Fig. 1

Comparison of pathogenesis in severe SARS-CoV-2 infection in nonallergic and allergic individuals. In nonallergic lungs. a Virus binds to the epithelium through protein S, which uses the receptor for angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 (1). Replication occurs by means of the union of RNA polymerase to a leader sequence encoding the virion’s structural proteins. The destruction of infected cells by SARS-CoV-2 and the release of the virus activate both innate and adaptive immunity through the recognition of molecular patterns by receptors on surrounding cells. A state of acute inflammation is induced by the release of cytokines and mediators. Local cells such as natural killer lymphocytes (NK) release interferon (IFN)-γ to stop viral replication (2) At the same time, antigen-presenting cells such as dendritic cells enter the circulation (not shown) to come into contact with T cells, which together with the IFN-γ and IL-12 environment allows them to be differentiated into effector Th1 cells. Th1 lymphocytes release IFN-γ (3), which activates nondifferentiated macrophages (MØ) into their classic macrophage M1 effector form with the release of more IFN-γ and other cytokines, such as IL-1β and tumor necrosis factor (TNF)-α, contributing to the cytokine storm (4). MØs release various cytokines, such as IL-15, which contributes to NK activation, as well as IL-6, IL-10 and IL-8. IL-8 recruits neutrophils (NEU) that release TNF-α and IL-17 and, in severe disease, release neutrophil extracellular traps (NETs), precipitating thrombus formation (5). IFN-γ, aside from decreasing viral replication, induces ACE2 expression in cells, facilitating the entry of the virus (6). Damaged epithelium secretes IL-33, an alarmin that promotes Th1 activation (7). In allergic lungs, b the Th2 phenotype is accompanied by the release of various cytokines, such as IL-13, that decrease ACE2 expression in epithelial cells, leading to a decrease in SARS-CoV-2 infection (8). Another Th2 cytokine, IL-4, inhibits Th1 cells and activates M2 macrophages while inhibiting M1 macrophages (9). In addition, IL-33 promotes the Th2 response, increasing the release of cytokines such as IL-5 and eosinophilia, and through IL-13 and IL-4, the release of transforming growth factor (TGF)-β, which is related to fibrosis (10). Finally, NK cells release IFN-γ to decrease viral infection and the Th2 response