key: cord-032222-i6gfp4me
authors: Xue, Ling; Li, Jiao; Wei, Lin; Ma, Cuiqing
title: A quick look at the latest developments in the COVID-19 pandemic
date: 2020-09-10
journal: J Int Med Res
DOI: 10.1177/0300060520943802
sha: 
doc_id: 32222
cord_uid: i6gfp4me

In December 2019, a new respiratory disease manifesting as viral pneumonia emerged in Wuhan, China. Isolation and identification of the virus showed that the pathogen causing this disease was a novel coronavirus. On January 12, 2020, the World Health Organization named the novel coronavirus causing the outbreak 2019 novel coronavirus (2019-nCoV). The disease caused by the virus was named coronavirus disease 2019 (COVID-19). Later, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses formally named this virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus shows strong infectivity and high lethality, arousing widespread concern. As an emerging virus, a comprehensive understanding of SARS-CoV-2 is missing. To provide a reference and a theoretical basis for further study of SARS-CoV-2, recent advances in our understanding of the virus are summarized in this review.

Coronaviruses are widespread in nature, only infect vertebrates and can cause respiratory, enteric, hepatic and neurologic system diseases in humans and animals. 1 Coronaviruses can be divided into four genera: alpha, beta, gamma, and delta coronaviruses. 2 Alpha and beta coronaviruses mainly infect mammals, while gamma and delta coronaviruses mainly infect birds. 3 Seven coronaviruses can infect humans including the alpha coronaviruses, HCoV-229E and HCoV-NL63, and the beta coronaviruses, HCoV-OC43, HCoV-HKU1, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and SARS-CoV-2. [4] [5] [6] [7] HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections are relatively common in human populations. These viruses generally cause only mild respiratory symptoms similar to the common cold. 8 However, SARS-CoV, MERS-CoV, 9 and SARS-CoV-2 have higher infection and death rates.

Structural characteristics SARS-CoV-2 is an enveloped coronavirus. The virion is round or elliptic, often pleomorphic, and has a diameter between 60 nm and 140 nm. 10, 11 The virion can look like a crown when observed under electron microscopy. The viral spike protein present on the envelope is the most important surface protein of the virus and mediates infection. The spike protein contains two subunits: S1 and S2. S1 comprises the receptor binding domain (RBD) that recognizes cellular receptors, and S2 plays an important role in the process of membrane fusion. 12 The spike protein determines the specificity and host range of the virus, and its sequence can be altered through gene recombination or mutation of the RBD. 13 In addition, the spike protein is an important target of host neutralizing antibodies and plays a vital role in vaccine design.

SARS-CoV-2 is a positive-sense, singlestranded RNA virus, and is prone to mutation. The viral genome is about 30 kb in length, 14 encoding several open reading frames including ORF1ab and the S, E, M, and N genes. 10 The genome encodes nonstructural proteins, structural proteins and helper proteins. The S, E, M, and N genes encode the spike protein, envelope protein, membrane protein and nucleoprotein, respectively. The SARS-CoV-2 genome shares high homology with the genomes of bat coronaviruses, 10, 15, 16 suggesting a likely origin of the virus in bats.

SARS-CoV-2 has difficulty surviving at high temperatures and in low humidity environments. 17 The virus can be effectively inactivated at 56 C for 30 minutes. 18 At least one study demonstrated a significant positive correlation between ambient average relative humidity levels (23.33%-82.67%) and confirmed cases of COVID-19. 17 Coronaviruses are enveloped lipophilic viruses that are easily dissolved and destroyed by lipid solvents. Most approved disinfectants including ether, 75% ethanol, chlorinated disinfectants, peroxyacetic acid, and chloroform can effectively kill coronaviruses. In addition, the virus is also sensitive to ultraviolet light. 18 Pathogenic mechanism SARS-CoV-2 is an emerging coronavirus whose effects on the human body are not yet fully understood. Preliminary studies have suggested that the pathogenic mechanism of SARS-CoV-2 is similar to that of SARS-CoV. Both viruses bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) in human airway epithelial cells via the S protein on the envelope and enter the host cell. 16, [19] [20] [21] [22] ACE2 is highly expressed in alveolar cells type 2 as well as in the esophagus, ileum, colon, heart, kidney, bladder and testis. [23] [24] [25] [26] [27] [28] These findings suggest that ACE2, which is highly expressed in esophageal epithelial cells, intestinal epithelial cells, cardiomyocytes, and bladder epithelial cells, may allow SARS-CoV-2 to invade several human organs and lead to multiple organ damage and failure.

Human populations are generally susceptible to SARS-CoV-2. As of June 15, 2020, there were 84,823 confirmed cases and 4,645 deaths in China, with 7,823,334 confirmed cases and 431,541 deaths globally. 29 Currently, the mortality rate is about 5.5% in China and globally, lower than that of SARS (10%) and MERS (36%). 30 Based on current epidemiological data, the incubation period of SARS-CoV-2 appears to be long, ranging from 1 to 14 days but lasting for 3 to 7 days in most cases. 11 The clinical manifestations of SARS-CoV-2 are similar to those of SARS-CoV. Both viruses primarily cause lower respiratory symptoms, but the clinical features associated with SARS-CoV-2 are milder than those associated with SARS-CoV. 14, 31 The symptoms of most patients are nonspecific: fever, cough, and fatigue are the main manifestations. A few patients have symptoms such as nasal congestion, runny nose, and diarrhea. Severe cases can develop into acute respiratory distress syndrome. 31-35 SARS-CoV-2 can be detected in sputum, nose and throat swabs, alveolar lavage fluid and other samples by real-time reverse transcription polymerase chain reaction. 36 Specific IgM and IgG antibodies can be detected in the sera of COVID-19 patients. 11 Laboratory examinations showed that lymphocytes were decreased while levels of C-reactive protein, aspartate aminotransferase, and alanine aminotransferase were increased in most patients. On imaging examination, bilateral pneumonia can be seen with patchy shadows or ground-glass opacity. Cases with milder symptoms may not show pneumonia. 31, 32, 34, 35 Most patients have a good prognosis, while a few progress to critical condition. The elderly, especially those with a history of chronic diseases and surgeries, are more susceptible to infection and have higher mortality rates and worse prognoses. 37, 38 Transmission and prevention SARS-CoV-2 can infect many animals as well as humans, and entry into human populations most likely represents a zoonotic transmission event. Some groups suggested that the natural host of the virus is the bat, 16, 39, 40 although the intermediate hosts remain unclear. Other wild animals may also be involved in transmission such as minks 39 and pangolins. 41, 42 SARS-CoV-2 is highly infectious and pathogenic. The affinity of the SARS-CoV-2 S protein for ACE2 is approximately 10-to 20-fold higher than that of SARS-CoV, which may explain why SARS-CoV-2 is highly infectious. 43 In the face of this outbreak, we need to raise our awareness of personal protection and do all we can to reduce the spread of the virus. Since the middle of December 2019, there has been persistent human-to-human transmission. [44] [45] [46] Sources of infection are primarily patients with COVID-19 and asymptomatic cases. [47] [48] [49] The modes of transmission include droplet, contact, and aerosol spread as well as potential transmission via the fecal-oral route. 11 No evidence of vertical transmission was observed in women who acquired SARS-CoV-2 infection in late pregnancy. 50 Thus, we should avoid eating wild animals, improve our knowledge of SARS-CoV-2, and enhance awareness of personal protection strategies. To prevent or reduce the spread of the pandemic, measures should be taken to maintain social distance, avoid gatherings, wear masks when going out, cut off routes of transmission, and protect susceptible populations.

SARS-CoV-2 is a novel coronavirus, and an effective vaccine has yet to be developed. 51 A recombinant adenovirus type 5 vector vaccine, developed by Chen Wei's team, showed good safety and immunogenicity in a phase I clinical trial, rapidly inducing both humoral and T-cell responses against SARS-CoV-2 in most participants. 52 Currently, this vaccine is in phase 2 clinical trials, where its safety, tolerability and immunogenicity will be further evaluated.

Detection of SARS-CoV-2 nucleic acid is the gold standard for diagnosis of SARS-CoV-2 infection. Methods for antigen detection, antibody detection and simpler nucleic acid detection are also being developed. IgM/IgG antibody rapid detection assays have appeared on the market and have been applied for clinical case detection. 11 Compared with nucleic acid detection, antibody detection is often faster and more convenient. Antibody detection also has good sensitivity and specificity, and can be used as a supplement to nucleic acid detection. 53 In general, diagnosis of COVID-19 is based on comprehensive analysis of epidemiological risk factors, clinical manifestations, laboratory examinations, imaging examinations and pathogen detection results.

There are no specific antiviral drugs against SARS-CoV-2, 54 and recovery from COVID-19 basically depends on immunity and complementary clinical therapy. Because of the urgency of the SARS-CoV-2 pandemic, current treatments for SARS-CoV-2 are largely based on clinical experience with SARS and MERS. The inhibitory effects of antiviral agents approved or under development on SARS-CoV-2 are being tested, including agents developed to treat human immunodeficiency virus or influenza virus infections. 55 Potential COVID-19 therapies include antiviral drugs (interferon-a, lopinavir/ritonavir, ribavirin, and hydroxychloroquine) as well as antimicrobial agents. 11 Respiratory support is provided in severe cases including oxygen therapy, non-invasive mechanical ventilation, invasive mechanical ventilation, and extracorporeal membrane oxygenation. 56, 57 Antibodies obtained from the plasma of convalescent patients have been used in clinical therapy. Passive antibody transfer was previously used to treat SARS 58 and influenza infection [59] [60] [61] and achieved good results. However, this therapy has some limitations, including limited availability of specific antibodies and the existence of certain safety risks. Thus, safe and effective specific therapeutic antibodies must be developed for clinical treatment. Clinical case studies showed that the antiviral drug remdesivir, which has broad spectrum antiviral effects, [62] [63] [64] [65] is effective in inhibiting SARS-CoV-2. [66] [67] [68] However, data from a clinical trial by a Chinese research team showed that remdesivir does not provide significant clinical or antiviral effects in severe cases of COVID-19. 69 Some clinical trials of remdesivir are still ongoing to determine whether the drug is effective for treatment of patients with COVID-19. In addition, baricitinib, 70 chloroquine 68 and some Chinese patent drugs 11 with antiviral activity were also found to have therapeutic effects on COVID-19.

Our understanding of the etiology, transmission route and pathogenic mechanism of SARS-CoV-2 is still preliminary and not comprehensive. Some countries, including China, have controlled the COVID-19 epidemic well, but the virus is still spreading in other parts of the world at an alarming rate. COVID-19 may become a seasonal disease coexisting with humans for a long time. 71 There are currently no safe and specific antiviral drugs for treatment of patients with COVID-19, and vaccine development will take time. Therefore, the basic biological characteristics, transmission mode, and strategies for prevention and treatment of SARS-CoV-2 need to be further studied. In addition, broadspectrum anti-coronavirus drugs and specific monoclonal antibodies against SARS-CoV-2 need to be developed. In this review, we aimed to provide a reference and theoretical basis for further studies of the prevention and treatment of COVID-19.

The authors declare that there is no conflict of interest.

This work was supported by grants from the National Natural Science Foundation of China (81971474) and the Scientific and the Key R&D Projects of Hebei Province (20277738D).

Ling Xue https://orcid.org/0000-0001-6910-4228

Coronavirus pathogenesis

Interspecies transmission and emergence of novel viruses: lessons from bats and birds

Discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus

SARS and other coronaviruses as causes of pneumonia

Identification of a novel coronavirus in patients with severe acute respiratory syndrome

Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia

Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission

Epidemiology, genetic recombination, and pathogenesis of coronaviruses

Origin and evolution of pathogenic coronaviruses

A novel coronavirus from patients with pneumonia in China

National Health Commission of the People's Republic of China. The notice of launching guideline on diagnosis and treatment of the novel coronavirus pneumonia

Evidence for a common evolutionary origin of coronavirus spike protein receptorbinding subunits

Host factors in coronavirus replication

Emerging coronaviruses: genome structure, replication, and pathogenesis

Genomic characterization of the 2019 novel humanpathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

A pneumonia outbreak associated with a new coronavirus of probable bat origin

On airborne transmission and control of SARS-Cov-2

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus

Functional assessment of cell entry and receptor usage for lineage B b-coronaviruses, including 2019-nCoV

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury

A new coronavirus associated with human respiratory disease in China

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism

Single-cell analysis of ACE2 expression in human kidneys and bladders reveals a potential route of 2019-nCoV infection

ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection

Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

scRNA-seq Profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia

Distribution of COVID-19 Epidemic

SARS and MERS: recent insights into emerging coronaviruses

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

A novel coronavirus outbreak of global health concern

Clinical characteristics of coronavirus disease 2019 in China

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm

The 2019 -new coronavirus epidemic: evidence for virus evolution

Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica)

Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-toperson transmission: a study of a family cluster

Importation and human-to-human transmission of a novel coronavirus in Vietnam

Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia

Evidence of SARS-CoV-2 infection in returning travelers from Wuhan, China

SARS-CoV-2 viral load in upper respiratory specimens of infected patients

Presumed asymptomatic carrier transmission of COVID-19

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development. Microbes Infect. Epub ahead of print 22

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, nonrandomised, first-in-human trial

Antibody detection and dynamic characteristics in patients with COVID-19

Therapeutic options for the 2019 novel coronavirus

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)

Drug treatment options for the 2019-new coronavirus (2019-nCoV)

Use of convalescent plasma therapy in SARS patients in Hong Kong

Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection

Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment?

Treatment with convalescent plasma for influenza A (H5N1) infection

GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses

Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys

Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

First case of 2019 novel coronavirus in the United States

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

Baricitinib as potential treatment for 2019-nCoV acute respiratory disease

Potential impact of seasonal forcing on a SARS-CoV-2 pandemic