key: cord-0850492-nkwujhl5
authors: Tazerji, Sina Salajegheh; Shahabinejad, Fatemeh; Tokasi, Mahya; Rad, Mohammad Ali; Khan, Muhammad Sajjad; Safdar, Muhammad; Filipiak, Krzysztof J.; Szarpak, Lukasz; Dzieciatkowski, Tomasz; Jurgiel, Jan; Duarte, Phelipe Magalhãses; Rahman, Md. Tanvir; Sobur, Md. Abdus; Islam, Md. Saiful; Ahmed, Adnan; Shahen, Mohamed N.F.; Shehata, Awad A.; Gharieb, Rasha; Fawzy, Mohamed; Malik, Yashpal Singh; Jaganathasamy, Nagaraj; Rajendran, Vinodhkumar Obli; Subbaram, Kannan; Pakeer, Shaik Syed Ali; Ali, Sheeza; Rehman, Saif Ur; Ozaslan, Mehmet; Khan, Gulfaraz; Saeed, Muhammad; Younas, Umair; Imran, Safdar; Junejo, Yasmeen; Arabkarami, Parmida; Hogan, Unarose; Rodriguez-Morales, Alfonso J.
title: Global data analysis and risk factors associated with morbidity and mortality of COVID-19()
date: 2022-01-15
journal: Gene Rep
DOI: 10.1016/j.genrep.2022.101505
sha: ba94b04f14a3112d38cb7eae2698e9b7f1930af3
doc_id: 850492
cord_uid: nkwujhl5

This review was focused on global data analysis and risk factors associated with morbidity and mortality of coronavirus disease 2019 from different countries, including Bangladesh, Brazil, China, Central Eastern Europe, Egypt, India, Iran, Pakistan, and South Asia, Africa, Turkey and UAE. Male showed higher confirmed and death cases compared to females in most of the countries. In addition, the case fatality ratio (CFR) for males was higher than for females. This gender variation in COVID-19 cases may be due to males' cultural activities, but similar variations in the number of COVID-19 affected males and females globally. Variations in the immune system can illustrate this divergent risk comparatively higher in males than females. The female immune system may have an edge to detect pathogens slightly earlier. In addition, women show comparatively higher innate and adaptive immune responses than men, which might be explained by the high density of immune-related genes in the X chromosome. Furthermore, SARS-CoV-2 viruses use angiotensin-converting enzyme 2 (ACE2) to enter the host cell, and men contain higher ACE2 than females. Therefore, males may be more vulnerable to COVID-19 than females. In addition, smoking habit also makes men susceptible to COVID-19. Considering the age-wise distribution, children and older adults were less infected than other age groups and the death rate. On the contrary, more death in the older group may be associated with less immune system function. In addition, most of these group have comorbidities like diabetes, high pressure, low lungs and kidney function, and other chronic diseases. Due to the substantial economic losses and the numerous infected people and deaths, research examining the features of the COVID-19 epidemic is essential to gain insight into mitigating its impact in the future and preparedness for any future epidemics.

By the end of December 2019, Wuhan, Hubei Province, China, reported outbreaks of severe pneumonia with unknown causes in human residents [1] . The responsible pathogen was identified as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and the disease it caused was referred to as Coronavirus Disease-19 (COVID-19) [2] . Coronaviruses are enveloped, icosahedral symmetric particles and one of the major groups of viruses within the order Nidovirales, suborder Coronavirinae, and family Coronaviridae. Coronaviridae is categorized as the Letovirinae and Orthocoronavirinae subfamilies. Letovirinae includes the genus named as Alphaletovirus, whereas

Orthocoronaviridae is ranked into four genera: Alphacoronavirus (αCoV), Betacoronavirus (βCoV), Gammacoronavirus (γCoV), and Deltacoronavirus (δCoV) [3, 4] . COVID-19 is an acute respiratory infectious disease, which spreads mainly through the respiratory tract via droplets, respiratory secretions transferred from an infected person, or to a lesser degree with direct contact with contaminated fomites. The incubation period of this disease varies from 2 to 14 days (average five days) [5] . Some cases have an incubation period of 21-27 days [6] . On October 9, 2021, a total of 238,275,286 cases of COVID-19 cases were confirmed worldwide, including 4,861,159 deaths [7] .

Due to the enormous economic losses and the numerous infected people and deaths, research examining the features of the COVID-19 epidemic is vital to gain insight into mitigating its impact in the future and preparedness for any future epidemics. Therefore, in this review, we analysed the global data and risk factors associated with morbidity and mortality of COVID-19 in different countries, including Africa, Bangladesh, Brazil, China, Eastern Europe, Egypt, India, Iran, Pakistan, Poland, Turkey and UAE.

In central China, Wuhan is the largest and capital city of Hubei Province, also known as the "Chicago of China". It is considered central China's leading economic and industrial part, and the J o u r n a l P r e -p r o o f Journal Pre-proof estimated population is over 11 million [8] . Towards the end of 2019, cases of mysterious pneumonia were reported around the globe. In late December 2019, patients with similar symptoms of concentrated pneumonia with unknown aetiology were also informed in Wuhan. The massive public movement at Chinese New Year escalated the epidemic outspread all over China, turning into a severe public health crisis, and deaths were also reported [9] . The Chinese government and researchers responded swiftly, and after intense etiological and sequencing investigation, it was concluded that the SARS-CoV-2 virus causes the ongoing viral pneumonia epidemic. On January 30 2020, the World Health Organization (WHO) had stated it as a public health emergency, and later on, March 11 has announced it was a global pandemic [10] . Therefore, the researcher's utmost priority was to trace the SARS-CoV-2 natural inhabitants' and origin to minimise health risk restricting the cross-species and human-to-human transmission. For genetic diversity understanding, systematic whole genome-based molecular phylogenetic analysis and comparative genomic studies revealed that SARS-CoV-2 belongs to Betacoronavirus genera conduced to concentrated pneumonia outbreaks. The phylogenetic analysis based on the full-length genome indicated that SARS/SARSlike CoVs are the eminent ancestor, including two Bat SARS-like CoVs (ZC45 and ZXC21) as adjoining relatives of SARS-CoV-2 [9] .

Moreover, full-length sequence analysis demonstrated a higher sequence resemblance (~96%) with RaTG13 identified from Yunnan Province far away from Wuhan, pointing towards a transitional host for decussating species barrier [11, 12] . Then pangolin-derived CoVs were also considered for the epidemic; however, human SARS-CoV-2 possesses a furin cleavage site that was not observed in the spike protein of both pangolin and RaTG13 CoVs. Furthermore, Rhinolophus malayanus isolated CoV (RmYN02) had insertions in spike protein share high genome homology (93.3%) was also believed as a probable predecessor for SARS-CoV-2 [11] .

Wuhan city as a transport hub station and connecting cities have a higher traffic volume connection with Wuhan. Public movement at the Chinese New Year causes the infected person to spread quickly J o u r n a l P r e -p r o o f Journal Pre-proof throughout the country, resulting in an epidemic outbreak. The infection rate of COVID-19 was observed much more than SARS which took six months, while SARS-CoV took 54 days to spread throughout the country [13] ; factors faced by China hindering the management of the initial COVID-19 cases were undefined aetiology, controlled release of information to the public, public anxiety, and backlash against restrictive movement measures. Additionally, the choice between dealing with viruses of unknown aetiology and nature and alleviating possible public panic in politically and culturally sensitive times contributed to lies and cover-ups [14] . Weak capacities for the autonomous management of local health structures do not ensure timely response to crises. The privatisation of public hospitals contributed to a lack of public health resources to treat affected patients [14, 15] . So far (October 2021), Hubei Province was the hotspot of COVID-19 patients, with confirmed 96,410 cases and 4,636 deaths ( Table 1) . Other provinces of China have a lower infection rate.

Despite the dominant factor that elevates the spread of COVID-19 throughout the country, the Government of the Chinese took serious comprehensive and national response actions to combat the COVID-19 and has attained practical consequences based on empirical evidence. Some of the crucial strategies adopted by the government to reduce the COVID-19 epidemic are the following: i) Wuhan city that was the epicentre of the epidemic was first declared as a quarantine area and on January 23 2020, ii) the quarantine radius was broadened to the other cities of Hubei Province, and up to January 30, 45 million individuals were quarantined [16] . iii) All public transportation, including subway, ferry, and bus services, was closed, and railway stations, expressways, airports temporarily shut down. iv) All new year celebrations and gatherings were cancelled. v) The incubation period of medical facilities [14] . viii) To treat more than 14,000 suspected, mild, and close contact patients, all more critical sites, including convention centres and stadiums, were changed into 14 mobile cabin hospitals. ix) Additionally, in the epidemic area, the Chinese People's Liberation Army and other provinces dispatched medical teams of more than 42,600 medical staff to Hubei province to ensure to provide the medical facilities [14, 16] . x) Digital technologies were also utilised to control the situation. Health codes were provided on widely used mobile apps Alipay and WeChat, and everyone was registered. The QR code colour showing red, yellow, or green indicate the health status of an individual. To enter or leave any community, assigned QR code scanning was made compulsory, which helped trace the route of confirmed cases and identify their close contact. These measures are indeed helpful to control the epidemic. xi) China Ministry of Education postpones the new semester opening time in kindergartens, primary and secondary schools, and universities on January 27.

Internet technologies were used to reduce the delay in education, and virtual education platforms were introduced. Many Universities played a significant role in preventing and controlling the pandemic, opening up a free of cost educational platform for society [17] .

Conclusively, China's strict control actions have been evidenced to minimise the epidemic spread significantly. Furthermore, China provides result-oriented approaches that prove the best practices to reduce and eradicate the COVID-19.

Bangladesh, a densely populated country (with 162 million people and the eighth-most populous country in the world) of Southeastern Asia, is no exception and has already faced the devastating complexion in the health care system, daily social life and domestic economy [18] . The first official case of COVID-19 was confirmed in Bangladesh on March 8 with three positive cases (two men and one woman), of which those two men returned from Italy-the epidemic centre of COVID-19 at that time [19] . The 1 st death (a 70-year-old male) was recorded on March 18, 2020 [20] . However, specialists speculated that the disease entered the country before those cases but could not be J o u r n a l P r e -p r o o f Table 2) .

However, many cases may be undetected in the country due to the utmost shortage of testing assays.

The number of tests is pivotal to reveal the exact situation of COVID-19, especially death and recovery cases. Nevertheless, at the beginning of the COVID-19 outbreak, very few tests were performed to detect the cases with limitations and a severe scarcity of testing kits-that is why the positive results were under satisfaction at the initial stage. After passing the time, the number of testing was gradually increased, but in recent times, it decreased again.

J o u r n a l P r e -p r o o f As per the WHO report on COVID-19 in Bangladesh, till August 30 2021 [21] , the male showed higher confirmed (67%) and death (65%) cases compared to female (33% and 35%, respectively), the case fatality ratio (CFR) for males was higher than females. This gender variation in COVID -19 cases may be due to the cultural activities of males in Bangladesh. In Bangladesh, males mainly dominate outdoor activities and have to communicate with almost every class of people, demonstrating males as more vulnerable to COVID-19 than females. However, similar kinds of variations in the number of COVID-19 affected males and females globally. Variations in the immune system can illustrate this divergent risk comparatively higher in males than females. The female immune system may have an edge to detect pathogens slightly earlier. In addition, women show comparatively higher innate and adaptive immune responses than men because of having a high density of immune-related genes in the X chromosome [22, 23] .

Furthermore, SARS-CoV-2 viruses use SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) to enter the host cell, and men contain higher ACE2 than females. Therefore, males may be more vulnerable to COVID-19 than females [24, 25] . In addition, smoking habits also might make men susceptible to COVID-19. Some scholars believe the prevalence of COVID-19 in Chinese men was higher than among women because the smoking rate among Chinese men was much higher than among women [26] .

Considering the age-wise distribution, children and older adults were less infected compared to other age groups and the death rate augmented with age. The age group of 25-34 years accounts for the bulk of COVID-19 cases (24%), followed by 23% for the group of 35-44 years, 17% for 45-54 years, 12% for 55-64 years, 10% for 15-24 years, 7% for 65-74 years, 4% for 14 years and below, and the remaining 3% in the age group of 75 and above. The age group 65-74 years accounts for 30.5% of all The frontline COVID-19 fighters, e.g., physicians, medical staff, nurses, polices, journalists, law enforcement officers, judiciary members, the army, and others, were infected (more than 20,000) with the SARS-CoV-2 the rampant run of the current pandemic situation. As of May 3 2021, a high CFR (5.36%) was revealed within frontline doctors. However, the number of death of nurses and medical staff could not be recorded. The highest number of doctors affected were recorded in Dhaka (852) districts, followed by Chittagong (492) and Sylhet (349) districts. In addition, 812 nurses and 471 medical staff were infected in Dhaka city with the COVID-19 [28] . Police headquarters' data showed that most police were affected in Dhaka Metropolitan Police (2,330) among 11,431 infected cases. In addition, more than 11,500 police members were in quarantine, with 4,781 isolated cases and 7,463 recovered cases [29] .

Bangladesh is at risk with rising non-communicable diseases (NCDs) like which accounts 67% of total deaths (cardiovascular diseases-30%, cancers-12%, chronic respiratory diseases-10%, diabetes-3% and other NCDs-12%); only 26% and 7% of total deaths occur due to communicable and injuries, respectively, [30] . However, these NCDs are playing a pivotal role in the morbidities due to COVID-19. Moreover, a person having multiple comorbidities who have COVID-19 is at greater mortality risk. NCDs, e.g., heart diseases, hypertension, diabetes, chronic obstructive pulmonary diseases, malnutrition, among others, contribute to COVID-19 in Bangladesh [31] . In Bangladesh, 48% of males smoke, which is a significant factor for severe COVID-19 by damaging the lungs severely and affecting other parts of the body [32] . In addition, about 50% of aged Bangladeshis hold multiple comorbid conditions that have potentialities to put them at high risk for the severe form of COVID-19 [33] . In addition, the increasing COVID-19 morbidities reveal the scarcity of ICU, ventilator supports, and oxygen cylinders in the communities and rural clinics [35] . In the initial stage of the COVID-19 outbreak, the policymakers and health professionals lack the coordination that results in the expansion of COVID-19 into the community level. With the outbreak of COVID-19, the Bangladesh government tried to tackle the spread of the disease by postponing mass gatherings. However, several mass gatherings have been ensued in the amid of COVID-19 juncture, e.g. occurring of special prayer Raipur in Lakshmipur district with more than ten of thousands of people; voting in three constituencies (Dhaka city, Pabna, and Naogoan) of the national parliament; celebrating different religious festivals; attending of more than hundreds of thousands of people in the funeral of famous persons without taking any protective measures; travelling to tourist sites, among others [36, 37] . In addition, thousands of government and non-government service and readymade garment factory workers from northern and southern Bangladesh returned to their workplace, especially in Dhaka city, Gazipur, Narayanganj, Chittagong, ignoring their lives and the outbreak of COVID-19.

Furthermore, the expansion of local markets helped to spread COVID-19 at the community level.

Robust implementation of the strict protocol for social distance was not possible by Bangladesh Government, as millions of people all over the country, particularly in Dhaka, had to come out for their basic needs. Social distance protocol recommended by WHO could not be maintained during public transportation, gathering in public offices and banks, living in slums. Dhaka city, the capital of Bangladesh, has about 20 million populace, and it is designated as the epicentre of the COVID-19 pandemic in Bangladesh. More than 1 million slum possessors and marginal communities reside in J o u r n a l P r e -p r o o f the city's vicinity who lack adequate hygienic management, especially toilets/bathrooms and water facilities. That is why these facilities have to be shared within several families [38] However, enforcement of social distance law is almost impossible in high density

In the middle of October 2020, more than 7.8 million people were infected due to COVID-19 in India. India is the second-largest affected country in the world). Nearly one percentage (0.6%) of the population was infected with this virus among the total population. The disease's morbidity and mortality pattern depend on population density, comorbidities, mode of transmission, nature of the virus, and environmental condition [40] .

The density leads to closer contact and more interaction among residents, making them potential hotspots for the rapid spread of emerging infectious diseases [41] . According to Census 2011, the average population density in India is 382 km2. The states of Maharashtra (20.9%), Andhra Pradesh (10.2%), Karnataka (10.2%) and Tamil Nadu (9.0%) share 50% of confirmed cases and 60.4% of COVID-19 deaths in India. The state of Maharashtra shares 36.5% of deaths among the national total [42] . The population density in these states is above the national average. Further, in India, higher mortality has been noted in densely populated cities such as Mumbai, Delhi and Chennai compared with the smaller urban centres.

J o u r n a l P r e -p r o o f India, unfortunately, has a high burden of non-communicable diseases (NCDs), especially heart diseases, Diabetes and Respiratory diseases. The study in 2017, "India: Health of the Nation's States", also revealed that among the total deaths observed, 61.8%, 27.5% and 10.7% were NCDs, communicable diseases and injuries, respectively, in India [43] . Comorbidities and conditions that have been commonly observed in COVID-19 patients in India include hypertension, diabetes, heart disease, asthma, chronic obstructive pulmonary disease (COPD), low immunity, malignancy, bronchitis, and chronic neuromuscular disease, among others [44] . "The health ministry's analysis also shows that 53% of the COVID-19 cases were aged 60 years and above, notably elderly people and those with comorbidities are at higher risk of mortality. The WHO reported that globally, the highest percentage of cases had been reported in the 25-39 age group, with approximately 50% of cases in the 25-64 age group. However, the percentage of deaths increases with age, and approximately 75% of deaths are in those aged 65 years and above. The state wise mortality was shown in Figure 2 .

A more significant number of COVID-19 infections started to spread from March 2020. The Government of India has implemented the nation wise lockdown on March 24 and extended it up to August 2020. Most Indian states are summer (April to June) and monsoon (July to September).

Nowadays, the lockdown has withdrawn all the states of India [45] , and most of the Indian states started to receive the monsoon. This favourable situation may support the virus spread in India.

The estimated population of India in 2020 is 1,380,004,385, according to UN data. India population is equivalent to 17.7% of the total world population, and it is the second-most populous country after

China. The Indian state-wise mortality and morbidity data were collected up to October 15, 2020, from the Ministry of Health, India [46] . The state-wise total population, male population, female Despite the vast population, India effectively controlled the spread by adopting lockdowns and relaxation the lockdowns in a phased manner. Indian media also came hand in hand with the government and sensitised the people about regular hand washing, compulsory masks, and avoiding crowded places. Strict regulations for interstate and intra-state movement also helped reduce the COVID-19 spread. Further, India efficiently managed the vaccination programme for a larger population of people, one of the most extensive vaccination drives of a kind. The Indian healthcare system was given a red alert to handle the COVID-19 case, and special wards were established. By adopting the intelligent strategies, India efficiently reduced the COVID-19 spread and related deaths.

The Islamic Republic of Pakistan is in Southern Asia that has a multi-cultural and ethnic society that hosts one of the youngest, largest refugee populations (Afghanistan). Despite its proximity with J o u r n a l P r e -p r o o f Table 3) .

According to the data collected, Pakistan appeared to pass the Coronavirus peak in mid-June of 1 st episode. However, fewer cases have been reported daily since August started. The cases have attributed the curve's flattening to a combination of successfully targeted lockdowns by the government and pre-existing immunity in the population. There might, however, be small spikes in cases till October 15 2020.

The distribution of COVID-19 in Pakistan is heavily concentrated in a few key cities. The city of Karachi (as of September 5 2020) has recorded about 84,000 confirmed cases, making up about 28% of all cases of COVID-19 in Pakistan. Meanwhile, Lahore, the country's second-largest city, has recorded (as of September 5 2020) 49,000 cases of COVID-19, making up about 16% of the country's cases. Islamabad Capital Territory and Peshawar District also have both recorded over 10,000 cases. Karachi, Lahore, Islamabad, and Peshawar account for about 163,000 cases, which make up nearly 55% of the country's total confirmed cases.

Further, in Pakistan, higher mortality has been noted in densely populated cities such as Karachi, Lahore, and Islamabad than in the smaller urban centres. The health experts said that women had less exposure to gatherings than men as they did not contract the infection more than males. It is also reported that COVID-19 killed fewer women than men [50] . Some reports also said that not only J o u r n a l P r e -p r o o f among ordinary people but the number of positive cases and deaths was also higher among male health workers as compared to female health workers [51] . Since the advent of the epidemic, 2,481 healthcare providers have got an infection in the province, including 1,810 men and 671 women [48] .

They considered causes that include less exposure of women to crowded places, such as congregations, jobs, and hormonal effects. In Pakistan may be fewer causes of COVID-19. Females have different hormones than males, providing them safety against Coronavirus and heart attack [52] . Some people believe that as compared to men, women wore a veil, which acted as a facemask, so they have fewer Corona cases in Pakistan. Except to all, adherence to social distancing measures, hand-washing and wearing masks are the main precautions against COVID-19. All people, including men, women, transgender people and children, should follow the standard operating procedures [53] .

A few vulnerable factors faced by Pakistan that caused hindrance to managing the COVID-19 were undetermined aetiology, which results in depression, hostility, and high anxiety-like negative psychological behaviour among the public.

Furthermore, strict government policy to control the information led the people unaware of COVID-19, and the public was remained improvised. Additionally, the choice between dealing with viruses of unknown aetiology and nature and alleviating notorious public panic in politically and culturally sensitive times leads to lies and cover-ups [53] [54] [55] [56] . Weak capacities for the autonomous management of local health structures do not ensure timely response to crises. Eventually, the privatisation of many public hospitals leads to a lack of public health resources to treat affected patients [55, 56] . Other essential factors that came under a critical lens in Pakistan, such as religious, political, health, sports and unemployment, should be discussed here. Starting from C, returning followers from Iran, a Tablighi Jamaat religious gathering and prayer congregations could cause concern due to their potential to exacerbate the outbreak in the country. However, sops were followed during five-time prayers later, and hence there was no spike in the cases reported. In a report on June 16, at least 97 members of national and provincial assemblies across political lines J o u r n a l P r e -p r o o f tested positive for COVID-19, and six of them succumbed to death [57] . The situation gradually worsened, and the Government of Pakistan announced a Rs 2.5 trillion loss due to the COVID-19 in April 2020. After a short break, the government started to uplift the ban on many exports, including Afghan and China, after taking COVID-19 measures. When we saw the doctors and co-workers, COVID-19 also infected healthcare workers and co-workers in Pakistan, and the ratio is so high [58] .

Fears of COVID-19 did not stop in sports that suspended the last two essential matches of Pakistan Super League (PSL) 2020 and other sports. Moreover, The COVID-19 is considered the most significant factor causing the unemployment rate to increase, particularly daily wage workers.

Pakistan estimates that the unemployment will reach 6.65 million in the 2020-2021 fiscal year, compared to the previous fiscal year ) [48] .

Eventually, a second wave of the pandemic exploded, according to the authorities, on October 28 2020. The ground was all set for such a situation in Pakistan [59] . However, the terrifying slice is that circulation of the SARS-CoV-2 will not stop here, and COVID-19 can probably become a source of persistent infection. The first wave claimed 6795 lives, infected 332,186, left behind 632 on ventilators and suffered millions. Now we must watch the fourth episode. It just started in the country on June 25, 2021, and now has subsided after an intelligent lockdown in the various cities of Pakistan.

In Iran, the number of positive cases or patients with COVID-19 diagnosed based on PCR test from 

Turkey is a large, roughly rectangular peninsula that bridges southeastern Europe and Asia. The year 2020 opened a new chapter in the history of this region when a man who had returned to Turkey from Europe tested positive on March 11 2020 [61] . On October 6 2021, the updated COVID-19 situation of Turkey has 7,296,879 confirmed cases, 6,751,667 recoveries, and 65,137 deaths (Worldometer). The rapid increase of the confirmed cases in Turkey did not overburden the public healthcare system [62] , and the preliminary case-fatality rate remained lower than in many European J o u r n a l P r e -p r o o f countries [63] . Discussions mainly attributed these to the country's relatively young population and the high number of available intensive care units. However, sociological aspects such as dietary similarities can also play a role in the population response to the pandemic. The COVID-19 in these countries was compering to others in the world (especially to GI symptoms). 

Egypt may be partially attributed to the country's early intake of BCG vaccination [68] . Mostafa et al. (2020) [69] found that breast milk samples from the COVID-19-positive mothers after the first lactation were negative for the virus. The authors stated that breastfeeding is effective against infectious diseases because it strengthens the immune system by transferring antibodies from the mother and other anti-infective factors; therefore, all confirmed or suspected COVID-19 mothers with any symptoms should follow standard infant feeding guidelines with appropriate precautions [70] .

Some studies [71] assessed the Egyptian Health Care Workers' knowledge, attitudes, and perception regarding COVID-19. Unavailability of personal protective equipment (PPE), fear of transmitting the disease to their families, and social stigma were the most frequently reported reasons for increased risk perception. The first case of death in Egypt was recorded on March 8 2020. Many COVID-19 deaths (˃30 cases) during the first wave in Egypt were recorded between May 29-August 2, 2020, and the highest daily reported death cases were recorded on June 27 2020. The case fatality rates have elevated from 5.7% in the third week of March to reach 8.5% in the second week of April, followed by a slow decline to 2.6% in the fourth week of May. The first week of August showed the highest fatality rates of 15.1%, which decreased to 9.9% at the end of August. Fluctuation in the fatality rates was recorded from September to October, with the highest rate (13.9%) in the third month of September and the lowest rate (7%) in the fourth month of October. Again, fluctuation in the fatality rates was recorded over the period from December 2020 to September 2021. viral infections (Klein et al., 2010) . The risk assessment revealed no significant association between gender and COVID-19 severity and mortality among Egyptian patients [72, 73] . Psychological distress during the COVID-19 pandemic is a gender-related factor which female Egyptian physicians were at higher risk for developing psychological distress during the COVID-19 pandemic [74] .

Obesity is also associated with increased mortality among COVID-19 Egyptian patients [73], but there is no significant association between smoking and COVID-19 in the studied Egyptian patients [72, 73] . There is also the relationship between job and COVID-19, and the most frequently reported reasons for increased risk perception were fear of transmitting the disease to their families and social stigma [71] . Among Egyptian physicians, chronic diseases [74] and comorbidities [75] are potential risk factors associated with COVID-19. Diabetes mellitus, hypertension, ischemic heart disease, chronic kidney disease, chronic obstructive pulmonary disease, other chronic diseases were significant risk factors associated with COVID-19 severity and mortality among Egyptian patients

[73].

South Asia and Africa constitute many countries that are developing in nature. It is to be noted that there are genetically and antigenically related SARS-CoV-2 viruses that might already exist among animals and humans. Therefore, there may be a possibility that the people in these countries might have been already exposed to mild, non-SARS-CoV-2 viruses that can stimulate immunity against SARS-CoV-2. Due to cross-immunity, contact with domestic animals, low water quality, low food quality and other personal practices might have been a few reasons for infections due to non-SARS- 

Central-Eastern Europe is a broad and not precise term that cannot be easily defined based on historical, sociological, or economic criteria. Countries of this part of the world share many similarities yet remain different. The year 2020 opened a new chapter in the history of this region, revealing the unknown aspect of their similarity-the population response to the COVID-19

pandemics. The pandemic outbreak in Western Europe started and progressed with many mortal cases and the paralyses of health services. The Central and Eastern part of the continent also reported thousands of cases, but, fortunately, without such horrific mortality. This fact is a topic of the scientific debate worldwide trying to explain the cause of this observation. The number of infections and deaths in countries of Central-Eastern Europe is shown in Table 4 .

Data suggest the disproportion between the high cumulative number of cases with infection and low death number. This observation suggests certain factors that promote effective transmission of the virus and low mortality from COVID-19. Indeed, there cannot be one aspect that leads to these observations, but the explanation might be a mix of a few hypotheses [76] . To those having the most significant impact, we should include:

 The younger age of the population; the countries of this region have younger ages of the population compared to the age in Western Europe. 

So far, Brazil has 21.499.074 confirmed cases of COVID-19 and 598.829 deaths. If analyses by region, the southeast has the highest number of reported cases and deaths (39.1% and 47.4%, respectively), followed by the regions northeast (22.3% and 19.5%, respectively), south ( 19.3% and 15.6%, respectively), midwest (10.6% and 9.6%, respectively) and north (8.6% and 7.8%, respectively) [77] . The southeast region has the highest CFR (3.38%), while the South region has the lowest CFR (2.25%) ( Table 5 ).

The Ministry of Health has published the Guidelines for Diagnosis and Treatment of COVID-19, which contains general measures to prevent and combat infection caused by SARS-CoV-2. Among the measures, we highlight hand washing, wearing a mask, social distance, respiratory etiquette and food security [78] . Unfortunately, although several measures have been implemented, Brazil appears as the third country with the most reported cases, behind only the United States of America and India As it is a continental country, the pandemic develops in conditions closely linked to regionality.

Issues such as demography and geography of the region, access to basic sanitation and hygiene items, the structure of the local health system, number of unemployed people or informal workers and the economy must be taken into account in each region and city, individually. In addition, political issues and corruption make it difficult to control the pandemic. Regarding the basic sanitation in the states, the average rate of urban service by water network indicates values above which means that there is one bed for every 8.456 people [83] .

It is essential to mention seasonal contagious infectious diseases, increasing the risk of death from COVID-19. An example of that is dengue [84] , a disease that has significant seasonal occurrence in hot months, corresponds to the first semester of the year and the beginning of the pandemic of SARS-CoV-2 in the country [85] . The 2017 epidemiological bulletin published by the Health Surveillance Secretariat of Health points to a number of 249,056 probable dengue cases in Brazil that

year [85] .

The relation between the confirmed cases, the economic crisis and unemployment, must be better studied since low-income people and out of the labour market tends to ignore the social distancing in the search for subsistence.

According to official data [86] , the unemployment rate in Brazil in September-October-November and October-November-December 2019 was 11.2 and 11%, respectively. In May-June-July 2020, with the pandemic ongoing, the unemployment rate was 13 [86] .

Another spotlight data is that 1 in 5 Brazilian workers received less than half of the minimum wage in 2019. The average income between the 20% with lesser work income was just R$ 471 in 2019 [89] .

Although the Federal Government has implemented a social protection program for the most vulnerable population, called Emergency Aid, to people in socioeconomic vulnerability, the amount J o u r n a l P r e -p r o o f was not able to guarantee people's subsistence, taking many of them to the streets to perform informal work activities to supplement family income [90] [91] [92] [91, [93] [94] [95] .

According to a survey, Brazil possesses 38,8 million people who work informal jobs, representing 41,4% [96] .

The problems generated by the pandemic culminate in a more There is no denying that corruption plays a fundamental role in the morbidity and mortality in the country since once these resources are diverted or arrive late to the health system, they end up exposing the vulnerable population to the disease without medical or hospital diagnosis or support.

Efficiency in controlling the pandemic is due to the coordination of measures adopted in all spheres.

Unfortunately, in Brazil, the federal public response is uncoordinated [102] . Recently, we had the first governor to be impeached in an impeachment process in the history of the Republic. The governor is accused of leading a scheme of corruption in the health's area during the construction of campaign hospitals [104] . These measures demonstrate difficulty in reaching consensus in a country with so many political disputes. In addition, the federal government has made several changes in the role of the Minister of Health during the pandemic, which made the enabling of beds from the ICU that depends on transfers from the federal government [105] [106] [107] .

Underreporting is a problem that aggravates crisis management caused by the new Coronavirus. In

Brazil, low availability of RT-PCR (reverse transcription-polymerase chain reaction) tests forced the Ministry of Health to recommend testing for only severe cases [77] at the beginning of the pandemic.

Unfortunately, this factor goes against the guidelines and strategies for coping with the pandemic since the practice of testing is a primary factor as an organizational measure of the health system [108] .

The use of medication without proven scientific evidence may also have contributed to morbidity and mortality. There are cases of purchase of these drugs that make up the "COVID kit" being delivered to the population upon prior consultation, diagnosis and medical prescription, specifically those seeking primary health care, to allow the early treatment of patients with COVID-19 [109, 110] . In addition, many people fail to compress proven effective measures, such as social distance, because they believe in the effectiveness of these drugs in case of contamination by the virus.

In a study realized with 11.330 adults, it was possible to see that remdesivir, hydroxychloroquine, lopinavir and interferon had little or no effects on patients hospitalized with COVID-19, as indicated by general mortality, the onset of ventilation and length of hospital stay [111] .

In a statement, a pharmaceutical company, developer of Ivermectin claimed their position about the use of the medicine during the pandemic of COVID-19. However, after analysis, the scientists from the company have observed, until the moment, not a single scientific base to a potential therapeutical effect. Furthermore, against the COVID-19 from pre-clinic studies, there is no significant evidence of the clinical activity or clinical efficiency on patients of COVID-19 and the alarming lack of security data in most studies [112] .

The flexibilization of the restriction measures without having the collaboration from the people may lead to an increase in the number of cases, being necessary new restrictions [113] , which in addition to damage the health and economy areas, leads to a lower population adherence due to the prolonged period of restrictions and flexibilities.

The holding of municipal elections in the country, followed by the Christmas celebration, new year and vacations, could contribute to the rise of the number of cases in the country [114, 115] .

However, although several factors favour the continuity and escalation of the pandemic, the population still has a free, unrestricted and universal health system, the Unified Health System (SUS) [116] . Among all the aspects pointed out during the pandemic, the SUS is undoubtedly strengthened.

Although it needs improvement, the system is fundamental in such an unequal country, mainly because it is not a system that discriminates or predilects. Its importance can be exemplified in the excerpt of Law 8.080 / 90, [117] known as the Organic Health Law, which brings as principles and guidelines the universality of access to health services at all levels of assistance and comprehensive care. In addition to the various social inequalities that plague the already vulnerable Brazilian population, such as lack of basic sanitation, access to essential health services, unemployment, and low income, it is clear that the political and economic instability that occurs in Brazil, as well as corruption, ends up catalyzing the pandemic and potentiate inequalities. Therefore, public policies aimed mainly at the poorest population must be implemented to minimize the damage caused by the pandemic to the population, whether directly or indirectly. Even having worked beyond its operating J o u r n a l P r e -p r o o f limit at various times during the pandemic, the SUS is unique and essential for the population. It is a system that does not discriminate against any individual who uses it. Therefore, investing in SUS is fundamental for health promotion in Brazil. [119] . Majority of the patients with severe disease were males, often with one or more commodities, such as diabetes, hypertension, obesity, liver and cardiovascular diseases [120, 121] . Notably, the mean age of UAE cases tended to be lower than that reported in many other countries, reflecting the younger population of the country. The highest peak of cases and deaths occurred in January 2021.

The overall mortality rate in UAE was much lower than many other highly developed nations, including UK, US, Germany and France. 2 There are a number factors which are likely to have contributed to the low mortality seen in UAE. UAE reported its first cases on 29 th Jan 2020 in a family of four who travelled from Wuhan, China [122] . UAE government's early, decisive and were established in record time [123] . Travel restrictions started as early as Jan 31 with suspension of all flights from China, except Beijing. On 9 th Feb, the Health Ministers of the six neighboring Gulf countries announced cross-border preventive measures. Travel restrictions were gradually extended to other countries reporting high rates of infection. By April, a number of other containment and mitigation measures were introduced, including, suspension of public events, closure of educational institutions and introduction of online teaching [124] . Tourist attractions, entertainment destinations, and places of public worship were suspended. Moreover, early implementation of social distancing, mandatory use of face masks, and rigorous contract tracing and isolation, were fundamental in containing and controlling the outbreak [124] .

Other essential measures and policies swiftly implemented early in the outbreak, included, free health care and treatment for all COVID-19 patients, establishing field hospitals and drive-through PCR testing, and introduction of digital platforms for recoding tests and facilitating quarantine and isolation procedures [123, 124] . Indeed, the country had the highest PCR testing rates in the world [124] . UAE was also amongst the first to launch phrase III clinical trial for COVID-19 inactivated vaccine (Sinopharm) in July 2020 [125] . The vaccine was approved for emergency use at the end of September 2020 and rolled out for mass vaccination by December. In addition to the inactive vaccine, the mRNA (Pfizer) vaccine was also used. By July 2021, more 65% of the population had been fully vaccinated and booster doses were being introduced. As of December 2021, a staggering 98% of the population had received at least 1 dose [119] .

To summarize, UAE's early and decisive response to the pandemic, coupled with implementation of appropriate public health measures and world-class healthcare facilities, contributed to limiting the mortality from COVID-19. Having a young population is also likely to have helped. their availability is questionable. Even the WHO itself has expressed concern about vaccine availability to cover the majority of the world's population at risk. Therefore, it is crucial to identify the risk factors in detail to take intervention measures to control the pandemic. 

Not applicable.

All data analysed or generated during this study are included in this publication and its additional files.

Not applicable.

Not applicable.

The authors declare that they have no competing interests. J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f

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We want to thank Dr. Baharak Akhtardanesh, Professor, The Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Iran and Dr. Farrokhreza Kabir, Assistant professor, The Department of Clinical Sciences, Faculty of specialized Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran for their critical comments on this paper.

J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Ethical approval: We have followed all ethical approvals for this study.Informed consent: All authors have read and approved the contents and manuscript.J o u r n a l P r e -p r o o f