Asthma, Severe Acute Respiratory Syndrome Coronavirus-2 and Coronavirus Disease 2019

Dylan T. Timberlake; Kasey Strothman; Mitchell H. Grayson


Curr Opin Allergy Clin Immunol. 2021;21(2):182-187. 

In This Article

Severe Acute Respiratory Syndrome Coronavirus 2 and Angiotensin-converting Enzyme 2 Receptors

HCoV contain a spike (S) protein that binds to cellular receptors allowing for viral entry into target cells. SARS-CoV was shown to utilize the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry.[13] This receptor subsequently has been shown to be the receptor to which SARS-CoV-2's S protein binds.[14] However, prior to binding to ACE2, the S protein of SARS-CoV-2 requires cleavage by the cellular serine protease TMPRSS2.[14] ACE2 and TMPRSS2 are co-expressed on nasal goblet secretory cells, type 2 pneumocytes, and ileal absorptive enterocytes, making these key targets for SARS-CoV-2 infection.[15]

ACE2 gene expression in nasal epithelium has been shown to increase with age,[16] and it is further increased in the small airway epithelial cells of smokers and patients with chronic obstructive pulmonary disease.[17] Age, chronic obstructive pulmonary disease, and a smoking status have been associated with increased risk for severe COVID-19 disease,[18,19] and therefore it has been theorized that increased ACE2 expression may serve as a mechanism for increased severity of disease.

When not stratified by allergic phenotype, ACE2 gene expression in patients with asthma has been shown to be similar to that seen in patients without asthma.[20] However, once stratified by allergic phenotype, patients with allergic asthma had significantly decreased ACE2 gene expression when compared to nonallergic asthmatics.[21] Since allergic asthma represents about 60% of patients with asthma,[22] atopic status may be an important consideration when investigating COVID-19 outcomes in patients with asthma. Lastly, ACE2 is an interferon stimulated gene and is therefore upregulated during viral infections.[15] Given that asthmatic bronchial epithelial cells have been shown to have a deficient IFN-β response to viral infection,[23] this could potentially dampen the natural increase in ACE2 expression during SARS-CoV-2 infection, ultimately decreasing the severity of illness (Figure 1).

Figure 1.

Relationship between SARS-CoV-2 and asthma. Unlike circulating nonpandemic CoV, pandemic CoV, such as SARS-CoV-2, do not appear to induce asthma exacerbations (top panel). Based on the current data, there appears to be no increased risk of becoming infected with SARS-CoV-2 or having more severe disease if infected in those with asthma (middle panel). In those with allergic asthma, it has been proposed that decreased IFNβ production leads to reduced ACE2 expression, which might attenuate disease or prevent infection (bottom panel); however, epidemiologic studies do not yet support this contention. ACE2, angiotensin-converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.