Jeremy D Ward1, Caleb Cornaby2, John Schmitz1,2. 1. Department of Pathology & Laboratory Medicine, UNC School of Medicine, Chapel Hill, NC, USA. 2. Immunology, Histocompatibility and Immunogenetics Laboratories/McLendon Clinical Laboratories UNC Hospitals, Chapel Hill, NC, USA.
Abstract
Background: SARS-CoV-2 is a novel positive-sense single stranded RNA virus that has caused a recent pandemic. Most patients have a mild disease course, while approximately 20 percent have moderate-to-severe disease, often requiring hospitalization and, in some cases, care in the intensive care unit. Results: By investigating a perceived increased rate of indeterminate QuantiFERON®-TB Gold Plus results in hospitalized COVID patients, we demonstrate that severely ill COVID-19 patients have at least a 6-fold reduction of interferon-gamma (IFN-γ) levels compared to control patients. What is more, over sixty percent of these severely ill COVID-19 patients' peripheral T-cells were found to be unable to produce measurable IFN-γ when stimulated with phytohemagglutinin (PHA), a potent IFN-γ mitogen, reflected by an indeterminate QuantiFERON®-TB Gold Plus. This defect of IFN-γ production was independent of absolute lymphocyte counts and immunosuppressive therapy. It was associated with increased levels of IL-6, which was a predictor of patient outcomes for our cohort when measured early in the course of disease. Finally, in a subset of COVID-19 patients, we found elevated IL-10 levels, in addition to IL-6 elevation. Conclusions: In addition to finding a significant limitation of IGRA testing severely ill COVID-19 patients, these data provide evidence that many of these patients demonstrate a focused Th2 immune response with inhibition of IFN-γ signaling and, in many cases, significant elevations of IL-6.
Background: SARS-CoV-2 is a novel positive-sense single stranded RNA virus that has caused a recent pandemic. Most patients have a mild disease course, while approximately 20 percent have moderate-to-severe disease, often requiring hospitalization and, in some cases, care in the intensive care unit. Results: By investigating a perceived increased rate of indeterminate QuantiFERON®-TB Gold Plus results in hospitalized COVIDpatients, we demonstrate that severely ill COVID-19patients have at least a 6-fold reduction of interferon-gamma (IFN-γ) levels compared to control patients. What is more, over sixty percent of these severely ill COVID-19patients' peripheral T-cells were found to be unable to produce measurable IFN-γ when stimulated with phytohemagglutinin (PHA), a potent IFN-γ mitogen, reflected by an indeterminate QuantiFERON®-TB Gold Plus. This defect of IFN-γ production was independent of absolute lymphocyte counts and immunosuppressive therapy. It was associated with increased levels of IL-6, which was a predictor of patient outcomes for our cohort when measured early in the course of disease. Finally, in a subset of COVID-19patients, we found elevated IL-10 levels, in addition to IL-6 elevation. Conclusions: In addition to finding a significant limitation of IGRA testing severely ill COVID-19patients, these data provide evidence that many of these patients demonstrate a focused Th2 immune response with inhibition of IFN-γ signaling and, in many cases, significant elevations of IL-6.
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