A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome

Johannes J Kovarik; Andrea Bileck; Gerhard Hagn; Samuel M Meier-Menches; Tobias Frey; Anna Kaempf; Marlene Hollenstein; Tarik Shoumariyeh; Lukas Skos; Birgit Reiter; Marlene C Gerner; Andreas Spannbauer; Ena Hasimbegovic; Doreen Schmidl; Gerhard Garhöfer; Mariann Gyöngyösi; Klaus G Schmetterer; Christopher Gerner

doi:10.1016/j.isci.2022.105717

A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome

iScience. 2023 Jan 20;26(1):105717. doi: 10.1016/j.isci.2022.105717. Epub 2022 Dec 5.

Authors

Johannes J Kovarik¹, Andrea Bileck^{2

3}, Gerhard Hagn³, Samuel M Meier-Menches^{2

3}, Tobias Frey⁴, Anna Kaempf⁴, Marlene Hollenstein⁴, Tarik Shoumariyeh¹, Lukas Skos³, Birgit Reiter⁴, Marlene C Gerner⁵, Andreas Spannbauer⁶, Ena Hasimbegovic⁶, Doreen Schmidl⁷, Gerhard Garhöfer⁷, Mariann Gyöngyösi⁶, Klaus G Schmetterer⁴, Christopher Gerner^{2

3}

Affiliations

¹ Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna 1090, Austria.
² Joint Metabolome Facility, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria.
³ Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria.
⁴ Department of Laboratory Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria.
⁵ Division of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna, Austria.
⁶ Department of Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria.
⁷ Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

Abstract

To investigate long COVID-19 syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3 months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as patients with long COVID-19 syndrome (LCS). Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to patients with LCS. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS. High levels of anti-inflammatory oxylipins including omega-3 fatty acids in LCS were detected by eicosadomics, whereas targeted metabolic profiling indicated high levels of anti-inflammatory osmolytes taurine and hypaphorine, but low amino acid and triglyceride levels and deregulated acylcarnitines. A model considering alternatively polarized macrophages as a major contributor to these molecular alterations is presented.

Keywords: Immunology; immune response; omics.