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
Affiliations
Johannes J. Kovarik
Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna 1090, Austria
Andrea Bileck
Joint Metabolome Facility, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria
Gerhard Hagn
Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria
Samuel M. Meier-Menches
Joint Metabolome Facility, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria
Tobias Frey
Department of Laboratory Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria
Anna Kaempf
Department of Laboratory Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria
Marlene Hollenstein
Department of Laboratory Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria
Tarik Shoumariyeh
Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna 1090, Austria
Lukas Skos
Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria
Birgit Reiter
Department of Laboratory Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria
Marlene C. Gerner
Division of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna, Austria
Andreas Spannbauer
Department of Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria
Ena Hasimbegovic
Department of Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria
Doreen Schmidl
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Gerhard Garhöfer
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Mariann Gyöngyösi
Department of Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria; Corresponding author
Klaus G. Schmetterer
Department of Laboratory Medicine, Medical University of Vienna, Waehringer Gürtel 18-20, Vienna, Austria; Corresponding author
Christopher Gerner
Joint Metabolome Facility, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria; Corresponding author
Summary: 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.
