Flipped Inflammatory Time and the Role of Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2: Optimizing Tocilizumab Against Coronavirus Disease 2019

• Published in: The Journal of infectious diseases Vol. 226; no. 1; pp. 1 - 5
• Main Authors: Guisado-Vasco, Pablo, Aguarles Gorines, José, Carralón González, María M, Sotres Fernández, Gabriel, Carnevali Ruiz, Daniel
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 12.08.2022
• Subjects: Autoantibodies; Clinical trials; Coronaviruses; COVID-19; Immune system; Immunopathogenesis; Inflammation; Innate immunity; Interferon; Interleukin 6; Monoclonal antibodies; Patients; Seroconversion; Severe acute respiratory syndrome coronavirus 2; Spike protein; COVID-19; SARS-CoV-2; tocilizumab; IL-6 inhibition; therapy
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiac090

Abstract Use of interleukin (IL-6) inhibitors has become one of the most complicated clinical issues in treating coronavirus disease 2019 (COVID-19). Recently, randomized open-label platform trials have found that IL-6 inhibitors have a beneficial effect on mortality in severe COVID-19. However, several questions arise around their mechanism of action in this disease, as well as how, when, and at which dose they should be used. IL-6 has both proinflammatory and anti-inflammatory effects, which may modulate the course of COVID-19, whose immunopathogenesis is driven by the innate immune system, autoantibodies, and interferon. Given that patients with delayed seroconversion against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein would be at the highest risk of complications beyond the second week of disease, we propose that considering patient serostatus at admission could optimize the use of IL-6 inhibitors in COVID-19. We predict that the net treatment benefits could be higher in the subgroup of patients with delayed seroconversion as compared to those who seroconvert more rapidly after SARS-CoV-2 infection. We propose that treatment with interleukin 6 inhibitors in COVID-19 can be guided by the patient’s serostatus at hospital admission, becoming higher in the subgroup of patients with delayed seroconversion as compared to those who seroconvert more rapidly after SARS-CoV-2 infection.