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What we know and still ignore on COVID-19 immune pathogenesis and a proposal based on experience of allergic disorders.
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  • Enrico Maggi,
  • Bruno Azzarone,
  • Walter Canonica,
  • Lorenzo Moretta
Enrico Maggi
Bambino Gesù Children's Hospital
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Bruno Azzarone
Bambino Gesù Children's Hospital
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Walter Canonica
Humanitas University & Research Hospital
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Lorenzo Moretta
Bambino Gesù Children's Hospital
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Abstract

The coronavirus disease 2019 (COVID-19) pandemic started over one year ago and produced almost 3.5 million deaths worldwide. We have been recently overwhelmed by a wide literature on how the immune system recognizes Severe Acute Respiratory Syndrome Coronavirus 2 and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is 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, 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 done for some inflammatory disorders as asthma, rhinosinusitis with polyposis and atopic dermatitis, herein we suggest to define 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.

Peer review status:IN REVISION

22 May 2021Submitted to Allergy
24 May 2021Assigned to Editor
24 May 2021Submission Checks Completed
26 May 2021Reviewer(s) Assigned
14 Jun 2021Review(s) Completed, Editorial Evaluation Pending
14 Jun 2021Editorial Decision: Revise Minor