Introduction
A novel coronavirus, recognized as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the pathogen resulting in the 2019-2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19) (Q. Li et al., 2020; F. Wu et al., 2020; P. Zhou et al., 2020; N. Zhu et al., 2020). Since then, the novel coronavirus (COVID-19) has been spread around the world and has continued to negatively affect the global public health and economies. COVID-19 is a brand-new respiratory disease triggered by SARS-CoV-2, a novel enveloped RNA β-coronavirus (N. Zhu et al., 2020). Coronavirus is a lipid enveloped, positive-sense and single-stranded RNA virus. Under the electron microscope, the virus has protrusions that resemble the corona, and looks like a crown, so it is called coronavirus. The clinical manifestations of SARS-CoV-2 are mainly fever, cough, occasional dyspnea, invasive bilateral lung pneumonic infiltrates, and other severe complications(C. Huang et al., 2020). Acute respiratory distress syndrome (ARDS) is a common complication of severe viral pneumonia, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) (Channappanavar & Perlman, 2017), which are the fatal coronavirus infections that have occurred over the past two decades. A high sequence identity between SARS-CoV-2 and SARS-CoV is known by gene sequence (Xiaolong Tian et al., 2020). The genome of SARS-CoV-2 partially resembles SARS-CoV (82%) and MERS-CoV (50%) (Chan et al., 2020), both of which are of bat origin. Therefore, bats are thought to be the most probable animal hosts of SARS-CoV-2. However, due to the existence of natural ecological isolation, the probability of bat coronovirus ((BatCoV)-ZC45, BatCoV-RmYN02, and BatCoV-RaTG13) infecting directly to humans is very low, so there may exist other mammalian species act as intermediate hosts. Pangolins is reported as the possible intermediate hosts due to approximately 85.5%–92.4% similarity in their genome with COVID-19 (Lam et al., 2020).
This review summarizes the clinical manifestations, epidemiology, and the infection mechanism of SARS-CoV-2. We found that hACE2 plays an important role in the infection process, which also provides new research directions for potential therapeutic targets. This study highlights the treatment of COVID-19. There is no vaccine or effective antiviral treatment against COVID-19 presently. Novel therapeutics continue to be developed with the emergence of viruses. This article introduces potential drug therapy (i.e. remdesivir, ribavirin, Lopinavir/ritonavir, chloroquine, chloroquine phosphate, Arbidol, and traditional Chinese medicine) and immunotherapy (i.e. IL-6 or vaccines) for the treatment of COVID-19.
The clinicalmanifestations and epidemiology of COVID-19
The COVID-19 disease has reached pandemic status with the rapid spread worldwide. The threat of the SARS-COV-2 virus has developed rapidly since the first cluster case appeared. However, the result from phyloepidemiologic analyses suggested that the root of the SARS-COV-2 virus is not the Huanan market; they show that the virus was imported from elsewhere and then boosted in the market due to the large population (Peng Zhou et al., 2020). The epidemic curve of COVID-19 shows a mixed epidemic pattern. Because the epidemic caught up with the Spring Festival, the epidemic began in mid-to-late January. Early cases suggested that there was a continuing common source. In the South China seafood wholesale market, there may be a spillover of zoonotic diseases. Later, the increasing number of infected health care workers suggested that person-to-person transmission occurs mainly through droplet or contact transmission (”Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States,” 2020; Phan et al., 2020; Rothe et al., 2020; N. Zhu et al., 2020). The latest report showed that the SARS-COV-2 virus was detected positive in the gastrointestinal tract, saliva, and urine.
Most current published data come from China, despite the severe situations around the world, and provides first-hand information on the epidemiology of COVID-19. The high-level details of patient from 72,314 cases, including patient characteristics, severity of manifestations and survival, are reported by the Chinese Center for Disease Control and Prevention; suspected (22%), clinical diagnosed (15%), asymptomatic (1%), and confirmed (62%) COVID-19 cases (Wu & McGoogan, 2020). Most of the confirmed cases (75%) were confirmed in Hubei and were predominantly identified by the degree of symptoms, most (87%) were mild, defined by no or mild pneumonia, 14% were severe with significant infiltrates or signs of dyspnea, and 5% were severe, with distinct syndromes of respiratory failure (e.g. mechanical ventilation), shock, or multiple system organ failure.
The resistance capacity of children to infection is better than adults or are rarely symptomatic. The report showed that 87% of the cases were between 30-79 years old, 8% were 20-29 years old, 3% were ≥ 80 years old, 1% were 10 -19 years old, and 1% were ≤ 9 years old (Wu & McGoogan, 2020). Early data from the U.S. Centers for Disease Control and Prevention showed that in 4,226 confirmed cases with symptoms or exposure, only 5% occurred in those ˂ 20 years of age (D. Wang et al., 2020; Wu & McGoogan, 2020). A study also shows that children are less susceptible to SARS-CoV-2, which may result from the maturity and function of ACE2 in children lower than that in adult (Cristiani et al., 2020). The total case fatality rate of the 44,672 confirmed cases was 2.3%, among which, there are no death cases for patients ≤ 9 years old, the case fatality rate for patients aged 70 to 79 years was only 8.0%, and the case fatality rate for 80 years old and above was 14.8%. There were no reports of death in mild or severe cases, but the fatality rate of critical cases was 49.0%. Patients with hidden diseases have a high case fatality rate, of which for cardiovascular disease is 10.5%, diabetes is 7.3%, chronic respiratory disease is 6.3%, hypertension is 6.0%, and cancer is 5.6%. Therefore these conditions are risk factors for SARS-CoV-2 infection, which is consistent with the conclusions of 138 cases reported from Wuhan Central South University (Qun Li et al., 2020). Compared with SARS and MERS, the total mortality of COVID-19 is higher, which may result from its larger base. The first confirmed case of COVID-19 in the United States, which has now surpassed other countries in the absolute number of cases, was confirmed on January 20, 2020. In contrast, the United States shows the reflecting experience with COVID-19 from a few published data, which is worth learning from.
The commonest symptoms reported were fever (up to 90%), then developing into cough, fatigue, sputum production, and shortness of breath (Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng, Yuen, Chen, Tang, Wang, Chen, Xiang, Li, Wang, Liang, Peng, Wei, Liu, Hu, Peng, Wang, Liu, Chen, Li, Zheng, Qiu, Luo, Ye, Zhu, & Zhong, 2020). Less common symptoms, including headache, myalgia, sore throat, nausea, vomiting, and diarrhea may occur (N. Chen et al., 2020; C. Huang et al., 2020; D. Wang et al., 2020). However, only 43.8% of COVID-19 patients developed fever initially, which progressed to 87.9% after hospitalization (Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng, Yuen, Chen, Tang, Wang, Chen, Xiang, Li, Wang, Liang, Peng, Wei, Liu, Hu, Peng, Wang, Liu, Chen, Li, Zheng, Qiu, Luo, Ye, Zhu, & Zhong, 2020). Therefore, if the surveillance method focuses on fever detection, patients with no fever or who are asymptomatic may be a hidden source of infection. A recent study (n = 214) concluded that, in addition to systemic and respiratory symptoms, of total patients with COVID-19, 36.4% develop neurological symptoms (Mao et al., 2020). The latest report from the American Association of Otolaryngology shows that anosmia and dyspepsia have been highlighted as possible symptoms of the disease. Additionally, most cases show differential results between males and females, suggesting that males are more susceptible to SARS-CoV-2 infection resulting from the innate X-chromosome, sex hormones, and adaptive immunity (Jaillon, Berthenet, & Garlanda, 2019).
Presently, the common methods for diagnosis of SARS-CoV-2 are chest radiographs and nucleic acid detection. The chest computed tomography (CT) was abnormal in 87% of patients at the time of admission, and the typical chest CT for COVID-19 pneumonia was the initial small pleural ground glass turbidity gradually becoming larger with insane-paving pattern and consolidation. The lesions were gradually absorbed after two weeks of growth, leaving a large number of patients with turbidity and subpleural parenchyma in the recovery phase. However, the latest report suggests the complexity of disease control due to patients with normal imaging performance on initial presentation; which occurs in severe and non-severe patients.
Moreover, the common lab derangements on admission included lymphopenia, elevations in C-reactive protein (CRP), lactate dehydrogenase, liver transaminases, and D-dimer. It is worth noting that procalcitonin is rarely elevated. The considerable decrease in the total number of lymphocytes is an effective sign, which developed as an indicator for the diagnosis of SARS-CoV-2 infection; it indicates the consumption of immune cells and the impairment of cellular immune function (N. Chen et al., 2020). Another report noted elevations in other inflammatory markers, such as ferritin, interleukin (IL)-6, and erythrocyte sedimentation rate (Arentz et al., 2020; Guo et al., 2020; D. Wang et al., 2020; C. Wu et al., 2020; F. Zhou et al., 2020).