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Id Subject Object Predicate Lexical cue
T1 0-122 Sentence denotes Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak
T2 124-326 Sentence denotes It is now 6 weeks since Chinese health authorities announced the discovery of a novel coronavirus (2019-nCoV) [1] causing a cluster of pneumonia cases in Wuhan, the major transport hub of central China.
T3 327-492 Sentence denotes The earliest human infections had occurred by early December 2019, and a large wet market in central Wuhan was linked to most, but not all, of the initial cases [2].
T4 493-709 Sentence denotes While evidence from the initial outbreak investigations seemed to suggest that 2019-nCoV could not easily spread between humans [3], it is now very clear that infections have been spreading from person to person [2].
T5 710-935 Sentence denotes We recently estimated that more than 75,000 infections may have occurred in Wuhan as at 25 January 2020 [4], and increasing numbers of infections continue to be detected in other cities in mainland China and around the world.
T6 936-1248 Sentence denotes A number of important characteristics of 2019-nCoV infection have already been identified, but in order to calibrate public health responses we need improved information on transmission dynamics, severity of the disease, immunity, and the impact of control and mitigation measures that have been applied to date.
T7 1250-1271 Sentence denotes Transmission dynamics
T8 1272-1484 Sentence denotes Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2.2, assuming a mean serial interval of 7.5 days [2].
T9 1485-1651 Sentence denotes The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number.
T10 1652-1776 Sentence denotes Control measures and changes in population behaviour later in January should have reduced the effective reproductive number.
T11 1777-2018 Sentence denotes However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1 because cases currently being detected and reported would have mostly been infected in mid- to late-January.
T12 2019-2254 Sentence denotes Average delays between infection and illness onset have been estimated at around 5–6 days, with an upper limit of around 11-14 days [2,5], and delays from illness onset to laboratory confirmation added a further 10 days on average [2].
T13 2255-2352 Sentence denotes Chains of transmission have now been reported in a number of locations outside of mainland China.
T14 2353-2536 Sentence denotes Within the coming days or weeks it will become clear whether sustained local transmission has been occurring in other cities outside of Hubei province in China, or in other countries.
T15 2537-2802 Sentence denotes If sustained transmission does occur in other locations, it would be valuable to determine whether there is variation in transmissibility by location, for example because of different behaviours or control measures, or because of different environmental conditions.
T16 2803-2988 Sentence denotes To address the latter, virus survival studies can be done in the laboratory to confirm whether there are preferred ranges of temperature or humidity for 2019-nCoV transmission to occur.
T17 2989-3214 Sentence denotes In an analysis of the first 425 confirmed cases of infection, 73% of cases with illness onset between 12 and 22 January reported no exposure to either a wet market or another person with symptoms of a respiratory illness [2].
T18 3215-3425 Sentence denotes The lack of reported exposure to another ill person could be attributed to lack of awareness or recall bias, but China’s health minister publicly warned that pre-symptomatic transmission could be occurring [6].
T19 3426-3629 Sentence denotes Determining the extent to which asymptomatic or pre-symptomatic transmission might be occurring is an urgent priority, because it has direct implications for public health and hospital infection control.
T20 3630-3713 Sentence denotes Data on viral shedding dynamics could help in assessing duration of infectiousness.
T21 3714-3909 Sentence denotes For severe acute respiratory syndrome-related coronavirus (SARS-CoV), infectivity peaked at around 10 days after illness onset [7], consistent with the peak in viral load at around that time [8].
T22 3910-4007 Sentence denotes This allowed control of the SARS epidemic through prompt detection of cases and strict isolation.
T23 4008-4183 Sentence denotes For influenza virus infections, virus shedding is highest on the day of illness onset and relatively higher from shortly before symptom onset until a few days after onset [9].
T24 4184-4343 Sentence denotes To date, transmission patterns of 2019-nCoV appear more similar to influenza, with contagiousness occurring around the time of symptom onset, rather than SARS.
T25 4344-4570 Sentence denotes Transmission of respiratory viruses generally happens through large respiratory droplets, but some respiratory viruses can spread through fine particle aerosols [10], and indirect transmission via fomites can also play a role.
T26 4571-4712 Sentence denotes Coronaviruses can also infect the human gastrointestinal tract [11,12], and faecal-oral transmission might also play a role in this instance.
T27 4713-4972 Sentence denotes The SARS-CoV superspreading event at Amoy Gardens where more than 300 cases were infected was attributed to faecal-oral, then airborne, spread through pressure differentials between contaminated effluent pipes, bathroom floor drains and flushing toilets [13].
T28 4973-5258 Sentence denotes The first large identifiable superspreading event during the present 2019-nCoV outbreak has apparently taken place on the Diamond Princess cruise liner quarantined off the coast of Yokohama, Japan, with at least 130 passengers tested positive for 2019-nCoV as at 10 February 2020 [14].
T29 5259-5451 Sentence denotes Identifying which modes are important for 2019-nCoV transmission would inform the importance of personal protective measures such as face masks (and specifically which types) and hand hygiene.
T30 5453-5482 Sentence denotes Disease severity and immunity
T31 5483-5651 Sentence denotes The first human infections were identified through a surveillance system for pneumonia of unknown aetiology, and all of the earliest infections therefore had pneumonia.
T32 5652-5961 Sentence denotes It is well established that some infections can be severe, particularly in older adults with underlying medical conditions [15,16], but based on the generally mild clinical presentation of 2019-nCoV cases detected outside China, it appears that there could be many more mild infections than severe infections.
T33 5962-6154 Sentence denotes Determining the spectrum of clinical manifestations of 2019-nCoV infections is perhaps the most urgent research priority, because it determines the strength of public health response required.
T34 6155-6406 Sentence denotes If the seriousness of infection is similar to the 1918/19 Spanish influenza, and therefore at the upper end of severity scales in influenza pandemic plans, the same responses would be warranted for 2019-nCoV as for the most severe influenza pandemics.
T35 6407-6564 Sentence denotes If, however, the seriousness of infection is similar to seasonal influenza, especially during milder seasons, mitigation measures could be tuned accordingly.
T36 6565-6664 Sentence denotes Beyond a robust assessment of overall severity, it is also important to determine high risk groups.
T37 6665-6919 Sentence denotes Infections would likely be more severe in older adults, obese individuals or those with underlying medical conditions, but there have not yet been reports of severity of infections in pregnant women, and very few cases have been reported in children [2].
T38 6920-7140 Sentence denotes Those under 18 years are a critical group to study in order to tease out the relative roles of susceptibility vs severity as possible underlying causes for the very rare recorded instances of infection in this age group.
T39 7141-7219 Sentence denotes Are children protected from infection or do they not fall ill after infection?
T40 7220-7388 Sentence denotes If they are naturally immune, which is unlikely, we should understand why; otherwise, even if they do not show symptoms, it is important to know if they shed the virus.
T41 7389-7520 Sentence denotes Obviously, the question about virus shedding of those being infected but asymptomatic leads to the crucial question of infectivity.
T42 7521-7779 Sentence denotes Answers to these questions are especially pertinent as basis for decisions on school closure as a social distancing intervention, which can be hugely disruptive not only for students but also because of its knock-on effect for child care and parental duties.
T43 7780-7949 Sentence denotes Very few children have been confirmed 2019-nCoV cases so far but that does not necessarily mean that they are less susceptible or that they could not be latent carriers.
T44 7950-8065 Sentence denotes Serosurveys in affected locations could inform this, in addition to truly assessing the clinical severity spectrum.
T45 8066-8271 Sentence denotes Another question on susceptibility is regarding whether 2019-nCoV infection confers neutralising immunity, usually but not always, indicated by the presence of neutralising antibodies in convalescent sera.
T46 8272-8440 Sentence denotes Some experts already questioned whether the 2019-nCoV may behave similarly to MERS-CoV in cases exhibiting mild symptoms without eliciting neutralising antibodies [17].
T47 8441-8558 Sentence denotes A separate question pertains to the possibility of antibody-dependent enhancement of infection or of disease [18,19].
T48 8559-8651 Sentence denotes If either of these were to be relevant, the transmission dynamics could become more complex.
T49 8653-8684 Sentence denotes Control and mitigation measures
T50 8685-8799 Sentence denotes A wide range of control measures can be considered to contain or mitigate an emerging infection such as 2019-nCoV.
T51 8800-9072 Sentence denotes Internationally, the past week has seen an increasing number of countries issue travel advisories or outright entry bans on persons from Hubei province or China as a whole, as well as substantial cuts in flights to and from affected areas out of commercial considerations.
T52 9073-9258 Sentence denotes Evaluation of these mobility restrictions can confirm their potential effectiveness in delaying local epidemics [20], and can also inform when as well as how to lift these restrictions.
T53 9259-9621 Sentence denotes If and when local transmission begins in a particular location, a variety of community mitigation measures can be implemented by health authorities to reduce transmission and thus reduce the growth rate of an epidemic, reduce the height of the epidemic peak and the peak demand on healthcare services, as well as reduce the total number of infected persons [21].
T54 9622-9771 Sentence denotes A number of social distancing measures have already been implemented in Chinese cities in the past few weeks including school and workplace closures.
T55 9772-10001 Sentence denotes It should now be an urgent priority to quantify the effects of these measures and specifically whether they can reduce the effective reproductive number below 1, because this will guide the response strategies in other locations.
T56 10002-10218 Sentence denotes During the 1918/19 influenza pandemic, cities in the United States, which implemented the most aggressive and sustained community measures were the most successful ones in mitigating the impact of that pandemic [22].
T57 10219-10499 Sentence denotes Similarly to international travel interventions, local social distancing measures should be assessed for their impact and when they could be safely discontinued, albeit in a coordinated and deliberate manner across China such that recrudescence in the epidemic curve is minimised.
T58 10500-10729 Sentence denotes Mobile telephony global positioning system (GPS) data and location services data from social media providers such as Baidu and Tencent in China could become the first occasion when these data inform outbreak control in real time.
T59 10730-10850 Sentence denotes At the individual level, surgical face masks have often been a particularly visible image from affected cities in China.
T60 10851-11041 Sentence denotes Face masks are essential components of personal protective equipment in healthcare settings, and should be recommended for ill persons in the community or for those who care for ill persons.
T61 11042-11219 Sentence denotes However, there is now a shortage of supply of masks in China and elsewhere, and debates are ongoing about their protective value for uninfected persons in the general community.
T62 11220-11302 Sentence denotes The Table summarises research gaps to guide the public health response identified.
T63 11303-11378 Sentence denotes Table Research priorities to guide the public health response to 2019-nCoV
T64 11379-11436 Sentence denotes Domain Priorities Study designs / data sources required
T65 11437-11661 Sentence denotes Transmission dynamics Provide robust estimates of the serial interval and generation time Detailed exposure and illness onset information from unselected case clusters in line lists, preferably from more than one epicentre
T66 11662-11944 Sentence denotes Estimate effective reproductive number (Rt) in other cities (i.e. ex-Wuhan) in China and elsewhere Epidemic curves for each city by dates of illness onset, preferably stratified by likely source of infection (zoonotic, environmental point source, local case vs imported index case)
T67 11945-12178 Sentence denotes Clarify the relative importance of pre-symptomatic / asymptomatic transmission Detailed reports of transmission events and symptomatic status of infectors; viral shedding data; special studies in households and other closed settings
T68 12179-12343 Sentence denotes Determine the role of different age groups in transmission, particularly children Transmission studies in households and other closed settings; serological studies
T69 12344-12600 Sentence denotes Determine the relative importance of possible modes of transmission Outbreak investigations, in particular for superspreading events; environmental sampling, air sampling and exhaled breath sampling; special studies in households and other closed settings
T70 12601-12749 Sentence denotes Determine environmental effects on virus survival and transmission Virus survival studies in situ vivo and in vitro; environmental sampling studies
T71 12750-12960 Sentence denotes Severity Provide robust estimates of the risk of fatality of hospitalised cases, by age or other important groupings Reports from unselected clinical cohorts of times to death or recovery among resolved cases
T72 12961-13139 Sentence denotes Provide robust estimates of the risk of fatality of symptomatic cases, by age or other important groupings Estimates of incidence from population-wide surveillance of mild cases
T73 13140-13226 Sentence denotes Identify groups at high risk of severe infection Case–control studies; cohort studies
T74 13227-13395 Sentence denotes Susceptibility Determine if children are infected, and if so, if they are infectious Transmission studies in households and other closed settings; serological studies
T75 13396-13531 Sentence denotes Determine if all infections result in neutralising immunity Convalescent serology from mild as well as severe cases, in all age groups
T76 13532-13720 Sentence denotes Control measures Provide impact estimates of travel restrictions, border screening and quarantine policies on non-local spread Modelling analyses of local and global spread of infections
T77 13721-13899 Sentence denotes Estimate the effects of social distancing measures and other non-pharmaceutical interventions on transmissibility Comparative analyses of transmissibility in different locations
T78 13900-14228 Sentence denotes Predict the most effective measures to reduce the peak burden on healthcare providers and other societal functions Modelling studies incorporating healthcare capacity and processes In conclusion, there are a number of urgent research priorities to inform the public health response to the global spread of 2019-nCoV infections.
T79 14229-14665 Sentence denotes Establishing robust estimates of the clinical severity of infections is probably the most pressing, because flattening out the surge in hospital admissions would be essential if there is a danger of hospitals becoming overwhelmed with patients who require inpatient care, not only for those infected with 2019-nCoV but also for urgent acute care of patients with other conditions including those scheduled for procedures and operations.
T80 14666-15036 Sentence denotes In addressing the research gaps identified here, there is a need for strong collaboration of a competent corps of epidemiological scientists and public health workers who have the flexibility to cope with the surge capacity required, as well as support from laboratories that can deliver on the ever rising demand for diagnostic tests for 2019-nCoV and related sequelae.
T81 15037-15256 Sentence denotes The readiness survey by Reusken et al. in this issue of Eurosurveillance testifies to the rapid response and capabilities of laboratories across Europe should the outbreak originating in Wuhan reach this continent [23].
T82 15257-15423 Sentence denotes In the medium term, we look towards the identification of efficacious pharmaceutical agents to prevent and treat what may likely become an endemic infection globally.
T83 15424-15635 Sentence denotes Beyond the first year, one interesting possibility in the longer term, perhaps borne of wishful hope, is that after the first few epidemic waves, the subsequent endemic re-infections could be of milder severity.
T84 15636-15809 Sentence denotes Particularly if children are being infected and are developing immunity hereafter, 2019-nCoV could optimistically become the fifth human coronavirus causing the common cold.
T85 15811-15825 Sentence denotes Editorial note
T86 15826-15889 Sentence denotes This editorial was published as an e-Alert on 11 February 2020.
T87 15891-15912 Sentence denotes Conflict of interest:
T88 15913-15927 Sentence denotes None declared.
T89 15928-15951 Sentence denotes Authors’ contributions:
T90 15952-15975 Sentence denotes Wrote first draft: BJC.
T91 15976-16041 Sentence denotes Critically revised draft and approved final version: BJC and GML.