key: cord-0870403-g5owhmzh
authors: Sing Ho, Kam; Howell, Daniel; Rogers, Linda; Narasimhan, Bharat; Verma, Hannah; Steiger, David
title: Commentary on Eosinophilic inflammation, COVID-19, and asthma – are inhaled corticosteroids the missing link?
date: 2021-05-08
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2021.04.039
sha: e00d7ac6fd57bda6b8eceaa8e8a04b5b809d5af6
doc_id: 870403
cord_uid: g5owhmzh

nan

Asthma, prevalence, COVID-19 infection, hospitalization, eosinophilia, T2 inflammation, ICU admission, mortality.

The Thank you for allowing us the opportunity to reply to Dr. Ramakrishnan's recent correspondence regarding "Eosinophilic inflammation, COVID-19, and asthmaare inhaled corticosteroids the missing link?" [1] . We are grateful for the kind remarks and insightful comments.

The correspondence reinforces the importance of eosinophils in COVID-19, from their protective role against severe COVID-19 illness, in patients with and without asthma to being a biological marker of recovery [1, 2] . Moreover, the benefits of systemic corticosteroids in COVID-19 raise the question of whether prior use of inhaled corticosteroids (ICS) has any role in COVID-19 outcomes in patients with asthma [3, 4] . The authors note that the magnitude of the protective effect of eosinophils ≥ 200 cells/µl was more significant in those with an asthma diagnosis than those without speculating whether inhaled corticosteroids may be responsible for this difference in outcomes. However, data on inhaled corticosteroid use before and during hospitalization was not available to us. There may be a complex interplay between viral infections, allergic or type 2 inflammation and the immunological response to viral infections and asthma beyond the effect of ICS [5] . Nonetheless, inhaled corticosteroids have been demonstrated to reduce coronavirus replication and have an essential role in reducing viral exacerbations of COPD [6] . The OPENSAFELY authors attributed the very slight increase in mortality in those using high-dose ICS in COVID-19 to unmeasured confounding factors.

In contrast, others have found that ICS use was not associated with worsened outcomes [7] . ICS reduces the expression of two proteins, TMRSS2 and ACE2, involved in SARS-COV-2 viral entry into host cells, thus providing a possible explanation for the protective effect of ICS.

However, it must be noted that our study demonstrated that improved outcomes were seen in non-asthmatics with elevated eosinophil counts who would not be on ICS, suggesting that ICS were not the only possible explanation for improved outcomes in patients with eosinophilia.

We read with great interest and applaud the work of Dr. Ramakrishnan and his team on their Phase 2 clinical trial describing the role of inhaled corticosteroids in outpatients with COVID-19 [8] . The study demonstrates that inhaled corticosteroids can reduce the risk of clinical deterioration and prevent increased health care resource utilization. The potential for an inhaled, locally acting, and readily available medication such as an inhaled corticosteroid to ameliorate the course of COVID-19 is very promising.

Eosinophilic inflammation, COVID-19, and asthmaare inhaled corticosteroids the missing link?

The Relationship Between Asthma, Eosinophilia, and Outcomes in COVID-19 Infection

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis

Impact of CORTICOSTEROIDS in hospitalised COVID-19 Patients

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