Eosinophilic inflammation, coronavirus disease 2019, and asthma: Are inhaled corticosteroids the missing link?

Abstract

We congratulate Dr Ho et al1Ho KS, Howell D, Rogers L, Narasimhan B, Verma H, Steiger D. The relationship between asthma, eosinophilia, and outcomes in coronavirus disease 2019 infection [e-pub ahead of print]. Ann Allergy Asthma Immunol. doi: http://dx.doi.org/10.1016/j.anai.2021.02.021, accessed March 18, 2021.Google Scholar on their work that further clarified the relationship between blood eosinophils, asthma, and the risk of severe coronavirus disease 2019 (COVID-19). They leveraged data from their large clinical network, which unlike others,2Bloom CI, Drake TM, Docherty AB, et al. Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK [e-pub ahead of print]. Lancet Respir Med. doi:10.1016/S2213-2600(21)00013-8, accessed March 18, 2021.Google Scholar,3Schultze A Walker AJ MacKenna B et al.Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform.Lancet Respir Med. 2020; 8: 1106-1120Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar includes outpatients diagnosed as having COVID-19. The authors effectively reveal that in asthma and in health, having a raised blood eosinophil count is protective against severe COVID-19 and associated mortality. Clinicians have repeatedly noticed that the peripheral blood eosinophil count is low in inpatients with severe COVID-19.4Zhang JJ Dong X Cao YY et al.Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China.Allergy. 2020; 75: 1730-1741Crossref PubMed Scopus (2210) Google Scholar,5Xie G Ding F Han L Yin D Lu H Zhang M. The role of peripheral blood eosinophil counts in COVID-19 patients.Allergy. 2021; 76: 471-482Crossref PubMed Scopus (82) Google Scholar Eosinophil counts also improve as patients recover from their COVID-19 illness.5Xie G Ding F Han L Yin D Lu H Zhang M. The role of peripheral blood eosinophil counts in COVID-19 patients.Allergy. 2021; 76: 471-482Crossref PubMed Scopus (82) Google Scholar Because the authors limited their data to the COVID-19 encounter of the patients, their conclusion that a high blood eosinophil count reduces the risk of mortality and hospitalization could simply be related to the suppression of blood eosinophil count in severe COVID-19. However, the authors try to account for this by using many surrogates for COVID-19 disease severity (blood and clinical markers), which could make their conclusions more robust. We would be interested if the authors could comment on whether inhaled corticosteroid use explains the difference in risk between patients with and without asthma with a blood eosinophil count of greater than or equal to 200 cells/µL in their cohort. We found the apparently increased protection of the raised blood eosinophil count among patients with asthma compared with patients without asthma (Table 4) in this cohort interesting.1Ho KS, Howell D, Rogers L, Narasimhan B, Verma H, Steiger D. The relationship between asthma, eosinophilia, and outcomes in coronavirus disease 2019 infection [e-pub ahead of print]. Ann Allergy Asthma Immunol. doi: http://dx.doi.org/10.1016/j.anai.2021.02.021, accessed March 18, 2021.Google Scholar Patients with asthma with a raised blood eosinophil count are more likely to derive benefit from inhaled corticosteroids,6Cowan DC Taylor DR Peterson LE et al.Biomarker-based asthma phenotypes of corticosteroid response.J Allergy Clin Immunol. 2015; 135 (e1): 877-883Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar whereas others have found that the use of inhaled corticosteroids reduces the risk of hospitalization and mortality among patients with asthma who develop COVID-19.2Bloom CI, Drake TM, Docherty AB, et al. Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK [e-pub ahead of print]. Lancet Respir Med. doi:10.1016/S2213-2600(21)00013-8, accessed March 18, 2021.Google Scholar Our phase 2 clinical trial also revealed that the initiation of inhaled corticosteroids early in COVID-19 can reduce the risk of clinical deterioration and prevent increased healthcare resource use.7Ramakrishnan S, Nicolau DV, Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial [e-pub ahead of print]. Lancet Respir Med. doi:10.1016/S2213-2600(21)00160-0, accessed April 9, 2021.Google Scholar