key: cord-0766868-16525ulw
authors: Heffler, Enrico; Detoraki, Aikaterini; Contoli, Marco; Papi, Alberto; Paoletti, Giovanni; Malipiero, Giacomo; Brussino, Luisa; Crimi, Claudia; Morrone, Daniela; Padovani, Marianna; Guida, Giuseppe; Gerli, Alberto Giovanni; Centanni, Stefano; Senna, Gianenrico; Paggiaro, Pierluigi; Blasi, Francesco; Canonica, Giorgio Walter
title: COVID‐19 in Severe Asthma Network in Italy (SANI) patients: clinical features, impact of comorbidities and treatments
date: 2020-08-01
journal: Allergy
DOI: 10.1111/all.14532
sha: cf672d49684ccc09686644d1613a111bb2cd8048
doc_id: 766868
cord_uid: 16525ulw

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symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. Demographic and clinical have been obtained from the registry platform and collected from the additional Center. Additional data about COVID-19 symptoms, treatment and clinical course have been collected for all cases reported.

Ethical issues and statistical analysis are reported in the online supplementary material.

The entire severe asthmatics population accounted for 1504 patients, 65% of them were treated with biologicals (anti-IL5 or anti-IL5R agents: 52.9%, anti-IgE: 47.1%). Twenty-six (1.73%) patients had confirmed (11) or highly suspect COVID-19 (15); eighteen (69.2%) were females and mean age was 56.2 ± 10 years. The geographical distribution of COVID-19 cases is presented in Figure 1 .

Nine (34.6%) infected patients experienced worsening of asthma during the COVID-19 symptomatic period; four of them needed a short course of oral corticosteroids for controlling asthma exacerbation symptoms.

The most frequent COVID-19 symptoms were fever (100% of patients), malaise (84.6%), cough (80.8%), dyspnea (80.8%), headache (42.3%) and loss of smell (42.3%). Four patients (15.3%) have been hospitalized, one of which in intensive care unit; among hospitalized patients, two (7.7%) died for COVID-19 interstitial pneumonia (no deaths among the non-hospitalized patients).

Severe asthmatics affected by COVID-19, had a significantly higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) compared to non-infected severe asthma patients (15.4% vs 3.8%, p=0.002; odds ratio: 4.7). No difference was found in other comorbidities, however patients with severe asthma and NIDDM had a not statistically significant trend of higher BMI (31.9 vs 26.9, p=0.09), suggesting a possible interaction between obesity and NIDDM as risk factors for COVID-19 in severe asthmatics.

Twenty-one patients with COVID-19 were on biologicals: 15 (71%) on anti-IL-5 or anti-IL5R agents (Mepolizumab n= 13; Benralizumab n=2 -counting for the 2.9% of all severe asthmatics treated with anti-IL5 in our study population) and 6 (29%) on anti IgE (Omalizumab -1.3% of all severe asthmatics treated with omalizumab in our study population). In conclusion, in our large cohort of severe asthmatics, COVID-19 was infrequent, not supporting the concept of asthma as a particularly susceptible condition to SARS-CoV2 infection. This is in line with the under-reported asthma cases among patients with COVID-19 patients 3 . The COVID-19 related mortality Accepted Article rate in our cohort of patients was 7.7%, lower than in the general population (14.5% in Italy 1 ). These findings suggest that severe asthmatics are not at high risk of SARS-CoV-2 infection and of severe forms of COVID-19. There are potentially different reasons for this. Self-containment is the first, because of the awareness of viruses acting as a trigger for exacerbations, and therefore they could have acted with greater caution, scrupulously respecting social distancing, lockdown and hygiene rules of prevention, and being more careful in regularly taking asthma medications.

Another possible explanation stands in the intrinsic features of type-2 inflammation, that characterizes a great proportion of severe asthmatics. Respiratory allergies and allergen exposures are associated with significant reduction in angiotensin-converting enzyme 2 (ACE2) expression 6 , the cellular receptor for SARS-CoV-2. Interestingly, ACE2 and Transmembrane Serine Protease 2 (TMPRSS2) (another protein mediating SARS-CoV-2 cell entry) have been found highly expressed in asthmatics with concomitant NIDDM 7 , the only comorbidity that was more frequent reported in our COVID-19 severe asthmatics.

The third possible explanation refers to the possibility that inhaled corticosteroids (ICS) might prevent or mitigate the development of Coronaviruses infections. Severe asthmatics, treated with high doses of ICS 4 , may have been protected from SARS-CoV-2 infection.

Noteworthy, among our case-series of severe asthmatics with COVID-19, the proportion of those treated anti-IL5 biologics was higher (71%) compared to those treated with anti-IgE (29%). Although the number of cases is too small to draw any conclusion, it is tempting to speculate that different biological treatments can have specific and different impact on antiviral immune response, as suggested for anti-IgE as protective for other viral infections 8 . Moreover we may speculate of the consequence of blood eosinophils reduction induced by anti-IL5 agents, as more than 70% of infected patients were treated with them: eosinopenia has been reported in 52-90% of COVID-19 patients worldwide and it has been suggested as a risk factor for more severe COVID-19 9 . So far, no other large series of severe asthmatics treated with biologicals infected by COVID-19 has been published, so our speculations on the role of biologicals in modulating the risk of COVID-19 need further evidence.

In conclusion, in our large cohort of severe asthmatics only a small minority experienced symptoms consistent with COVID-19, and these patients had peculiar clinical features including high prevalence of NIDDM as comorbidity. Further real-life registry-based studies are needed to confirm our findings and to extend the evidence that severe asthmatics are at low risk of developing COVID-19.

This article is protected by copyright. All rights reserved TABLES: Table I 

Role of viral respiratory infections in asthma and asthma exacerbations

Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

The Severe Asthma Network in Italy: Findings and Perspectives

Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2

National Heart, Lung, and Blood Institute Severe Asthma Research Program-3 Investigators. COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids

Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma