Asthma as a Risk Factor (or Lack Thereof) for Coronavirus Disease 2019 Outcomes
Overall, children are less symptomatic with COVID-19 than adults and the risk of severe COVID-19 outcomes is very low. Based on data from the Centers for Disease Control and Prevention (CDC), children comprise less than 0.1% of all COVID-19 mortality. Among the reported cases of COVID-19 for which age is known in the United States, only 2572 (1.7%) occurred in children 18 years and younger. While among the patients with information on underlying conditions, 23% had at least one underlying condition such as asthma, only 5.7% of children infected with COVID-19 required hospitalization (compared with 10% of adults aged 18–64 years). A summary of 72 314 cases from the Chinese CDC found only 1% of case patients were 9 years or younger, and no deaths occurred in this age group.
Intrinsically, one would assume that asthma would serve as a risk factor for more severe COVID-19 outcomes. Childhood asthma involves an 'umbrella of high risk factors' including airway inflammation, epithelial damage, mucous hypersecretion, and reduced innate immune response, all of which would seem to increase the risk associated with a respiratory virus. This theoretical risk and pathophysiologic reasoning has led multiple international organizations including the CDC to list asthma as a risk factor for COVID-19 morbidity and mortality based on the theoretical risk that infection may increase the risk of an acute respiratory process.
However, to date there is no evidence that asthma is a risk factor for more severe COVID-19 outcomes, especially in children. A national prospective Canadian study of 264 children admitted to hospital with COVID-19 infection found that while 39.3% of those children admitted had at least one comorbidity including chronic lung disease, asthma was an exception. A systematic review (though not limited to the pediatric population) did not find any increased risk of COVID-19 among those with asthma. In fact, it was stated in the European Academy of Allergy and Clinical Immunology (EAACI) pediatric section statement that a classification of asthma as a risk factor is 'based more on common sense rather than mounting evidence'. A systematic review on whether asthma constitutes a risk factor for COVID-19 severity in children, conducted in three stages noted in the first stage that, of 67 studies, none included data on pediatric asthma as a comorbidity for COVID-19. In the second search (34 studies), none included data on children and in the third search, none included data on children. The conclusion of the systematic review, in the words of the authors was that 'there is scarcely any data on whether childhood asthma…constitute risk factors for severe acute respiratory syndrome (SARS)-CoV-2 infection or COVID-19 severity'.
It is possible that the hyperinflammation causing severity and complications with COVID-19 may be downregulated with asthma (due to inefficient IFN-α production and the anti-inflammatory influence of the Th2 pathway).[13,14] A prevailing theory is also related to the host angiotensin converting enzyme 2 (ACE2) receptor, which facilitates SARS-CoV-2 attachment to host cell membranes in the nasal epithelium and lung. ACE2 expression has been shown to be lower in children overall, and further reduced in those with both allergic sensitization and asthma. The Th2 pathway has a role in ACE2 regulation. In a retrospective examination of nasal epithelium from 305 individuals aged 4–60 years in New York, it was found that compared with younger children, ACE2 gene expression was significantly higher in older children (P = 0.01), young adults (P < 0.001), and adults (P = 0.001).
Curr Opin Allergy Clin Immunol. 2022;22(2):95-100. © 2022 Lippincott Williams & Wilkins