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Letter to the Editor

Eosinophilic esophagitis: is the Th2 inflammation protective against the severe form of COVID-19?

Franceschini, Lauraa,,b; Macchiarelli, Raffaelea; Rentini, Silviaa; Biviano, Ivanoa; Farsi, Alessandrob

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European Journal of Gastroenterology & Hepatology: December 2020 - Volume 32 - Issue 12 - p 1583
doi: 10.1097/MEG.0000000000001909
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Since it was initially reported on 31 December 2019, the disease known as coronavirus disease (COVID-19) has spread rapidly across the globe, leading the WHO to declare it a pandemic on 11 March 2020, and Italy was the first European country to encounter its effects.

Between 09 March and 04 June 2020, we observed that none of the 36 adult patients (25 male and 11 female; 20–56 years) with eosinophilic esophagitis (EoE), living in Siena and its Province and referring to our Gastroenterology Unit, were hospitalized for COVID-19 infection. All our patients continued their treatment regimens (orally administered topical corticosteroids, proton pump inhibitors, elimination diet) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. These findings are consistent with recently published data from another Italian group, because in their high-risk area in northern Italy no cases of severe COVID-19 infection were reported in patients with EoE [1].

Several studies support that patients with EoE are not a homogeneous population and different phenotypes and endotypes exist. A subset of EoE is characterized by Th2-predominant inflammation (Th2-high EoE endotype) and is positively associated with other allergic diseases such as atopic dermatitis, allergic rhinitis, food allergies and type-2 high asthma [2].

Cardiovascular diseases, hypertension, malignancies, diabetes and age have been recognized as adverse prognostic factors for the severity of COVID-19 disease. Up to now, there are no pieces of evidence concerning an increased risk of COVID-19 disease in patients with allergic diseases and some reports indicate that atopy does not represent a risk factor for SARS-CoV2 severity [3]. Eosinophils, for a long time identified as an effector cell in allergic diseases, recently has been postulated, besides their proinflammatory effects, to play a fundamental role in antiviral responses. Accumulating data indicate that patients with severe form of COVID-19 show a trend towards eosinopenia, leading to consider this condition a biomarker of poor prognosis in these patients, on the other hand, the higher proportion of activated eosinophils that characterized allergy could play some protective role [4].

Moreover, some studies show that type-2 asthma, associated with high level of eosinophils, was not a risk factor for increased hospitalization and ICU admission due to COVID-19 and a protective effect of type-2 inflammation has been postulated because the Th2-dominant environment seems to be able to downregulate the late phase hyper-inflammation which characterized the severe form of COVID-19 [5].

Taken together these pieces of evidence could suggest that EoE and other allergic diseases, characterized by a Th2-skewed immunity, may be protective against severe COVID-19 disease and could support the hypothesis that eosinophils have a protective effect on SARS-CoV-2 infection.

In any case, the younger age of patients with EoE compared to the mean age of those with severe SARS-CoV-2 infection in Italy must be taken into account.


Conflicts of interest

There are no conflicts of interest.


1. Savarino E, Lorenzon G, Ghisa M, et al.Lack of complications in patients with eosinophilic gastrointestinal diseases during SARS-CoV-2 outbreakJ Allergy Clin Immunol Pract2020
2. Ruffner MA, Cianferoni APhenotypes and endotypes in eosinophilic esophagitisAnn Allergy Asthma Immunol2020124233239
3. Maggi E, Canonica GW, Moretta LCOVID-19: unanswered questions on immune response and pathogenesisJ Allergy Clin Immunol20201461822
4. Lindsley AW, Schwartz JT, Rothenberg MEEosinophil responses during COVID-19 infections and coronavirus vaccinationJ Allergy Clin Immunol202014617
5. Carli G, Cecchi L, Stebbing J, Parronchi P, Farsi AIs asthma protective against COVID-19?Allergy2020Published online ahead of print, 1 June 202010.1111/all.14426
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