Coronavirus disease 2019: What we know?

Abstract In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID‐19) by the World Health Organization, respectively. The COVID‐19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID‐19, but also to comment briefly on the epidemiology and pathology based on the current evidence.

comment briefly on the epidemiology and pathology based on the current evidence.

| THE PATHOGEN
The pathogen that causes COVID-19 is a nCoV that was first identified in the late January 2020, named SARS-CoV-2 (also known as 2019-nCoV). [2][3][4] SARS-CoV-2 is a novel member of CoVs, which are a large group of highly diverse, enveloped, positive-sense, and single-stranded RNA viruses. 5 Recent research reported that SARS-CoV-2 likely originated in bats, based on the similarity of its genetic sequence to that of other CoVs. 14 The intermediate animal host of SARS-CoV-2 between a probable bat reservoir and humans is still unknown. 15 Although this nCoV has genetic features that are compatible with the family of CoV, nevertheless it has distinct gene sequences that are significantly different from previously sequenced CoVs (Table 1). The analysis of samples from seven SARS-CoV-2 infected patients suggested that SARS-CoV-2 shares 79.5% sequence identity to SARS-CoV. 3 Simplot analysis showed that SARS-CoV-2 share 96.2% overall genome sequence identity to RaTG13, which is a short RdRp region from a bat CoV. 3 Phylogenetic analysis revealed that SARS-CoV-2 falls into the subgenus Sarbecovirus of the genus Betacoronavirus and is distinct from SARS-CoV. 2,4 The envelope spike (S) protein is important for CoV. 19 The S protein mediates receptor binding and membrane fusion and is crucial for determining host tropism and transmission capacity. 17,20,21 Generally, the S protein is functionally divided into the S1 domain, responsible for receptor binding, and S2 domain, responsible for cell membrane fusion. 22 Structure analysis suggested that receptorbinding domain was composed of a core and an external subdomain. 19 Angiotensin-converting enzyme 2 (ACE2) was known as cell receptor for SARS-CoV. 16,23,24 Similar to SARS-CoV, SARS-CoV-2 also use ACE2 as an entry receptor in the ACE2-expressing cells, 3 indicating SARS-CoV-2 may share the same life cycle with SARS-CoV ( Figure 1).
The biophysical and structural analysis indicated that S protein of SARS-CoV-2 binds ACE2 with approximately10-to 20-fold higher affinity than S protein of SARS-CoV. 18 The high affinity of S protein for human ACE2 may facilitate the spread of SARS-CoV-2 in human populations. Meanwhile, SARS-CoV-2 does not use other CoV receptors, such as aminopeptidase N and dipeptidyl peptidase 4 to enter cells. 3

| EPIDEMIOLOGY
Briefly, cases tend to be in clusters which arrive in waves, and develop into larger outbreaks all over the world. The first documented outbreak occurred primarily in Wuhan. 1 According to the daily report of the World Health Organization, the epidemic of SARS-CoV-2 so far registered 78 630 cases and 2747 deaths in China, spread to 46 other countries that reported a total of 3664 cases by 27 February 2020.
There are evidence suggest that transmission mode is human to human. 25,26 The major route of transmission of COVID-19 is droplet and close contact. 26 Whether infection can occur through the oral or conjunctival routes is unknown, but SARS-CoV-2 has been detected in tears, 27 which is resemble to SARS-CoV. 28 Reproductive number (R 0 ) was estimated by some studies. On the basis of clinical data of patients in COVID-19 early outbreak, the mean R 0 was ranging from 2.20 to 3.58, meaning that each patient has been spreading infection to two or three other people. 25,29 It is still too early to develop an accurate R 0 estimate or to assess the dynamics of transmission. More research is needed in the future.
The mean incubation period is about 5 days, ranging from 1 to 14 days and 95% of patients are likely to experience symptoms within 12.5 days of contact. 25,30 These data suggest a 14-day medical observation period or quarantine for exposed and close contact persons. However, an asymptomatic carrier was reported and the incubation period was 19 days, suggesting the complicated challenge to contain the outbreak. 31

| CLINICAL FEATURES
Most case patients were 30 to 79 years of age. 32 The median age is ranging from 49 to 59 years. 25,26,33,34 There were few cases in children below 15 years of age. More than half the patients were male.
Nearly half the cases had one or more coexisting medical conditions, such as hypertension, diabetes, and cardiovascular disease. 25,26,33,34 A large cases study indicated that the case-fatality rate was elevated among those patients with coexisting medical conditions. 32 The spectrum of clinical presentations of COVID-19 has been reported ranging from asymptomatic infection to severe respiratory failure. 25,26,30,[32][33][34] The main symptoms include a self-reported fever, fatigue, dry cough, myalgia, and dyspnea. The uncommon symptoms include sputum production, headache, hemoptysis, and diarrhea. 25,26,30,[32][33][34] Although pneumonia is present in most SARS-CoV-2 infected patients, few cases complained of pleuritic chest pain. 26,33 According to the severity of symptoms, patients can be classified as mild, severe, and critical types 32 ( procalcitonin, but the C-reactive protein was above the normal range.
One-third of patients had the elevation of D-dimer. 25,30,33,34 One study investigated the changes of several cytokines in serum in the COVID-19 patients. 34  the condition was improved. 37 One report suggested that there are four stages defined on CT scan. 36 In early stage, GGO was the main radiological demonstration distributed in the lower lobes unilaterally or bilaterally. In progressive stage, diffuse and bilateral GGO and consolidation in more than two lobes became the main manifestation. In peak stage, the diffuse GGO and dense consolidation became more prevalent. In absorption stage, extensive GGO could be observed and the consolidation was gradually absorbed.

| PATHOLOGY
The were designed to detect viral RNA in clinical specimens. 44 Lower respiratory tract samples provide the higher viral loads. 45 The sampling source or operation may affect RT-PCR testing results. 43 The positive rate of RT-PCR for throat swab samples was reported to be about 60% in early stage of COVID-19. 46 These findings suggested that the result of RT-PCR should be interpret with caution.
One study investigated the diagnostic value and consistency of chest The antibiotics used generally covered common pathogens and some atypical pathogens. When secondary bacterial infection occurred, medication was administered according to the results of bacterial culture and drug sensitivity. 33  The WHO issued a public health emergency of international concern on 30 January 2020. SARS-CoV-2 epidemic is becoming a global concern. At the moment, there is no vaccine and no specific should encourage people to stay at home; discourage mass gathering; postpone or cancel public events; and close public institutions. These control measures will help COVID-19 infected countries to prevent the epidemic effectively. Future research will focus on improving the accuracy of early diagnostic tests, developing the vaccine and identifying effective drugs. Therefore, elucidating the pathogenesis of SARS-CoV-2 infection is imperative for achieving such goals.

ACKNOWLEDGMENT
The authors would like to thank all the doctors and nurses who fight the virus during the COVID-19 epidemic bravely.