Immunometabolic analysis shows a distinct cyto-metabotype in Covid-19 compared to sepsis from other causes

Francesca M Trovato; Salma Mujib; Ellen Jerome; Anna Cavazza; Phillip Morgan; John Smith; Maria Theresa Depante; Kevin O'Reilly; James Luxton; Tracey Mare; Salvatore Napoli; Mark Jw McPhail

doi:10.1016/j.heliyon.2022.e09733

Immunometabolic analysis shows a distinct cyto-metabotype in Covid-19 compared to sepsis from other causes

Heliyon. 2022 Jun;8(6):e09733. doi: 10.1016/j.heliyon.2022.e09733. Epub 2022 Jun 24.

Authors

Francesca M Trovato^{1

2}, Salma Mujib¹, Ellen Jerome^{1

2}, Anna Cavazza^{1

2}, Phillip Morgan¹, John Smith³, Maria Theresa Depante³, Kevin O'Reilly³, James Luxton⁴, Tracey Mare⁴, Salvatore Napoli¹, Mark Jw McPhail^{1

2}

Affiliations

¹ Institute of Liver Studies, King's College Hospital, London, United Kingdom.
² Department of Inflammation BIology, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, Kings College London, United Kingdom.
³ Anaesthetics, Critical Care, Emergency and Trauma Research Delivery Unit, Kings College Hospital, London, United Kingdom.
⁴ Contract R&D Department (Viapath), Kings College Hospital, London, United Kingdom.

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.

Keywords: Covid-19; Immune checkpoint; Immunometabolism; Phosphatidylcholine; Tryptophan.