Coronaviruses are positive‐stranded RNA viruses that taxonomically come under the family Coronaviridae and subfamily Coronavirinae, which can be divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. In their structure, they are enveloped viruses with a positive‐sense single‐stranded RNA genome having spherical, oval or pleomorphic shape. Viruses from this family may infect a wide variety of hosts, producing symptoms and diseases that can be mild, moderate or fatal, such as the Severe Acute Respiratory Syndrome (SARS), caused by the SARS-CoV, and the Middle East Respiratory Syndrome (MERS), caused by MERS-CoV. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) belongs to genus Betacoronavirus ^{1 , 2} .

The SARS-CoV-2, baptized by the International Committee on Taxonomy of Viruses (ICTV), contains higher conserved sequences in open reading frame (ORF) 1a/1b. SARS-CoV-2 infects humans, and it is the etiologic agent of the Coronavirus Disease 2019 (COVID-19) ^{1 , 2} . The structure of SARS‐CoV‐2 contains a positive‐sense single‐stranded RNA genome packed in the virus membrane envelope. The ORF1a is the longest ORF that occupies almost two thirds of the genome. The ORF1b overlaps with ORF1a following shorter subgRNAs (sgRNA) that encodes four structural proteins, spike (S), membrane (M), envelope (E) and nucleocapsid (N), in addition to others accessory proteins. The M protein promotes membrane curvature that helps to bind the nucleocapsid. Protein E executes an important role in viral pathogenesis. The N protein assembles two domains that are able to bind the viral RNA genome by different mechanisms. N protein also interacts with nsp3, helping to pack and to encapsulate the genome structure inside the virions. The SARS-CoV-2 virus surface possesses S proteins that play pivotal roles in viral attachment, fusion and entry, establishing a hot spot to the development of therapeutics against the virus. SARS-CoV-2 S protein includes the receptor binding domain (RBD), known to interact strongly with the receptor angiotensin converting enzyme 2 (ACE2) ^{2 , 3 , 4} .

On March 11, 2020, the outbreak of COVID-19 was elevated to a pandemic status by the World Health Organization (WHO), meaning that the disease affects several different countries ⁵ . The first case was described in the Chinese city of Wuhan on December 1, 2019. In Brazil, the first case was reported on February 25, 2020, in the city of São Paulo, whereas the first case in Uberaba was reported on March 18, 2020 ⁶ .

The high transmission of SARS-CoV-2 has caused a greater absolute number of deaths than the combination of the epidemics caused by SARS-CoV and MERS-CoV. By the end of this work, at the end of October, Brazil had a lethality rate of 2.8%, a mortality rate of 289 per 100,000 inhabitants ⁶ . The epidemiological data of individuals infected by the virus, as analyzed in a Brazilian study, showed a number of 514,200 patients in the period ranging from February 25 to May 31 of 2020. Patients were predominantly male, with an average age of 59 years. The death rate was approximately 5.7% and 83.7% of these individuals confirmed with COVID-19 showed at least one medical condition: 66.5% had cardiovascular disease and 54.5% had diabetes ⁷ .

Several studies have been carried out in Brazil with the aim of evaluating the incidence and prevalence of COVID-19 in states such as Ceará ^{8 , 9} , Roraima ¹⁰ , Paraná ¹¹ , regions such as the Ribeira Valley ¹² , Amazônia ¹³ , South ¹⁴ and Brazilian municipalities such as Uberlândia ¹⁵ and Patos de Minas, in the State of Minas Gerais ¹⁶ , and Teixeira de Freitas in Bahia ¹⁷ .

Uberaba, a city in the Triângulo Mineiro, has a land area of 4,539.57 km ² and an estimated population of 340,277 people ¹⁸ . Isolation measures in the city of Uberaba began on March 18, 2020, with the suspension of surgical services, attendance in clinics and other areas related to health. Soon after, the isolation measures took greater proportions, with the closing of commercial establishments, leisure places and restaurants, leaving only services considered essential, such as supermarkets, pharmacies and hospitals open. Establishments were allowed to reopen with mandatory protective measures, such as social distancing, hygiene, and mandatory use of masks in May 2020. By the end of 2020, a decree prevented the operation of in-person teaching networks, restaurants, gyms, parties and the like ¹⁹ .

With the continuous unfolding of the pandemic, the COVID-19 Observatory - Uberaba ²⁰ was created – an initiative by researchers from the Federal University of Triangulo Mineiro (UFTM) in partnership with the Uberaba City Hall. The group presents weekly reports with information about the epidemiology of the disease, helping to provide the population with safe information via website (https://coviduberaba.github.io) and contributing to raise awareness about the situation.

Given that, this work aimed to outline an epidemiological profile and to understand the dynamics of the disease in the city of Uberaba.

The study presents an analysis of reported cases of COVID-19 in the city of Uberaba, state of MG, Brazil, during one year of the pandemic. The first reported case was on March 18, 2020 and, by March 17, 2021 the city accounted for 17,254 reported cases of people infected by the new coronavirus. The first peak in the city occurred on September 21, 2020, with a moving average of daily cases of 107 cases. After this date, the moving average of daily cases started to decelerate, returning to break records in the second wave that started in the first half of January 2021, with 120 daily cases reported in the moving average and a new peak on March 10, 2021, with a moving average of daily cases of 129 cases.

Figure 1 shows the frequency of reported cases of COVID-19 by epidemiological weeks. The first peak occurred in epidemiological week number 38 (S38) in the year 2020, with 735 cases, while the second peak, in the studied period, was in S10 in the 2021, with 885 cases. This represents a 20.00% increase of the reported cases. In addition, the city reported 9,741 cases in the year 2020. Until March 17, 2021, the city already had 7,513 cases, which represents 77.00% of the total of the previous year.

Figure 1 Source: Elaborated by the authors, 2021.

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 female group was, on average, older (41.64 years ± 16.97) than the male group (40.67 years ± 16.27). Figure 2(b) shows, in green, the relative frequency of reported cases of COVID-19 by age group in the city of Uberaba from March 18, 2020, to March 17, 2021. The most affected age group was the one ranging from 30 to 39 years, with 25.83% of total cases. The 20 to 49 age group accounts for 64.75% of the reported cases of COVID-19 in Uberaba. The average age of the total number of cases was 41 years ± 16.64.

Figure 2 Source: Elaborated by the authors, 2021.

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. Figure 4(a) shows that the average age of confirmed deaths was 68.85 years (± 15.68). Figure 4(b) shows the relative frequency of reported deaths of COVID-19 in the city of Uberaba grouped by age. As of March 17, 424 deaths were reported, indicating a general lethality rate of 2.45%. The minimum age was one 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%.

Figure 3 Source: Elaborated by the authors, 2021.

Figure 4 Source: Elaborated by the authors, 2021.

It is possible to analyze the lethality degree of the new coronavirus by age group. Figure 2(b) , in purple, also compares confirmed deaths with reported cases of COVID-19 by age group of affected population. The younger age population shows the highest incidence of cases, yet with a very low lethality rate. The highest lethality was found in the age group of 90 years or older, with 34.62% of deaths among the reported cases from this age group, as shown in Figure 4(b) . Most deaths were from the male sex (57.78%). The lethality rate among men was 2.93%, whereas among women, the rate was 2.00%. The females showing higher average age (71.41 years ± 15.92) than male (67.00 years ± 15.30).

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) . The mean age of the group with no comorbidities who died was lower (61.90 years ± 17.01) than the group that reported having medical conditions (70.58 years ± 14.86).

Figure 5(b) groups the number of comorbidities in individuals who died from coronavirus. In relation to 424 deaths, 85 (20.04%) did not indicate any previous comorbidities. Among these, 32.94% were female and 67.05% were male.

This study traced the epidemiological profile of the city of Uberaba-MG in the first year of the COVID-19 pandemic. The results of this epidemiological investigation indicate a greater involvement of females, aged between 20 and 49 years. Regarding deaths, there is a higher mortality rate in males, aged over 60 years, with a history of hypertension, heart disease, diabetes, obesity, among others.

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 men were, on average, younger than women. Men dying from COVID-19 are younger and have fewer medical conditions compared to women.

As of March 17, 2021, the COVID-19 pandemic in Uberaba resulted in 17,254 reported cases, with a peak of 129 cases on March 10, 2021. It is observed that the total number of cases in 2021 until March 17, in just eleven weeks, represents more than 77.00% of the total cases in 2020. The biggest peak of the second wave in the city of Uberaba happened in epidemiological week number 20, in mid-June, with more than 1,300 cases per week ²⁰ . The difference in the total number of cases from the first peak to the second, in the period studied and throughout the rest of the year, is explained by the new variants that emerged in the country that contributed to the increase in the incidence of cases and deaths ²¹ . The disease was also responsible for 424 deaths in the city, of which 42.60% were notified in the period studied in 2021, coinciding again with the emergence of new variants.

The first peak of reported cases in Brazil occurred on July 29, 2020 ⁶ , and a possible explanation to this difference relates to the fact that the pandemic started in the Brazilian capitals, mainly those with international airports. Based on the sequencing and analysis of viral genomes, another Brazilian study showed that there were more than 100 international entries of the virus in Brazil, mainly from European countries. During the initial stage of the pandemic, capitals with international airports suffered the first peaks of the disease, progressively spreading to interior regions such as the Triângulo Mineiro.

Our study also revealed that the 20–49-year age category gathered the highest number of contaminated individuals. On average, they were 41 years old. These data are in accordance with studies carried out in Pakistan, where contaminated individuals were, on average, 47 years old, with the 20–69 age category showing a higher frequency of infections ²² . Similar results were observed in one of the first descriptions of the epidemiological characteristics in Wuhan, with a mean age of 49 years old ²³ and Australia, mean age of 37 ²⁴ . National studies also came to the same conclusions with the example of Macapá ²⁵ , with a mean age of 40 years old, and the state of Santa Catarina ²⁶ , with 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 testosterone, estrogen and progesterone are potent regulators of immune and inflammatory regulatory responses. Estrogen in women can have immune-boosting effects while testosterone secreted by testicles can have immunosuppressive ones ^{40 , 41} . Testosterone can also predispose men to COVID-19 infection by means of co-regulation of the expression of the angiotensin-converting enzyme 2, which may facilitate the entry of virus in cells, thus increasing the number of infected men and the disease severity ⁴² .

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 .

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 year of the pandemic. The beginning of the year 2021 contributed with many cases and deaths and this increase coincided with the emergence of new variants. The patterns of incidence, age group and biological sex found in this study are similar in different regions of the country and the world. Young people are more affected by the disease; however, older adults show higher lethality rates. Factors such as lifestyle and prevalence of medical conditions are associated with the results and conclusions found.

The analysis of the epidemiological characteristics of individuals affected by the COVID-19 is important so that all branches of the government can determine actions and measures in favor of public health. The dissemination of the epidemiological characteristics and its analysis also serve to alert the population of their conduct in the midst of an unprecedented pandemic like this. The recent vaccination of the population should not be used as a relief to reduce care and prevention against the virus. New variants are spreading faster than the December 2019 Wuhan version, which makes the coronavirus epidemiological surveillance permanent.

Vaccination in the city of Uberaba began on January 20th with health professionals. Until the period studied on March 17, 2021, only the elderly over 85 years old had received the doses. Within the period, it was not possible to affirm a decrease in the mortality rate of the elderly.

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 .

Figure 5 Source: Elaborated by the authors, 2021.