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README.md CHANGED
@@ -2,8 +2,182 @@
2
  license: mit
3
  pipeline_tag: question-answering
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  widget:
5
- - text: "What is the delay between illness onset and infection?"
6
- context: "Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029449/ SHA: 90de2d957e1960b948b8c38c9877f9eca983f9eb Authors: Cowling, Benjamin J; Leung, Gabriel M Date: 2020-02-13 DOI: 10.2807/1560-7917.es.2020.25.6.2000110 License: cc-by Abstract: 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]. The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. 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. 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]. Text: 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. 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] . 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] . 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. 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. 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] . The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. 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. 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] . Chains of transmission have now been reported in a number of locations outside of mainland China. 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. 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. 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. 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] . 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] . 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. Data on viral shedding dynamics could help in assessing duration of infectiousness. 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] . This allowed control of the SARS epidemic through prompt detection of cases and strict isolation. 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] . To date, transmission patterns of 2019-nCoV appear more similar to influenza, with contagiousness occurring around the time of symptom onset, rather than SARS. 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. Coronaviruses can also infect the human gastrointestinal tract [11, 12] , and faecal-oral transmission might also play a role in this instance. 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] . 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] . 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. The first human infections were identified through a surveillance system for pneumonia of unknown aetiology, and all of the earliest infections therefore had Modelling studies incorporating healthcare capacity and processes pneumonia. 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. 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. 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. If, however, the seriousness of infection is similar to seasonal influenza, especially during milder seasons, mitigation measures could be tuned accordingly. Beyond a robust assessment of overall severity, it is also important to determine high risk groups. 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] . 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. Are children protected from infection or do they not fall ill after infection? 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. Obviously, the question about virus shedding of those being infected but asymptomatic leads to the crucial question of infectivity. 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. 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. Serosurveys in affected locations could inform this, in addition to truly assessing the clinical severity spectrum. 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. Some experts already questioned whether the 2019-nCoV may behave similarly to MERS-CoV in cases exhibiting mild symptoms without eliciting neutralising antibodies [17] . A separate question pertains to the possibility of antibody-dependent enhancement of infection or of disease [18, 19] . If either of these were to be relevant, the transmission dynamics could become more complex. A wide range of control measures can be considered to contain or mitigate an emerging infection such as 2019-nCoV. 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. 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. 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] . A number of social distancing measures have already been implemented in Chinese cities in the past few weeks including school and workplace closures. 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. 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] . 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. 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. At the individual level, surgical face masks have often been a particularly visible image from affected cities in China. 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. 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. The Table summarises research gaps to guide the public health response identified. In conclusion, there are a number of urgent research priorities to inform the public health response to the global spread of 2019-nCoV infections. 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. 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. 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] . 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. 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. Particularly if children are being infected and are developing immunity hereafter, 2019-nCoV could optimistically become the fifth human coronavirus causing the common cold. None declared."
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7
  ---
8
 
9
  # Model Card for Model longluu/Medical-QA-gatortrons-COVID-QA
 
2
  license: mit
3
  pipeline_tag: question-answering
4
  widget:
5
+ - text: What is the delay between illness onset and infection?
6
+ context: 'Epidemiological research priorities for public health control of the ongoing
7
+ global novel coronavirus (2019-nCoV) outbreak https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029449/
8
+ SHA: 90de2d957e1960b948b8c38c9877f9eca983f9eb Authors: Cowling, Benjamin J; Leung,
9
+ Gabriel M Date: 2020-02-13 DOI: 10.2807/1560-7917.es.2020.25.6.2000110 License:
10
+ cc-by Abstract: Infections with 2019-nCoV can spread from person to person, and
11
+ in the earliest phase of the outbreak the basic reproductive number was estimated
12
+ to be around 2.2, assuming a mean serial interval of 7.5 days [2]. The serial
13
+ interval was not precisely estimated, and a potentially shorter mean serial interval
14
+ would have corresponded to a slightly lower basic reproductive number. Control
15
+ measures and changes in population behaviour later in January should have reduced
16
+ the effective reproductive number. However, it is too early to estimate whether
17
+ the effective reproductive number has been reduced to below the critical threshold
18
+ of 1 because cases currently being detected and reported would have mostly been
19
+ infected in mid- to late-January. Average delays between infection and illness
20
+ onset have been estimated at around 5–6 days, with an upper limit of around 11-14
21
+ days [2,5], and delays from illness onset to laboratory confirmation added a further
22
+ 10 days on average [2]. Text: It is now 6 weeks since Chinese health authorities
23
+ announced the discovery of a novel coronavirus (2019-nCoV) [1] causing a cluster
24
+ of pneumonia cases in Wuhan, the major transport hub of central China. The earliest
25
+ human infections had occurred by early December 2019, and a large wet market in
26
+ central Wuhan was linked to most, but not all, of the initial cases [2] . While
27
+ evidence from the initial outbreak investigations seemed to suggest that 2019-nCoV
28
+ could not easily spread between humans [3] , it is now very clear that infections
29
+ have been spreading from person to person [2] . We recently estimated that more
30
+ than 75,000 infections may have occurred in Wuhan as at 25 January 2020 [4] ,
31
+ and increasing numbers of infections continue to be detected in other cities in
32
+ mainland China and around the world. A number of important characteristics of
33
+ 2019-nCoV infection have already been identified, but in order to calibrate public
34
+ health responses we need improved information on transmission dynamics, severity
35
+ of the disease, immunity, and the impact of control and mitigation measures that
36
+ have been applied to date. Infections with 2019-nCoV can spread from person to
37
+ person, and in the earliest phase of the outbreak the basic reproductive number
38
+ was estimated to be around 2.2, assuming a mean serial interval of 7.5 days [2]
39
+ . The serial interval was not precisely estimated, and a potentially shorter mean
40
+ serial interval would have corresponded to a slightly lower basic reproductive
41
+ number. Control measures and changes in population behaviour later in January
42
+ should have reduced the effective reproductive number. However, it is too early
43
+ to estimate whether the effective reproductive number has been reduced to below
44
+ the critical threshold of 1 because cases currently being detected and reported
45
+ would have mostly been infected in mid-to late-January. Average delays between
46
+ infection and illness onset have been estimated at around 5-6 days, with an upper
47
+ limit of around 11-14 days [2, 5] , and delays from illness onset to laboratory
48
+ confirmation added a further 10 days on average [2] . Chains of transmission have
49
+ now been reported in a number of locations outside of mainland China. Within the
50
+ coming days or weeks it will become clear whether sustained local transmission
51
+ has been occurring in other cities outside of Hubei province in China, or in other
52
+ countries. If sustained transmission does occur in other locations, it would be
53
+ valuable to determine whether there is variation in transmissibility by location,
54
+ for example because of different behaviours or control measures, or because of
55
+ different environmental conditions. To address the latter, virus survival studies
56
+ can be done in the laboratory to confirm whether there are preferred ranges of
57
+ temperature or humidity for 2019-nCoV transmission to occur. In an analysis of
58
+ the first 425 confirmed cases of infection, 73% of cases with illness onset between
59
+ 12 and 22 January reported no exposure to either a wet market or another person
60
+ with symptoms of a respiratory illness [2] . The lack of reported exposure to
61
+ another ill person could be attributed to lack of awareness or recall bias, but
62
+ China''s health minister publicly warned that pre-symptomatic transmission could
63
+ be occurring [6] . Determining the extent to which asymptomatic or pre-symptomatic
64
+ transmission might be occurring is an urgent priority, because it has direct implications
65
+ for public health and hospital infection control. Data on viral shedding dynamics
66
+ could help in assessing duration of infectiousness. For severe acute respiratory
67
+ syndrome-related coronavirus (SARS-CoV), infectivity peaked at around 10 days
68
+ after illness onset [7] , consistent with the peak in viral load at around that
69
+ time [8] . This allowed control of the SARS epidemic through prompt detection
70
+ of cases and strict isolation. For influenza virus infections, virus shedding
71
+ is highest on the day of illness onset and relatively higher from shortly before
72
+ symptom onset until a few days after onset [9] . To date, transmission patterns
73
+ of 2019-nCoV appear more similar to influenza, with contagiousness occurring around
74
+ the time of symptom onset, rather than SARS. Transmission of respiratory viruses
75
+ generally happens through large respiratory droplets, but some respiratory viruses
76
+ can spread through fine particle aerosols [10] , and indirect transmission via
77
+ fomites can also play a role. Coronaviruses can also infect the human gastrointestinal
78
+ tract [11, 12] , and faecal-oral transmission might also play a role in this instance.
79
+ The SARS-CoV superspreading event at Amoy Gardens where more than 300 cases were
80
+ infected was attributed to faecal-oral, then airborne, spread through pressure
81
+ differentials between contaminated effluent pipes, bathroom floor drains and flushing
82
+ toilets [13] . The first large identifiable superspreading event during the present
83
+ 2019-nCoV outbreak has apparently taken place on the Diamond Princess cruise liner
84
+ quarantined off the coast of Yokohama, Japan, with at least 130 passengers tested
85
+ positive for 2019-nCoV as at 10 February 2020 [14] . Identifying which modes are
86
+ important for 2019-nCoV transmission would inform the importance of personal protective
87
+ measures such as face masks (and specifically which types) and hand hygiene. The
88
+ first human infections were identified through a surveillance system for pneumonia
89
+ of unknown aetiology, and all of the earliest infections therefore had Modelling
90
+ studies incorporating healthcare capacity and processes pneumonia. It is well
91
+ established that some infections can be severe, particularly in older adults with
92
+ underlying medical conditions [15, 16] , but based on the generally mild clinical
93
+ presentation of 2019-nCoV cases detected outside China, it appears that there
94
+ could be many more mild infections than severe infections. Determining the spectrum
95
+ of clinical manifestations of 2019-nCoV infections is perhaps the most urgent
96
+ research priority, because it determines the strength of public health response
97
+ required. If the seriousness of infection is similar to the 1918/19 Spanish influenza,
98
+ and therefore at the upper end of severity scales in influenza pandemic plans,
99
+ the same responses would be warranted for 2019-nCoV as for the most severe influenza
100
+ pandemics. If, however, the seriousness of infection is similar to seasonal influenza,
101
+ especially during milder seasons, mitigation measures could be tuned accordingly.
102
+ Beyond a robust assessment of overall severity, it is also important to determine
103
+ high risk groups. Infections would likely be more severe in older adults, obese
104
+ individuals or those with underlying medical conditions, but there have not yet
105
+ been reports of severity of infections in pregnant women, and very few cases have
106
+ been reported in children [2] . Those under 18 years are a critical group to study
107
+ in order to tease out the relative roles of susceptibility vs severity as possible
108
+ underlying causes for the very rare recorded instances of infection in this age
109
+ group. Are children protected from infection or do they not fall ill after infection?
110
+ If they are naturally immune, which is unlikely, we should understand why; otherwise,
111
+ even if they do not show symptoms, it is important to know if they shed the virus.
112
+ Obviously, the question about virus shedding of those being infected but asymptomatic
113
+ leads to the crucial question of infectivity. Answers to these questions are especially
114
+ pertinent as basis for decisions on school closure as a social distancing intervention,
115
+ which can be hugely disruptive not only for students but also because of its knock-on
116
+ effect for child care and parental duties. Very few children have been confirmed
117
+ 2019-nCoV cases so far but that does not necessarily mean that they are less susceptible
118
+ or that they could not be latent carriers. Serosurveys in affected locations could
119
+ inform this, in addition to truly assessing the clinical severity spectrum. Another
120
+ question on susceptibility is regarding whether 2019-nCoV infection confers neutralising
121
+ immunity, usually but not always, indicated by the presence of neutralising antibodies
122
+ in convalescent sera. Some experts already questioned whether the 2019-nCoV may
123
+ behave similarly to MERS-CoV in cases exhibiting mild symptoms without eliciting
124
+ neutralising antibodies [17] . A separate question pertains to the possibility
125
+ of antibody-dependent enhancement of infection or of disease [18, 19] . If either
126
+ of these were to be relevant, the transmission dynamics could become more complex.
127
+ A wide range of control measures can be considered to contain or mitigate an emerging
128
+ infection such as 2019-nCoV. Internationally, the past week has seen an increasing
129
+ number of countries issue travel advisories or outright entry bans on persons
130
+ from Hubei province or China as a whole, as well as substantial cuts in flights
131
+ to and from affected areas out of commercial considerations. Evaluation of these
132
+ mobility restrictions can confirm their potential effectiveness in delaying local
133
+ epidemics [20] , and can also inform when as well as how to lift these restrictions.
134
+ If and when local transmission begins in a particular location, a variety of community
135
+ mitigation measures can be implemented by health authorities to reduce transmission
136
+ and thus reduce the growth rate of an epidemic, reduce the height of the epidemic
137
+ peak and the peak demand on healthcare services, as well as reduce the total number
138
+ of infected persons [21] . A number of social distancing measures have already
139
+ been implemented in Chinese cities in the past few weeks including school and
140
+ workplace closures. It should now be an urgent priority to quantify the effects
141
+ of these measures and specifically whether they can reduce the effective reproductive
142
+ number below 1, because this will guide the response strategies in other locations.
143
+ During the 1918/19 influenza pandemic, cities in the United States, which implemented
144
+ the most aggressive and sustained community measures were the most successful
145
+ ones in mitigating the impact of that pandemic [22] . Similarly to international
146
+ travel interventions, local social distancing measures should be assessed for
147
+ their impact and when they could be safely discontinued, albeit in a coordinated
148
+ and deliberate manner across China such that recrudescence in the epidemic curve
149
+ is minimised. Mobile telephony global positioning system (GPS) data and location
150
+ services data from social media providers such as Baidu and Tencent in China could
151
+ become the first occasion when these data inform outbreak control in real time.
152
+ At the individual level, surgical face masks have often been a particularly visible
153
+ image from affected cities in China. Face masks are essential components of personal
154
+ protective equipment in healthcare settings, and should be recommended for ill
155
+ persons in the community or for those who care for ill persons. However, there
156
+ is now a shortage of supply of masks in China and elsewhere, and debates are ongoing
157
+ about their protective value for uninfected persons in the general community.
158
+ The Table summarises research gaps to guide the public health response identified.
159
+ In conclusion, there are a number of urgent research priorities to inform the
160
+ public health response to the global spread of 2019-nCoV infections. Establishing
161
+ robust estimates of the clinical severity of infections is probably the most pressing,
162
+ because flattening out the surge in hospital admissions would be essential if
163
+ there is a danger of hospitals becoming overwhelmed with patients who require
164
+ inpatient care, not only for those infected with 2019-nCoV but also for urgent
165
+ acute care of patients with other conditions including those scheduled for procedures
166
+ and operations. In addressing the research gaps identified here, there is a need
167
+ for strong collaboration of a competent corps of epidemiological scientists and
168
+ public health workers who have the flexibility to cope with the surge capacity
169
+ required, as well as support from laboratories that can deliver on the ever rising
170
+ demand for diagnostic tests for 2019-nCoV and related sequelae. The readiness
171
+ survey by Reusken et al. in this issue of Eurosurveillance testifies to the rapid
172
+ response and capabilities of laboratories across Europe should the outbreak originating
173
+ in Wuhan reach this continent [23] . In the medium term, we look towards the identification
174
+ of efficacious pharmaceutical agents to prevent and treat what may likely become
175
+ an endemic infection globally. Beyond the first year, one interesting possibility
176
+ in the longer term, perhaps borne of wishful hope, is that after the first few
177
+ epidemic waves, the subsequent endemic re-infections could be of milder severity.
178
+ Particularly if children are being infected and are developing immunity hereafter,
179
+ 2019-nCoV could optimistically become the fifth human coronavirus causing the
180
+ common cold. None declared.'
181
  ---
182
 
183
  # Model Card for Model longluu/Medical-QA-gatortrons-COVID-QA
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