Circulating Proteins Associated with Anti-IL6 Receptor Therapeutic Resistance in the Sera of Patients with Severe COVID-19

• Published in: Journal of proteome research Vol. 23; no. 11; pp. 5001 - 5015
• Main Authors: Michot, Jean-Marie, Dozio, Vito, Rohmer, Julien, Pommeret, Fanny, Roumier, Mathilde, Yu, Haochen, Sklodowki, Kamil, Danlos, François-Xavier, Ouali, Kaissa, Kishazi, Edina, Naigeon, Marie, Griscelli, Franck, Gachot, Bertrand, Groh, Matthieu, Bacciarello, Giulia, Stoclin, Annabelle, Willekens, Christophe, Sakkal, Madona, Bayle, Arnaud, Zitvogel, Laurence, Silvin, Aymeric, Soria, Jean-Charles, Barlesi, Fabrice, Beeler, Kristina, André, Fabrice, Vasse, Marc, Chaput, Nathalie, Ackermann, Felix, Escher, Claudia, Marabelle, Aurélien
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.11.2024
• Subjects: acute respiratory distress syndrome; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - therapeutic use; Blood Proteins - analysis; Blood Proteins - metabolism; blood serum; Chromatography, Liquid - methods; complement; COVID-19 - blood; COVID-19 - mortality; COVID-19 - virology; COVID-19 Drug Treatment; COVID-19 infection; cytokines; distress; drugs; Female; Humans; Interleukin-6 - blood; intravenous injection; liquid chromatography; Male; Middle Aged; mortality; patients; physiological state; proteome; Proteome - analysis; proteomics; Proteomics - methods; Receptors, Interleukin-6 - antagonists & inhibitors; Receptors, Interleukin-6 - blood; SARS-CoV-2 - physiology; viruses; COVID-19; candidate proteins; proteomics; thrombospondin-1; anti-interleukin 6 receptor therapy; calprotectin
• ISSN: 1535-3893; 1535-3907; 1535-3907
• DOI: 10.1021/acs.jproteome.2c00422

Circulating proteomes provide a snapshot of the physiological state of a human organism responding to pathogenic challenges and drug interventions. The outcomes of patients with COVID-19 and acute respiratory distress syndrome triggered by the SARS-CoV2 virus remain uncertain. Tocilizumab is an anti-interleukin-6 treatment that exerts encouraging clinical activity by controlling the cytokine storm and improving respiratory distress in patients with COVID-19. We investigate the biological determinants of therapeutic outcomes after tocilizumab treatment. Overall, 28 patients hospitalized due to severe COVID-19 who were treated with tocilizumab intravenously were included in this study. Sera were collected before and after tocilizumab, and the patient’s outcome was evaluated until day 30 post-tocilizumab infusion for favorable therapeutic response to tocilizumab and mortality. Hyperreaction monitoring measurements by liquid chromatography–mass spectrometry-based proteomic analysis with data-independent acquisition quantified 510 proteins and 7019 peptides in the serum of patients. Alterations in the serum proteome reflect COVID-19 outcomes in patients treated with tocilizumab. Our results suggested that circulating proteins associated with the most significant prognostic impact belonged to the complement system, platelet degranulation, acute-phase proteins, and the Fc-epsilon receptor signaling pathway. Among these, upregulation of the complement system by activation of the classical pathway was associated with poor response to tocilizumab, and upregulation of Fc-epsilon receptor signaling was associated with lower mortality.