Abstract
Background
In Covid-19, profound systemic inflammatory responses are accompanied by both metabolic risk factors for severity and, separately, metabolic mechanisms have been shown to underly disease progression. It is unknown whether this reflects similar situations in sepsis or is a unique characteristic of Covid-19.
Aims
Define the immunometabolic signature of Covid-19.
Methods
65 patients with Covid-19,19 patients with sepsis and 14 healthy controls were recruited and sampled for plasma, serum and peripheral blood mononuclear cells (PBMCs) through 10 days of critical illness. Metabotyping was performed using the Biocrates p180 kit and multiplex cytokine profiling undertaken. PBMCs underwent phenotyping by flow cytometry. Immune and metabolic readouts were integrated and underwent pathway analysis.
Results
Phopsphatidylcholines (PC) are reduced in Covid-19 but greater than in sepsis. Compared to controls, tryptophan is reduced in Covid-19 and inversely correlated with the severity of the disease and IFN-ɣ concentrations, conversely the kyneurine and kyneurine/tryptophan ratio increased in the most severe cases. These metabolic changes were consistent through 2 pandemic waves in our centre. PD-L1 expression in CD8+ T cells, Tregs and CD14+ monocytes was increased in Covid-19 compared to controls.
Conclusions
In our cohort, Covid-19 is associated with monocytopenia, increased CD14+ and Treg PD-L1 expression correlating with IFN-ɣ plasma concentration and disease severity (SOFA score). The latter is also associated with metabolic derangements of Tryptophan, LPC 16:0 and PCs. Lipid metabolism, in particular phosphatidylcholines and lysophosphatidylcolines, seems strictly linked to immune response in Covid-19. Our results support the hypothesis that IFN-ɣ -PD-L1 axis might be involved in the cytokine release syndrome typical of severe Covid-19 and the phenomenon persisted through multiple pandemic waves despite use of immunomodulation.
【저자키워드】 COVID-19, immunometabolism, Tryptophan, immune checkpoint, Phosphatidylcholine, 【초록키워드】 immune response, pandemic, severity, disease severity, CD8+ T cells, Sepsis, cytokine, flow cytometry, metabolism, Pathway analysis, Cytokine release syndrome, PD-L1, Peripheral blood, Disease progression, serum, Cohort, Patient, severe cases, PBMC, plasma, multiplex, characteristic, expression, change, Critical, mechanism, Treg, Hypothesis, Lipid, PBMCs, mononuclear cell, SOFA score, Support, plasma concentration, healthy control, systemic inflammatory response, CD14+, controls, concentrations, monocytopenia, Result, greater, shown, involved, recruited, the disease, was performed, reduced, unique, correlated, reflect, accompanied, CD14+ monocyte, metabolic derangement, metabolic risk factor, was increased, 【제목키워드】 Sepsis, Analysis, cause,