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.