Comorbid Asthma May Not Increase Risk for Severe COVID-19

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Patients with COVID-19 who had comorbid asthma did not necessarily have more severe disease compared with patients without asthma.

Individuals with coronavirus disease 2019 (COVID-19) with comorbid asthma may not have an increased risk for more severe disease, compared with those without asthma, according to a literature analysis published in The Journal of Allergy and Clinical Immunology.1

The impairment of antiviral responses in patients with asthma, which can, in turn, aggravate type 2 inflammation, suggests that these individuals may be at a high risk for morbidity and mortality from COVID-19. Recognizing that the most common trigger of asthma exacerbation is airway infection, particularly with such weakly virulent viruses as rhinovirus and respiratory syncytial virus, which typically cause upper respiratory tract infections in healthy individuals,2 investigators sought to explore whether patients with asthma may be at a high risk for COVID-19 morbidity and mortality. They conducted an unbiased literature search of epidemiologic studies on COVID-19.

The research was premised on the fact that since airway epithelial cells and leukocytes from individuals with asthma can reveal impaired production of antiviral interferons (IFN-α, IFN-β, and IFN-γ), either primarily or secondarily to allergic inflammation, a person’s innate immune system cannot prevent the spread of these viruses to the lower respiratory tract.3

Of the 8 studies yielded from the literature search, which included >17,000 individuals from multiple geographic areas, comorbidity rates of COVID-19 with asthma were significantly lower than the reported prevalence of asthma in these regions. Furthermore, 2 independent studies had similar results, establishing that patients with COVID-19 who had comorbid chronic obstructive pulmonary disease or diabetes tended to have more severe disease,4,5 whereas those with comorbid asthma did not.

According to recent research, 2 host molecules play critical roles in the initiation of severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) infection. It has been shown that SARS-CoV-2 utilizes the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for cell entry and a serine protease transmembrane serine protease 2 (TMPRSS2) for S protein priming of the virus.6 In vitro treatment of airway epithelial cells with IFNs has been shown to enhance their ACE2 expression.

In contrast, other investigators have reported that interleukin (IL)-13 exposure reduced ACE2 and increased TMPRSS2 expression in airway epithelial cells from patients with asthma and atopy. Further, tissue from type 2 cytokine-high allergic individuals demonstrated a significantly lower expression of ACE2, with ACE2 expression levels inversely correlated with the T2 cytokine levels and T2 signature molecule expression. Thus, expression of ACE2 is likely to be regulated reciprocally by IFNs and T2 cytokines. In fact, ACE2 expression in the bronchial epithelium of patients with asthma has been shown to be significantly lower than that in healthy individuals. Patients with serious COVID-19 disease had significantly higher IFN-related molecular expression.

The investigators concluded that the findings suggest a hypothesis that patients with asthma appear to be protected from COVID-19 because they have a low expression of ACE2 in their epithelial cells. A major limitation of the current analysis is the fact that all of the epidemiologic data were obtained retrospectively or on a cross-sectional basis, with no tests conducted for IFN production or ACE2 expression in patients with COVID-19, particularly in those who had comorbid asthma.


1. Matsumoto K, Saito H. Does asthma affect morbidity or severity of Covid-19? [published online May 26, 2020]. Editorial. J Allergy Clin Immunol. doi:10.1016/j.jaci.2020.05.017 

2. Zheng X-y, Xu Y-j, Guan W-j, Lin L-f. Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review. Arch Virol. 2018;163(4):845-853.

3. Edwards MR, Strong K, Cameron A, Walton RP, Jackson DJ, Johnston SL.Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness. J Allergy Clin Immunol. 2017;140(4):909-920.

4. Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 patients in Wuhan [published online April 12, 2020]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2020.04.006.

5. Singer AJ, Morley EJ, Meyers K, et al. Cohort of 4404 persons under investigation for COVID-19 in a NY hospital and predictors of ICU care and ventilation [published online May 11, 2020]. Ann Emerg Med. doi:10.1016/j.annemergmed.2020.05.011

6. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8.