Pathobiological bases of asthma-COVID-19 interaction: A theoretical viewpoint

Patients with asthma are susceptible to viral respiratory infections, due to weakened cellular immunity, chronic airway inflammation, and some other reasons. In fact, asthma was found to be a comorbidity to the Middle East respiratory syndrome coronavirus infection. Moreover, some asthma therapies like systemic corticosteroids used to manage severe asthma were found to be associated with severe acute respiratory syndrome coronavirus (SARS-CoV) viremia in the previous pandemic. However, from the epidemiological studies conducted so far across the globe, asthma patients are not exceptionally susceptible to COVID-19 compared to the general public; as opposed to the association seen with chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and other known comorbidities of COVID-19. The bases for this interaction are not adequately understood. However, the heterogeneity of asthma disease as it relates to its various endotypes, altered angiotensin-converting enzyme (ACE2) expression in the airways, effect of rhinoviral infections, and effect of inhaled corticosteroids and biological response modifiers (BRMs), are the proposed mechanisms behind this interaction. Increased activity of ADAM 17 as induced by interleukin-13 at apical portion of pneumocytes may be responsible for the shedding of ACE2 on asthmatic airways. Furthermore, inhaled corticosteroids may prevent the occurrence of acute lung injury and, hence, acute respiratory distress by transrepression of pro-inflammatory pathways and transactivation of anti-inflammatory pathways. The antiviral effects of some inhaled corticosteroids whose molecular targets are not known may involve downregulation and competitive binding to the chaperone proteins heat shock proteins 90 and 70 between glucocorticoid receptor and nucleoprotein of SARS-CoV-2. MEDLINE was searched for terms such as asthma and COVID-19, antiviral effects of inhaled corticosteroids, BRM, and mechanisms of asthma-COVID-19 interaction. The reference lists of the obtained articles were also searched for additional literature.