Asthmatic patients usually present an increased susceptibility to respiratory viral infections 1 . Nevertheless according to the available evidence asthma prevalence among COVID-19 patients is surprisingly low [2] [3] [4] [5] . A lower expression of ACE 2 receptors described in T2-high asthma as well as the effects of inhaled corticosteroids, may account for this finding 6, 7 , although the protective role of inhalation therapy is under debate 8 . On the other side, asthmatic patients admitted to intensive care for COVID-19 seemed to experience a more severe disease 9 . However the clinical profile of asthmatics hospitalized for COVID 19 have been scarcely investigated 4, 5, 10 , and the relationship between asthma and SARS-Cov-2 remains controversial 2,3,6 .
Our retrospective study aimed to describe the prevalence and features of asthmatic patients hospitalized for COVID-19 and to explore the association between their clinical asthma profile and COVID-19 severity.
Electronic medical records of patients admitted to COVID-Units of six cities major hospitals in the North and Center of Italy during the Italian pandemic peak (1st March -30th April 2020) were reviewed. COVID-or need for ventilation were identified as markers of more severe COVID-related illness (worse outcome subgroup) whilst patients discharged at home without requiring invasive procedures were grouped as better outcome. The study was approved by the Institutional Review Boards (2649CESC).
A preliminary Shapiro-Wilk test was performed. Data are reported as percentages for categorical variables and as mean (standard deviation) or median [interquartile range] for continuous variables. Categorical variables were compared by the χ2 test or the Fisher exact test, while continuous variables were assessed by the independent t-test or the non-parametric Mann-Whitney U test. A univariate regression analysis was used to identify predictors of a worse outcome (the dependent variables). All analyses were performed using IBM SPSS, version 17.0 (IBM Corp., Armonk, NY, USA) and p-values of <0.05 was considered statistically significant.
Overall 42 asthmatic patients were identified, representing 2.1% of the whole COVID-Units population (n= 2000). Table 1 summarizes demographic and clinical characteristics of the study population. Atopy characterized around half of the asthmatic patients, and blood eosinophilia was reported to be within the reference range (<0.45 10^9/L) in 91.6% of patients. The occurrence of asthma exacerbation in the 6 months before the Covid Unit admittance was reported by 18% of patients,. Only 5% were treated with biologics for severe asthma.
By reviewing the prescribed asthma treatment, 24% of patients were classified as severe asthmatics according to GINA recommendations; nevertheless 31% of patients at the admission were not on regular treatment. In patients with worse outcome a prevalence of males was detected; they suffered from more severe asthma (GINA level 4 and 5) and were more frequently current or former smokers. Higher C-reactive protein level and longer hospital stay were associated with worse outcome ( Table 2 ).
According to the univariate regression analysis (Table 3) hospitalized patients. The overall prevalence is similar to previous studies [2] [3] [4] [5] and, interestingly, is much lower than asthma prevalence in the general Italian population (6%) 11 .
The unexpected low proportion of asthmatics among the COVID-19 hospitalized patients is still under debate. Of note, up to now asthma has not been specifically and extensively investigated as potential risk factor and few studies clearly report its frequency among the baseline clinical features of COVID-19
patients. Further focused research may clarify the issue.
In our study population, the higher number of females (60%) is consistent with the general trends of asthma distribution 12 . On the opposite, US reports described a higher prevalence of asthmatics within COVID-19 population when compared to our findings and to asthma prevalence in the US general population 10 . Of note, the US study included non-hospitalized patients, who might have experienced mild or no symptoms. Furthermore, US population includes a not-negligible component of Afro Americans; in those racial minorities, both higher prevalence of asthma and more severe COVID-19 have been described, mainly due to socio-economic and environmental conditions acting as specific risk factors 13 .
When stratifying the patients according to COVID-19 severity, atopy was equally distributed. This observation seems in contrast with the hypothetical "protective" role of atopic status 6 . Of note in our study atopy was defined on the basis of clinical history only, that may hamper the accuracy of the information.
However, when looking at the clinical profile of our patients, including the low eosinophil count, the proportion of smokers, the low prevalence of nasal polyposis, the negligible use of biologics for asthma, a prevalent T2 low phenotype can be hypothesized. The proportion of current/former smokers in our population could suggest a potential differential diagnosis with COPD; however the exemption code for asthma, as detailed in Material and Methods paragraph, allowed us to specifically identify asthmatic patients.
Regarding eosinophils, no significant differences in terms of baseline peripheral eosinophilia were detected in our sub-populations, which seems in contrast with the finding from other authors 2 . Of note they reported an association between worse COVID-19 outcome and low levels of eosinophils during the illness course, whilst our observation refers to baseline values. However, further studies are needed to address and clarify the issue.
J o u r n a l P r e -p r o o f 31% of patients at the admission were not on regular treatment but they only used rescue medications. It has been hypothesized that inhaled steroids could somehow modulate the susceptibility to Covid-19 infection 6 .
Our observation did not seem to confirm the same hypothesis, in fact the lack of a regular inhaled treatment was equally distributed among patients with better and worse outcome. However the small sample size does not allow generalizing our results, and the protective role of inhalation therapy is still under debate 8 . Of note, the proportion of GINA 4 and 5 stage patients was significantly higher in the worse outcome subgroup. It suggests that severe asthma might act as a risk factor for worse COVID-19 disease, as supported by the results of the univariate regression analysis (Table 3) , especially when not adequately treated. However the hypothesis needs to be confirmed by larger studies.
When comparing the two subpopulations stratified by COVID-19 outcome, smoking habit more frequently characterized the worse outcome patients, which is quite expected, as smoke acts as independent risk factor in many conditions. However it can be hypothesized that smoke may amplify the relevance of asthma in determining a higher susceptibility. The more significant increase of C-reactive protein and the longer duration of hospitalization in our patients with poorer outcome reflect what has been previously described in COVID-19 populations, although they seem to be non-specific markers associated with severe COVID infection independently of the presence or severity of asthma 2,3 . In contrast with previous reports 2,3 no difference in D-Dimer was observed between the groups in our study. Of note, differently from the mentioned reports, our values refer to baseline assessment and not the illness course.
A major limitation of our study is the lack of direct comparison with a COVID-19 non-asthmatic population.
Also, due to its retrospective design, some baseline patients' characteristics potentially impacting on the disease outcomes, including asthma subtype baseline blood eosinophil count, IgE level, previous thromboembolic events, information on influenza vaccination, are missing.
However our data provide a first asthma prevalence report in a large Italian population of COVID-19 hospitalized patients, confirming that the proportion of asthmatics is very small and suggesting that asthma itself cannot be considered an independent risk factor for COVID 19. On the other side patients with asthma 