What we know and still ignore on COVID-19 immune pathogenesis and a
proposal based on experience of allergic disorders.
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.