Implications of preexisting asthma on COVID-19 pathogenesis

Abstract

The coronavirus disease 2019 (COVID-19) pandemic spreading at an alarming rate has taken a heavy toll on the public healthcare systems and economies worldwide. An abnormal and overactivated inflammatory response is occasionally elicited by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and this hyperinflammation is associated with worse prognosis of COVID-19. Theoretically, one would expect asthma patients to be at a greater risk of SARS-CoV-2 infection considering their increased susceptibility to common respiratory virus-associated exacerbations. Surprisingly, current data do not consistently suggest an increased prevalence of asthma among COVID-19 patients. Considering the high global prevalence of asthma, the characteristics of the disease and/or their conventional therapy might play a role in their potential defense against COVID-19. This may be attributed to the T helper type 2 immune response predominantly seen in asthmatics. Likewise, asthma therapeutics, including corticosteroids and biologics, may in fact benefit the asthmatics by alleviating the development of hyperinflammation. On the other hand, elevated IL-17 levels are characteristically seen in a subset of asthma patients with severe disease as well as in COVID-19 patients. Targeting the IL-17 pathway as a treatment strategy could plausibly alleviate acute respiratory distress syndrome (ARDS) in COVID-19 patients with asthma demonstrating a predominant T helper type 17 response. A clinical trial including a drug targeting this pathway may thus, constitute a logical addition to the global pursuit for effective therapeutics against COVID-19. The complex interplay between the asthma endotypes and COVID-19 is not very well understood and will be discussed in this mini-review.

Impact of asthma on COVID-19 mortality in the United States: Evidence based on a meta-analysis

“…Asthma can be triggered exacerbation by respiratory viruses, inducing the severity of the infectious condition [67] , but we found the association of asthma with the protective risk for mortality among coronavirus disease 2019 patients. At the same time, the detailed mechanisms of the association between asthma and the risk for COVID-19 mortality are unclear due to several hypotheses taken willingly to accept: (1) asthma in COVID-19 patients may take caution to build a fence to isolate themselves from the crowd and get more medical care from the paramedical practice; (2) the use of medicine to cope with asthma in convention, allergen immunotherapy, inhaled corticosteroids and biological agents, may resist the severe prognoses of COVID-19 in term of suppressing viral replication and relieving inflammation [68] ; (3) type 2 immune response modulating the expression of ACE2 and TMPRSS2 further supports an important role in inflammatory process in COVID-19 pathogenesis [69] .…”

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

“…Higher percentages of circulating Th2 cells were found in the patients with M.tuberculosis infection compared to the controls [ 49 , 50 ]. Within different autoimmune disorders, the majority of patients with asthma demonstrated a predominantly Th2 immune response [ 51 ]. Previous investigations have demonstrated that allergen provocation of the upper and lower respiratory tract inducing allergic airway inflammation leads to a significant decrease in ACE-2 expression, suggesting a possible relationship between allergic inflammation and a lower susceptibility to SARS-CoV-2 infection [ 48 ].…”

Asthma and COVID-19: an update

“…Moreover, circulating soluble ACE2, which is upregulated in asthma, could act as a competitive interceptor, limiting the ability of SARS-CoV-2 to bind to airway cell membranes. In patients with Th2-high inflammation, ACE2 gene expression is downregulated [ 4 , 57 , 58 ]. Analysis of nasal airway transcriptome data from 695 children demonstrated that TMPRSS2 is highly upregulated by Th2 inflammation through the action of IL-13 [ 59 ].…”