One year of COVID-19 pandemic: Epidemiological characteristics of COVID-19 in the city of Uberaba, Minas Gerais, Brazil epidemiológicas

Introduction: The new coronavirus pandemic (COVID-19) is unprecedented in recorded human history. It spread from Wuhan, China, in early December, 2019, crossing the entire planet and reaching Brazilian shores in the following February. It was declared a pandemic on March 11, 2020, with the first case recorded in the city of Uberaba, state of Minas Gerais, Brazil, on March 18, 2020. Since then, we have been collecting data and assessing the evolution of this fatal disease. Objective: In this work, we report the epidemiological characteristics of one year of the COVID-19 in Uberaba, and discuss its implications to the general public. Method: This is an observational, descriptive, documentary and retrospective study to describe the epidemiological profile of COVID-19 cases in the city of Uberaba from March 18, 2020 to March 17, 2021. Results: The study shows that the young-working age population are those who most spread the virus; however, the elderly are those who suffer and die the most, with slight differences regarding sex. This is in line with the reported national and international epidemiological profiles that show a shifting tendency of younger generations to be increasingly active on the evolution of the pandemic. We observed two major peaks on the two epidemiological time-series, confirmed cases and deaths, with an average age of 41 years old for the confirmed cases and 68 for the confirmed deaths. It was also reported that the lethality rate was 2.45%, and 80.00% of the confirmed deaths suffered from some previous health condition. Conclusions: In this sense, a permanent epidemiological surveillance has to take place in order to guide public health counter-measurements. The epidemiological characteristics of COVID-19 in Uberaba and related analyses are reported in the online observatory at https://coviduberaba.github.io.


Ethics statement
Strict ethical and professional aspects were followed, main-

Statistical analysis
Data were compiled and tabulated to determine simple frequencies (n), relative frequencies (%), means and standard deviation (±). Results are presented in contingency tables and graphs.

RESULTS
The study presents an analysis of reported cases of COVID-19 in  Considering the sex variable, in Figure 2(a) 51.69% of the reported cases of COVID-19 were female, whereas 48.31% were male. The

1.000
First peak was in S38* with 735 cases. Second peak, in this period, was in S10** with 885 cases. A 20% increase.  COVID-related deaths were also investigated and can be visualized in Figure 3 according to the epidemiological weeks. The first peak occurred in S41 in the year 2020 with 12 deaths, while the second peak appeared in S11 in the year 2021 with 38 deaths.
This represents a 216.00% increase. The record in confirmed daily deaths was registered in March 2021, with ten reported deaths. year and the highest age was 103 years. 75.00% of the deceased were older than 59. Figure 4(b) indicates that the age group that stands out is the one from 70 to 79 years, 26.18%.
It is possible to analyze the lethality degree of the new coronavirus by age group. Figure 2(

40
First peak was in S41* with 12 deaths. Second peak, in this period, was in S11** with 38 deaths. A 216% increase.   Medical conditions of the deceased were also analyzed and organized in Figure 5(a). According to the frequency of diagnosis, the prevailing medical conditions were: hypertension (39.00%), heart disease (21.43%), diabetes (21.43%), obesity (8.30%) and other medical conditions (18.15%), as indicated in Figure 5(a).

A B
Frequency of diagnosis  With respect to contamination, our results show that the most affected age group is the 30-39-year age category, and the most affected sex -despite the slight difference -is the female one.
On average, the age of the infected individuals is 41 and females were older than males. That is, infected men are younger than women.
With respect to deaths, the occurrence is more frequent in individuals over 60, with at least one medical condition. The lethality rate for men is 1.5 times higher than that of women, and Our study also revealed that the 20-49-year age category gathe- the same age group revealed as the most affected one. This scenario can also be explained by the risk factors to which this group is exposed, such as professional occupations, lifestyle, absence of comorbidities or use of medications, which may reflect social and cultural factors 27 . Possible genetic explanations will be necessary to complete the interaction of age, sex and risk factors 28 .
With respect to the biological sex of reported cases, our study shows that, although subtle, there are differences both in the frequencies of man and women and in the rate of incidence between the sexes. Women stand out in this phase of the study, a result that differs from the investigation that analyzes the pandemic in Brazil and reveals that 57.00% of those affected are men 7 . However, the frequency of infected men (49.10%) and women (50.90%) is identical to the results presented in January 2021 in Southeast Asia and the Western Mediterranean and is also close to African frequencies (47.00% and 53.00%, respectively) 29 . The statistical analysis of the data supports that there is a relationship between age and biological sex, and that infected women are older than men 20 .
Our data revealed that until March 17,2021, 305 deaths from COVID-19 were registered, indicating a general lethality rate of 2.45%. the mortality rate in Uberaba is higher than the average mortality rate in Brazil (2.45, Uberaba, 2.40, Brazil) 6 , and that of the state of Minas Gerais -2.09%, considering the same period of study 30 .
The median age of the individuals who died in the city was 71 years old, most of them were older than 60 and the age category with the highest lethality was that of 90 years old or over.
This age pattern found in Uberaba relates with data found in the USA, where 80.00% of the deceased were elderly patients aged 65 or older, and patients aged 85 31 . Also, in national studies such as the one in the state of Macapá 13 , the highest lethality rate was observed in elderly people older than 70. One of the possible explanations is that, in general, infections in older people are atypical and some factors may contribute to the high incidence of death, such as physiological changes caused by the aging process, medical conditions and use of various medications. Advanced age, therefore, is considered the main risk factor for complications of COVID-19 31 . The senescence also affects immune cells, and features of immunosenescence characterized by decreased native T-cells, increased memory T-cells, and poor response to newly encountered antigens 32 .
In addition to the age factor, some investigations reveal that the biological sex may be associated with the increase in deaths from COVID-19 33 . In our study, most deaths are from the male sex. Investigations conducted in China, South Korea, USA and Italy showed a higher death rate in male patients 22,34,35 . This difference between sexes may be due to a combination of biological factors, such as differences in chromosomal composition, reproductive organs and sex-related hormones. Gender-specific factors may also play a role, such as behavioral differences (smoking and drinking habits) and many medical conditions which are more frequent in men 28,36 .
Regarding the chromosome difference, human females have two X chromosomes, while human males have just one. It is known that the process of X-inactivation in women occurs so that, physiologically, there can be dosage compensation. However, 15% to 20% of the genes escape from inactivation in humans, resulting in a higher number of copies in women than in men 37,38 . Hence, as the X chromosome encodes some genes related to immune responses, women have a lower level of viral load and less inflammation compared to men 38 . Our data showed no difference between contamination of men and women, yet it is documented that women have stronger innate and humoral immune responses than men, and therefore are less susceptible to bacterial, fungal, parasitic and viral infections 39 .
When it comes to hormonal differences, sex steroids, including When analyzing the age of death in men and women, it can be noticed that male individuals have a lower mean age than females. A study that investigated the immune response to SARS-CoV-2 infection showed that male patients have a high level of interleukin 18 (IL-18) with a more robust induction of non-classical monocytes, while women have a more robust activation of T cells than men during infection. A low correlation between the patients´ age was associated with a worse prognosis in men than women 43 , which may also explain the higher frequency of deaths in men at an earlier age. It is also important to note that many factors can accelerate the individual's biological age, including diet, physical exercise, habits and some comorbidities 44 .
Studies analyzing COVID-19 clinical and epidemiological data suggest that some medical conditions increase the risk of infections with worsening lung injury and death. The most common medical conditions are hypertension, cardiovascular diseases and diabetes 45 , in line with our study in which the majority of patients who died presented these medical conditions. Our study shows that the mean age of those from the group with no medical condition who died is lower than those from the group with at least one medical condition who died.
In addition, women, on average, have more medical conditions than men.
It is well established that the virus uses angiotensin-converting enzyme 2 (ACE2) receptors, which are on the surface of host cells, to enter the cell. Several comorbidities are associated with this receptor. Hypertensive patients often use ACE2 inhibitors and angiotensin receptor blockers in their treatments.
These inhibitors increase the expression of the ACE2 receptor, leading to an increased susceptibility to SARS-CoV-2 infection 44 . This increase in the expression of recipient cells in the lungs raises the chances of severe lung injury and respiratory failure 45 . When it comes to cardiac patients, there is a high risk due to the presence of ACE2 receptors in the cardiac muscles, increasing the occurrence of acute coronary syndrome that can lead to myocardial injury or infarction. An increase in inflammatory cytokines in COVID-19 can lead to ischemia and thrombosis 46 . In relation to diabetes, there is a protein called furin that is expressed at high levels in patients with this disease. The SARS-CoV-2 spike protein (S) is activated by increased levels of furin. This pre-activation of the protein S allows the entry of the virus into the cell by the ACE2 receptors, which can be life-threatening to diabetic patients 45 .

CONCLUSIONS
Finally, as we already know, the COVID-19 pandemic has brought relevant impacts on people's health and on the mobility dynamics of populations. In Uberaba, the epidemiological characteristics of the pandemic showed a total of more than 17,000 reported cases and more than 400 deaths recorded in a We must make sure we use those tools effectively, which means using them in all countries to protect the most at-risk groups. That's the best way to save lives, end the pandemic, restore confidence and reboot the global economy. But we're making progress 47 .