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Discrimination of COVID-19 From Inflammation-Induced Cytokine Storm Syndromes Using Disease-Related Blood Biomarkers.
Kessel, Christoph; Vollenberg, Richard; Masjosthusmann, Katja; Hinze, Claas; Wittkowski, Helmut; Debaugnies, France; Nagant, Carole; Corazza, Francis; Vély, Frédéric; Kaplanski, Gilles; Girard-Guyonvarc'h, Charlotte; Gabay, Cem; Schmidt, Hartmut; Foell, Dirk; Tepasse, Phil-Robin.
  • Kessel C; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
  • Vollenberg R; Department of Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, Muenster, Germany.
  • Masjosthusmann K; Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany.
  • Hinze C; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
  • Wittkowski H; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
  • Debaugnies F; Laboratory of Translational Research, Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels, Belgium and Medical Biology Department, Laboratoire National de Santé, Dudelange, Luxembourg.
  • Nagant C; Immunology Department, LHUB-ULB, Université Libre de Bruxelles, Brussels, Belgium.
  • Corazza F; Laboratory of Translational Research, Centre Hospitalier Universitaire Brugmann and Immunology Department, LHUB-ULB, Université Libre de Bruxelles, Brussels, Belgium.
  • Vély F; Aix Marseille Université, CNRS, INSERM, CIML and Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Immunology, Marseille Immunopole, Marseilles, France.
  • Kaplanski G; Assistance Publique-Hôpitaux de Marseille, Centre Hospitalier Universitaire Conception, Service de Médecine Interne et Immunologie Clinique, Aix-Marseille Universitô and Center for Cardiovascular Research and Nutrition, Aix-Marseille Université, INSERM UMRS1263, Marseilles, France.
  • Girard-Guyonvarc'h C; Division of Rheumatology, Department of Medicine, University Hospital of GenevaDepartment of Medicine, University Hospital of Geneva, University of Geneva, Geneva, Switzerland.
  • Gabay C; Division of Rheumatology, Department of Medicine, University Hospital of GenevaDepartment of Medicine, University Hospital of Geneva, University of Geneva, Geneva, Switzerland.
  • Schmidt H; Department of Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, Muenster, Germany.
  • Foell D; Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
  • Tepasse PR; Department of Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Muenster, Muenster, Germany.
Arthritis Rheumatol ; 73(10): 1791-1799, 2021 10.
Article in English | MEDLINE | ID: covidwho-1391545
ABSTRACT

OBJECTIVE:

Infection with the novel coronavirus SARS-CoV-2 triggers severe illness with high mortality in a subgroup of patients. Such a critical course of COVID-19 is thought to be associated with the development of cytokine storm, a condition seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (HLH). However, specific data demonstrating a clear association of cytokine storm with severe COVID-19 are still lacking. The aim of this study was to directly address whether immune activation in COVID-19 does indeed mimic the conditions found in these classic cytokine storm syndromes.

METHODS:

Levels of 22 biomarkers were quantified in serum samples from patients with COVID-19 (n = 30 patients, n = 83 longitudinal samples in total), patients with secondary HLH/MAS (n = 50), and healthy controls (n = 9). Measurements were performed using bead array assays and single-marker enzyme-linked immunosorbent assay. Serum biomarker levels were assessed for correlations with disease outcome.

RESULTS:

In patients with secondary HLH/MAS, we observed pronounced activation of the interleukin-18 (IL-18)-interferon-γ axis, increased serum levels of IL-1 receptor antagonist, intercellular adhesion molecule 1, and IL-8, and strongly reduced levels of soluble Fas ligand in the course of SARS-CoV-2 infection. These observations appeared to discriminate immune dysregulation in critical COVID-19 from the well-recognized characteristics of other cytokine storm syndromes.

CONCLUSION:

Serum biomarker profiles clearly separate COVID-19 from MAS or secondary HLH in terms of distinguishing the severe systemic hyperinflammation that occurs following SARS-CoV-2 infection. These findings could be useful in determining the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID-19.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-8 / Interleukin-18 / Lymphohistiocytosis, Hemophagocytic / Macrophage Activation Syndrome / Cytokine Release Syndrome / COVID-19 Type of study: Diagnostic study / Observational study / Prognostic study Topics: Long Covid Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Arthritis Rheumatol Year: 2021 Document Type: Article Affiliation country: Art.41763

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-8 / Interleukin-18 / Lymphohistiocytosis, Hemophagocytic / Macrophage Activation Syndrome / Cytokine Release Syndrome / COVID-19 Type of study: Diagnostic study / Observational study / Prognostic study Topics: Long Covid Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Arthritis Rheumatol Year: 2021 Document Type: Article Affiliation country: Art.41763