INTRODUCTION
The pandemic due to the infection caused by the betacoronavirus called
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that began
in Wuhan, China in December 2019, causing the infectious disease COVID19
(1,2,3), surpassed fifteen million infections and more than six hundred
thousand deaths globally (4), numbers that continue to rise. In severe
cases, severe pneumonia and other complications that can be
life-threatening for patients are common (1,2,3).
The first case diagnosed in the community of Castilla La Mancha was on
March 1, 2020 and infections increased exponentially in the following
weeks (5). The prognosis of SARS-CoV-2 infection worsens when
comorbidities such as high blood pressure, chronic obstructive pulmonary
disease, diabetes mellitus, cardiovascular disease, and obesity are
associated (6,7).
There are communications that suggest that asthma may be a factor that
determines the severity of the disease, compared to others that indicate
that it does not imply an increased risk (6,8,9). Asthma is a chronic
inflammatory disease of the airways, where different cells and
inflammation mediators participate, with bronchial hyperresponsiveness
and variable airflow obstruction, which is totally or partially
reversible (10). The prevalence of asthma in Spain is estimated at 6.3%
of the population (10). Differentiating an asthma exacerbation from
SARS-CoV-2 pneumonia may be clinically difficult because the symptoms of
dry cough and dyspnoea may be present in both (11). The prevalence of
asthma in SARS-CoV-2 infection published in a cohort of hospitalized
patients in Spain was 8.4% (12).
The Castilla la Mancha’s health system is universal and provides medical
care to all citizens. Using a new computer system (Savana®) that works
on clinical reports generated in the Community, all the information is
found in an accessible electronic medical record system. This system is
a powerful tool for conducting epidemiological studies and has been used
in this work to evaluate the epidemiology of COVID 19 and its
association with asthma in our population.
The main objective of this study is to analyse how the SARS-CoV-2
infection has affected asthmatic patients in terms of prevalence,
morbidity, hospitalization and mortality.
MATERIAL AND METHODS
For the analysis of information contained in electronic health records
(EHR), we use Savana®, an artificial intelligence (AI)-enabled system
based on natural language processing and neural networks, which combines
computational skills with natural language processing by joining Big
Data and AI approaches, capable of reusing information expressed in
natural language in clinical reports. It does this by combining its
channelling modules with, among others, sentence segmentation,
tokenization, spell checking, acronym detection, expansion, negation,
identification, and a multidimensional classification scheme that unites
linguistic knowledge, statistical evidence, and the latest in continuous
vector representations of words (13). The information that doctors write
in the EHR during their daily practice generates large amounts of
valuable information.
Savana® maximizes this huge amount of data by dynamically exploiting it
all in real time. It performs an immediate statistical analysis of all
patients seen on the platform and provides relevant results for the
input variables provided by the user (13,14). To ensure the privacy of
all patients, Savana® anonymised the data.
From its implementation in January 2011 until July 2020, 260,810,000 EHR
were generated belonging to 3,191,485 patients, which includes, in fact,
the entire population of Castilla la Mancha.
Savana® carried out the search in the entire population, extracting data
from primary care, specialized care, hospitals and emergency
departments, until July 2020, detecting COVID19 diagnoses, and in this
group, patients diagnosed with asthma. For this study, we considered it
appropriate to include only patients who tested positive for SARS-CoV-2
with reverse transcriptase polymerase chain reaction (RT-PCR) and
analysed demographic characteristics, hospitalization data,
comorbidities (high blood pressure, dyslipidaemia, diabetes mellitus,
smoking), and mortality.
RESULTS
A total of 6,310 patients were diagnosed with SARS-CoV-2 infection,
confirming their positivity by RT-PCR. 577 were diagnosed with asthma,
resulting in a prevalence of 9.14%. The mean age of SARS-CoV-2 (SC2)
patients was 59 ±19 years and of asthmatic SARS-CoV-2 (SC2-A) 55 ±20
years. Among SC2 2,983, (41%) were men, while 3,327 (59%) women, among
SC2-A 198, (31%) were men, while 379 (69%) were women. In the analysis
of comorbidities we found the following data when analysing SC2/SC2-A:
High blood pressure 3239 (51%) / 296 (51%), dyslipidaemia 2283 (36%)
/ 216 (37%), diabetes mellitus 1641 (26%) / 142 (25%) and smoking 873
(14%) / 103 (18%) (Table I).
Hospitalization was required for 2,164 (34.2%) SC2 and 131 (22.7%)
SC2-A, with a prevalence of 6.05% of hospitalised asthmatics. The mean
age of hospitalized patients was 68±17 years in SC2 and 64±17 years in
SC2-A. Gender distribution in SC2 was 912 (42%) women, and 1,252 (58%)
men, and in SC2-A 79 (60%) women and 52 (40%) men. The average
hospital stay was 5.5 days for both groups. In these hospitalizations
there were 10 deaths (7.6%) in SC2-A and 203 in SC2 (9.3%). The
analysed comorbidities presented the following SC2/SC2-A figures: High
blood pressure 1,253 (58%)/ 73 (56%), dyslipidaemia 761 (35%)/49
(37%) diabetes mellitus 574 (27%)/ 27 (21%)/, and smoking 137 (6%) /
9 (7%) (Table II)
Deaths in the SC2 population were 250 (3.96%), with an average age of
73±12 years, 158 (63%) men and 92 (37%) women, who presented 200
(80%) arterial hypertension, 137 (55%) dyslipidaemia, 110 (44%)
diabetes mellitus and 45 (18%) smoking. In the SC2-A population there
were 21 (3.64%) deaths, with an average age of 71±10 years, being 10
(52%) men and 11 (52%) women and associating 16 (76%) high blood
pressure, 14 (67%) dyslipidaemia, 5 (24%) diabetes mellitus, and 5
(24%) smoking (Table III).
DISCUSSION
Our cohort is one of the first studies in Europe to describe the
prevalence of infection, hospitalization and morbidity/mortality of
asthmatic patients with SARS-CoV-2 infection.
The prevalence of infections in our asthmatic population is 9.14%
similar to that obtained in a review of patients hospitalized with COVID
19 in Spain (12). In the study by Chibba et al. , the prevalence
of SARS-CoV-2 infection in asthmatic patients in the Chicago, Illinois
area, requiring hospitalization or not was 14.4% (6). These data
suggest that the prevalence may vary by geographical area. In both
groups (SC2/SC2-A) the average age is in the range of 50-60 years. There
is a higher percentage of women in infected patients with asthma, in
those requiring hospitalization, and in deaths. In SC2, hospitalization
and death occurred more frequently in men (Tables II and III).
Mortality is lower in SC2-A. The average age in both groups is similar
in a range of 71-73 years.
Of the analysed comorbidities, high blood pressure is the most common in
both groups, dyslipidaemia and diabetes mellitus are similar in
proportion, and smoking is more common in asthmatics. It is important to
stress that these comorbidities may increase the risk of a more severe
form of SARS-CoV-2 infection (7,17) and therefore increase mortality,
although data analysis only found statistical significance with smoking.
There is controversy in the literature as to whether asthma is a
comorbidity that increases the risk of a more severe form of SARS-CoV2
infection (8,9,15,16,23). The data from our study shows that there is
lower mortality in the asthmatic population. A possible explanation is
based on the fact that one of the targeted mechanisms of entry of the
virus into the host cell is through the angiotensin converting enzyme 2
(ACE2) receptor, a process dependent on the TMPRSS2 protease, allowing
the adhesion of the spike protein and performing the fusion between the
virus and the membrane cells (19, 20, 21, 23). The possibility of a
reduced expression of genes related to this receptor has been assessed
in asthmatic patients. In the study by Radzikowska et al. , no
difference was found between the expression of ACE2 in asthmatic
patients with the general population (19). Peters et al. measured
the expression of ACE2 and TMPRSS2 genes in sputum from asthmatic
patients and found no difference compared with the general population,
but when associating other variables such as male gender, black race,
and a history of diabetes mellitus, their expression may show an
increase (20). The use of inhaled corticotherapy in asthma, which is
very widespread in our environment, could have a protective effect by
decreasing the expression of the ACE2 receptor and the TMPRSS2 protein,
although more studies are needed to prove this (20,21). To date, the
recommendations for the asthmatic patient is to maintain their treatment
trying to achieve the best therapeutic adherence (24).
We consider the limitations of our study to be retrospective and that it
does not consider other variables that could influence the results,
besides, the basic treatment of each asthmatic patient has not been
assessed. The laboratory data that determine, to some extent, the
evolution and severity of the SARS-CoV-2 infection have not been
measured either. It is possible that there is a selection bias, as there
is more surveillance of asthmatic patients, who are assumed to be more
vulnerable, than on the general population and more RT-PCR
determinations are made on them.
CONCLUSION
Our study shows a prevalence of asthma in the total number of SARS-CoV-2
infections in the Community of Castilla la Mancha of 9.14% and a
hospitalization rate of 6.05%. High blood pressure is the most
associated comorbidity analysed in both groups (SC2/SC2-A). We found a
difference in mortality, being lower in asthmatics, although due to the
small number of patients in this group, it does not reach statistical
significance. More studies are needed to conclude whether asthma is a
factor that increases the severity of the SARS-CoV-2 infection.
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TABLES
Table I: Characteristics of SARS-CoV-2 patients