key: cord-1039355-tf67rbnz
authors: Carli, Giulia; Cecchi, Lorenzo; Stebbing, Justin; Parronchi, Paola; Farsi, Alessandro
title: Is asthma protective against COVID‐19?
date: 2020-06-17
journal: Allergy
DOI: 10.1111/all.14426
sha: 3e6735d468559d6027e610ba1c6ea0f150f687e2
doc_id: 1039355
cord_uid: tf67rbnz

nan

As well as age, co-morbidities including cardiovascular diseases and hypertension, malignancies and diabetes, and other host-related factors are adverse prognostic factors for COVID-19 disease. 1 Asthma is a heterogenous condition, characterized by a type 2 eosinophilic inflammation in more than 50% of those with a formal asthma diagnosis. Despite a prevalence of 4.2%, surprisingly to us, asthma was not listed in co-morbidities in a Chinese study on 140 hospitalized patients. 2 Herein, we share some clues supporting the hypothesis that type 2 conditions do not represent a risk factor, despite the most morbidity occurring due to SARS-CoV-2 induced lung damage.

Immune responses to viruses are characterized by initial activation of innate immunity and production of type I and III Interferons (IFN-α/β and -λ, respectively), crucial to control propagation. 3 

the predominant source of IFN-α produced in the peripheral blood, despite representing at most 0.2%-0.8% of the circulating mononuclear cells. 3, 4 Intriguingly, a defective production of IFNs by pDC and epithelial cells has been described in severe atopic patients 4,5 with a consequent delayed and inefficient antiviral defence. IFNs serve as negative regulators of Th2 development, differentiation and function. 6 A negative link exists between IgE and IFN-α, since IgE cross-linking down-regulates Toll-like receptor (TLR) 9 expression and dampens TLR-7 signalling, abrogating viral-induced type I and III IFN production from pDCs. Of note, the magnitude of the IFN-α responses after ex vivo viral challenge of pDCS is inversely related to serum IgE levels. Furthermore, pDCs are sensitive to histamine through H2 receptors, which also enhance this negative regulatory pathway 4 (Figure 1 ). This suggests that pDC antiviral responses may be suppressed in a similar way in atopy. Indeed, asthmatics have a greater susceptibility to respiratory viral infections which may be a trigger for exacerbations. 7 However, the Th2-dominant environment might be also protective, able to down-regulate the late phase hyper-inflammation which typically marks severe respiratory viral diseases, when the viral load decreases but immunopathologic events are the hallmarks of tissue damage. This seems to be particularly the case in SARS-CoV infections.

In SARS-CoV-1 infection, poor outcomes were linked to an early robust type I IFN expression together with high levels of IFN-related chemokines (ie CXCL-10) and IFN-ɣ. 8 This dysregulated and hyperactivated innate response may preclude a regular switch towards protective adaptive immune responses as speculated by Richardson in COVID-19 patients 9 and demonstrated in a mouse model of SARS-CoV infection where early (or absent/low) IFN signalling appeared beneficial in preventing monocyte/macrophage lung infiltration, vascular leakage, cytokine storm and impaired T-cell responses. 3 Thus, timing and robustness of type I IFN production is able to affect the outcome.

Further, the role of eosinophils, foes in asthma but possibly friends in COVID-19 infected lungs, needs to be established.

Eosinophils are reduced in peripheral blood of SARS-CoV-2-infected patients. 2 It is tempting to speculate that increased numbers of eosinophils in the airways of asthmatic patients might be protective against the exaggerated inflammatory responses of the severe COVID-19 phenotype.

There is reason to suggest here that antiviral and immunomodulatory activities of inhaled asthma medications (with particular focus on steroids) should be investigated, expanding previous evidence from past coronaviruses. 10, 11 F I G U R E 2 Suggested Type I Interferon responses in SARS-Cov-2 infection in nonasthmatic and Th2 high asthmatic patients

Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis

Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan

Dysregulated Type I interferon and inflammatory monocyte-macrophage responses cause lethal Pneumonia in SARS-CoV-Infected Mice

Interferon at the crossroads of allergy and viral infections

Aberrant function of peripheral blood myeloid and plasmacytoid dendritic cells in atopic dermatitis patients

Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones

How rhinovirus infections cause exacerbations of asthma

Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome

Baricitinib for COVID-19: a suitable treatment? -Authors' reply

Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells

Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells