Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium‐derived cytokines, namely IL‐25, IL‐33, and TSLP, as key regulatory factors that link in immune‐pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium‐derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.

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The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-d-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.The outcomes of a viral infection and disease progression are determined by complex host-virus interactions 1,2 . Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), presents highly heterogeneous clinical manifestations in humans 3,4 . The majority of individuals infected with SARS-CoV-2 have asymptomatic, mild or moderate disease; however, elderly individuals and patients with comorbidities such as type 2 diabetes mellitus are at a much higher risk of serious illness and even death 5 . Although complex immunological changes may underlie the vulnerability of these

Retinoids, a group of compounds including vitamin A and its active metabolite all- trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA.