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{{ANETextoAsociado|titulo=Major comorbidities|contenido= National and international studies have shown differences in the mortality and fatality of SARS-CoV-2 infected patients between territories. Part of these differences may be attributed to different levels of access to healthcare. In this regard, the Spanish National Health System is made up of the Regional Health Systems. There may be differences in the health service management and organisation from one region to another. However, all of them are based on the same principles, i.e. universal and free access.
Another part of these differences is linked to risk factors or pathologies of the affected person (comorbidities), which determine the possible severity of the infection and, therefore, the need for healthcare resources. It shall always be borne in mind that advanced age and being male are the two main demographic factors linked to the severity and lethality of infection by this virus. However, the scientific community is unanimous in identifying the comorbidities included in this section as additional risk factors.
COPD
Chronic Obstructive Pulmonary Disease (COPD) does not appear to be a predisposing factor for SARS-CoV-2 infection. However, once infection occurs and the disease develops, there is an increased risk of hospital admission, admission to intensive care unit (ICU) and death. Furthermore, the respiratory symptoms of COVID-19 may sometimes be confused with COPD exacerbations, which may delay diagnosis and affect the clinical course. The underlying pathophysiological mechanism would be an increased expression of ACE2 receptors (to which the virus binds to penetrate the cell) in the bronchial epithelium, amongst others.
The SEMI-COVID-19 registry of the Spanish Society of Internal Medicine provides clinical data on patients from hospitals across the country, including a history of COPD in 7% of those patients.
The map shows clear differences in reported prevalence between territories. Galicia, Asturias, Extremadura, Aragón and Castile and León (Castilla y León) stand out, with prevalences of around 5%, compared to regions such as the Balearic Islands (Illes Balears) and the Canary Islands (Canarias), with less than 3%. In relation to gender, it is interesting to note that the prevalence in women is higher or equal to that of men in some regions even though COPD is associated with smoking.
There are two major limitations to the data shown. The first is that they are based on self-reported data, which may constitute a reporting bias. The second is that the data are not age- or sex-adjusted, so the differences shown in prevalence may be explained by a different population structure. COPD is an age-associated disease; the regions with the highest prevalence are those with a large elderly population.
HYPERTENSION
Hypertension is an important risk factor that has been discovered in 19% of patients with COVID-19 in Spain. The biological concept is based on its effect on the renin-angiotensin-aldosterone system and on angiotensin-converting enzyme 2 (ACE-2) overexpression.
Two facts stand out in the data shown: on the one hand, the reported prevalence shows figures of 20-25% in all regions, except for the Balearic Islands (Illes Balears) that registers around 10%; on the other hand, the similarity of figures between men and women, except in the cases of Navarre (Navarra) and Melilla. However, the interpretation of the data has the same limitations as in the case of COPD.
This risk factor is associated with greater severity. However, according to different studies, its influence does not seem to be as clear as that of COPD, cardiovascular diseases or diabetes.
OBESITY
Obesity is considered the epidemic of the 21st century, as its numbers are increasing in the adult population and, what is more worrying, in children. Being overweight/obese has been identified in numerous studies as a predictor of hospital admission and admission to the ICU, especially in patients under 65 years of age. The SEMI-COVID-19 registry shows its presence in 21% of patients.
The increased risk in these patients has been attributed to a higher level of
pro-inflammatory cytokines (aggravating hyperinflammatory processes) and to baseline lung volume changes due to mechanical factors.
There is considerable variability in the prevalence of obesity, with some regions close to 20% and others to 15%. Even more important is the difference between sexes, both between regions and within the same region. It is important to note that there may be a certain geographical pattern according to the wealth of the territory: regions with lower obesity prevalence rates are those with higher Gross Domestic Product. There is a reason for this, as obesity is clearly linked to socio-economic variables.
In this case, the reporting bias is reduced –not fully eliminated– as the survey methodology specifies a limit for considering obesity or not. However, it is impossible to determine geographical patterns that imply statistically significant differences if no adjustment for age and sex is carried out.
DIABETES
This risk factor has been identified in 17% of the cases reported (8.9% of hospital admissions in Spain). It is clearly a higher risk factor for hospital admission, admission to the ICU and death. The biological mechanism on which this risk factor is based is that described for hypertension.
The prevalence of reported diabetes also shows important geographical differences, with regions registering a prevalence of around 5%, such as the Balearic Islands (Illes Balears), La Rioja and Cantabria, and others around 10%, such as Galicia and Extremadura. The difference between men and women may also be significant (see the Basque Country [Euskadi/País Vasco]).
Type II diabetes is basically a chronic age-associated pathology that could lie behind differences in mortality or lethality from COVID-19 between regions. However, as already mentioned in the comment on other variables, nothing can be inferred from the unadjusted data, which are subject to possible reporting biases.
HEART FAILURE
Heart failure has been described, either under this term or as a cardiovascular disease, as the most prevalent risk factor in the population diagnosed with COVID-19 (up to 30%) and is present in more than 50% of COVID-19 patients admitted to the ICU in Spain, according to several studies. Its mechanism of action is the same as for diabetes and hypertension.
There are two clear patterns: one geographical and the other by sex. Castile and León (Castilla y León) and the Region of Valencia (Comunitat Valenciana) show a very high prevalence, around 14%. The data for Extremadura and Castile-La Mancha (Castilla-La Mancha) warrant a separate reading, with prevalences that are 30% lower than those in the regions with higher prevalence.
Heart failure is more prevalent in women. However, as this figure is not adjusted by sex, it may be influenced by the higher life expectancy of women, since heart failure is more prevalent with age.
The primary healthcare model in Spain, based on the primary care team that covers the care of the population in a healthcare area, is the same in all regions and its information system has been consolidated for years. Significant geographical differences in prevalence may certainly be explained in part by differences in population structure; but it is very likely that there are other additional factors, e.g. lifestyle and those linked to the follow-up care of the population.
CHRONIC KIDNEY DISEASE
Chronic Kidney Disease (CKD) is included in the range of comorbidities that are associated with worse COVID-19 outcomes. Kidneys have ACE-2 receptors and are primarily involved in the renin-angiotensin-aldosterone system that regulates blood pressure. These are usually patients with added comorbidities, such as diabetes and hypertension, who have a weakened immune system.
Although studies linking CKD and COVID-19 are limited, increased mortality has been observed in these patients, especially in advanced stages of CKD. Other researches have not found an increased admission to the ICU of CKD patients infected by SARS-CoV-2.
The regions of Catalonia (Catalunya/Cataluña), Valencia, Murcia, the Canary Islands (Canarias) and the town of Ceuta have higher adjusted rates than the other regions. Conversely, the lowest rates are recorded in Cantabria and Castile and León (Castilla y León). When rates are analysed by sex, men are clearly seen to have higher rates than women in all regions, except in the Balearic Islands (Illes Balears), Ceuta and Melilla, being almost twice as high in several regions.
The Spanish Registry of Kidney Diseases was founded in 2006 as a result of merging the data provided by all regional registries. These consolidated data show a real difference in the prevalence of this pathology.
HIV-AIDS
HIV infection and AIDS diagnosis is not usually listed as a risk factor in most studies as such; immunodeficiency is. However, this term is very broad and difficult to define. So a pathology like VIH-AIDS, with a well-established information system and a clear impact on the immune system, especially cell-mediated immunity, was opted for in this study.
How the vulnerability of an immunocompromised patient fits in with immune hyperactivation is not fully understood. There is no strong evidence to support an increased risk in immunocompromised patients. In the case of HIV/AIDS, studies suggest not so much an association with increased susceptibility to infection, but some association with rising fatalities. In the SEMI-COVID-19 registry, COVID-19 cases with HIV infection represent 0.7%. It is not possible to draw conclusions on its possible implication for the clinical severity of COVID-19 with such a low number of cases.
HIV/AIDS prevalence in Spain is low in general, yet it shows significant differences between regions. It mainly affects males. There is an increasing number of cases in the Balearic Islands (Illes Baleares), the Canary Islands (Canarias) and the Region of Valencia (Comunitat Valenciana) that are linked to tourism, which could be a reason for relaxing protection/prevention measures. The Region of Madrid (Comunidad de Madrid) also follows this pattern of prevalence. On the other hand, Catalonia (Catalunya/Cataluña) shows a very low prevalence even though it is also a region where tourism plays an important role.
Although the data are unadjusted for age and sex, it is very likely that these differences between regions are real, as the age group of people affected is more limited (young, young adults and adults) and the demographic differences between regions are somewhat smaller in these age groups than in the case of the elderly.
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