key: cord-0926131-3r0r20bn authors: Meskini, Maryam; Rezghi Rami, Mina; Maroofi, Parang; Ghosh, Soumya; Siadat, Seyed Davar; Sheikhpour, Mojgan title: An overview on the epidemiology and immunology of COVID-19 date: 2021-08-04 journal: J Infect Public Health DOI: 10.1016/j.jiph.2021.07.021 sha: d182ad10ced90a8ebb4a0861b4a54ce75787729a doc_id: 926131 cord_uid: 3r0r20bn Coronaviruses are a large family of viruses that cause illnesses ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and the 2019 novel coronavirus infection (COVID-19). Currently, there is no analyzed data to examine the outbreak of COVID-19 by continent and no determination of prevalence trends; this article reviews COVID-19 epidemiology and immunology. This article reviewed original research, reviews, governmental databases, and treatment guidelines to present the epidemiology and immunology of COVID-19. Reports from patients who were COVID-19 infected showed typical symptoms of neutrophilia, lymphopenia, and increased systemic inflammatory proteins of IL-6 and C reactive protein (CRP). These observations agree with the results of severe conditions of MERS or lethal cases of SARS, in which there is an increased presence of neutrophils and macrophages in the airways. Additionally, analyzed data showed that Europe (49.37%), the Americas (27.4%), and Eastern Mediterranean (10.07%) had the most cumulative total per 100,000 population confirmed cases, and Africa (6.9%), Western Pacific (3.46%), and South-East Asia (2.72%) had the lowest cumulative total per 100,000 population confirmed cases. In general, the trend lines showed that the number of confirmed cases (cumulative total) and deaths (cumulative total) would decrease. In December 2019, unidentified pneumonia emerged in Wuhan, China, where many of the original patients had visited the seafood market of Wuhan. The isolation of the related virus from patients and subsequent molecular analyses indicated a 2019 novel coronavirus infection, which was named coronavirus disease 2019 (COVID- 19) by the World Health Organization (WHO) [1, 2] . The explosive growth of COVID-19 infection in January 2020 necessitated that the WHO declare this outbreak a public health emergency of international concern (PHEIC) [3, 4] . Unfortunately, international travel spread the virus worldwide, and 192,284,207 confirmed cases, including 4,136,518 deaths, were reported by the WHO on 23 July 2021. After the shocking health threat from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), a significant negative impact was felt on affected countries' economies. Searches on SARS-CoV showed a 'bat' origin and the transmission to humans via Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) [5] [6] [7] [8] . Afterward, the well-known Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged with rare transmission to humans with a higher fatality rate. Alpha and beta coronaviruses dispersed in China are mainly and naturally carried in bats. The study of the genetic diversity and molecular evolution of these coronaviruses has gained intense interest [9] [10] [11] . J o u r n a l P r e -p r o o f 5 Due to the many human casualties caused by the COVID-19 in a short time around the world, many scientists sought to find the infection's mechanism and to collect the following demographic data. There is, however, no analyzed data to study the course of the disease and its prevalence trend. Therefore, this study reviewed COVID-19 epidemiology and immunology using original research, reviews, governmental databases, and treatment guidelines. The COVID-19 epidemic started with the first announcement on Feb. 20, 2020, of the fatalities (2239 cases) in China, including 75 cases on the mainland, 68 in Hong Kong, 10 in Macao, 26 in Taiwan, and the confirmed reports (1200 cases) elsewhere [12] . Three stages can roughly be observed from the epidemiology of COVID-19 ( Fig. 1 ). In the first stage, the epidemiologic analysis showed close contact was the key factor in-person-to-person transmission [13, 14] . In the second stage, the reported cases outside Wuhan, in Beijing City and Guangdong indicated the spread of the virus, with the total number of infected cases rising to 205. Then 29 provinces of China and six countries conveyed 846 confirmed reports with an increase of 20 times faster than the first stage. Even though Wuhan's lock-down was implemented, more than 5 million people had already left Wuhan due to the Chinese New Year. In the third stage, 50-80% of all confirmed cases were clustered around Beijing, Shanghai, Jiangsu, and Shandong on Feb. 10, 2020 [15] . When the numbers increased 240 times and reached 9826 confirmed cases, the WHO declared PHEIC. About 44730 infected cases and 16067 suspected cases were recorded in 1386 counties and regions in China on Feb. 11, 2020 [16] . In this stage, the fatality rate was high in China (1114 reported deaths) and low outside China (one fatality in the Philippines). With the growth of new clinical definitions for diagnosis, the confirmed cases bounded to 14840 in China. In contrast, 60329 reported cases were recognized in 25 countries, with a 1471 times increase since the last report [15] . Regrettably, as of Feb. 11, 2020, 1716, medical-related staff from 422 medical institutions were infected. Among them, 64% were infected in Wuhan city and 23.3% in the rest of Hubei [17] . Preliminary evaluation of the dynamics of COVID-19 transmission indicated the basic reproductive number of about 1.4-3.9 for COVID-19 [18] . The R0 of SARS-CoV and MERS-CoV was 2.3-3.7 and 0.50-0.92 respectively in the absence of interventions [19] . The weekly operational reports of the WHO until July 23, 2021is given in Table 1 . The July 23, 2021 report of the WHO showed 192,284,207 confirmed cases of COVID-19, including 4,136,518 deaths. Globally, over 192 million confirmed cases of COVID-19 were reported by the WHO until July 23, 2021. The updated data from confirmed cases and related deaths worldwide can be found on the WHO website. Since the first reports of cases from Wuhan at the end of 2019, cases have been reported in all continents except Antarctica. The number of confirmed cases and related deaths are reported in Table 2 . J o u r n a l P r e -p r o o f Until July 23, 2021, Europe (45.35%), the Americas (27.24%), and Africa (9.89%) had the most newly reported cases in the last seven days per 100000 population confirmed cases. In the same period, Western Pacific (8.18%), Eastern Mediterranean (6.3%), and South-East Asia (3.01%) had the lowest newly reported cases in the last seven days per 100000 population confirmed cases. Furthermore, Europe (52.91%), the Americas (31.32%), and Eastern Mediterranean (6.93%) had the most cumulative total per 100000 population death cases until July 23, 2021, Africa (5.36%), Western Pacific (2.2%), and South-East Asia (1.24%) had the lowest cumulative total per 100000 population death cases. Until July 23, 2021, the Americas (60.46%), Africa (17.18%), and Europe (7.14%) had the most newly reported death cases in the last seven days per 100000 population. In the same period, Western Pacific (5.82%), Eastern Mediterranean (5.44%), and South-East Asia (3.92%) had the lowest newly reported death cases in the last seven days per 100000 population. By comparison, the confirmed cases-cumulative and confirmed cases-cumulative total per 100000 population, the confirmed cases in Africa, Eastern Mediterranean, Western Pacific, and Europe increased but confirmed cases in the Americas and South-East Asia decreased. Inside, by comparison, the rate of death cases-cumulative and death cases-cumulative total per 100000 population, an increase in death cases of Africa, Eastern Mediterranean, Western Pacific, and Europe was evaluated, and a decrease in death cases of Americas and South-East Asia was considered (Fig. 2 ). Cases -cumulative total Cases -cumulative total per 100000 population Deaths -cumulative total J o u r n a l P r e -p r o o f The Cases-newly reported in seven last days trend line in Fig. 3 , shows that until July 23, 2021, the number of newly cumulative total cases increased, and the cases-newly reported in seven last days per 100000 population trend line in Fig. 3 , shows that until July 23, 2021, the cumulative total cases per 100000 population in the last seven days decreased. In this period, Europe had the highest, and South-East Asia had the lowest number of newly cumulative total cases and cumulative total cases per 100000 population in the last seven days. 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 Most infected people (more than 80%) will develop mild to moderate illness without symptoms and recover without hospitalization, but less than 20% of infected patients have severe symptoms and are critically ill [20, 21] . Presently, there is incomplete evidence on host factors affecting individual outcomes in COVID-19. Fever, dry cough, and tiredness are the most common symptoms; less common symptoms include aches and pains, sore throat, diarrhea, conjunctivitis, headache, loss of taste or smell, skin rash, and discoloration fingers or toes To find the escape mechanism of COVID- 19 J o u r n a l P r e -p r o o f The expression of ACE2 on cardiac and vascular endothelial cells may elucidate cardiovascular complications in patients [16] . It is not evident whether and how the SARS-CoV-2 can also infect immune cells containing monocytes/macrophages and T cells. On monocytes and macrophages, the expression of ACE2 is not ubiquitously observed, and for SARS-CoV-2 this may offer a mechanism of entry into immune cells. Immune To some extent, the novel coronaviruses may also discharge these mechanisms inducing T cell apoptosis [44, 45] . Lymphocytes may also become exhausted due to pro-inflammatory cytokine expression by native immune cells engaged in the lungs and trigger hyper-inflammation during a cytokine storm [46, 47] . In some cohort studies, the key results were associated with negative consequences in COVID-19, as in SARS [49] . These observations agree with the results of severe conditions of MERS or lethal cases of SARS in which the presence of neutrophils and macrophages were increased in the airways [49, 50] . Other studies of severe clinical phenotypes and ICU J o u r n a l P r e -p r o o f dependency of patients have presented a link with higher levels of plasma from innate chemokines, definitely the pro-inflammatory cytokine TNF-α, chemokine (C-C motif) ligand 2 (CCL2), C-X-C motif chemokine 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), interferon gamma-induced protein 10 (IP-10), and macrophage inflammatory protein (MIP-)1 A/CCL3 [51, 52] . This is a condition previously described in SARS and MERS inflammation with poor consequences. Enhanced activation of the innate immune system contributes to morbidity and mortality in COVID-19, contradictory to immune evasion mechanisms, including expression activation of T1IFN, IL-1β, IL-6, and TNFα. One probable description is that the endothelial induction, vascular cell damage, and cell death have resulted from replicating the COVID-19 virus. Cell deaths are due to inflammation, including necrosis or pyroptosis in pro-inflammatory cytokine expression, recruitment, and activation of immune cells [53] . It is proposed that uninfected immune cells recruited to the infection site show inflammatory responses of unwell and robust control, leading to damage of tissues and systemic inflammation [54] . The other probable explanation relates to the production of neutralizing antibodies against coronaviruses in the early stages of damaged organs. The phenomenon of antibody-dependent enhancement (ADE) increases damage throughout viral infections. It should be noted that the promotion of virus particle uptake is connected to immune system complexes in binding to Fcγ receptors (FcγR). Viral replication in immune cells and immune complexes are both mediated inflammatory responses in the damaged tissues of acute respiratory distress syndrome (ARDS) (Fig. 7) [46, 55] . The histopathologic reports of tissues from COVID-19 patients showed the advanced features associated with immune complex-mediated vasculitis, including monocyte infiltration, thickening of blood vessels, and hemorrhage [56] [57] [58] . Generally, patients with severe symptoms of COVID-19 experience cytokine storm, lymphopenia, and often lymphatic tissue atrophy, specifically lymph nodes [59, 60] . This cytokine storm corresponds to the reports of hemophagocytic lymphohistiocytosis (HLH), inspiring cell death and hypo-cellularity of lymphatic organs [61] [62] [63] . J o u r n a l P r e -p r o o f The available data associated with age is insufficient, but children seemingly do not progress to severe indicators or difficulties associated with COVID-19. This is surprising as children are prone to viral infections comprising seasonal coronaviruses (75%) before four years. Nonetheless, increasing age leads to antibody decrease, especially over sixty years [64] . It can diminish the effective response of immune systems to COVID-19 in the elderly, as the reactivity is restricted to anti-seasonal coronavirus and anti-SARS antibodies with increased inflammation and complications. The other age-dependent mechanism may be allied with live vaccinations (e.g., BCG). Vaccines protect the target antigen, which le ads to non-specific heterologous effects due to the induction of innate immune mechanisms-individuals who receive BCG vaccinations as infants in response to S. aureus or Candida spp. produce increased pro-inflammatory IL-1β and TNF-α levels and reduced infection-related mortality [38] . Conversely, immune responses in a non-homogenous manner may also contribute to inflammation complications. Normally in adults, T cells do not have a memory of antigens they have not been exposed to, but cross-reactive memory T cells lead to slender responses by preferring clones with high affinity. The feature of immune senescence is due to the limited memory T cell repertoires, associated with disease progression and damage of T cell-mediated infections of hepatitis and virulent mononucleosis [65, 66] . Lately it has been recommended that in children and young women, a higher expression of ACE2 is expected, which decreases with age. In contrast, the lowest expression is seen in chronic diseases such as diabetes and hypertension, in reverse correlation with risk for severe disease and negative effects [66] . According to earlier SARS, MERS studies, and COVID-19 cohort studies, the determinants of old age, diabetes, metabolic syndrome, obesity, male, coronary heart disease, chronic obstructive pulmonary disease, and kidney disease are among the most reported risk factors [67] . It is noteworthy that in China and Italy, the suppression of the immune system was not acknowledged among these risk factors [68] . However, immune suppression and its associated functions may enhance virus spread. Moreover, the infected cases receiving immune-modulating treatment may be prone to secondary infections due to the association of COVID-19 with lymphopenia. Some immune-modulating drugs can defend against viral infections. Unrestrained treatment termination of immune-modulating drugs may cause disease flares in autoimmune/inflammatory conditions or organ rejection. As evident, the risk for a viral infection is increased. Thus, international communities recommend treatment continuation in the absence of symptoms and modifications of current treatment regimens with clinical service monitoring [68, 69] . J o u r n a l P r e -p r o o f The outbreak of COVID-19 has caused concern around the world, and it is not evident whether and how SARS-CoV-2 can also infect immune cells. Different studies reported neutrophilia, lymphopenia, leukopenia, thrombopenia, anemia, hypofibrinogenemia, hypo-albuminemia, and increased systemic inflammatory proteins of IL-6 CRP. In severe conditions of MERS or lethal cases of SARS, neutrophils and macrophages are increased in the airways. The analysis of available data can help authorities in deciding how to control the virus worldwide. Thus, this study collected and analyzed data from articles and databases. Various researchers in different parts of the world analyze the available data to predict the prevalence of coronavirus in different countries; still, no analysis has been published that can predict the situation and future peaks. After reviewing and analyzing the data published on the WHO website, this study predicts that the number of confirmed cases (cumulative total) and deaths (cumulative total) of coronavirus in different continents will decrease, based on diagrams and trend lines. Although the trend lines showed that the number of confirmed cases (newly reported in the last 24 hours and last seven days) would increase, the number of deaths cases (newly reported in the last 24 hours and last seven days) will decrease. However, additional analyses are necessary to confirm the prediction of this study. This review has not received funding. There was no conflict of interest. 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