Coronavirus Disease 2019 and Asthma, Allergic Rhinitis

Molecular Mechanisms and Host-Environmental Interactions

Mako Wakabayashi; Ruby Pawankar; Hidehiko Narazaki; Takahiro Ueda; Toshikazu Itabashi


Curr Opin Allergy Clin Immunol. 2021;21(1):1-7. 

In This Article

Abstract and Introduction


Purpose of Review: Coronavirus disease 2019 (COVID-19), a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), is a pandemic in over 120 countries worldwide. Risk factors for severe COVID-19 include older age, ethnicity, sex, comorbidities, and living conditions. Although asthmatics and those with allergies are susceptible to more severe outcomes to viral infections, interestingly, asthma has not been reported to be a major comorbidity of COVID-19. However, there are some conflicting reports on the impact of asthma on COVID-19. The underlying immunological and molecular mechanisms may explain at least in part these observations. Furthermore, environmental factors like air pollution that have detrimental effects on asthma and respiratory illnesses also have an impact on COVID-19.

Recent Findings: Angiotensin-converting enzyme 2 (ACE2) is the receptor for the attachment and entry of SARS-CoV-2 into the host cells that is upregulated by Th1-mediated responses. In asthmatics, ACE2 gene expression is generally reduced and recent studies have shown a negative correlation between the levels of Th2 cytokines including IL-4, IL-5, and IL-13 in airway epithelial cells and other type 2 biomarkers with ACE2 expression. This may explain in part the potential protective role of asthma on COVID-19. Here, we review the relation of respiratory viral illnesses and asthma, the immune-molecular mechanisms of SARS-CoV-2 infection, the impact of asthma on COVID-19 and that of SARS-CoV-2 on asthma and allergic rhinitis, and the impact of environmental factors like air pollution on COVID-19.

Summary: Expression of ACE2 in airway epithelial cells in SARS-COV-2 is influenced by inflammatory profile. Respiratory allergic diseases like asthma appear to have a protective effect against SARS-COV-2 infection. However, the clinical association between asthma and SARS-COV-2 is not fully established and the underlying immune-molecular mechanisms may explain these observations.


COVID-19 is a respiratory disease caused by a highly infectious virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), that was declared a pandemic by the WHO on 11 March 2020. SARS-CoV-2 infection can present as asymptomatic but most often manifests with acute respiratory illness which results in severe pneumonia and progresses to acute respiratory distress syndrome and even multiple organ failure. Abnormal, overactivated innate immunity and 'cytokine storms' are potential pathological mechanisms for the rapid COVID-19 progression. Conventionally, respiratory viral infections are known to exacerbate asthma and asthmatic patients should have increased susceptibility and severity for SARS-CoV-2 infection due to a deficient antiviral immune response. Therefore, asthma was initially considered to be an important comorbidity for COVID-19. Furthermore, allergic sensitization is a risk factor for wheezing with rhinovirus (RV) infection, particularly in children. However, several early and subsequent reports have suggested that the prevalence of asthma in COVID-19 infection is low, and that asthma may not be a comorbidity of COVID-19.[1,2]

In reviewing the pathophysiology of both asthma and COVID-19, asthma may even have a protective effect against COVID-19.[3] Certain aspects of the type 2 inflamation seen in asthmatics like increased type 2 cytokines (IL-4, IL-13, etc.) and accumulation of eosinophils, might provide potential protective effects against COVID-19. Furthermore, asthma therapies, like inhaled corticosteroids, allergen immunotherapy, and anti-IgE mAb, might also reduce the risks of asthmatics to infection of the virus via alleviating inflammation or enhancing the antiviral defense. By contrast, some recent reports suggest the possibility of severe asthma being a risk factor in the more severe forms of COVID-19[4] ( In addition to these conflicting observations, it may be difficult to differentiate whether asthma exarcebations are due to COVID-19 or that asthma acts as a risk factor for COVID-19 given the similarity of symptoms in their severe forms (Figure 1). In this context, it is important to discuss asthma as a comorbid condition of COVID-19.

Figure 1.

Overlapping symptom profile of asthma and coronavirus disease 2019.

In this review, we summarize recently published studies of asthma and immune response to SARS-CoV-2 infection, the regulation of angiotensin-converting enzyme 2 (ACE2) and transmembrane peptidase serine 2 (TMPRSS2), in airway epithelial cells and its regulation by inflammatory markers, how SARS-CoV-2 may impact patients with upper airways disease like allergic rhinitis, an important comorbidity of asthma, the relation between air pollution and COVID-19, and the effect of asthma therapies including inhaled steroids on COVID-19.