| Popis: |
Although originally considered a situation of cytokine storm, severe coronavirus disease (COVID-19) and COVID-19 acute respiratory distress syndrome (ARDS) seem to have considerable heterogeneity. Pathogenesis is driven by monocytes, levels of which are increased in the blood and which migrate from the circulation to the alveolar space to propagate pro-inflammatory phenomena. At the stage of severe illness, the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome is stimulated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, priming of monocytes for pro-interleukin-1β (pro-IL-1β) takes place through the action of alarmins, which are released in the body of the human host. When ARDS develops, patients present either with macrophage activation syndrome or with complex immune dysregulation. Complex immune dysregulation is characterized by decreased expression of the human leukocyte antigen (HLA)-DR on CD14-monocytes with simultaneous maintenance of monocyte capacity for the production of pro-inflammatory cytokines. The concept of severe COVID-19 as a situation of cytokine storm led early to the use of anakinra and tocilizumab as strategies aimed at blocking the deleterious effect of excess production of IL-1 and of IL-6, respectively. A PubMed search as of February 15th 2021 retrieved 12 studies of patient cohorts comparing the clinical efficacy of these drugs versus comparator groups receiving standard-of-care; in six studies, tocilizumab was administered and treatment benefit was reported in three; and in six studies, anakinra was administered and treatment benefit was reported in five. The lack of homogeneity in clinical efficacy underlines the need to follow a strategy of personalized treatment guided by biomarkers. |
