Analysis of fatality of cases by the new coronavirus, in the Mexican state of Guanajuato: A cross-sectional study

Background. The spread of infection and disease of SARS-CoV-2 is in all the world affecting more than 200 countries. Mexico has high new cases of disease and death for COVID-19. Although Guanajuato state also has a high number of new cases, the fatality of cases is below the mean in Mexico. Methods. It was a cross-sectional design, using the database of National Epidemiological Surveillance System in Mexico. It was collected data about age, sex, comorbidities (diabetes, chronic obstructive pulmonary disease, asthma, hypertension, cardiovascular disease, immunosuppression, chronic kidney disease, obesity and smoking), date of death, and real-time reverse transcription polymerase test. The statistical analysis was using Case Fatality Ratio, Chi squared test and P-value to show relationship among variables and Odds Ratio and condence intervals at 95% to show the effect of comorbidities on death due to COVID-19.

is likely to re ect low CFRs in previous reports [5], compared to that reported throughout Mexico. In addition, on June 22, the COVID Mobile Hospital began operations, also dedicated to treating the same type of patients.
The rst con rmed case of disease by the new coronavirus  in Guanajuato state was reported as beginning of clinical data on March 10, 2020 [3], and the two deaths were registered April 5, 2020 [6].
The World Health Organization (WHO), in the document Diagnostic Tests for SARS-CoV-2: Interim Guidance, recommends the real-time reverse transcription polymerase test (rRT-PCR) for the diagnosis of SARS infection. CoV-2 and COVID-19 [7].
In July 2020, when the number of new cases increased notably in the state, the case fatality ratio was 4.72% at the state level and 10.99% at the national level [5].
The objective was to analyze the fatality among con rmed cases of COVID-19 in Guanajuato State from Mexico, until October 2, 2020, and the effect of comorbidities on it.
Methods It is a cross-sectional analytical study of fatality by COVID-19 con rmed cases, in Guanajuato State from Mexico, registered in the database of the Sistema Nacional de Vigilancia Epidemiológica (SINAVE) de la Dirección General de Epidemiología (DGE), of con rmed and discarded cases of COVID-19 [10].
The database was used until October 2, 2020, of the con rmed cases of COVID-19 in Guanajuato state from Mexico and the deaths registered as result of COVID-19. The database from SINAVE is the registry of all suspected, con rmed and discarded cases from COVID-19, from Secretary of Health from Mexico.
As a universe, all the records included in the database were up to October 2, 2020.
The selected records in the analysis were those registries with complete data There were no exclusion criteria and the elimination criteria were incomplete records in their data.
According to the guidelines of SINAVE/DGE, a suspected case was one with a clinical nding considered greater (cough, fever, headache or dyspnea and accompanied by at least one of the following: myalgia, arthralgia, odynophagia, chills, chest pain, rhinorrhea, anosmia, dysgeusia or conjunctivitis) [11].
A con rmed case of COVID-19 is a person with a positive rRT-PCR test for SARS-CoV-2, regardless of the clinical data presented [12].
The sociodemographic variables age and sex were included. As independent variables, the presence of comorbidities (diabetes, chronic obstructive pulmonary disease, asthma, immunosuppression, hypertension, cardiovascular disease, renal chronic disease, obesity, smoking), health system where the patient was attended, if the patient was in Intensive Care Unit (ICU) and result positive to rRT-PCR test.
The dependent variable was the date of death and COVID-19 as cause of death, registered in database of SINAVE/DGE [10].

Procedures
After approval by the Research Ethics Committee of the Campus Celaya-Salvatierra of the University of Guanajuato, the Excell ® (Microsoft Corp.), database was reviewed and it was copied to the STATA 13.0 ® database (Stata Corp., College Station, TX, USA). All procedures were accord of General Law of Health (Mexico) and Declaration of Helsinki.

Statistical analysis.
Descriptive statistics were performed for all variables and an epidemiological curve was designed for con rmed cases with a date of death. CFR was computed, by health institution, with the number of deaths and total of con rmed cases of COVID-19. Tabulation of comorbidities for con rmed cases and death was performed. To show associations of comorbidities and deaths between con rmed and discarded cases, was calculated the Chi-squared test, degrees of freedom and P value were calculated; in case of not calculate Chi-squared test, were calculated Z for two proportions, to show the effect of the comorbidities on deaths in con rmed cases, Odds Ratio (OR) and 95% con dence intervals (95% CI) were calculated.
Logistic regression models were generated and it was determined whether age group and sex acted as confounders, with the Likelihood Ratio Test (LRT) and P-value.
In all cases, to demonstrate statistical signi cance, the alpha value was set at .05.
Statistical analysis was performed in STATA 13.0 (Stata Corp., College Station, TX, USA). Results 100,919 records were obtained from the SINAVE/DGE database [10] until October 2, 2020. 810 records (0.8%) were eliminated due the absence of the rRT-PCR test result, leaving 100,109 records of suspected cases.
Of the 100,109 suspected cases, 41.69% were positive for SARS-CoV-2 (Table 1).  Table 2 shows that among those who died from COVID-19, those over 60 years of age predominated with 61.75% and men with 64.62%. Among the con rmed cases that did not die, those aged between 12 and 49 years and female (52.62%) predominated. Regarding deaths, they remained at low levels from March to May, with less than 10 deaths per day, but they increased notably as of June 2020, reaching more than 50 deaths in a single day in July 2020 ( Figure 2)   Among the con rmed and deceased cases, 78.45% were hospitalized, showing a strong effect of being hospitalized and dying; this re ects to the severity of COVID-19 (Table 4). Only 12.90% of the con rmed cases that died were in the ICU (Table 5).  Following the elimination criteria, the numbers of records eliminated due to incomplete data are presented; the percentages of records deleted are very small and do not affect the result of the statistical analysis (Table 7). In the population of con rmed COVID-19 cases, it was found that the greatest effect is obtained with chronic kidney disease, COPD, diabetes, hypertension and cardiovascular disease with OR higher than 5, for immunosuppression conditions, the OR was 3.91. In all these comorbidities age group and sex acted as confounders. For obesity and smoking as risk factors to death in COVID-19 the OR 2.20 and 1.71, respectively. Asthma shown a protective effect for death to COVID-19 (Table 8). Discussion Worldwide, con rmed cases had been reported in 215 countries with 34,161,721 cases, of which there have been 1,016,986 deaths, with a case fatality ratio of 2.98%; in Mexico, 753,090 con rmed cases with 78,492 deaths had been reported, with a case fatality ratio of 10.42% [13].
In the Guanajuato population, as of October 2, 2020, 41,734 con rmed cases had been detected, of which 2,993 died, having a case fatality ratio of 7.17% [10].
Advanced age is a risk factor for dying from COVID-19 [14,15]. In the Guanajuato population, 40.93% of the deaths were in persons aged 60 to 69 years and 20.82% in persons aged 70 or over (Table 2), con rming that the highest fatality is in ages over 60 years.
Male sex has also been considered as a risk factor for severity of COVID-19 or fatality from the same disease; 67.4% of the deceased were men according to Leung's review [14] and in the Guanajuato population, 64.62% of the deceased were men ( Table 2]. On June 1, 2020 throughout Mexico the social distancing campaign was concluded and this led to an increase in con rmed cases and deaths from COVID-19 as shown in gure 1, starting in June. deaths increased, with the month of July showing the highest daily numbers of deaths ( Figure 1).
In the state of Guanajuato, con rmed cases were treated more frequently in SSG, IMSS, ISSSTE [10] and the CFR were very different between institutions; SSG despite attending to most of the con rmed cases (72.89%) in the state, the CFR was much lower than in the IMSS (4.1 and 15.63%, respectively) ( Table 3).
Smoking showed a signi cant relationship on fatality from COVID-19 and the effect on fatality was that those who died were almost twice as likely to have been smokers (Table 8). Despite reports of absence of association between smoking and severity of COVID-19 by Liuppi and Henry [16] and in further analysis of that data, by Guo [17], demonstrates a signi cant association between smoking and COVID-19 severity and is considered the most important preventive risk factor [18].
Some risk factors for dying from COVID 19 have been identi ed as obesity, diabetes and cardiovascular disease [19][20][21], SARS-CoV-2 enters the cell by binding to the angiotensin converting enzyme 2 (ACE2); ACE2 dysregulation in diabetes can predispose to severe lung damage [22] and this protein has a protective role in diabetes and cardiovascular disease [23], losing this effect in the presence of SARS-CoV-2 and explaining why people with diabetes and vascular disease have worse clinical outcomes [24]. Among the con rmed deceased cases, 47.1% had hypertension, 41.82% diabetes, 28.21% obesity (Table 8), con rming that people with these pathologies develop more severe courses of COVID-19 [24].
The effect of comorbidities in relation to death from COVID-19 showed a signi cant effect for all, except asthma, HIV / AIDS, with ORs greater than 1 (Table 8). HIV / AIDS did not show any effect on fatality of cases and asthma showed a protective effect for dying from COVID, which has been consistent in the Mexican population [5,25].
When analyzing age and sex as potential confounders of the different pathologies, both showed that they have a confounding effect on the effect of comorbidities on fatalities from COVID-19 (Table 8). And this is explained by the fact that age and sex are known to be risk factors for dying from SARS-CoV-2 disease [14][15].

Strengths
Some cases were eliminated from the analysis because they did not have the rRT-PCR result (0.8%), and some did not have data about comorbidities however they were very low percentages, none reached 1%, so they did not affect the nal result.
The number of records is large, which gives greater strength to the statistical analysis of the data, which is re ected in the narrow 95% con dence intervals.

Weaknesses
When using a Mexican government database, the quality of the data depends on who collected the information, considering that they are o cial data for the state of Guanajuato and that they may be subject to bias. In database is not registered the severity of asthma and the protective effect on death could be a bias.

Conclusion
Among the Guanajuato population with COVID-19, it is con rmed that advanced age and male sex are risk factors for dying.
Diabetes, COPD, immunosuppression, cardiovascular disease, chronic kidney disease, obesity, and smoking are risk factors for dying from COVID-19 in the Guanajuato population.
HIV / AIDS has no effect on fatality from SARS-CoV-2 disease.
Asthma is shown as a protective factor for dying from COVID-19 in the Guanajuato population, which had already been reported in the Mexican population.

Declarations
Ethics approval and consent to participate.
The protocol was approved by Bioethics Committee of Campus Celaya-Salvatierra of the University of Guanajuato with registry CBCCS-05230042020. Informed consent was waived by Ethics committee. Informed consent was not used because only work with database from Secretary of Health. Personnel identi ers were not obtained.

Consent for publication
Not applicable.