The coronavirus disease 2019 (COVID-19) pandemic started in March 2020 and caused over 5 million confirmed deaths worldwide as far August 2021. We have been recently overwhelmed by a wide literature on how the immune system recognizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is now recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response at the start, or in advanced disease, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently applied to some inflammatory disorders as asthma, rhinosinusitis with polyposis, and atopic dermatitis, herein we suggest defining different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.

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关于 COVID-19 免疫发病机制我们所知道的和仍然被忽视的以及基于过敏性疾病经验的建议

2019 年冠状病毒病 (COVID-19) 大流行于 2020 年 3 月开始，截至 2021 年 8 月，已在全球范围内造成超过 500 万人确诊死亡。最近，有关免疫系统如何识别严重急性呼吸综合征冠状病毒 2（SARS）的大量文献让我们不知所措。 -CoV-2）并导致 COVID-19 发病机制。尽管 COVID-19 最初被认为是一种呼吸道病毒性疾病，但现在被认为是一种更为复杂、多器官、免疫介导且大多异质性的疾病。尽管有效的先天免疫和适应性免疫可以控制感染，但当患者在开始时或在疾病晚期未能产生足够的免疫反应时，高先天诱导的炎症可能会通过异质的补偿机制导致不同的临床结果。病毒载量和持久性的变异性、病毒驱动的受体/信号通路的遗传改变以及先天和适应性反应的可塑性都可能解释发病机制和临床模式的极端异质性。正如最近应用于哮喘、鼻窦炎伴息肉病和特应性皮炎等炎症性疾病一样，我们建议定义 COVID-19 的不同内型和相关表型。应根据不断变化的症状对患者进行分层，并严格监测先天性和适应性免疫的替代生物标志物。这将有助于预防性地识别每种内型（及其相关表型），并使用针对致病机制的药物精确治疗患者。