reduce CD8 + effector cells [20-22]. In line, some authors have proposed the association of various ICs including soluble TIM-3 with COVID-19 severity [9]. Our data suggest that soluble Gal-9 and TIM-3 expression on T cells could be biomarkers for those COVID-19 patients at high risk of suffering from sepsis and secondary infections.…”

“…These data suggest an impairment of the immune system, allowing secondary infections [5, 6]. T-cell exhaustion and increased inhibitory receptor expression on peripheral T cells have been reported in this disease [7-9]. Moreover, although there is evidence of T-cell activation in COVID-19 patients [10], several studies have found polyfunctionality or cytotoxicity decreases [6, 11].…”

Interrogation of the cellular immunome of cancer patients with regard to the COVID-19 pandemic

“…An investigation of soluble checkpoints in patients with confirmed COVID-19 infection found that increased baseline levels of sIDO, s4-1BB, sTIM-3, and sCD27 were associated with higher disease severity rates and longer ICU stays. 34 This may reflect complex dysregulation of the T-cell responses needed to overcome SARS-CoV-2 infection through a combination of hyperactivation followed by exhaustion. 28 A study of inflammatory cytokines in over 1400 hospitalized patients found initial levels of both IL-6 and TNF-α to be independent predictors of disease severity and mortality.…”