DISCUSSION
In our large cohort of severe asthmatics, COVID-19 was infrequent. This finding does not support the concept of asthma as a particularly susceptible condition to SARS-COV2 infection 4. This is in line with the first published large epidemiological data on COVID-19 patients, in which asthma is under-reported as comorbidity8-10. Two of the 26 severe asthmatics with COVID-19 died of SARS-CoV-2 infection; with a rate that is lower (7.7%) the COVID-19 mortality rate in the general population (14.5% in Italy1). All together these findings suggest that patients with severe asthma are not at high risk of the 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 virus infections acting as a trigger for exacerbations, and therefore they could have acted with greater caution, scrupulously respecting social distancing and lockdown, constantly applying the hygiene rules of prevention, and being more careful in regularly taking asthma medications. Indeed, recent publications report a significant increase in adherence to inhalation therapy during the COVID-19 pandemic among asthma patients 14.
Another possible explanation stands in the intrinsic features of type-2 inflammation, that characterizes a great proportion of severe asthmatics. It has been recently reported that respiratory allergies and controlled allergen exposures are associated with significant reduction in angiotensin-converting enzyme 2 (ACE2) expression15, the cellular receptor for SARS-CoV-216. The opposite relationship occurs between Rhinovirus and allergies, where Intercellular Adhesion Molecule 1 (ICAM1), the adhesion molecule used by the virus to enter respiratory cells, is overexpressed in allergic airways 17,18. 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 19, the only comorbidity that was more frequent reported in COVID-19 severe asthmatics compared to the remaining population of patients with severe asthma.
The third possible explanation refers to the possibility that ICS might prevent or mitigate the development of Coronaviruses infections: in-vitro studies have shown that ICS alone or combined with bronchodilators inhibit coronavirus replication and the related cytokine production 20. By definition, patients with severe asthma are treated with high doses of ICS 11 and this may have had a protective effect for SARS-CoV-2 infection.
Noteworthy, among the patients of our case-series of severe asthmatics with COVID-19, the proportion of those treated anti-IL5 biologic agents was higher (71%) compared to the number of patients 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 21,22. In addition we may speculate of the consequence of blood eosinophils reduction: eosinopenia has been reported in 52-90% of COVID-19 patients worldwide 23and it has been suggested as a risk factor for more severe COVID-19, and increase in eosinophils has been associated with better response to anti-viral therapy 24.
In conclusion, we reported that in a large cohort of severe asthmatic patients 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.