DISCUSSION
Coronavirus disease 2019 (COVID-19), has become in a short period of
time, one of the worst infection disease ever known around the world,
declaring a Public Health Emergency of International Concern. Spain has
been one of the most severely affected countries in Europe. Data dated
on the 6 of July 2020, declared 2.648.971 confirmed cases in all of
Europe, 250.545 of which correspond to Spain. Castellon’s Health
Department attends a total of 283,021 people. From these, 927 (0.33%)
patients with COVID-19 have been detected until now. In our Hospital, a
total of 234 patients required hospitalization due to COVID-19, of whom
34 (14.5%) required hospitalization in the intensive care unit. The
first hospitalization was reported on the 13 of March 2020. Out of the
234 patients, no one had asthma as comorbidity.
This study underlines that external factors surrounding asthma patients
do not influence the probability of being affected by the disease. It is
important to emphasize that most of severe asthma patients studied,
comply with risk factors described for COVID-19 disease, without seeming
to affect their susceptibility to the infection.
Moreover, it shows that a poor asthma control is the main reason that
conditioned the need for medical assistance during the pandemic,
highlighting that, the period of most impact in Spain coincided with
pollination season, reason why allergic asthma patients might of have
been less controlled.
When studying severe asthma patients in treatment with MAB,
corresponding to our Medical Department, it is seen that none of them
corresponded to any of the 234 patients hospitalized, suggesting a low
prevalence of the disease in these patients. This same evidence has been
reported by Haroun-Diaz et al in Madrid, Spain, where the disease has
had a much greater impact.14 The main limitation of
this study is that exact prevalence of the disease in these patients
cannot be known, as most of the patients did not have a RT-PCR or
serological test done; however taking into account that until June,
diagnostic tests were only done to patients with moderate to severe
symptoms who required hospitalization, exact prevalence of COVID-19 in
our population is unknown. The next step is to perform total antibody
serological test to the 106 patients, in order to determine exact
prevalence, taking into consideration the high sensitivity of the test
(86.43%) and its high specificity (99.57%).
In the case that severe asthma patients contracted the disease, this
study suggests they would have shown very weak to no symptoms. The
thesis is also supported by Haroun-Diaz et al [14]. Reasoning for
this include a series of factors recently studied in the wake of COVID
-19 pandemic. Speculations emphasize on type 2 immune response as a
potential protective factor against COVID -19 [15]. Proinflammatory
type I and III immune response, with the production of IFN, are the base
for an antiviral response. Asthmatics have greater susceptibility to
respiratory viral infections due to a defective production of IFNs in
severe atopic patients [16, 17]. However, in this case, some authors
hypothesize that Th-2 dominant environment might be protective against
COVID -19 as it may be able to downregulate the late phase of
hyper-inflammation, responsible of tissue damage and cytokine storm
[5, 18-20].
Treatment with inhaled corticoids in asthma patients seem also to be
protective [2], as seen in in-vitro studies, where inhaled
corticosteroids alone or in combination with bronchodilators were able
to suppress coronavirus replication and cytokine production [21,22].
Michael et al. reported that inhaled corticosteroids reduce genes
expression of viral membrane receptors (ACE2 and TMPRSS2) in asthmatic
patients’ sputum [23]. Angiotensin converting enzyme 2 (ACE2) and
transmembrane protease serine 2 (TMPRSS2) are the receptors used by
SARS-CoV-2 for viral infection [24]. The higher the ACE2 expression
is, the greater the susceptibility to SARS-Cov [25]. Up regulation
of ACE2 receptors gene expression is associated with smoking, diabetes
and hypertension [26], while down regulation has been proved to be
associated with respiratory allergy and controlled allergen exposures,
being lower in those with both high levels of allergic sensitization and
asthma [27]. Shi Wendan et al. found that combined allergies might
reduce the destructive power of SARS-CoV-2, as COVID-19 patients with
allergy, had less severe initial conditions and lower degree of lung
lesions. At the same time, the interval of RT-PCR negativization was
shorter in allergic patients [28].
Both theories above mentioned, are supported by the study’s
observations, as both patients with a positive serological test, had an
eosinophilic asthma, and followed treatment with high doses of inhaled
corticoids.
Eosinophils play an important role in the defense against virus
[29]. Early observations described eosinopenia in hospitalized
COVID-19 patients, and correlated it with more severe cases, however
further studies suggested that eosinopenia may not be associated with a
bad progression of the disease [30-33].
Currently, studies focusing on the pathway in which biologicals
targeting type 2 disease, may affect the patient’s response to COVID-19
is scarce. There is no evidence neither for a protective effect nor a
negative effect of these biologicals regarding SARS-Cov-2 infection
[34]. Further studies are needed in this regard.
To our knowledge, this is the first published study describing the
external factors surrounding severe asthma patients and if these affect
their susceptibility for the disease. The conclusions drawn from this
study, underline personal and clinical factors in these patients are not
risk factors, and do not influence the probability of being affected by
the disease. Therefore, it can be hypothesized that severe asthma
patients in treatment with MAB, do not have an increased susceptibility
for being infected by the virus.
ACKNOWLEDGEMENTS: For the statistical analysis of the results,
we appreciate the collaboration of Paqui Corpas Burgos (FISABIO).
DATA SHARING: The data that support the findings of this study
are available from the corresponding author upon reasonable request.