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.