LitCovid-sentences  

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Id Subject Object Predicate Lexical cue
T25 0-15 Sentence denotes 1 Introduction
T26 16-158 Sentence denotes Coronaviruses (CoVs) are named for the crown-like spikes on their surface and belong to the family Coronaviridae within the order Nidovirales.
T27 159-273 Sentence denotes Coronaviruses broadly infect vertebrates including humans, birds, bats, snakes, mice and other wild animals [1,2].
T28 274-362 Sentence denotes Since the mid-1960s, seven known human coronaviruses (HCoVs) have been identified [3,4].
T29 363-422 Sentence denotes Four commonly detected HCoVs are 229E, OC43, NL63 and HKU1.
T30 423-557 Sentence denotes In one study, 229E and OC43 accounted for approximately 15–29% of respiratory pathogens with relatively low virulence in humans [3,5].
T31 558-662 Sentence denotes Another epidemiological study in adults estimates that coronavirus causes about 15% of common colds [6].
T32 663-842 Sentence denotes Other significant causes of upper respiratory infections include influenza virus, rhinovirus, parainfluenza virus, Group A Streptococci, EBV and respiratory syncytial virus (RSV).
T33 843-1145 Sentence denotes The three other strains of HCoVs, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have a different pathogenicity and lead to higher mortality rates in human populations.
T34 1146-1376 Sentence denotes MERS-CoV was isolated from a male patient who died from acute pneumonia and renal failure in Saudi Arabia in 2012 [7], and was subsequently responsible for 2494 cases and 858 deaths from 27 different countries (case-fatality rate:
T35 1377-1388 Sentence denotes 34.4%) [8].
T36 1389-1449 Sentence denotes Both SARS-CoV and SARS-CoV-2 were first recognized in China.
T37 1450-1547 Sentence denotes SARS-CoV caused a total of 8422 probable SARS cases, 919 SARS-related deaths (case-fatality rate:
T38 1548-1643 Sentence denotes 11%) and spread to 32 different countries or regions between November 2002 and August 2003 [9].
T39 1644-1750 Sentence denotes Since December 2019, the SARS-CoV-2 has infected 73,230 people and caused 1871 deaths (case-fatality rate:
T40 1751-1876 Sentence denotes 2.6%) and has spread to 25 countries, according to the State Council Information Office in Beijing, China (updated as of Feb.
T41 1877-1892 Sentence denotes 17, 2020) [10].
T42 1893-2088 Sentence denotes As of this date, the number of confirmed and suspected cases is still increasing, as is the number of deaths, although there is a significant increase in the number of recovered patients as well.
T43 2089-2138 Sentence denotes Coronaviruses were first identified in the 1960s.
T44 2139-2186 Sentence denotes It is not known for how long they have existed.
T45 2187-2296 Sentence denotes Most of the time they are associated with mild disease, but every few years a highly virulent strain appears.
T46 2297-2351 Sentence denotes The pathogenesis of these deadly epidemics is unclear.
T47 2352-2538 Sentence denotes An examination of the structure of the viruses and the mechanism of infection may help elucidate and provide information for the development of effective treatment and possibly vaccines.
T48 2539-2668 Sentence denotes Our purpose of this review is to provide a brief summary of the epidemiology and history of SARS, as well as the lessons learned.
T49 2669-2921 Sentence denotes The other aim is to review the epidemiology, pathogenesis, clinical characteristics, diagnosis and management of patients infected with SARS-CoV-2 to better understand this deadly coronavirus and suggest prevention, treatment and management strategies.
T50 2923-2985 Sentence denotes 2 Characteristics of coronaviruses and coronavirus infections
T51 2987-3020 Sentence denotes 2.1 Biology of the coronaviruses
T52 3021-3143 Sentence denotes CoVs are enveloped with a non-segmented, positive-sense, single-strand RNA, with size ranging from 26,000 to 37,000 bases.
T53 3144-3200 Sentence denotes This is the largest known genome among RNA viruses [11].
T54 3201-3245 Sentence denotes The genomic structure of CoVs is as follows:
T55 3246-3342 Sentence denotes 5′-leader-UTR-replicase-S (Spike)–E (Envelope)-M (Membrane)-N (Nucleocapsid)-3′UTRpoly (A) tail.
T56 3343-3524 Sentence denotes There are accessory genes interspersed within the structural genes at the 3′ end of genome [12], some of which have been shown to play an important roles in viral pathogenesis [13].
T57 3525-3737 Sentence denotes The S protein is responsible for receptor-binding and subsequent viral entry into host cells, the M and E proteins play important roles in viral assembly, and the N protein is necessary for RNA synthesis [12,14].
T58 3739-3768 Sentence denotes 2.2 Coronavirus transmission
T59 3769-3811 Sentence denotes CoVs can transmit across species barriers.
T60 3812-3951 Sentence denotes SARS-CoV originated from bats of the Hipposideridae family, using palm civets as intermediary hosts before dissemination to humans [15,16].
T61 3952-4086 Sentence denotes The earliest patients infected with SARS-CoV-2 in Wuhan ultimately caused the epidemic known as COronaVIrus Disease 2019 (COVID-2019).
T62 4087-4223 Sentence denotes Some of these patients had a history of contact with a wholesale seafood market in the early stages, suggesting animal-to-person spread.
T63 4224-4393 Sentence denotes Subsequently, a large number of patients reportedly did not have exposure to the markets, suggesting the development of person-to-person spread [[17], [18], [19], [20]].
T64 4394-4555 Sentence denotes There are three primary ways to transmit the virus, including close person-to-person contact, aerosol transmission, and transmission by touch [[21], [22], [23]].
T65 4556-4663 Sentence denotes The virus is thought to be transmitted to other people by respiratory droplets during coughing or sneezing.
T66 4664-4907 Sentence denotes Droplet spread can occur when an infected person sneezes or coughs, whereupon virus containing droplets are propelled up to 3 feet through the air and are deposited on the mucous membranes of the mouth, nose, or eyes of persons who are nearby.
T67 4908-5000 Sentence denotes A recent report suggests that transmission through the ocular surface is also possible [24].
T68 5001-5214 Sentence denotes The other avenues for the spread of the virus are shaking hands with an infected person, touching an infected object/surface, frequent touching of the nose or mouth or coming into contact with a patient's excreta.
T69 5215-5380 Sentence denotes Another avenue is through “hidden transmission” [19], in which asymptomatic infected individuals or carriers unknowingly transmit the virus to unsuspecting contacts.
T70 5382-5423 Sentence denotes 2.3 Variability of clinical presentation
T71 5424-5648 Sentence denotes Before the first outbreak of SARS, a limited number of HCoVs such as HCoV-229E were frequently found to infect humans, and were widely circulating in human populations causing only mild illnesses like the common cold [3,25].
T72 5649-5806 Sentence denotes However, SARS, MERS and SARS-CoV-2 present with a spectrum of disease severity ranging from flu-like symptoms to acute respiratory distress syndrome [25,26].
T73 5807-5958 Sentence denotes Early on, these patients are usually treated with conventional medications which had no clinical benefit, resulting in spread to health care personnel.
T74 5959-6117 Sentence denotes For those with flu-like symptoms or even more severe disease, it would not be immediately evident that this is an atypical and virulent form of a coronavirus.
T75 6118-6190 Sentence denotes For comparison, influenza has an estimated mortality rate of 0.07%–0.2%.
T76 6191-6246 Sentence denotes A high index of suspicion is helpful but not foolproof.
T77 6248-6270 Sentence denotes 2.4 Genetic diversity
T78 6271-6462 Sentence denotes The various CoVs of animal origin undergo evolution and genetic recombination, thereby resulting in mutated CoVs that may be highly pathogenic and potentially be more deadly to humans [3,27].
T79 6463-6799 Sentence denotes For SARS-CoV, the mutation rate in the SARS-CoV genome was estimated to be 0.80–2.38 × 10−3 nucleotide substitutions per site per year, and the nonsynonymous and synonymous substitution rates were estimated to be 1.16–3.30 × 10−3 and 1.67–4.67 × 10−3 per site per year, respectively, which are similar to that of other RNA viruses [28].
T80 6800-6953 Sentence denotes The various CoVs of animal origin undergo evolution and genetic recombination either within the host species or upon jumping from one species to another.
T81 6954-7093 Sentence denotes Such changes thus have the potential to lead to variants that have high pathogenic potential when transmitted to humans [[29], [30], [31]].
T82 7094-7203 Sentence denotes Recently, two mutations of the S protein and N protein SARS-CoV-2 may explain its zoonotic transmission [32].
T83 7204-7418 Sentence denotes Genomic alignment of 54 SARS-CoV-2 genomes identified two hotspots of hypervariability at positions 8789 (synonymous variant) and 28,151(Ser/Leu change), located in the polyprotein and ORF8 genes respectively [33].
T84 7420-7438 Sentence denotes 2.5 Comorbidities
T85 7439-7568 Sentence denotes Most patients who have died from the virus had other chronic medical conditions, were elderly patients or were immunocompromised.
T86 7569-7673 Sentence denotes One study reported that 6.7% of SARS patients had acute renal impairment and 84.6% had proteinuria [34].
T87 7674-7784 Sentence denotes Hematological abnormalities such as thrombocytopenia and lymphopenia were frequently observed in SARS [35,36].
T88 7785-7977 Sentence denotes Complications encountered for SARS-CoV-2 include acute respiratory distress syndrome (29%,12/41), anemia (15%, 6/41), acute cardiac injury (12%, 5/41) and secondary infection (10%, 4/41) [26].
T89 7978-8103 Sentence denotes In a SARS-CoV-2 descriptive study, 11 of 99 patients died of multiple organ failure, and seven were older than 60 years [37].
T90 8105-8137 Sentence denotes 2.6 Lack of effective treatment
T91 8138-8262 Sentence denotes To date, there is no anti-viral therapeutics that specifically targets human coronaviruses, so treatment is only supportive.
T92 8263-8348 Sentence denotes In vitro, interferons (IFNs) are only partially effective against coronaviruses [38].
T93 8349-8441 Sentence denotes In vivo, the effectiveness of IFNs combined with ribavirin requires further evaluation [39].
T94 8442-8591 Sentence denotes A variety of other agents, including antiviral peptides and corticosteroids have been shown to be effective in vitro and/or in animal models [40,41].
T95 8592-8704 Sentence denotes However, clinical evidence does not support the use of corticosteroid treatment for SARS-CoV-2 lung injury [42].
T96 8705-8910 Sentence denotes Vaccines that have been developed are either not effective, or in some cases have been reported to be involved in the selection of novel pathogenic CoVs via recombination of circulating strains [12,22,40].
T97 8911-8950 Sentence denotes Vaccine development can be a challenge.
T98 8951-9043 Sentence denotes It is noteworthy that almost 20 years after SARS, there is still no vaccine for coronavirus.
T99 9045-9120 Sentence denotes 3 A historical review of the epidemiology of SARS and how it was contained
T100 9121-9252 Sentence denotes It has been 17 years since the outbreak of severe acute respiratory syndrome (SARS) caused by the SARS coronavirus (SARS-CoV) [43].
T101 9253-9357 Sentence denotes This highly contagious atypical pneumonia first appeared in Guangdong Province, China, in November 2002.
T102 9358-9456 Sentence denotes The initial cases were animal handlers in Guangzhou city having close contact with wild game food.
T103 9457-9536 Sentence denotes It was suggested that civets could serve as an intermediate amplification host.
T104 9537-9663 Sentence denotes Three months later, the SARS pandemic was rapidly and globally disseminated due to person-to-person transmission of the virus.
T105 9664-9823 Sentence denotes On the February 21, 2003, a medical professor from Foshan in Guangdong province who was considered a “super-spreader” went to Hong Kong to visit his relatives.
T106 9824-9959 Sentence denotes During his stay in Hong Kong, he transmitted the virus to 2 family members, 4 health care workers (HCWs) and 12 other nearby residents.
T107 9960-10126 Sentence denotes Because of international travel and transmission to HCWs, these patients spread the SARS-CoV to Hong Kong and other countries including Vietnam, Singapore and Canada.
T108 10127-10204 Sentence denotes Eventually, 8422 people were infected in 32 countries and 919 (11%) died [9].
T109 10205-10311 Sentence denotes In China, 5328 cases were reported and 349 (6.5%) perished between November 16, 2002 and June 3, 2003 [9].
T110 10312-10436 Sentence denotes At the beginning of the outbreaks in Hong Kong, mainland China and other areas, we were unfamiliar with the deadly SARS-CoV.
T111 10437-10512 Sentence denotes It took about 3 months to complete the sequencing of this coronavirus [44].
T112 10513-10658 Sentence denotes The global success in the fight against SARS was partly based on epidemiological and biological characteristics of the infectious agent SARS-CoV.
T113 10659-10852 Sentence denotes An understanding of transmission patterns and the ability to diagnose and confirm affected patients ultimately led to effective containment measures and a slowdown in the spread of the disease.
T114 10853-10977 Sentence denotes Due to the lack of medications or a vaccine, the options for early intervention were limited to public health measures [45].
T115 10978-11082 Sentence denotes The steps that led to the containment of SARS can be illustrated by the events that occurred in Beijing.
T116 11083-11163 Sentence denotes Beijing experienced the largest outbreak of SARS beginning on the March 5, 2003.
T117 11164-11286 Sentence denotes The outbreak peaked within 6 weeks on the April 25, 2003 when 173 newly suspected SARS cases were hospitalized daily [46].
T118 11287-11434 Sentence denotes On the June 20, 2003, the last batch of 18 SARS patients recovered and were discharged from hospital, signaling the end of the pandemic in Beijing.
T119 11435-11565 Sentence denotes The prompt resolution of the outbreak in Beijing was attributed to the rapid adoption of a series of effective control measures.1.
T120 11566-11668 Sentence denotes Thousands of local and military health workers were deployed for emergency management of the outbreak.
T121 11669-11814 Sentence denotes Large quantities of emergency supplies including personal protective equipment (PPE) and medical apparat were sent to front-line medical sectors.
T122 11815-11883 Sentence denotes These people and materials were key to winning the war against SARS.
T123 11884-11886 Sentence denotes 2.
T124 11887-11978 Sentence denotes More than 100 fever clinics were set up in all secondary and tertiary hospitals in Beijing.
T125 11979-12112 Sentence denotes People visiting the fever clinics had a physical examination including body temperature, white blood cell count and chest radiograph.
T126 12113-12176 Sentence denotes Fever clinics played an important role in screening and triage.
T127 12177-12179 Sentence denotes 3.
T128 12180-12263 Sentence denotes All actively ill patients with SARS were concentrated in designated hospital wards.
T129 12264-12391 Sentence denotes On the May 1, 2003, a new 1000-bed SARS hospital (Xiaotangshan Hospital, Beijing) was built and put into operation immediately.
T130 12392-12589 Sentence denotes The advantages of having such a facility was that it was more conducive to the centralized management of SARS patients, and at the same time, it reduced transmission of the virus to healthy people.
T131 12590-12592 Sentence denotes 4.
T132 12593-12759 Sentence denotes During the period of the SARS outbreak, more than 60,000 HCWs received medical training in the management of patients with SARS, infection control and the use of PPE.
T133 12760-12762 Sentence denotes 5.
T134 12763-13024 Sentence denotes Multiple measures were taken to reduce person-to-person transmission, including isolation of patients with SARS, tracing and quarantine of close contacts, transit site surveillance and closing poorly maintained facilities that could enhance spread of the virus.
T135 13025-13027 Sentence denotes 6.
T136 13028-13067 Sentence denotes Information dissemination was critical.
T137 13068-13286 Sentence denotes Timely and accurate reporting of the status of the epidemic and scientific guidance on prevention and infection control played important roles in stabilizing people and overcoming the epidemic [[45], [46], [47], [48]].
T138 13288-13334 Sentence denotes 4 Lessons learned from the 2003 SARS pandemic
T139 13335-13483 Sentence denotes SARS was the very first coronavirus pandemic with the ability to spread from people to people mainly by droplets, but it would not be the last [49].
T140 13484-13545 Sentence denotes This section presents lessons learned from the SARS pandemic.
T141 13546-13750 Sentence denotes Although the SARS-CoV rapidly spread throughout the world and caused great damages to human health, the global success in the fight against SARS ultimately demonstrated that containment was possible [50].
T142 13752-13782 Sentence denotes 4.1 Animal source containment
T143 13783-13887 Sentence denotes Early on, there were clues suggesting the link between SARS-CoV and civets, bred for food in China [51].
T144 13888-14037 Sentence denotes Strengthening the monitoring of these wild animal sources was an important factor in controlling emergence of these virus and their spread in humans.
T145 14038-14150 Sentence denotes Some scholars advocated that the trading of wild animals in wet markets in Southern China should be banned [52].
T146 14151-14307 Sentence denotes In fact, the Chinese government had issued bans on rearing, trading, transporting and slaughtering wild animals for dietary purposes over 10 years ago [53].
T147 14308-14383 Sentence denotes This however, did not stop the practice of illegal trading of wild animals.
T148 14385-14419 Sentence denotes 4.2 Early detection and diagnosis
T149 14420-14568 Sentence denotes The nonspecific symptoms and signs of SARS and the long incubation period accentuated the transmission to HCWs and people in close communities [54].
T150 14569-14656 Sentence denotes Early identification of suspect cases is the key to inhibiting the spread of the virus.
T151 14657-14818 Sentence denotes Rapid identification of the viral genome and the development of rapid diagnostic tests will facilitate the isolation of those who are confirmed as infected [50].
T152 14820-14851 Sentence denotes 4.3 Rigorous infection control
T153 14852-14969 Sentence denotes a) Environmental hygiene in medical sectors and personal hygiene of health care workers should be maintained [55,56].
T154 14970-15098 Sentence denotes b) Contact tracing, strict isolation of actively ill patients and quarantine of close contacts should be implemented early [54].
T155 15099-15188 Sentence denotes c) Training in the use of personal protective equipment protects the safety of HCWs [57].
T156 15189-15317 Sentence denotes d) Establishing fever clinics, setting up designated hospital wards and SARS hospitals reduced human-to-human transmission [58].
T157 15318-15434 Sentence denotes e) Education of the public on communicable diseases and what measures to take on a personal basis to prevent spread.
T158 15436-15495 Sentence denotes 4.4 Timely case report and rapid information dissemination
T159 15496-15620 Sentence denotes A number of studies have shown that clear and timely dissemination of information is essential in handling an outbreak [54].
T160 15621-15683 Sentence denotes Infection control is based on rapid information dissemination.
T161 15684-15896 Sentence denotes Since SARS in 2003, China has implemented legislation on the surveillance, reporting and early warning system of infectious diseases, requiring the regular release of information during public health emergencies.
T162 15897-16067 Sentence denotes There is a clearly defined procedure and schedule for reporting public health emergencies which requires designated medical centers to submit relevant information online.
T163 16068-16210 Sentence denotes If confirmed, reports on SARS and other infectious diseases can be submitted and received directly within two hours through the Internet [53].
T164 16212-16236 Sentence denotes 4.5 Vaccine development
T165 16237-16344 Sentence denotes After SARS, development of a vaccine appeared to be the best approach to prevent future SARS-CoV epidemics.
T166 16345-16408 Sentence denotes However, there were many obstacles in SARS vaccine development.
T167 16409-16513 Sentence denotes Firstly, researchers did not have a comprehensive understanding of the pathogenic mechanism of SARS-CoV.
T168 16514-16632 Sentence denotes Secondly, animal models of SARS-CoV infection could not simulate human disease because of an incongruent pathogenesis.
T169 16633-16736 Sentence denotes Thirdly, in order to test the efficacy, many people must be tested in areas where the virus is endemic.
T170 16737-16803 Sentence denotes Once the SARS epidemic ended, human trials were not possible [59].
T171 16804-16961 Sentence denotes Although several candidate vaccines against SARS-CoV have been produced and tested, at present, unfortunately, there is no FDA approved vaccine against SARS.
T172 16963-17007 Sentence denotes 5 The current SARS-CoV-2 infection in China
T173 17009-17038 Sentence denotes 5.1 The origin of SARS-CoV-2
T174 17039-17237 Sentence denotes A cluster of cases of viral pneumonia of unknown etiology, now known as SARS-CoV-2 pneumonia, occurred in Wuhan, Hubei Province and were reported to health authorities on the December 29, 2019 [60].
T175 17238-17311 Sentence denotes This outbreak was associated with a large seafood and animal market [61].
T176 17312-17388 Sentence denotes Further investigations are ongoing to determine the origin of the infection.
T177 17389-17477 Sentence denotes To date, many reports have described possible original and intermediate hosts (Fig. 1 ).
T178 17478-17760 Sentence denotes Researchers found that the SARS-CoV-2 showed a higher sequence homology to Bat-CoV-RaTG13 that was previously detected in Rhinolophus affinis from Yunnan Province than Bat-SL-CoVZC21 and Bat-SL-CoVZC45, which suggested that the Chinese chrysanthemum bat is the origin of SARS-CoV-2.
T179 17761-18032 Sentence denotes More recently, the pangolin was believed to be the likely intermediate host due to the fact that there appeared to be approximately 99% sequence homology between SARS-Co V-2 and the consensus sequence derived from >1000 metagenomic samples from the pangolin species [62].
T180 18033-18089 Sentence denotes Fig. 1 The origin and inter-host timeline of SARS-CoV-2.
T181 18090-18141 Sentence denotes All the information is derived from published data.
T182 18142-18375 Sentence denotes Journal name: (a) Emerging Microbes & Infections, (b) bioRvix, (c) J Med Virol, (d) The Lancet, (e) the New England Journal of Medicine, (f) J Virol, (g) Chin Med J (Engl), (h) https://www.scau.edu.cn/2020/0207/c1300a219015/page.htm.
T183 18376-18385 Sentence denotes Bat-ZC21:
T184 18386-18439 Sentence denotes Bat-SL-CoVZC21, GenBank Accession MG772934; Bat-ZC45:
T185 18440-18553 Sentence denotes Bat-SL-CoVZC45, GenBank Accession MG772933; Bat-RaTG13: yun-nan-Bat-CoV-RaTG13, GISAID accession EPI_ISL_402,131.
T186 18555-18592 Sentence denotes 5.2 New epidemiological developments
T187 18593-18781 Sentence denotes Currently, person to person transmission from patients with pneumonia or even asymptomatic patients during the incubation period are the main conduits for the spread of the infection [63].
T188 18782-19008 Sentence denotes Respiratory droplets are the main route of transmission, but the virus can also be transmitted through contact or through the fecal-oral route based on a study which demonstrated the presence of the virus in rectal swabs [64].
T189 19009-19143 Sentence denotes Fifteen health care workers in a Wuhan hospital were infected while caring for patients with confirmed or suspected infection [65,66].
T190 19144-19254 Sentence denotes As of February 11, 2020, a total of 1716 health care workers have become infected and 5 have died (0.3%) [67].
T191 19255-19391 Sentence denotes A study of a family cluster reported that five members of a family of six traveled to Wuhan, and four were infected with the SARS-CoV-2.
T192 19392-19526 Sentence denotes The family member who did not travel became infected with the virus after several days of contact with the four infected members [19].
T193 19527-19656 Sentence denotes Li et al. [65] showed that human-to-human transmission among close contacts has been occurring since the middle of December 2019.
T194 19657-19725 Sentence denotes Further dissemination has continued rapidly over the ensuing months.
T195 19726-19872 Sentence denotes The authors estimated that the reproduction number (R0) for SARS-CoV-2 is 2.2, meaning that every infected person can infect a mean of 2.2 people.
T196 19873-19990 Sentence denotes In another study, the reproduction number of the SARS-CoV-2 was 2.68 with an epidemic doubling time of 6.4 days [68].
T197 19991-20182 Sentence denotes It is worth noting that a nucleic acid fragment of the SARS-CoV-2 was detected by Guangzhou Centers for Disease Control and Prevention (CDC) on a doorknob touched by a confirmed patient [69].
T198 20183-20546 Sentence denotes China Daily reported that scientists have discovered that stool samples from patients infected with the SARS-CoV-2 have also tested positive for the virus [70], and that the virus was also detected in the loose stool of the first patient in the US infected with the virus [71], meaning the virus has the potential to be spread through contaminated fecal material.
T199 20547-20697 Sentence denotes On the January 22, 2020, a member of the national expert panel on pneumonia reported that he was infected by SARS-CoV-2 during an inspection in Wuhan.
T200 20698-20754 Sentence denotes He had worn an N95 mask but did not wear eye protection.
T201 20755-20836 Sentence denotes Several days before the onset of pneumonia, he complained of redness of the eyes.
T202 20837-20960 Sentence denotes Unprotected exposure of the eyes to SARS-CoV-2 in the Wuhan Fever Clinic may have allowed the virus to enter his body [24].
T203 20961-21011 Sentence denotes The situation with SARS-CoV-2 is evolving rapidly.
T204 21012-21215 Sentence denotes According to the National Health Commission (NHC) of China update on February 17, 2020 [10], a total of 72,436 cases were confirmed in the Chinese mainland, including 11,741 severe cases and 1868 deaths.
T205 21216-21283 Sentence denotes A total of 12,552 patients have recovered and have been discharged.
T206 21284-21335 Sentence denotes An additional total of 6242 suspected cases remain.
T207 21336-21466 Sentence denotes Most patients (59,989 cases) have been in Hubei province, where the outbreak began, including 10,970 severe cases and 1789 deaths.
T208 21467-21637 Sentence denotes The Hong Kong and Macao Special Administrative Regions as well as Taiwan reported 92 confirmed cases of the disease, including 2 deaths and 9 patients who have recovered.
T209 21638-21725 Sentence denotes There are significantly more SARS-CoV-2 cases than SARS cases during the 2003 outbreak.
T210 21726-21806 Sentence denotes The current spread of the epidemic in China is shown in Fig. 2, Fig. 3, Fig. 4 .
T211 21807-21937 Sentence denotes Fig. 2 Confirmed cases of SARS-CoV-2, February 17, 2020. (Data from the government website of China's National Health Commission).
T212 21938-22128 Sentence denotes Fig. 3 Numbers of suspected, confirmed and severe cases of SARS-CoV-2 in China and Hubei province, February 17, 2020. (Data from the government website of China's National Health Commission.
T213 22129-22257 Sentence denotes Since February 12, 2020, Hubei Province has included the number of clinical diagnosis cases into the number of confirmed cases).
T214 22258-22429 Sentence denotes Fig. 4 Numbers of deaths and recovered cases of SARS-CoV-2 in China and Hubei, February 17, 2020. (Data from the government website of China's National Health Commission).
T215 22430-22648 Sentence denotes According to World Health Organization (WHO) SARS-CoV-2 Situation Report [72], additional cases have been identified in a growing number of other international locations, including 25 countries outside China (Fig. 5 ).
T216 22649-22774 Sentence denotes There are now three deaths that have been reported outside of China (one in the Philippines, one in Japan and one in France).
T217 22775-22981 Sentence denotes The WHO declared the SARS-CoV-2 epidemic a Public Health Emergency of International Concern (PHEIC) on January 30, 2020, citing that human-to-human infections have been confirmed in multiple countries [73].
T218 22982-23161 Sentence denotes Fig. 5 Countries, territories or areas with reported confirmed cases of SARS-CoV-2, February 17, 2020. (Data from the WHO Coronavirus disease 2019 (COVID-19) Situation Report-28).
T219 23162-23345 Sentence denotes According to Fang et al. [74], fifteen cases of childhood infection had been identified as of January 30, 2020, including 8 boys and 7 girls, ranging in age from 8 months to 12 years.
T220 23346-23426 Sentence denotes Of the 15 pediatric cases, 13 had a clear history of family clustering in Wuhan.
T221 23427-23517 Sentence denotes At present, several confirmed pregnant women in Wuhan have given birth during the illness.
T222 23518-23759 Sentence denotes On February 2, 2020, Wuhan local media reported that a confirmed pregnant woman gave birth to a newborn by cesarean section under strict level three protection, but the newborn's throat swab was positive for the nucleic acid virus test [75].
T223 23760-24145 Sentence denotes However, Chen et al. tested the SARS-CoV-2 in amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six confirmed SARS-CoV-2 pregnant women, and all samples tested negative for the virus, which suggests that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy [76].
T224 24146-24202 Sentence denotes No cases of newborns or child deaths have been reported.
T225 24203-24292 Sentence denotes The NHC has called for close monitoring of outbreaks in children and pregnant women [77].
T226 24293-24473 Sentence denotes The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team of the Chinese CDC reported the epidemiology characteristics of 44,672 confirmed cases as of February 11, 2020.
T227 24474-24589 Sentence denotes Among the confirmed 44,672 cases (74.7% in Hubei Province), 51.4% were male, and 80.9% were mild or moderate cases.
T228 24590-24739 Sentence denotes The majority of the cases were between 30 and 69 years old (77.8%), while 0-9 year-olds and 10-19 year-olds accounted for 0.9% and 1.2% respectively.
T229 24740-24850 Sentence denotes Hypertension (12.8%), diabetes (5.3%), cardiovascular disease (4.2%) were the most common underlying diseases.
T230 24851-24993 Sentence denotes A total of 1023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%, and 81% of the deaths were over 60 years old.
T231 24994-25100 Sentence denotes The mortality rates of those aged 60–69, 70–79 and over 80 years were 3.6%, 8.0%, and 14.8%, respectively.
T232 25101-25151 Sentence denotes The mortality rate of critical cases was 49% [67].
T233 25152-25270 Sentence denotes Based on this evidence, the current SARS-CoV-2 is easily transmissible in humans, even in children and pregnant women.
T234 25271-25336 Sentence denotes It should also be noted that most patients have a good prognosis.
T235 25337-25429 Sentence denotes The symptoms in children are relatively mild, and only a minority are in critical condition.
T236 25430-25518 Sentence denotes The death cases involved mostly the elderly and those with a chronic underlying disease.
T237 25519-25589 Sentence denotes This fact, however, does not diminish the seriousness of the epidemic.
T238 25590-25825 Sentence denotes During the early stages of the epidemic, several hospitals, including Wuhan Union Hospital, Wuhan Tongji Hospital, and Peking Union Medical College Hospital, had created different diagnosis and treatment programs [37,[78], [79], [80]].
T239 25826-25966 Sentence denotes The WHO and the NHC of China have since then published guidelines for the diagnosis and clinical management of SARS-CoV-2 pneumonia [81,82].
T240 25968-25992 Sentence denotes 6 Clinical presentation
T241 25994-26022 Sentence denotes 6.1 Clinical manifestations
T242 26023-26194 Sentence denotes According to the guidelines published by the NHC and based on current epidemiological studies, the incubation period is typically 3–7 days, with a maximum of 14 days [82].
T243 26195-26261 Sentence denotes Common symptoms of COVID-19 include fever, fatigue, and dry cough.
T244 26262-26355 Sentence denotes A few patients have symptoms such as nasal congestion, runny nose, sore throat, and diarrhea.
T245 26356-26424 Sentence denotes Some patients only have a low fever, mild fatigue, and no pneumonia.
T246 26425-26569 Sentence denotes In severe cases, the infection can cause pneumonia, shortness of breath and breathing difficulties occurring more than one week after infection.
T247 26570-26730 Sentence denotes Critical patients may progress rapidly to acute respiratory distress syndrome (ARDS), septic shock, metabolic acidosis, coagulation dysfunction, and even death.
T248 26731-26872 Sentence denotes It is worth noting that during the course of severe and critical patients, there can be moderate to low-grade fever or even no obvious fever.
T249 26873-26935 Sentence denotes Huang et al. provided first-hand data regarding COVID-19 [26].
T250 26936-27107 Sentence denotes Their study reported the clinical features of the first 41 patients admitted to the designated hospital in Wuhan who were laboratory-confirmed COVID-19 by January 2, 2020.
T251 27108-27192 Sentence denotes Twenty-seven (66%) of the 41 patients had been exposed to the Huanan seafood market.
T252 27193-27293 Sentence denotes Common symptoms at the onset of illness were fever (98%), cough (76%), and myalgia or fatigue (44%).
T253 27294-27374 Sentence denotes Less common symptoms were sputum production, headache, hemoptysis, and diarrhea.
T254 27375-27464 Sentence denotes Dyspnea developed in 22 (55%) of 40 patients and 26 (63%) of 41 patients had lymphopenia.
T255 27465-27608 Sentence denotes The median time from onset of symptoms to first hospital admission was 7.0 days, to shortness of breath was 8.0 days, and to ARDS was 9.0 days.
T256 27609-27759 Sentence denotes Almost a third of patients developed ARDS requiring intensive care, 5 patients had acute cardiac injury, and 4 patients required assisted ventilation.
T257 27760-27879 Sentence denotes Eventually 28 patients were discharged, 13 patients were admitted to the intensive care unit (ICU) and 6 patients died.
T258 27880-27988 Sentence denotes Chen et al. reported 99 patients with SARS-CoV-2 pneumonia admitted to the Jinyintan Hospital in Wuhan [37].
T259 27989-28130 Sentence denotes Forty-nine (49%) patients had a history of exposure to the local Huanan seafood market and 50 patients (51%) had chronic underlying diseases.
T260 28131-28345 Sentence denotes Patients had clinical manifestations of fever (83%), cough (82%), shortness of breath (31%), muscle aches (11%), confusion (9%), headache (8%), sore throat (5%), rhinorrhea (4%), chest pain (2%), and diarrhea (2%).
T261 28346-28399 Sentence denotes Eighty-nine (90%) patients had more than one symptom.
T262 28400-28652 Sentence denotes According to their study, many cases presented with organ function damage, including 17 cases with ARDS, 8 cases with acute respiratory injury, 3 cases with acute renal injury, 4 cases with septic shock, and 1 case with ventilator-associated pneumonia.
T263 28653-28764 Sentence denotes Eventually 31 patients were discharged, 11 patients died, and the remaining 57 patients were still in hospital.
T264 28765-28894 Sentence denotes At Zhongnan Hospital of Wuhan University in Wuhan, Wang et al. [83] enrolled 138 hospitalized patients with SARS-CoV-2 pneumonia.
T265 28895-29008 Sentence denotes Common symptoms included fever (98.6%), fatigue (69.6%), dry cough (59.4%), myalgia (34.8%), and dyspnea (31.2%).
T266 29009-29130 Sentence denotes The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days.
T267 29131-29211 Sentence denotes Major complications during hospitalization included ARDS, arrhythmia, and shock.
T268 29212-29347 Sentence denotes Of the 138 hospitalized patients, 47 recovered and have been discharged, 36 patients were admitted to the ICU and 6 patients have died.
T269 29348-29464 Sentence denotes Chang et al. [84] reported 13 confirmed patients outside of Wuhan, including 2 children (aged 2 years and 15 years).
T270 29465-29520 Sentence denotes Twelve patients (92%) had fever before hospitalization.
T271 29521-29623 Sentence denotes Other symptoms included upper airway congestion (62%), cough (46%), myalgia (23%), and headache (23%).
T272 29624-29651 Sentence denotes All the patients recovered.
T273 29652-29766 Sentence denotes Guan et al. [85] reported 1099 confirmed patients from 552 hospitals in the whole of China as of January 29, 2020.
T274 29767-29889 Sentence denotes The most common symptoms including fever (87.9%) and cough (67.7%), whereas diarrhea (3.7%) and vomiting (5.0%) were rare.
T275 29890-30021 Sentence denotes They also pointed out that only 43.8% of the patients had fever on presentation but 87.9% developed fever after being hospitalized.
T276 30022-30135 Sentence denotes Moreover, compared with non-severe cases, any underlying diseases were significantly more common in severe cases.
T277 30136-30217 Sentence denotes The most common complication was pneumonia (79.1%), ARDS (3.4%) and shock (1.0%).
T278 30218-30299 Sentence denotes Of the 1099 patients, 55 patients were admitted to the ICU, and 15 patients died.
T279 30300-30542 Sentence denotes There were therefore a total of 41, 99 and 138 (total 278) cases of SARS-CoV pneumonia admitted in the 3 regional hospitals closest to the Huanan Seafood Market that resulted in 6, 11 and 6 deaths (23 deaths) or a case fatality rate of 0.82%.
T280 30544-30565 Sentence denotes 6.2 Laboratory tests
T281 30566-30793 Sentence denotes In the early stages of the disease, the total number of leukocytes in peripheral blood is normal or decreased, the lymphocyte count is decreased, and some patients show increases in liver enzymes, muscle enzymes, and myoglobin.
T282 30794-30924 Sentence denotes The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are increased in most patients, and procalcitonin is normal.
T283 30925-31017 Sentence denotes In severe cases, D-dimer increases, and peripheral blood lymphocytes decrease progressively.
T284 31018-31133 Sentence denotes Coronavirus nucleic acid can be detected in the throat, sputum, lower respiratory tract secretions, blood and tool.
T285 31134-31233 Sentence denotes In Huang's study [26], the blood counts of patients on admission showed leucopenia and lymphopenia.
T286 31234-31311 Sentence denotes Prothrombin time and D-dimer levels on admission were higher in ICU patients.
T287 31312-31442 Sentence denotes Compared with non-ICU patients, ICU patients had higher plasma levels of IL-2, IL-7, IL-10, G-SCF, IP-10, MCP-1, MIP-1α, and TNFα.
T288 31443-31599 Sentence denotes In Chen's study [37], all patients were tested for nine respiratory pathogens and nucleic acids of influenza viruses A and B, as well as bacteria and fungi.
T289 31600-31711 Sentence denotes No other respiratory viruses were detected, but 4 cases of fungal and 1 case of bacterial infection were found.
T290 31712-31803 Sentence denotes The absolute number of leukocytes was decreased in 9 patients and increased in 24 patients.
T291 31804-31926 Sentence denotes The absolute neutrophil count was increased in 38 patients and the absolute lymphocyte count was decreased in 35 patients.
T292 31927-32099 Sentence denotes Forty-three patients had varying degrees of liver dysfunction, seven patients had varying degrees of renal dysfunction, and most patients had abnormal myocardial zymograms.
T293 32100-32193 Sentence denotes Seventy-three patients were tested for C-reactive protein which was increased in 63 patients.
T294 32194-32315 Sentence denotes In Guan's study, 82.1%, 36.2%, and 33.7% of the patients had lymphopenia, thrombocytopenia, and leukopenia, respectively.
T295 32316-32410 Sentence denotes Compared with non-severe cases, severe cases had more prominent laboratory abnormalities [85].
T296 32412-32432 Sentence denotes 6.3 Imaging studies
T297 32433-32582 Sentence denotes In Huang's study [26], all 41 patients had pneumonia with abnormal findings on chest computed tomography (CT) and 40 (98%) had bilateral involvement.
T298 32583-32684 Sentence denotes The ICU patients on admission had bilateral multiple lobular and subsegmental areas of consolidation.
T299 32685-32781 Sentence denotes The non-ICU patients had bilateral ground-glass opacity and subsegmental areas of consolidation.
T300 32782-32887 Sentence denotes Subsequent chest CT images showed bilateral ground-glass opacity, whereas the consolidation was resolved.
T301 32888-33061 Sentence denotes In Chen's study [37], imaging showed that 74 patients had bilateral pneumonia, 14 patients had multiple mottled and ground-glass opacities, and 1 patient had a pneumothorax.
T302 33062-33170 Sentence denotes In Wang's study [83], imaging showed that 138 patients had bilateral patchy shadows or ground-glass opacity.
T303 33171-33359 Sentence denotes In Guan's study, 840 of 1099 patients received chest CT on admission which showed that 76.4% had pneumonia, but 23.9% of severe cases had no radiologic abnormality on initial presentation.
T304 33360-33460 Sentence denotes Ground-glass opacity (50.0%) and bilateral patchy shadow (46.0%) were the most common findings [85].
T305 33462-33474 Sentence denotes 7 Diagnosis
T306 33475-33619 Sentence denotes The earliest cases of SARS-CoV-2 were identified as “pneumonia of unknown etiology”, which was defined as an illness of unknown etiology with 1.
T307 33620-33667 Sentence denotes Fever with or without a recorded temperature 2.
T308 33668-33705 Sentence denotes Radiographic evidence of pneumonia 3.
T309 33706-33800 Sentence denotes Low or normal leukocyte count or low lymphocyte count during the early stage of disease and 4.
T310 33801-33918 Sentence denotes No improvement or worsening symptoms after 3–5 days of antimicrobial treatment per standard clinical guidelines [61].
T311 33919-34040 Sentence denotes With increasing research and knowledge of the disease, diagnosis and treatment guidelines have been continuously updated.
T312 34041-34108 Sentence denotes At present, the NHC has issued the fifth edition of the guidelines.
T313 34109-34352 Sentence denotes However, because of a shortage of diagnostic reagents for SARS-CoV-2 detection, different guidelines or programs emphasized comprehensive analysis based on epidemiological history, clinical manifestations and imaging examinations in diagnosis.
T314 34354-34412 Sentence denotes 7.1 Diagnostic criteria [37,[78], [79], [80], [81], [82]]
T315 34413-34498 Sentence denotes The diagnostic criteria of suspected and confirmed cases were summarized in Table 1 .
T316 34499-34599 Sentence denotes Table 1 The diagnostic criteria for suspected and confirmed cases [37,[77], [78], [79], [80], [81]].
T317 34600-34624 Sentence denotes Case Diagnostic criteria
T318 34625-34841 Sentence denotes Suspected case Anyone with a history of epidemiology and any two of the clinical manifestations or anyone without epidemiological history and three of the clinical manifestations is considered to be a suspected case:
T319 34842-34998 Sentence denotes (1) Epidemiological history:1) within 14 days before the disease onset, there is a travel history or living history in Wuhan or other areas with local cases
T320 34999-35154 Sentence denotes 2) within 14 days before the disease onset, there is contact with patients who had fever or respiratory symptoms from Wuhan or other areas with local cases
T321 35155-35238 Sentence denotes 3) a clustering of patients or a contact with patients infected with the SARS-CoV-2
T322 35239-35303 Sentence denotes (2) Clinical manifestations:1) fever and/or respiratory symptoms
T323 35304-35368 Sentence denotes 2) with the above-mentioned imaging characteristics of pneumonia
T324 35369-35497 Sentence denotes 3) the total number of leukocytes in the early stage of the disease is normal or decreased, or the lymphocyte count is decreased
T325 35498-35614 Sentence denotes Confirmed case Any suspected case with one of the following pathogenic features is reclassified as a confirmed case:
T326 35615-35707 Sentence denotes (1) Positive results of SARS-CoV-2 nucleic acids by RT-PCR of respiratory or blood specimens
T327 35708-35818 Sentence denotes (2) DNA highly homologous to SARS-CoV-2 by genetic sequencing of viral genes in respiratory or blood specimens
T328 35819-35885 Sentence denotes RT-PCR: real-time reverse-transcriptase polymerase-chain-reaction.
T329 35887-35914 Sentence denotes 7.2 Differential diagnosis
T330 35915-36230 Sentence denotes The SARS-CoV-2 needs to be distinguished from other known viral pneumonias including influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, SARS coronavirus, MERS coronavirus, as well as Mycoplasma pneumoniae, chlamydia pneumonia, and bacterial pneumonias.
T331 36231-36342 Sentence denotes For patients with underlying diseases, attention should be paid to the detection of invasive fungal infections.
T332 36343-36470 Sentence denotes The differential diagnosis also includes non-infectious diseases such as vasculitis, dermatomyositis, and organizing pneumonia.
T333 36471-36671 Sentence denotes It should be noted that often patients with viral pneumonia may test positive to multiple viruses, and the potential lethality of a combined SARS-CoV-2/influenza virus infection should not be ignored.
T334 36673-36755 Sentence denotes 8 The effectiveness of SARS-CoV-2 rapid diagnosis in preventing spread of disease
T335 36756-36878 Sentence denotes Several rapid and sensitive detection tests have been developed for the prevention and control of the SARS-CoV-2 outbreak.
T336 36879-37122 Sentence denotes At present, seven products including the SARS-CoV-2 nucleic acid detection kit (fluorescent PCR method) and the SARS-CoV-2 nucleic acid sequencing system have been approved on an emergency basis by the National Medical Products Administration.
T337 37123-37219 Sentence denotes Biological product companies have expanded production of detection kits for the new coronavirus.
T338 37220-37433 Sentence denotes The use of detection kits can accelerate accurate diagnosis of patients, help to determine quarantine and isolation requirements, assist in determining the treatment of patients and save limited medical resources.
T339 37434-37533 Sentence denotes However, the rapidity of spread of the disease has led to an insufficient supply of detection kits.
T340 37534-37817 Sentence denotes It is worth noting that there have been confirmed patients whose viral nucleic acid tests are negative multiple times in the early stages, and there have also been confirmed cases whose throat swabs were negative for the viral nucleic acid test but positive in alveolar lavage fluid.
T341 37818-37962 Sentence denotes Correlation of Chest CT and RT-PCR testing of 1014 cases showed that CT had a 88% had a positive CT scan but only 59% had positive RT-PCR. [86].
T342 37963-38059 Sentence denotes The poor sensitivity of the current tests makes diagnosis and epidemic control more challenging.
T343 38060-38182 Sentence denotes Sampling techniques, extraction and detection of viral nucleic acids, and diagnostic reagents may affect the test results.
T344 38183-38429 Sentence denotes More attention should be paid to the sensitivity and specificity of diagnostic reagents, and diagnostic decisions should rely on comprehensive judgment based on the clinical manifestations, laboratory results and imaging examinations of patients.
T345 38430-38639 Sentence denotes According to the latest guideline of the NHC [82], if the suspected cases in Hubei Province have imaging characteristic of pneumonia, the CT image results can be used as a basis for “clinical diagnosis cases”.
T346 38641-38672 Sentence denotes 9 The pathogenesis of COVID-19
T347 38673-38778 Sentence denotes Current understanding of the pathogenesis of HCoVs infection is still limited, especially for SARS-CoV-2.
T348 38779-38867 Sentence denotes Before 2019, there were six CoVs that could infect humans and cause respiratory disease.
T349 38868-39053 Sentence denotes HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 are sometimes attributed to the “common cold”, but in rare cases can cause severe infections in infants, young children and elderly people.
T350 39054-39190 Sentence denotes On the other hand, SARS-CoV and MERS-CoV can infect the lower respiratory tract and cause a severe respiratory syndrome in human [3,12].
T351 39191-39324 Sentence denotes The new coronavirus SARS-CoV-2 is similar to SARS-CoV and MERS-CoV and can infect lower respiratory tract and cause severe pneumonia.
T352 39325-39419 Sentence denotes The origin of SARS-CoV-2 was thought to be wild animals in the Huanan Seafood Market in Wuhan.
T353 39420-39518 Sentence denotes However, not all cases have an apparent connection with the Wuhan Huanan Seafood Wholesale Market.
T354 39519-39594 Sentence denotes It is evident now that SARS-CoV-2 is capable of person-person transmission.
T355 39595-39698 Sentence denotes We list the major pathogenic CoVs in Table 2 for better understanding of the pathogenesis of HCoV [87].
T356 39699-39769 Sentence denotes Table 2 Partial list of important pathogenic human coronaviruses [87].
T357 39770-39790 Sentence denotes Virus Genus Symptoms
T358 39791-39840 Sentence denotes HCoV-229E alpha mild respiratory tract infections
T359 39841-39890 Sentence denotes HCoV-NL63 alpha mild respiratory tract infections
T360 39891-39939 Sentence denotes HCoV-OC43 beta mild respiratory tract infections
T361 39940-39964 Sentence denotes HCoV-HKU1 beta pneumonia
T362 39965-40032 Sentence denotes SARS-CoV beta severe acute respiratory syndrome, 11% mortality rate
T363 40033-40100 Sentence denotes MERS-CoV beta severe acute respiratory syndrome, 34% mortality rate
T364 40101-40171 Sentence denotes SARS-CoV-2 beta severe acute respiratory syndrome, 2.6% mortality rate
T365 40172-40231 Sentence denotes The term “cell pyroptosis” was first proposed in 2001 [88].
T366 40232-40369 Sentence denotes In recent decades, there has been increasing evidence suggesting that “pyroptosis” is a novel inflammatory form of programmed cell death.
T367 40370-40587 Sentence denotes In 2019, Chen et al. found that SARS-CoV Viroporin 3a triggered the activation of the NLRP3 inflammasome and the secretion of IL-1β in bone marrow-derived macrophages, suggesting SARS-CoV induced cell pyroptosis [89].
T368 40588-40685 Sentence denotes Studies have shown that patients infected with SARS-CoV-2 have increased IL-1β in the serum [26].
T369 40686-40880 Sentence denotes As the rise of IL-1β is a downstream indicator of cell pyroptosis, this may suggest that cell pyroptotic activity is likely to be activated and involved in the pathogenesis of COVID-19 patients.
T370 40881-41037 Sentence denotes Nevertheless, as both classical and non-classical pyroptosis signaling can induce the release of IL-1β, it is unclear which pathway is involved in COVID-19.
T371 41038-41181 Sentence denotes Based on existing data, SARS-CoV-2 is likely to cause cell pyroptosis, especially in lymphocytes, through the activation of NLRP3 inflammasome.
T372 41182-41371 Sentence denotes The pathways involved in the activation of the signaling between NLRP3m IL-1β, IL-18 and GSDMD are illustrated in Fig. 6 and are a subject of study in samples from SARS-CoV-2 patients [90].
T373 41372-41451 Sentence denotes Fig. 6 A hypothesis of the relationship between SARS-CoV-2 and cell pyroptosis.
T374 41452-41574 Sentence denotes The COVID-19 may be linked to cell pyroptosis, especially in lymphocytes through the activation of the NLRP3 inflammasome.
T375 41575-41810 Sentence denotes Morphological changes in lymphocytes and macrophages, nucleic acid and protein levels in classical and non-classical cells, detection of NLRP3 and GSDMD, and the role of inflammatory cytokines IL-1β and IL-18 requires further research.
T376 41812-41852 Sentence denotes 9.1 The genomic structure of SARS-CoV-2
T377 41853-42089 Sentence denotes The rapid sequencing of the nearly 30,000 nucleotide SARS-CoV-2 genome was accomplished in approximately 3 weeks from the time of the first hospitalized patient on the December 12, 2019 by Zhang's group and several others in China [91].
T378 42090-42206 Sentence denotes The genomic structure is shown in Fig. 7 and shows greater than 99.9% consistency [19,[91], [92], [93], [94], [95]].
T379 42207-42262 Sentence denotes Fig. 7 Schematic diagram of the SARS-CoV-2 genome [95].
T380 42263-42394 Sentence denotes The genomic structure of SARS-CoV-2 is 5′-UTR-orf1a-orf1ab-S (Spike)–E (Envelope)-M (Membrane)-N (Nucleocapsid)-3′UTRpoly (A) tail.
T381 42395-42480 Sentence denotes Accessory genes are interspersed within the structural genes at the 3′ end of genome.
T382 42481-42603 Sentence denotes The pp1a protein encoded by the orf1a gene and the pp1ab protein encoded by the orf1ab gene contains 10 nsps (nsp1-nsp10).
T383 42604-42648 Sentence denotes The pp1ab protein also includes nsp12-nsp16.
T384 42649-42721 Sentence denotes The SARS-CoV-2 genome was found to possess 14 ORFs encoding 27 proteins.
T385 42722-42883 Sentence denotes The orf1ab and orf1a genes are located at the 5′-terminus of the genome and encode 15 non-structural proteins (nsps) from nsp1 to nsp10, and from nsp12 to nsp16.
T386 42884-43025 Sentence denotes The 3′-terminus of the genome contains 4 structural proteins (S, E, M and N) and 8 accessory proteins (3a, 3b, p6, 7a, 7b, 8b, 9b and orf14).
T387 43026-43143 Sentence denotes At the amino acid level, the SARS-CoV-2 is quite similar to that of SARS-CoV, but there are some notable differences.
T388 43144-43318 Sentence denotes For example, the 8a protein is present in SARS-CoV and absent in SARS-CoV-2; the 3b protein is 154 amino acids in SARS-CoV but shorter in SARS-CoV-2 with only 22 amino acids.
T389 43319-43445 Sentence denotes Further studies are needed to characterize how these differences affect the functionality and pathogenesis of SARS-CoV-2 [95].
T390 43446-43722 Sentence denotes The phylogenetic tree based on whole genomes showed that SARS-CoV-2 is most closely related to bat SARS-like coronavirus bat-SL-CoVZC21 (NCBI accession number MG772934) and bat-SL-CoVZC45 (NCBI accession number MG772933), which share ~89% sequence homology [[91], [92], [93]].
T391 43723-43793 Sentence denotes Their genomic organization is typical of a lineage B beta coronavirus.
T392 43794-44175 Sentence denotes Further phylogenetic analysis has posited that SARS-CoV-2 is a product of recombination with previously identified bat coronaviruses, but a recent report has subsequently identified a bat CoVs sequence, RaTG13, with 92–96% sequence identity with the novel virus, demonstrating that RaTG13 is the closest relative of the SARS-CoV-2 and forms a distinct lineage from other SARS-CoVs.
T393 44176-44262 Sentence denotes This rejects the hypothesis of emergence as a result of a recombination event [94,96].
T394 44263-44731 Sentence denotes Even though there are high similarities between SARS-CoV-2 S and RaTG13 S, there are two distinct differences: one is an “RRAR” furin recognition site formed by an insertion residues in the S1/S2 protease cleavage site in SARS-CoV-2, rather than the single Arginine in SARS-CoV [[97], [98], [99], [100], [101]]; the other difference is the presence of 29 variant residues between SARS-CoV-2 S and RaTG13 S, 17 of which mapped to the receptor binding domain (RBD) [97].
T395 44732-44866 Sentence denotes The identities of 5′- and 3′-UTR sequences are more than 83.6% consistent between SARS-CoV-2 and other β-CoVs, such as SARS-CoV [102].
T396 44867-45095 Sentence denotes The replicase polyproteins ppla and pp1ab encoded by the largest genes orf1ab are proteolytic and have been reported to function in the replication of CoVs by regulatory elements located within the non-structural proteins [102].
T397 45096-45189 Sentence denotes Four structural proteins (S, E, M and N) contribute to virion assembly and infection of CoVs.
T398 45190-45358 Sentence denotes The spike protein located on the surface of viral particles is made up of homotrimers of S proteins and is the key for the viral attachment to host receptors [103,104].
T399 45359-45409 Sentence denotes Spike glycoprotein consists of S1 and S2 subunits.
T400 45410-45655 Sentence denotes The S1 subunit contains a signal peptide, an N-terminal domain (NTD) and RBD, while the S2 subunit includes the conserved fusion peptide (FP), heptad repeat 1 and 2 (HR1 and HR2), transmembrane domain (TM), and cytoplasmic domain (CP) [102,105].
T401 45656-45814 Sentence denotes Furthermore, the S2 subunit of SARS-CoV-2 is highly conserved and shares 99% similarity with those of Bat-SL-CoVZC45, Bat-SL-CoVZC21 and human SARS-CoV [102].
T402 45815-46007 Sentence denotes The S2 subunit is therefore targeted when screening broad spectrum antiviral peptides, which is an important piece of information that can be used to develop preventive and treatment measures.
T403 46008-46223 Sentence denotes Most recently, the 3D structure of S protein was elucidated using Cryo-electron microscopy (Cryo-EM), and the RBD structure of the S protein is closer to the central location of SARS-CoV-2 compared to SARS-CoV [97].
T404 46224-46325 Sentence denotes The E protein plays a role in virus assembly and release, and is required for pathogenesis [106,107].
T405 46326-46428 Sentence denotes The N protein contains two domains, both of which can bind virus RNA genomes via different mechanisms.
T406 46429-46620 Sentence denotes It has been reported that the N protein can bind nsp3 protein to help tether the genome to replicase-transcriptase complex (RTC) and package the encapsulated genome into virions [12,108,109].
T407 46621-46772 Sentence denotes The N protein is also an antagonist of interferon and viral encoded repressor (VSR) of RNA interference (RNAi), which benefits viral replication [110].
T408 46774-46799 Sentence denotes 9.2 Entry into host cell
T409 46800-46894 Sentence denotes Cell entry is an essential component of cross-species transmission, especially for the β-CoVs.
T410 46895-47006 Sentence denotes All CoVs encode a surface glycoprotein, spike, which binds to the host receptor and mediates viral entry [111].
T411 47007-47092 Sentence denotes For β-CoVs, the RBD of the spike protein mediates the interaction with host receptor.
T412 47093-47277 Sentence denotes Upon binding the receptor, the spike protein is cleaved by nearby host proteases and releases the signal peptide to facilitate virus entry into host cells [[112], [113], [114], [115]].
T413 47278-47437 Sentence denotes Angiotensin converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4) are known host receptors for the β-CoVs SARS-CoV and MERS-CoV, respectively [116,117].
T414 47438-47526 Sentence denotes In similar fashion to SARS-CoV, SARS-CoV-2 also uses ACE2 to gain entry into host cells.
T415 47527-47670 Sentence denotes Hoffmann et al. found that the cellular protease MPRSS2 blocks entry by cleaving the spike protein and may constitute a treatment option [118].
T416 47671-47981 Sentence denotes Zhou et al. also confirmed that SARS-CoV-2 is able to use all but mouse ACE2 as an entry receptor for ACE2-expressing cells, but not cells without ACE2, indicating that the cell receptor for SARS-CoV-2 could be ACE2, and not other coronavirus receptors such as aminopeptidase N and dipeptidyl peptidase 4 [94].
T417 47982-48124 Sentence denotes Huang also showed that the affinity of the SARS-CoV-2 S-RBD binding to ACE2 is less than that of SARS-CoV through Monte Carlo algorithm [119].
T418 48125-48360 Sentence denotes However, Wrapp et al. found that SARS-CoV-2 S binding to ACE2 has approximately 10- to 20- fold higher affinity than SARS-CoV S, which can provide one explanation why SARS-CoV-2 has more human-to human spread compared to SARS-CoV [97].
T419 48361-48543 Sentence denotes The combination of SARS-CoV-2 S and ACE2 of host cells is similar to the combination of SARS-CoV and ACE2, indicating that they have the same mechanism to entry into host cells [97].
T420 48544-48702 Sentence denotes The S protein of metastable prefusion conformation undergoes a series of structural rearrangements to combine with the viral membrane of host cells [111,120].
T421 48703-48938 Sentence denotes This process consists of the S1 subunit binding to the host cell receptor, triggering of the prefusion trimer's instability, and shedding of the S1 subunit, resulting in a highly stable post-fusion conformation of the S2 subunit [121].
T422 48939-49265 Sentence denotes During the binding of the subunit S1 to its cognate receptor, it is important to note that the S1 subunit exists in 2 different states, a “down” conformation and an “up” conformation state, which corresponds to a receptor-inaccessible state and an unstable receptor-accessible state, respectively [[122], [123], [124], [125]].
T423 49266-49472 Sentence denotes Unfortunately, there are significant conformational differences between SARS-CoV and SARS-CoV-2 such that the commercially available monoclonal antibodies against SARS-CoV do not react with SARS-CoV-2 [97].
T424 49473-49680 Sentence denotes SARS-CoV-2 may directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes via specific expression of ACE2 in healthy liver tissues using cell RNA-seq data of two independent cohorts [126].
T425 49681-50107 Sentence denotes Though the respiratory systems is a primary target of SARS-CoV-2, bioinformatic analysis of single-cell transcriptomes datasets of lung, esophagus, gastric, ileum and colon reveal that the digestive system is also a potential route of entry for COVID-19, as ACE2 was not only highly expressed in lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from the ileum and colon [127].
T426 50109-50128 Sentence denotes 10 Recommendations
T427 50130-50168 Sentence denotes 10.1 Preventing the spread of disease
T428 50169-50320 Sentence denotes In response to the outbreak of pneumonia caused by the SARS-CoV-2, China has activated Level I public health emergency response for the entire country.
T429 50321-50426 Sentence denotes This activates the most comprehensive and rigorous prevention and control measures for health and safety.
T430 50427-50573 Sentence denotes A team of professionals from the NHC and China CDC was sent to conduct field investigations and implement disease control and prevention measures.
T431 50574-50619 Sentence denotes The virus was quickly isolated and sequenced.
T432 50620-50802 Sentence denotes On January 3, 2020, the first complete genome of the SARS-CoV-2 was determined and shared internationally, which led to the rapid development and deployment of diagnostic tests [60].
T433 50803-50996 Sentence denotes The NHC announced that preventive and control measures of category A infectious diseases would be implemented to effectively fight SARS-CoV-2 and has also introduced public education campaigns.
T434 50997-51119 Sentence denotes At the same time, all medical expenses of confirmed patients would be covered by central and local financial institutions.
T435 51121-51137 Sentence denotes 10.2 Quarantine
T436 51138-51271 Sentence denotes Quarantine is a traditional but very effective measure to counter a deadly epidemic, but quarantine protocols can be hard to enforce.
T437 51272-51483 Sentence denotes The local government in Wuhan announced the suspension of public transportation, with closure of airports, railway stations, and highways in the city, to prevent further disease transmission on January 23, 2020.
T438 51484-51578 Sentence denotes Subsequently, the Chinese government imposed travel bans on several Chinese cities near Wuhan.
T439 51579-51774 Sentence denotes At the same time, the Chinese government extended the Lunar New Year holidays and postponed the reopening of schools and factories to keep the nationwide migration of the population to a minimum.
T440 51775-51936 Sentence denotes Travelers from Wuhan and other epidemic areas were advised to report their travel history and to self-quarantine for two weeks to prevent community transmission.
T441 51937-52095 Sentence denotes In addition, most local governments required that all passengers must wear medical surgical masks or N95 masks when accessing public places, taxis or subways.
T442 52096-52298 Sentence denotes Temperature screening checkpoints have been set up at subway stations, railway stations, high-speed rail exits and airports to screen passengers in an effort to curb the spread of the novel coronavirus.
T443 52300-52324 Sentence denotes 10.3 Mobilize resources
T444 52325-52475 Sentence denotes With the rapid spread of the epidemic, more designated treatment hospitals and health care workers were needed to meet the growing number of patients.
T445 52476-52752 Sentence denotes On January 24, 2020, the local government in Wuhan announced the construction of a 1000-bed infirmary, named Huoshenshan hospital, and a 1500-bed infirmary, named Leishenshan hospital within 10 days, to ease the shortage of beds and treat people diagnosed with the SARS-CoV-2.
T446 52753-52879 Sentence denotes These facilities are specialty hospitals for infectious diseases, rather than simply units to receive and quarantine patients.
T447 52880-53170 Sentence denotes Wuhan has also been building 11 mobile Fangcang hospitals (a Chinese name which came from Noah's Ark) and creating tens of thousands of beds, to centralize quarantine and provide medical treatment for confirmed patients with mild symptoms, suspected patients and those who need observation.
T448 53171-53241 Sentence denotes The new facilities further enhance the local public health capacities.
T449 53242-53454 Sentence denotes Hospitals offer online consultants and medical services to symptomatic patients and suspected patients, which help reduce the frequency that patients go to hospitals and thereby reduce the risk of being infected.
T450 53455-53594 Sentence denotes Health care workers, including military medical teams, from across the Chinese mainland arrived in Hubei to provide much needed assistance.
T451 53595-53711 Sentence denotes At present, more than 30,000 health care workers have arrived in Hubei to help fight the novel coronavirus epidemic.
T452 53712-53957 Sentence denotes In order to prevent health care workers from being infected, the NHC ensured enough supplies of isolation gowns, gloves and masks and issued a technical guideline for the prevention and control of infection caused by the novel coronavirus [128].
T453 53959-53988 Sentence denotes 10.4 Disseminate information
T454 53989-54184 Sentence denotes The NHC also formulated a community prevention and control program for SARS-CoV-2 pneumonia to strengthen community-level epidemic prevention measures to control the spread of the outbreak [129].
T455 54185-54302 Sentence denotes All communities screen patients with fever within the community and monitor and report suspected cases with COVID-19.
T456 54303-54485 Sentence denotes Various forms of health education have been carried out in the community to disseminate knowledge of epidemic prevention and control, such as using masks and washing hands correctly.
T457 54486-54588 Sentence denotes The NHC issued guidelines for the protection of people at different levels of risk for COVID-19 [130].
T458 54590-54618 Sentence denotes 11 Treatment and management
T459 54619-54688 Sentence denotes There is no clear, unified and effective treatment plan for COVID-19.
T460 54689-54791 Sentence denotes Most guidelines emphasize early identification, early isolation, early diagnosis, and early treatment.
T461 54792-54926 Sentence denotes The treatment and management of SARS-CoV-2 pneumonia mainly include the following aspects (Fig. 8 ) [37,[78], [79], [80], [81], [82]].
T462 54927-54985 Sentence denotes Fig. 8 The treatment and management of COVID-19 pneumonia.
T463 54986-55054 Sentence denotes ICU: intensive care unit; ECMO: extracorporeal membrane oxygenation.
T464 55055-55211 Sentence denotes Suspected and confirmed cases should be isolated and treated in designated hospitals with effective isolation and protective conditions as soon as possible.
T465 55212-55264 Sentence denotes Suspected cases should be isolated in a single room.
T466 55265-55479 Sentence denotes WHO suggests that patients with mild symptoms and without underlying chronic diseases (such as lung or heart disease, renal failure, or immunodeficiency) may be cared for in the home environment in isolation [131].
T467 55480-55595 Sentence denotes However, severe cases should be hospitalized, and critical cases should be admitted to the ICU as soon as possible.
T468 55596-55783 Sentence denotes Supportive therapy includes bedrest, adequate nutrition, monitoring vital signs and oxygen saturation, prevention of dehydration and maintaining water, electrolyte, and acid-base balance.
T469 55784-56119 Sentence denotes For severe cases, it may be necessary to proactively prevent complications and secondary infections, treat underlying diseases and provide organ function support according to the patients’ condition such as that reported by Chen et all that involved the administration of intravenous immunoglobulin therapy to 27 of such patients [37].
T470 56120-56208 Sentence denotes Supplemental oxygen should be administered to patients with decreased oxygen saturation.
T471 56209-56352 Sentence denotes In Huang's study [26], four (10%) patients needed invasive mechanical ventilation, and two received extracorporeal membrane oxygenation (ECMO).
T472 56353-56585 Sentence denotes In Chen's study [37], 75 of 99 patients received oxygen therapy, 13 patients required non-invasive mechanical ventilation, four patients needed an invasive ventilator to assist ventilation, and three patients were treated with ECMO.
T473 56586-56814 Sentence denotes In Wang's study [83], of the 36 patients in the ICU, four patients received high-flow oxygen therapy, 15 patients received non-invasive ventilation, and 17 patients received invasive ventilation (four patients switched to ECMO).
T474 56815-56967 Sentence denotes In Guan's study, 418 of 1099 patients received oxygen therapy, 67 patients received mechanical ventilation, and ECMO was adopted in 5 severe cases [85].
T475 56968-57104 Sentence denotes Due to lack of valid evidence and possible adverse effects, routine use of corticosteroid should be avoided unless for specific reasons.
T476 57105-57332 Sentence denotes Baillie JK et al. [42] suggested that corticosteroid should not be used for the treatment of SARS-CoV-2-induced lung injury or shock, because of the lack of evidence that patients with COVID-19 will benefit from corticosteroid.
T477 57333-57445 Sentence denotes In the first 41 patients, only 22% (9/41) patients were given corticosteroid, with six of these in the ICU [26].
T478 57446-57546 Sentence denotes Chen et al. reported that 19% (19/99) patients received corticosteroid treatment for 3–15 days [37].
T479 57547-57625 Sentence denotes In Wang's study [83], 45% (62/138) patients received corticosteroid treatment.
T480 57626-57713 Sentence denotes In Guan's study, 18.6% (204/1099) of patients were given systemic corticosteroids [85].
T481 57714-57847 Sentence denotes Indiscriminate or inappropriate antimicrobial treatment, especially the combination of broad-spectrum antibiotics, should be avoided.
T482 57848-57928 Sentence denotes However, in Huang's study [26], all his 41 patients received antibiotic therapy.
T483 57929-58104 Sentence denotes In Chen's study [37], 70 patients were given antibiotic treatment, among whom 25 patients were treated with a single antibiotic and 45 patients were given combination therapy.
T484 58105-58156 Sentence denotes The duration of antibiotic treatment was 3–17 days.
T485 58157-58227 Sentence denotes In addition, there were 15 patients who received antifungal treatment.
T486 58228-58390 Sentence denotes In Wang's study [83], the 138 hospitalized patients all received antibacterial therapy, including moxifloxacin (64.4%), ceftriaxone (24.6%), azithromycin (18.1%).
T487 58391-58512 Sentence denotes In Guan's study, 632 patients were given intravenous antibiotics, and 30 patients were given antifungal medications [85].
T488 58513-58622 Sentence denotes At present, there is no evidence-based medicine to support the effectiveness of antiviral drugs for COVID-19.
T489 58623-58756 Sentence denotes The previous experience of treating SARS-CoV, MERS-CoV or influenza infections guides the selection of antiviral agents for COVID-19.
T490 58757-58864 Sentence denotes The current guideline of the NHC recommends IFN-α, lopinavir/ritonavir, and ribavirin as antiviral therapy.
T491 58865-58935 Sentence denotes In Huang's study [26], 38 of 41 patients were given antiviral therapy.
T492 58936-59063 Sentence denotes The Jinyintan hospital has launched a randomized, controlled trial of the anti-HIV drug combination of lopinavir and ritonavir.
T493 59064-59243 Sentence denotes In Chen's study [37], 75 patients received antiviral treatment, including oseltamivir, ganciclovir, and lopinavir/ritonavir, and the duration of antiviral treatment was 3–14 days.
T494 59244-59327 Sentence denotes In Wang's study [83], there were 89.9% (124/138) patients who received oseltamivir.
T495 59328-59404 Sentence denotes And in Guan's study, 35.8% (393/1099) of patients received oseltamivir [85].
T496 59405-59501 Sentence denotes The anti-viral drug remdesivir (Gilead®) is in clinical trials to treat COVID-19 in Wuhan [132].
T497 59502-59577 Sentence denotes Chloroquine phosphate has also been shown to be effective in some patients.
T498 59578-59709 Sentence denotes Identifying or developing novel drug treatment options as soon as possible is critical for the response to the SARS-CoV-2 outbreak.
T499 59710-59959 Sentence denotes Based on the structural information of clinical effective medicines for SARS-CoV-2, Liu et al. predicted 10 commercial medicines which may function as inhibitors of SARS-CoV-2, including colistin, valrubicin, icatibant, bepotastine, epirubicin, etc.
T500 59960-60045 Sentence denotes Some of these may be more resistant to viral mutation than lopinavir/ritonavir [133].
T501 60046-60144 Sentence denotes Stebbing et al. suggested that baricitinib may reduce both the viral entry and inflammation [134].
T502 60145-60334 Sentence denotes Lu reported that remdesivir may have the greatest potential for the successful treatment of SARS-CoV-2, but the efficacy and safety of remdesivir in COVID-19 needs further evaluation [135].
T503 60335-60555 Sentence denotes The antiviral efficiency of five FAD-approved drugs and two well-known broad-spectrum antiviral drugs have been studied and it has been found that remdesivir and chloroquine effectively inhibit SARS-CoV-2 in vitro [136].
T504 60556-60747 Sentence denotes The New England Journal of Medicine reported that the first case of COVID-19 confirmed in the United States was treated with intravenous remdesivir and demonstrated clinical improvement [71].
T505 60748-60921 Sentence denotes At present, a randomized, double-blind, placebo-controlled phase III clinical trial of remdesivir has been launched and already 761 confirmed cases have been enrolled [132].
T506 60922-61042 Sentence denotes Lu also pointed out that there is no direct evidence that oseltamivir is effective in the treatment of SARS-CoV-2 [135].
T507 61043-61151 Sentence denotes However, we found that oral oseltamivir or abidol has been used for suspected or confirmed SARS-CoV-2 cases.
T508 61152-61338 Sentence denotes Favilavir, formerly known as Fapilavir, was the first anti-novel coronavirus drug that has been approved for marketing by the National Medical Products Administration since the outbreak.
T509 61339-61491 Sentence denotes The drug was developed by Zhejiang Hisun Pharmaceutical Company and is expected to play an important role in preventing and treating the epidemic [137].
T510 61492-61660 Sentence denotes The role of intestinal microecological regulators that can be used to maintain intestinal microecological balance and prevent secondary bacterial infections is unclear.
T511 61661-61857 Sentence denotes Chinese traditional medicine suggests Shufengjiedu and Lianhuaqingwen, which have played a role in the prevention and treatment of new infectious respiratory diseases, may be of benefit [138,139].
T512 61858-61922 Sentence denotes Anxiety and fear often exist in suspected or confirmed patients.
T513 61923-62174 Sentence denotes Emergency psychological crisis intervention [140], and the implementation of classified intervention for different groups of people, is helpful in order to strengthen psychological counseling and reduce the psychological damage caused by the epidemic.
T514 62175-62293 Sentence denotes Mass hysteria has also led to incidences of racial discrimination against Asians, particularly in non-Asian countries.
T515 62295-62338 Sentence denotes 12 Development of vaccines for coronavirus
T516 62339-62467 Sentence denotes Research institutions and pharmaceutical companies worldwide are stepping up research and development for a coronavirus vaccine.
T517 62468-62614 Sentence denotes Virus strains have been isolated from patients’ samples and provide the basis for research and development of a vaccine for the novel coronavirus.
T518 62615-62729 Sentence denotes Although vaccines have been developed for SARS-CoV and MERS-CoV, these are not commercially available [12,14,141].
T519 62730-62930 Sentence denotes Since the emergence of SARS-CoV and MERS-CoV, basic research on coronaviruses and advances in vaccine preparation technology can significantly shorten the development time of new coronavirus vaccines.
T520 62931-63183 Sentence denotes However, the difficulties and challenges of developing an effective vaccine have been discussed earlier, and the key to a successful vaccine program is to vaccinate people before an outbreak occurs, not begin to develop the vaccine during the outbreak.
T521 63184-63457 Sentence denotes Development of animal models that faithfully mimic SARS-CoV-2 infection in humans is critical not only in providing a more refined understanding of the pathogenic mechanisms involved but also to serve as a screening model for potential chemotherapeutic agents and vaccines.
T522 63459-63488 Sentence denotes 13 Guidelines for the future
T523 63489-63590 Sentence denotes Recommendations for the prevention and management of coronavirus epidemics are summarized in Fig. 9 .
T524 63591-63776 Sentence denotes Since both SARS and SARS-CoV-2 appear to have an exotic animal origin, the purchase, trafficking, and sale of wild animals should be banned, and illegal activities should be prosecuted.
T525 63777-63949 Sentence denotes Early recognition of the problem, early identification of infected patients and early mobilization of healthcare resources are critical in limiting morbidity and mortality.
T526 63950-64096 Sentence denotes When an outbreak occurs, it is very important to rapidly identify and characterize the pathogen, in order to be able to develop diagnostic assays.
T527 64097-64455 Sentence denotes In the early stage of the disease epidemic, summarizing the clinical characteristics and treatment efficacy, formulating the diagnosis procedures, defining suspected cases and locations, determining transmission patterns, isolating contagious patients and formulating the appropriate quarantine strategy are all necessary and need to be implemented promptly.
T528 64456-64508 Sentence denotes Fig. 9 Keys to the control of future hCoV epidemics.
T529 64509-64569 Sentence denotes Lessons learned from both the SARS and SARS-CoV-2 epidemics.
T530 64570-64693 Sentence denotes The strict control of cross-infection in medical institutions is also key to preventing the further spread of the epidemic.
T531 64694-64888 Sentence denotes In addition, actively mobilizing the population to participate in epidemic prevention and control is critical, and this can be achieved by accurate information dissemination and ongoing updates.
T532 64889-65006 Sentence denotes Real-time updating the information of the epidemic situation can help to alleviate panic and reduce societal anxiety.
T533 65007-65161 Sentence denotes A strong public health surveillance system to guide the response to the outbreak is important in the face of a lack of effective therapeutics or vaccines.
T534 65162-65333 Sentence denotes Big data and artificial intelligence systems are tools that can be used to fully integrate the information, conduct comprehensive research and analyze public health risks.
T535 65334-65642 Sentence denotes Last but not least, use of the Internet and the media to conduct health education for the people, publicize the correct knowledge of prevention, and offer online consultation to guide patients to seek medical treatment correctly are additional strategies that can be implemented to achieve viral containment.
T536 65644-65658 Sentence denotes 14 Discussion
T537 65660-65709 Sentence denotes 14.1 The differences between SARS and SARS-CoV-2
T538 65710-65871 Sentence denotes Although SARS-CoV-2 and SARS-CoV have certain similarities in biological, epidemiological and pathological characteristics, there are some important differences.
T539 65872-65963 Sentence denotes First, the most fundamental difference between the two viruses lies in their gene sequence.
T540 65964-66114 Sentence denotes Second, during the SARS epidemic, a total of 8422 patients worldwide were infected with SARS-CoV, of whom 919 died, with a mortality rate of 9.5% [9].
T541 66115-66230 Sentence denotes A total of 5328 patients in China were infected with SARS-CoV, of whom 349 died, with a mortality rate of 6.5% [9].
T542 66231-66372 Sentence denotes As of February 17, 2020, there were 72,436 confirmed cases of 2019-nCoV in China, of whom 1868 have died, with a mortality rate of 2.6% [10].
T543 66373-66515 Sentence denotes Compared to SARS, there are more confirmed cases, suspected cases and deaths of SARS-CoV-2, but the mortality rate is lower than that of SARS.
T544 66516-66676 Sentence denotes From 2017 to 2018, influenza ravaged the world, affecting up to 45 million people and killing about 95,000 people, with a reported mortality rate of about 0.2%.
T545 66677-66775 Sentence denotes Every year millions of people are infected by influenza despite the existence of a yearly vaccine.
T546 66776-66936 Sentence denotes According to the United States CDC weekly report, the number of childhood deaths in the United States so far from influenza during this flu season alone is 105.
T547 66937-67109 Sentence denotes Compared with influenza, the number of patients who have died of coronavirus infection is less, but the virulence and mortality rate of coronavirus is significantly higher.
T548 67110-67228 Sentence denotes Clinically, the patients with COVID-19 have no upper respiratory symptoms (such as runny nose, sneezing, sore throat).
T549 67229-67334 Sentence denotes In 2003, a large number of medical personnel were infected, and iatrogenic transmission occurred in SARS.
T550 67335-67456 Sentence denotes In contrast, although there are cases of nosocomial infection in SARS-CoV-2, most of them are out-of-hospital infections.
T551 67458-67519 Sentence denotes 14.2 What can we learn from the 2020 nCoV epidemic in China?
T552 67520-67661 Sentence denotes The SARS-CoV-2 epidemic of 2020 in China is an international crisis, affecting human lives, the global economy, societal views and lifestyle.
T553 67662-67739 Sentence denotes During times of crisis, misinformation, blame and conspiracy theories abound.
T554 67740-67879 Sentence denotes It is probably prudent to not entirely trust the media, whether local, regional or international, as each most likely has their own agenda.
T555 67880-68066 Sentence denotes On the other hand, it is the responsibility of doctors and scientists to evaluate the events to ascertain whether or not more effective management of the crisis could have been attained.
T556 68067-68139 Sentence denotes This comes with its own set of challenges, as hindsight is always 20/20.
T557 68140-68225 Sentence denotes The quarantining of an entire country has been extreme, astounding and unprecedented.
T558 68226-68464 Sentence denotes This not only involves quarantining measures within China but also internationally, as countries canceled flights into China, quarantined their own nationals as they returned from China and installed thermal scanners to detect ill people.
T559 68465-68532 Sentence denotes But the quarantine measures inside China are certainly eye-opening.
T560 68533-68623 Sentence denotes The entire city of Wuhan was shut off, and this was extended to every other city in China.
T561 68624-68748 Sentence denotes In effect, the entire country was told to stay home, creating an enormous impact on the economy and on people's daily lives.
T562 68749-68793 Sentence denotes Roads and stores became deserted (Fig. 10 ).
T563 68794-68892 Sentence denotes In Ningbo, each household was only permitted to send one person out for groceries every other day.
T564 68893-68935 Sentence denotes Schools were closed till the end of March.
T565 68936-68957 Sentence denotes Everyone wears masks.
T566 68958-69016 Sentence denotes The objective was to starve the virus, to eliminate hosts.
T567 69017-69077 Sentence denotes Yet even with these measures, new cases continued to appear.
T568 69078-69291 Sentence denotes The quarantine measures in China have obviously come under a great deal of scrutiny, with so called “experts” weighing in, some saying that it will not work, that isolating a city deprives it of medical resources.
T569 69292-69399 Sentence denotes Whatever the criticism, it is humbling to think of what may have happened without these draconian measures.
T570 69400-69583 Sentence denotes It is also difficult to comprehend if such measures could actually take place in other parts of the world, or if the implementation of these changes could have taken place as quickly.
T571 69584-69744 Sentence denotes For example, hand shaking is not part of Chinese culture, but it is almost automatic in other parts of the world, and it is normally done without even thinking.
T572 69745-69819 Sentence denotes This is the first thing that would have to stop to help contain the virus.
T573 69820-69890 Sentence denotes Fig. 10 Life in China in Beijing and Hubei during quarantine measures.
T574 69891-69958 Sentence denotes Quarantine measures have led to empty streets and shopping centers.
T575 69959-70123 Sentence denotes Then there is the matter of the ophthalmologist and others who voiced concerns in the media about a cluster of cases of a flu-like illness near the end of December.
T576 70124-70309 Sentence denotes At the present time, it is difficult to say whether or not the response could have been faster than it actually was, as this corresponds to the time when work began on viral sequencing.
T577 70310-70394 Sentence denotes It is possible that medical teams were already working on the sequence at that time.
T578 70395-70522 Sentence denotes It is also quite possible that officials did not initially sound the alarm publicly because they did not want to cause a panic.
T579 70523-70654 Sentence denotes Perhaps this was the wrong decision, but these decisions are difficult in times of crisis and it is of course easy to second guess.
T580 70655-70773 Sentence denotes It is easy to understand that this can be perceived as withholding information and why the public would be frustrated.
T581 70774-70926 Sentence denotes The lesson here is that dissemination of accurate and validated information and establishing guidelines to prevent the spread of infections is critical.
T582 70927-71205 Sentence denotes There are many “heroes” in these crises, people who have risked their lives and made incredible sacrifices to help society rid itself of this scourge, including those who work on the front lines, epidemiologists, scientists, doctors, first responders, and members of the public.
T583 71206-71269 Sentence denotes Unfortunately, these events also bring out the worst in people.
T584 71270-71408 Sentence denotes Numerous accounts of racial discrimination have been perpetrated against Asians across the world, many rising to the level of hate crimes.
T585 71409-71566 Sentence denotes One must not forget the psychological impact of an infection such as this on people who are not even infected or who will never encounter an infected person.
T586 71567-71693 Sentence denotes The emergence of SARS-CoV, MERS-CoV, and now SARS-CoV-2, suggests that coronavirus will pose a lasting threat to human beings.
T587 71694-71795 Sentence denotes The epidemic will eventually be contained, and people's memory of the coronavirus may gradually blur.
T588 71796-71989 Sentence denotes But we must not forget the lessons learned from this crisis, and already begin to take measures to prevent the next new outbreak of Coronavirus or some other virus from appearing in the future.
T589 71990-72035 Sentence denotes If it does appear, how will we respond to it?
T590 72036-72072 Sentence denotes What if it does not happen in China?
T591 72073-72236 Sentence denotes Will other countries have the fortitude to implement even more drastic measures and mobilize resources to prevent the spread of the virus and to care for the sick?
T592 72237-72308 Sentence denotes We can always improve on the handling of global pandemics or epidemics.
T593 72309-72453 Sentence denotes From the lessons learned during the SARS and now the SARS-CoV-2 epidemics, we can nearly provide a roadmap for the response to future outbreaks.
T594 72454-72624 Sentence denotes The development of a vaccine for coronavirus is a critical step in prevention, but it may not be effective for future strains, and we must be ready for the next epidemic.
T595 72626-72633 Sentence denotes Funding
T596 72634-72728 Sentence denotes 10.13039/501100005089Beijing Municipal Natural Science Foundation General Program (7,192,197).
T597 72730-72763 Sentence denotes Declaration of competing interest
T598 72764-72808 Sentence denotes The authors declare no conflict of interest.