Pala Daniele, Pistis Marco
Unit of Clinical Pharmacology, University Hospital Agency of Cagliari, Cagliari, Italy.
Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Front Pharmacol. 2021 Mar 9;12:622554. doi: 10.3389/fphar.2021.622554. eCollection 2021.
SARS-CoV-2 infection stimulates a complex activation of the immune system. Eosinophils belong to the host's defense equipment against respiratory viruses. In the first phase of the infection, eosinophils contribution is probably appropriate and beneficial, as they facilitate the suppression of the viral replication. However, in severe COVID-19 patients, during the second and third phases of the disease, eosinophils may participate in a maladaptive immune response and directly contribute to immunopathology. In fact, in severe patients, the immune response is prevalently T helper 1 type, but T helper 2 is also present. Eosinophils' expansion and activation are stimulated by Type 2 cytokines, especially IL-5. Moreover, bronchial asthma, in which eosinophils play a central role, seems not to be a major risk factor for severe COVID-19. Among possible explanations, asthmatic patients are often treated with corticosteroids, which have been demonstrated to reduce the progression to critical COVID-19 in hospitalized patients. In addition to steroids, severe asthmatic patients are currently treated with biological drugs that target Type 2 immune response. Because IL-5 is necessary for the growth, survival, and activation of eosinophils, IL-5 inhibitors, such as mepolizumab, decrease the peripheral blood count of eosinophils, but do not influence eosinophils activation in the airway. In severe COVID-19 patients, the blockade of eosinophils' activation might contrast harmful immunity.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染会刺激免疫系统发生复杂的激活。嗜酸性粒细胞属于宿主抵御呼吸道病毒的防御机制。在感染的第一阶段，嗜酸性粒细胞的作用可能是适当且有益的，因为它们有助于抑制病毒复制。然而，在重症新型冠状病毒肺炎（COVID-19）患者中，在疾病的第二和第三阶段，嗜酸性粒细胞可能参与适应性不良的免疫反应，并直接导致免疫病理学变化。事实上，在重症患者中，免疫反应主要是辅助性T细胞1型，但辅助性T细胞2型也存在。嗜酸性粒细胞的扩增和激活受到2型细胞因子的刺激，尤其是白细胞介素-5（IL-5）。此外，嗜酸性粒细胞起核心作用的支气管哮喘似乎不是重症COVID-19的主要危险因素。在可能的解释中，哮喘患者经常接受皮质类固醇治疗，已证明这种治疗可降低住院患者发展为重症COVID-19的风险。除了类固醇，重症哮喘患者目前还接受针对2型免疫反应的生物药物治疗。由于IL-5对嗜酸性粒细胞的生长、存活和激活是必需的，IL-5抑制剂，如美泊利单抗，可降低外周血嗜酸性粒细胞计数，但不影响气道中嗜酸性粒细胞的激活。在重症COVID-19患者中，阻断嗜酸性粒细胞的激活可能对抗有害的免疫反应。
