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LitCovid-PubTator

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T1","span":{"begin":7030,"end":7034},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"fma_id","subj":"T1","obj":"http://purl.org/sig/ont/fma/fma25000"}],"text":"Introduction\nAs of February 20, 2020, the 2019 novel coronavirus (now named SARS-CoV-2, causing the disease COVID-19) has caused over 75,000 confirmed cases inside of China and has spread to 25 other countries (World Health Organization, 2020b). (HCoV-19 has been proposed as an alternate name for the virus; Jiang et al., 2020). Until now, local transmission remained limited outside of China, but as of this week, new epidemic hotspots have become apparent on multiple continents (World Health Organization, 2020a; Jankowicz, 2020; Sang-Hun, 2020; Schnirring, 2020a). Many jurisdictions have imposed traveller screening in an effort to prevent importation of COVID-19 cases to unaffected areas. Some high-income countries have escalated control measures beyond screening-based containment policies, and now restrict or quarantine inbound travellers from countries known to be experiencing substantial community transmission. Meanwhile, in many other countries, screening remains the primary barrier to case importation (Guardian reporting team, 2020; Schengen Visa Info, 2020). Even in countries with the resources to enforce quarantine measures, expanded arrival screening may be the first logical response as the source epidemic expands to regions outside China. Furthermore, symptom screening has become a ubiquitous tool in the effort to contain local spread of COVID-19, in settings from affected cities to cruise ships to quarantines. Our analysis is pertinent to all of these contexts.\nIt is widely recognized that screening is an imperfect barrier to spread (Bitar et al., 2009; Cowling et al., 2010; Gostic et al., 2015; Mabey et al., 2014; Quilty et al., 2020), due to: the absence of detectable symptoms during the incubation period; variation in the severity and detectability of symptoms once the disease begins to progress; imperfect performance of screening equipment or personnel; or active evasion of screening by travellers. Previously we estimated the effectiveness of traveller screening for a range of pathogens that have emerged in the past, and found that arrival screening would miss 50–75% of infected cases even under optimistic assumptions (Gostic et al., 2015). Yet the quantitative performance of different policies matters for planning interventions and will influence how public health authorities prioritize different measures as the international and domestic context changes. Here we use a mathematical model to analyse the expected performance of different screening measures for COVID-19, based on what is currently known about its natural history and epidemiology and on different possible combinations of departure and arrival screening policies.\nFirst we assess the probability that any single individual infected with SARS-CoV-2 would be detected by screening, as a function of time since exposure. This individual-level analysis is not a comprehensive measure of program success, but serves to illustrate the various ways in which screening can succeed or fail (and in turn the ways it can or cannot be improved). Further, these analyses emphasize the importance of the incubation period, and the fraction of subclinical cases, as determinants of individual screening outcomes. We define subclinical cases as those too mild to show symptoms detectable in screening (fever or cough) after passing through the incubation period (i.e. once any symptoms have manifested). The true fraction of subclinical COVID-19 cases remains unknown, but anecdotally, many lab-confirmed COVID-19 cases have not shown detectable symptoms on diagnosis (Hoehl et al., 2020; Nishiura et al., 2020; Hu et al., 2020). About 80% of clinically attended cases have been mild (The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020), and clinically attended cases have been conspicuously rare in children and teens (Chen et al., 2020; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Huang et al., 2020; Li et al., 2020), raising the possibility that subclinical cases may be common.\nNext, we assess the overall effectiveness of a screening program by modeling screening outcomes in a hypothetical population of infected travellers, each with a different time since exposure (and hence a different probability of having progressed through incubation to show detectable symptoms). Crucially, the distribution of times since exposure will depend on the epidemiology of the source population, so this overall measure is not a simple average of the individual-level outcomes. We estimate the fraction of infected travellers detected, breaking down the ways in which screening can succeed or fail. An alternate measure of program success is the extent to which screening delays the first importation of cases into the community, possibly providing additional time to train medical staff, deploy public health responders or refine travel policies (Cowling et al., 2010). To quantify the potential for screening to delay case importation, we estimate the probability that a given screening program would detect the first n or more imported cases before missing an infected person.\nScreening will be less effective in a growing epidemic, due to an excess of recently-exposed and not-yet-symptomatic travellers (Gostic et al., 2015). In the context of COVID-19, we consider both growing and stable epidemic scenarios, but place greater emphasis on the realistic assumption that the COVID-19 epidemic is still growing. Since late January 2020, the Chinese government has imposed strict travel restrictions and surveillance on population centers heavily affected by COVID-19 (BBC News, 2020; Cellan-Jones, 2020), and numerous other countries have imposed travel and quarantine restrictions on travellers inbound from China. Until about Feb. 20, 2020, these measures had appeared to successfully limit community transmission outside of China, but all the while multiple factors pointed to on-going risk, including evidence that transmission is possible prior to the onset of symptoms (Yu et al., 2020; Hu et al., 2020), and reports of citizens seeking to elude travel restrictions or leaving before restrictions were in place (Ma and Pinghui, 2020; Mahbubani, 2020). Now, in the week following Feb. 20, 2020, new source epidemics have appeared on multiple continents (World Health Organization, 2020a), and the the risk of exportation of cases from beyond the initial travel-restricted area is growing.\nAs the epidemic continues to expand geographically, arrival screening will likely be continued or expanded to prevent importation of cases to areas without established spread. At the same time, there is great concern about potential public health consequences if COVID-19 spreads to developing countries that lack health infrastructure and resources to combat it effectively (de Salazar et al., 2020). Limited resources also could mean that some countries cannot implement large-scale arrival screening. In this scenario, departure screening implemented elsewhere would be the sole barrier -- however leaky -- to new waves of case importation. It is also important to recognize that, owing to the lag time in appearance of symptoms in imported cases, any weaknesses in screening would continue to have an effect on known case importations for up to two weeks, officially considered the maximum incubation period (World Health Organization, 2020c). Accordingly, we consider scenarios with departure screening only, arrival screening only, or both departure and arrival screening. The model can also consider the consequences when only a fraction of the traveller population is screened, due either to travel from a location not subject to screening, or due to deliberate evasion of screening.\nOur analysis also has direct bearing on other contexts where symptom screening is being used, beyond international air travel. This includes screening of travelers at rail stations and roadside spot checks, and screening of other at-risk people including people living in affected areas, health-care workers, cruise ship passengers, evacuees and people undergoing quarantine (Hoehl et al., 2020; Japan Ministry of Health, Labor and Welfare, 2020; Nishiura et al., 2020; Schnirring, 2020c). Below, we chiefly frame our findings in terms of travel screening, but these other screening contexts are also in the scope of our analysis. Any one-off screening effort is equivalent to a departure screen (i.e. a single test with no delay), and our findings on symptom screening effectiveness over the course of infection are directly applicable to longitudinal screening in quarantine or occupational settings.\nThe central aim of our analysis is to assess the expected effectiveness of screening for COVID-19, taking account of current knowledge and uncertainties about the natural history and epidemiology of the virus. We therefore show results using the best estimates currently available, in the hope of informing policy decisions in this fast-changing environment. We also make our model available for public use as a user-friendly online app, so that stakeholders can explore scenarios of particular interest, and results can be updated rapidly as our knowledge of this new viral threat continues to expand."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T1","span":{"begin":6932,"end":6937},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0002542"}],"text":"Introduction\nAs of February 20, 2020, the 2019 novel coronavirus (now named SARS-CoV-2, causing the disease COVID-19) has caused over 75,000 confirmed cases inside of China and has spread to 25 other countries (World Health Organization, 2020b). (HCoV-19 has been proposed as an alternate name for the virus; Jiang et al., 2020). Until now, local transmission remained limited outside of China, but as of this week, new epidemic hotspots have become apparent on multiple continents (World Health Organization, 2020a; Jankowicz, 2020; Sang-Hun, 2020; Schnirring, 2020a). Many jurisdictions have imposed traveller screening in an effort to prevent importation of COVID-19 cases to unaffected areas. Some high-income countries have escalated control measures beyond screening-based containment policies, and now restrict or quarantine inbound travellers from countries known to be experiencing substantial community transmission. Meanwhile, in many other countries, screening remains the primary barrier to case importation (Guardian reporting team, 2020; Schengen Visa Info, 2020). Even in countries with the resources to enforce quarantine measures, expanded arrival screening may be the first logical response as the source epidemic expands to regions outside China. Furthermore, symptom screening has become a ubiquitous tool in the effort to contain local spread of COVID-19, in settings from affected cities to cruise ships to quarantines. Our analysis is pertinent to all of these contexts.\nIt is widely recognized that screening is an imperfect barrier to spread (Bitar et al., 2009; Cowling et al., 2010; Gostic et al., 2015; Mabey et al., 2014; Quilty et al., 2020), due to: the absence of detectable symptoms during the incubation period; variation in the severity and detectability of symptoms once the disease begins to progress; imperfect performance of screening equipment or personnel; or active evasion of screening by travellers. Previously we estimated the effectiveness of traveller screening for a range of pathogens that have emerged in the past, and found that arrival screening would miss 50–75% of infected cases even under optimistic assumptions (Gostic et al., 2015). Yet the quantitative performance of different policies matters for planning interventions and will influence how public health authorities prioritize different measures as the international and domestic context changes. Here we use a mathematical model to analyse the expected performance of different screening measures for COVID-19, based on what is currently known about its natural history and epidemiology and on different possible combinations of departure and arrival screening policies.\nFirst we assess the probability that any single individual infected with SARS-CoV-2 would be detected by screening, as a function of time since exposure. This individual-level analysis is not a comprehensive measure of program success, but serves to illustrate the various ways in which screening can succeed or fail (and in turn the ways it can or cannot be improved). Further, these analyses emphasize the importance of the incubation period, and the fraction of subclinical cases, as determinants of individual screening outcomes. We define subclinical cases as those too mild to show symptoms detectable in screening (fever or cough) after passing through the incubation period (i.e. once any symptoms have manifested). The true fraction of subclinical COVID-19 cases remains unknown, but anecdotally, many lab-confirmed COVID-19 cases have not shown detectable symptoms on diagnosis (Hoehl et al., 2020; Nishiura et al., 2020; Hu et al., 2020). About 80% of clinically attended cases have been mild (The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020), and clinically attended cases have been conspicuously rare in children and teens (Chen et al., 2020; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Huang et al., 2020; Li et al., 2020), raising the possibility that subclinical cases may be common.\nNext, we assess the overall effectiveness of a screening program by modeling screening outcomes in a hypothetical population of infected travellers, each with a different time since exposure (and hence a different probability of having progressed through incubation to show detectable symptoms). Crucially, the distribution of times since exposure will depend on the epidemiology of the source population, so this overall measure is not a simple average of the individual-level outcomes. We estimate the fraction of infected travellers detected, breaking down the ways in which screening can succeed or fail. An alternate measure of program success is the extent to which screening delays the first importation of cases into the community, possibly providing additional time to train medical staff, deploy public health responders or refine travel policies (Cowling et al., 2010). To quantify the potential for screening to delay case importation, we estimate the probability that a given screening program would detect the first n or more imported cases before missing an infected person.\nScreening will be less effective in a growing epidemic, due to an excess of recently-exposed and not-yet-symptomatic travellers (Gostic et al., 2015). In the context of COVID-19, we consider both growing and stable epidemic scenarios, but place greater emphasis on the realistic assumption that the COVID-19 epidemic is still growing. Since late January 2020, the Chinese government has imposed strict travel restrictions and surveillance on population centers heavily affected by COVID-19 (BBC News, 2020; Cellan-Jones, 2020), and numerous other countries have imposed travel and quarantine restrictions on travellers inbound from China. Until about Feb. 20, 2020, these measures had appeared to successfully limit community transmission outside of China, but all the while multiple factors pointed to on-going risk, including evidence that transmission is possible prior to the onset of symptoms (Yu et al., 2020; Hu et al., 2020), and reports of citizens seeking to elude travel restrictions or leaving before restrictions were in place (Ma and Pinghui, 2020; Mahbubani, 2020). Now, in the week following Feb. 20, 2020, new source epidemics have appeared on multiple continents (World Health Organization, 2020a), and the the risk of exportation of cases from beyond the initial travel-restricted area is growing.\nAs the epidemic continues to expand geographically, arrival screening will likely be continued or expanded to prevent importation of cases to areas without established spread. At the same time, there is great concern about potential public health consequences if COVID-19 spreads to developing countries that lack health infrastructure and resources to combat it effectively (de Salazar et al., 2020). Limited resources also could mean that some countries cannot implement large-scale arrival screening. In this scenario, departure screening implemented elsewhere would be the sole barrier -- however leaky -- to new waves of case importation. It is also important to recognize that, owing to the lag time in appearance of symptoms in imported cases, any weaknesses in screening would continue to have an effect on known case importations for up to two weeks, officially considered the maximum incubation period (World Health Organization, 2020c). Accordingly, we consider scenarios with departure screening only, arrival screening only, or both departure and arrival screening. The model can also consider the consequences when only a fraction of the traveller population is screened, due either to travel from a location not subject to screening, or due to deliberate evasion of screening.\nOur analysis also has direct bearing on other contexts where symptom screening is being used, beyond international air travel. This includes screening of travelers at rail stations and roadside spot checks, and screening of other at-risk people including people living in affected areas, health-care workers, cruise ship passengers, evacuees and people undergoing quarantine (Hoehl et al., 2020; Japan Ministry of Health, Labor and Welfare, 2020; Nishiura et al., 2020; Schnirring, 2020c). Below, we chiefly frame our findings in terms of travel screening, but these other screening contexts are also in the scope of our analysis. Any one-off screening effort is equivalent to a departure screen (i.e. a single test with no delay), and our findings on symptom screening effectiveness over the course of infection are directly applicable to longitudinal screening in quarantine or occupational settings.\nThe central aim of our analysis is to assess the expected effectiveness of screening for COVID-19, taking account of current knowledge and uncertainties about the natural history and epidemiology of the virus. We therefore show results using the best estimates currently available, in the hope of informing policy decisions in this fast-changing environment. We also make our model available for public use as a user-friendly online app, so that stakeholders can explore scenarios of particular interest, and results can be updated rapidly as our knowledge of this new viral threat continues to expand."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T1","span":{"begin":3966,"end":3968},"obj":"Chemical"}],"attributes":[{"id":"A1","pred":"chebi_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CHEBI_30145"}],"text":"Introduction\nAs of February 20, 2020, the 2019 novel coronavirus (now named SARS-CoV-2, causing the disease COVID-19) has caused over 75,000 confirmed cases inside of China and has spread to 25 other countries (World Health Organization, 2020b). (HCoV-19 has been proposed as an alternate name for the virus; Jiang et al., 2020). Until now, local transmission remained limited outside of China, but as of this week, new epidemic hotspots have become apparent on multiple continents (World Health Organization, 2020a; Jankowicz, 2020; Sang-Hun, 2020; Schnirring, 2020a). Many jurisdictions have imposed traveller screening in an effort to prevent importation of COVID-19 cases to unaffected areas. Some high-income countries have escalated control measures beyond screening-based containment policies, and now restrict or quarantine inbound travellers from countries known to be experiencing substantial community transmission. Meanwhile, in many other countries, screening remains the primary barrier to case importation (Guardian reporting team, 2020; Schengen Visa Info, 2020). Even in countries with the resources to enforce quarantine measures, expanded arrival screening may be the first logical response as the source epidemic expands to regions outside China. Furthermore, symptom screening has become a ubiquitous tool in the effort to contain local spread of COVID-19, in settings from affected cities to cruise ships to quarantines. Our analysis is pertinent to all of these contexts.\nIt is widely recognized that screening is an imperfect barrier to spread (Bitar et al., 2009; Cowling et al., 2010; Gostic et al., 2015; Mabey et al., 2014; Quilty et al., 2020), due to: the absence of detectable symptoms during the incubation period; variation in the severity and detectability of symptoms once the disease begins to progress; imperfect performance of screening equipment or personnel; or active evasion of screening by travellers. Previously we estimated the effectiveness of traveller screening for a range of pathogens that have emerged in the past, and found that arrival screening would miss 50–75% of infected cases even under optimistic assumptions (Gostic et al., 2015). Yet the quantitative performance of different policies matters for planning interventions and will influence how public health authorities prioritize different measures as the international and domestic context changes. Here we use a mathematical model to analyse the expected performance of different screening measures for COVID-19, based on what is currently known about its natural history and epidemiology and on different possible combinations of departure and arrival screening policies.\nFirst we assess the probability that any single individual infected with SARS-CoV-2 would be detected by screening, as a function of time since exposure. This individual-level analysis is not a comprehensive measure of program success, but serves to illustrate the various ways in which screening can succeed or fail (and in turn the ways it can or cannot be improved). Further, these analyses emphasize the importance of the incubation period, and the fraction of subclinical cases, as determinants of individual screening outcomes. We define subclinical cases as those too mild to show symptoms detectable in screening (fever or cough) after passing through the incubation period (i.e. once any symptoms have manifested). The true fraction of subclinical COVID-19 cases remains unknown, but anecdotally, many lab-confirmed COVID-19 cases have not shown detectable symptoms on diagnosis (Hoehl et al., 2020; Nishiura et al., 2020; Hu et al., 2020). About 80% of clinically attended cases have been mild (The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020), and clinically attended cases have been conspicuously rare in children and teens (Chen et al., 2020; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Huang et al., 2020; Li et al., 2020), raising the possibility that subclinical cases may be common.\nNext, we assess the overall effectiveness of a screening program by modeling screening outcomes in a hypothetical population of infected travellers, each with a different time since exposure (and hence a different probability of having progressed through incubation to show detectable symptoms). Crucially, the distribution of times since exposure will depend on the epidemiology of the source population, so this overall measure is not a simple average of the individual-level outcomes. We estimate the fraction of infected travellers detected, breaking down the ways in which screening can succeed or fail. An alternate measure of program success is the extent to which screening delays the first importation of cases into the community, possibly providing additional time to train medical staff, deploy public health responders or refine travel policies (Cowling et al., 2010). To quantify the potential for screening to delay case importation, we estimate the probability that a given screening program would detect the first n or more imported cases before missing an infected person.\nScreening will be less effective in a growing epidemic, due to an excess of recently-exposed and not-yet-symptomatic travellers (Gostic et al., 2015). In the context of COVID-19, we consider both growing and stable epidemic scenarios, but place greater emphasis on the realistic assumption that the COVID-19 epidemic is still growing. Since late January 2020, the Chinese government has imposed strict travel restrictions and surveillance on population centers heavily affected by COVID-19 (BBC News, 2020; Cellan-Jones, 2020), and numerous other countries have imposed travel and quarantine restrictions on travellers inbound from China. Until about Feb. 20, 2020, these measures had appeared to successfully limit community transmission outside of China, but all the while multiple factors pointed to on-going risk, including evidence that transmission is possible prior to the onset of symptoms (Yu et al., 2020; Hu et al., 2020), and reports of citizens seeking to elude travel restrictions or leaving before restrictions were in place (Ma and Pinghui, 2020; Mahbubani, 2020). Now, in the week following Feb. 20, 2020, new source epidemics have appeared on multiple continents (World Health Organization, 2020a), and the the risk of exportation of cases from beyond the initial travel-restricted area is growing.\nAs the epidemic continues to expand geographically, arrival screening will likely be continued or expanded to prevent importation of cases to areas without established spread. At the same time, there is great concern about potential public health consequences if COVID-19 spreads to developing countries that lack health infrastructure and resources to combat it effectively (de Salazar et al., 2020). Limited resources also could mean that some countries cannot implement large-scale arrival screening. In this scenario, departure screening implemented elsewhere would be the sole barrier -- however leaky -- to new waves of case importation. It is also important to recognize that, owing to the lag time in appearance of symptoms in imported cases, any weaknesses in screening would continue to have an effect on known case importations for up to two weeks, officially considered the maximum incubation period (World Health Organization, 2020c). Accordingly, we consider scenarios with departure screening only, arrival screening only, or both departure and arrival screening. The model can also consider the consequences when only a fraction of the traveller population is screened, due either to travel from a location not subject to screening, or due to deliberate evasion of screening.\nOur analysis also has direct bearing on other contexts where symptom screening is being used, beyond international air travel. This includes screening of travelers at rail stations and roadside spot checks, and screening of other at-risk people including people living in affected areas, health-care workers, cruise ship passengers, evacuees and people undergoing quarantine (Hoehl et al., 2020; Japan Ministry of Health, Labor and Welfare, 2020; Nishiura et al., 2020; Schnirring, 2020c). Below, we chiefly frame our findings in terms of travel screening, but these other screening contexts are also in the scope of our analysis. Any one-off screening effort is equivalent to a departure screen (i.e. a single test with no delay), and our findings on symptom screening effectiveness over the course of infection are directly applicable to longitudinal screening in quarantine or occupational settings.\nThe central aim of our analysis is to assess the expected effectiveness of screening for COVID-19, taking account of current knowledge and uncertainties about the natural history and epidemiology of the virus. We therefore show results using the best estimates currently available, in the hope of informing policy decisions in this fast-changing environment. We also make our model available for public use as a user-friendly online app, so that stakeholders can explore scenarios of particular interest, and results can be updated rapidly as our knowledge of this new viral threat continues to expand."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T1","span":{"begin":3309,"end":3314},"obj":"Phenotype"},{"id":"T2","span":{"begin":3318,"end":3323},"obj":"Phenotype"},{"id":"T3","span":{"begin":3714,"end":3723},"obj":"Phenotype"},{"id":"T4","span":{"begin":3892,"end":3901},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/HP_0001945"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/HP_0012735"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/HP_0002090"}],"text":"Introduction\nAs of February 20, 2020, the 2019 novel coronavirus (now named SARS-CoV-2, causing the disease COVID-19) has caused over 75,000 confirmed cases inside of China and has spread to 25 other countries (World Health Organization, 2020b). (HCoV-19 has been proposed as an alternate name for the virus; Jiang et al., 2020). Until now, local transmission remained limited outside of China, but as of this week, new epidemic hotspots have become apparent on multiple continents (World Health Organization, 2020a; Jankowicz, 2020; Sang-Hun, 2020; Schnirring, 2020a). Many jurisdictions have imposed traveller screening in an effort to prevent importation of COVID-19 cases to unaffected areas. Some high-income countries have escalated control measures beyond screening-based containment policies, and now restrict or quarantine inbound travellers from countries known to be experiencing substantial community transmission. Meanwhile, in many other countries, screening remains the primary barrier to case importation (Guardian reporting team, 2020; Schengen Visa Info, 2020). Even in countries with the resources to enforce quarantine measures, expanded arrival screening may be the first logical response as the source epidemic expands to regions outside China. Furthermore, symptom screening has become a ubiquitous tool in the effort to contain local spread of COVID-19, in settings from affected cities to cruise ships to quarantines. Our analysis is pertinent to all of these contexts.\nIt is widely recognized that screening is an imperfect barrier to spread (Bitar et al., 2009; Cowling et al., 2010; Gostic et al., 2015; Mabey et al., 2014; Quilty et al., 2020), due to: the absence of detectable symptoms during the incubation period; variation in the severity and detectability of symptoms once the disease begins to progress; imperfect performance of screening equipment or personnel; or active evasion of screening by travellers. Previously we estimated the effectiveness of traveller screening for a range of pathogens that have emerged in the past, and found that arrival screening would miss 50–75% of infected cases even under optimistic assumptions (Gostic et al., 2015). Yet the quantitative performance of different policies matters for planning interventions and will influence how public health authorities prioritize different measures as the international and domestic context changes. Here we use a mathematical model to analyse the expected performance of different screening measures for COVID-19, based on what is currently known about its natural history and epidemiology and on different possible combinations of departure and arrival screening policies.\nFirst we assess the probability that any single individual infected with SARS-CoV-2 would be detected by screening, as a function of time since exposure. This individual-level analysis is not a comprehensive measure of program success, but serves to illustrate the various ways in which screening can succeed or fail (and in turn the ways it can or cannot be improved). Further, these analyses emphasize the importance of the incubation period, and the fraction of subclinical cases, as determinants of individual screening outcomes. We define subclinical cases as those too mild to show symptoms detectable in screening (fever or cough) after passing through the incubation period (i.e. once any symptoms have manifested). The true fraction of subclinical COVID-19 cases remains unknown, but anecdotally, many lab-confirmed COVID-19 cases have not shown detectable symptoms on diagnosis (Hoehl et al., 2020; Nishiura et al., 2020; Hu et al., 2020). About 80% of clinically attended cases have been mild (The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020), and clinically attended cases have been conspicuously rare in children and teens (Chen et al., 2020; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Huang et al., 2020; Li et al., 2020), raising the possibility that subclinical cases may be common.\nNext, we assess the overall effectiveness of a screening program by modeling screening outcomes in a hypothetical population of infected travellers, each with a different time since exposure (and hence a different probability of having progressed through incubation to show detectable symptoms). Crucially, the distribution of times since exposure will depend on the epidemiology of the source population, so this overall measure is not a simple average of the individual-level outcomes. We estimate the fraction of infected travellers detected, breaking down the ways in which screening can succeed or fail. An alternate measure of program success is the extent to which screening delays the first importation of cases into the community, possibly providing additional time to train medical staff, deploy public health responders or refine travel policies (Cowling et al., 2010). To quantify the potential for screening to delay case importation, we estimate the probability that a given screening program would detect the first n or more imported cases before missing an infected person.\nScreening will be less effective in a growing epidemic, due to an excess of recently-exposed and not-yet-symptomatic travellers (Gostic et al., 2015). In the context of COVID-19, we consider both growing and stable epidemic scenarios, but place greater emphasis on the realistic assumption that the COVID-19 epidemic is still growing. Since late January 2020, the Chinese government has imposed strict travel restrictions and surveillance on population centers heavily affected by COVID-19 (BBC News, 2020; Cellan-Jones, 2020), and numerous other countries have imposed travel and quarantine restrictions on travellers inbound from China. Until about Feb. 20, 2020, these measures had appeared to successfully limit community transmission outside of China, but all the while multiple factors pointed to on-going risk, including evidence that transmission is possible prior to the onset of symptoms (Yu et al., 2020; Hu et al., 2020), and reports of citizens seeking to elude travel restrictions or leaving before restrictions were in place (Ma and Pinghui, 2020; Mahbubani, 2020). Now, in the week following Feb. 20, 2020, new source epidemics have appeared on multiple continents (World Health Organization, 2020a), and the the risk of exportation of cases from beyond the initial travel-restricted area is growing.\nAs the epidemic continues to expand geographically, arrival screening will likely be continued or expanded to prevent importation of cases to areas without established spread. At the same time, there is great concern about potential public health consequences if COVID-19 spreads to developing countries that lack health infrastructure and resources to combat it effectively (de Salazar et al., 2020). Limited resources also could mean that some countries cannot implement large-scale arrival screening. In this scenario, departure screening implemented elsewhere would be the sole barrier -- however leaky -- to new waves of case importation. It is also important to recognize that, owing to the lag time in appearance of symptoms in imported cases, any weaknesses in screening would continue to have an effect on known case importations for up to two weeks, officially considered the maximum incubation period (World Health Organization, 2020c). Accordingly, we consider scenarios with departure screening only, arrival screening only, or both departure and arrival screening. The model can also consider the consequences when only a fraction of the traveller population is screened, due either to travel from a location not subject to screening, or due to deliberate evasion of screening.\nOur analysis also has direct bearing on other contexts where symptom screening is being used, beyond international air travel. This includes screening of travelers at rail stations and roadside spot checks, and screening of other at-risk people including people living in affected areas, health-care workers, cruise ship passengers, evacuees and people undergoing quarantine (Hoehl et al., 2020; Japan Ministry of Health, Labor and Welfare, 2020; Nishiura et al., 2020; Schnirring, 2020c). Below, we chiefly frame our findings in terms of travel screening, but these other screening contexts are also in the scope of our analysis. Any one-off screening effort is equivalent to a departure screen (i.e. a single test with no delay), and our findings on symptom screening effectiveness over the course of infection are directly applicable to longitudinal screening in quarantine or occupational settings.\nThe central aim of our analysis is to assess the expected effectiveness of screening for COVID-19, taking account of current knowledge and uncertainties about the natural history and epidemiology of the virus. We therefore show results using the best estimates currently available, in the hope of informing policy decisions in this fast-changing environment. We also make our model available for public use as a user-friendly online app, so that stakeholders can explore scenarios of particular interest, and results can be updated rapidly as our knowledge of this new viral threat continues to expand."}

2_test

{"project":"2_test","denotations":[{"id":"32091395-19215720-27032124","span":{"begin":1583,"end":1587},"obj":"19215720"},{"id":"32091395-20353566-27032125","span":{"begin":1605,"end":1609},"obj":"20353566"},{"id":"32091395-32069388-27032126","span":{"begin":3590,"end":3594},"obj":"32069388"},{"id":"32091395-32064853-27032127","span":{"begin":3762,"end":3766},"obj":"32064853"},{"id":"32091395-32064853-27032128","span":{"begin":3940,"end":3944},"obj":"32064853"},{"id":"32091395-20353566-27032129","span":{"begin":4920,"end":4924},"obj":"20353566"},{"id":"32091395-32067043-27032130","span":{"begin":6046,"end":6050},"obj":"32067043"},{"id":"32091395-32069388-27032131","span":{"begin":8135,"end":8139},"obj":"32069388"}],"text":"Introduction\nAs of February 20, 2020, the 2019 novel coronavirus (now named SARS-CoV-2, causing the disease COVID-19) has caused over 75,000 confirmed cases inside of China and has spread to 25 other countries (World Health Organization, 2020b). (HCoV-19 has been proposed as an alternate name for the virus; Jiang et al., 2020). Until now, local transmission remained limited outside of China, but as of this week, new epidemic hotspots have become apparent on multiple continents (World Health Organization, 2020a; Jankowicz, 2020; Sang-Hun, 2020; Schnirring, 2020a). Many jurisdictions have imposed traveller screening in an effort to prevent importation of COVID-19 cases to unaffected areas. Some high-income countries have escalated control measures beyond screening-based containment policies, and now restrict or quarantine inbound travellers from countries known to be experiencing substantial community transmission. Meanwhile, in many other countries, screening remains the primary barrier to case importation (Guardian reporting team, 2020; Schengen Visa Info, 2020). Even in countries with the resources to enforce quarantine measures, expanded arrival screening may be the first logical response as the source epidemic expands to regions outside China. Furthermore, symptom screening has become a ubiquitous tool in the effort to contain local spread of COVID-19, in settings from affected cities to cruise ships to quarantines. Our analysis is pertinent to all of these contexts.\nIt is widely recognized that screening is an imperfect barrier to spread (Bitar et al., 2009; Cowling et al., 2010; Gostic et al., 2015; Mabey et al., 2014; Quilty et al., 2020), due to: the absence of detectable symptoms during the incubation period; variation in the severity and detectability of symptoms once the disease begins to progress; imperfect performance of screening equipment or personnel; or active evasion of screening by travellers. Previously we estimated the effectiveness of traveller screening for a range of pathogens that have emerged in the past, and found that arrival screening would miss 50–75% of infected cases even under optimistic assumptions (Gostic et al., 2015). Yet the quantitative performance of different policies matters for planning interventions and will influence how public health authorities prioritize different measures as the international and domestic context changes. Here we use a mathematical model to analyse the expected performance of different screening measures for COVID-19, based on what is currently known about its natural history and epidemiology and on different possible combinations of departure and arrival screening policies.\nFirst we assess the probability that any single individual infected with SARS-CoV-2 would be detected by screening, as a function of time since exposure. This individual-level analysis is not a comprehensive measure of program success, but serves to illustrate the various ways in which screening can succeed or fail (and in turn the ways it can or cannot be improved). Further, these analyses emphasize the importance of the incubation period, and the fraction of subclinical cases, as determinants of individual screening outcomes. We define subclinical cases as those too mild to show symptoms detectable in screening (fever or cough) after passing through the incubation period (i.e. once any symptoms have manifested). The true fraction of subclinical COVID-19 cases remains unknown, but anecdotally, many lab-confirmed COVID-19 cases have not shown detectable symptoms on diagnosis (Hoehl et al., 2020; Nishiura et al., 2020; Hu et al., 2020). About 80% of clinically attended cases have been mild (The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020), and clinically attended cases have been conspicuously rare in children and teens (Chen et al., 2020; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Huang et al., 2020; Li et al., 2020), raising the possibility that subclinical cases may be common.\nNext, we assess the overall effectiveness of a screening program by modeling screening outcomes in a hypothetical population of infected travellers, each with a different time since exposure (and hence a different probability of having progressed through incubation to show detectable symptoms). Crucially, the distribution of times since exposure will depend on the epidemiology of the source population, so this overall measure is not a simple average of the individual-level outcomes. We estimate the fraction of infected travellers detected, breaking down the ways in which screening can succeed or fail. An alternate measure of program success is the extent to which screening delays the first importation of cases into the community, possibly providing additional time to train medical staff, deploy public health responders or refine travel policies (Cowling et al., 2010). To quantify the potential for screening to delay case importation, we estimate the probability that a given screening program would detect the first n or more imported cases before missing an infected person.\nScreening will be less effective in a growing epidemic, due to an excess of recently-exposed and not-yet-symptomatic travellers (Gostic et al., 2015). In the context of COVID-19, we consider both growing and stable epidemic scenarios, but place greater emphasis on the realistic assumption that the COVID-19 epidemic is still growing. Since late January 2020, the Chinese government has imposed strict travel restrictions and surveillance on population centers heavily affected by COVID-19 (BBC News, 2020; Cellan-Jones, 2020), and numerous other countries have imposed travel and quarantine restrictions on travellers inbound from China. Until about Feb. 20, 2020, these measures had appeared to successfully limit community transmission outside of China, but all the while multiple factors pointed to on-going risk, including evidence that transmission is possible prior to the onset of symptoms (Yu et al., 2020; Hu et al., 2020), and reports of citizens seeking to elude travel restrictions or leaving before restrictions were in place (Ma and Pinghui, 2020; Mahbubani, 2020). Now, in the week following Feb. 20, 2020, new source epidemics have appeared on multiple continents (World Health Organization, 2020a), and the the risk of exportation of cases from beyond the initial travel-restricted area is growing.\nAs the epidemic continues to expand geographically, arrival screening will likely be continued or expanded to prevent importation of cases to areas without established spread. At the same time, there is great concern about potential public health consequences if COVID-19 spreads to developing countries that lack health infrastructure and resources to combat it effectively (de Salazar et al., 2020). Limited resources also could mean that some countries cannot implement large-scale arrival screening. In this scenario, departure screening implemented elsewhere would be the sole barrier -- however leaky -- to new waves of case importation. It is also important to recognize that, owing to the lag time in appearance of symptoms in imported cases, any weaknesses in screening would continue to have an effect on known case importations for up to two weeks, officially considered the maximum incubation period (World Health Organization, 2020c). Accordingly, we consider scenarios with departure screening only, arrival screening only, or both departure and arrival screening. The model can also consider the consequences when only a fraction of the traveller population is screened, due either to travel from a location not subject to screening, or due to deliberate evasion of screening.\nOur analysis also has direct bearing on other contexts where symptom screening is being used, beyond international air travel. This includes screening of travelers at rail stations and roadside spot checks, and screening of other at-risk people including people living in affected areas, health-care workers, cruise ship passengers, evacuees and people undergoing quarantine (Hoehl et al., 2020; Japan Ministry of Health, Labor and Welfare, 2020; Nishiura et al., 2020; Schnirring, 2020c). Below, we chiefly frame our findings in terms of travel screening, but these other screening contexts are also in the scope of our analysis. Any one-off screening effort is equivalent to a departure screen (i.e. a single test with no delay), and our findings on symptom screening effectiveness over the course of infection are directly applicable to longitudinal screening in quarantine or occupational settings.\nThe central aim of our analysis is to assess the expected effectiveness of screening for COVID-19, taking account of current knowledge and uncertainties about the natural history and epidemiology of the virus. We therefore show results using the best estimates currently available, in the hope of informing policy decisions in this fast-changing environment. We also make our model available for public use as a user-friendly online app, so that stakeholders can explore scenarios of particular interest, and results can be updated rapidly as our knowledge of this new viral threat continues to expand."}

LitCovid-sentences

MyTest

{"project":"MyTest","denotations":[{"id":"32091395-19215720-27032124","span":{"begin":1583,"end":1587},"obj":"19215720"},{"id":"32091395-20353566-27032125","span":{"begin":1605,"end":1609},"obj":"20353566"},{"id":"32091395-32069388-27032126","span":{"begin":3590,"end":3594},"obj":"32069388"},{"id":"32091395-32064853-27032127","span":{"begin":3762,"end":3766},"obj":"32064853"},{"id":"32091395-32064853-27032128","span":{"begin":3940,"end":3944},"obj":"32064853"},{"id":"32091395-20353566-27032129","span":{"begin":4920,"end":4924},"obj":"20353566"},{"id":"32091395-32067043-27032130","span":{"begin":6046,"end":6050},"obj":"32067043"},{"id":"32091395-32069388-27032131","span":{"begin":8135,"end":8139},"obj":"32069388"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Introduction\nAs of February 20, 2020, the 2019 novel coronavirus (now named SARS-CoV-2, causing the disease COVID-19) has caused over 75,000 confirmed cases inside of China and has spread to 25 other countries (World Health Organization, 2020b). (HCoV-19 has been proposed as an alternate name for the virus; Jiang et al., 2020). Until now, local transmission remained limited outside of China, but as of this week, new epidemic hotspots have become apparent on multiple continents (World Health Organization, 2020a; Jankowicz, 2020; Sang-Hun, 2020; Schnirring, 2020a). Many jurisdictions have imposed traveller screening in an effort to prevent importation of COVID-19 cases to unaffected areas. Some high-income countries have escalated control measures beyond screening-based containment policies, and now restrict or quarantine inbound travellers from countries known to be experiencing substantial community transmission. Meanwhile, in many other countries, screening remains the primary barrier to case importation (Guardian reporting team, 2020; Schengen Visa Info, 2020). Even in countries with the resources to enforce quarantine measures, expanded arrival screening may be the first logical response as the source epidemic expands to regions outside China. Furthermore, symptom screening has become a ubiquitous tool in the effort to contain local spread of COVID-19, in settings from affected cities to cruise ships to quarantines. Our analysis is pertinent to all of these contexts.\nIt is widely recognized that screening is an imperfect barrier to spread (Bitar et al., 2009; Cowling et al., 2010; Gostic et al., 2015; Mabey et al., 2014; Quilty et al., 2020), due to: the absence of detectable symptoms during the incubation period; variation in the severity and detectability of symptoms once the disease begins to progress; imperfect performance of screening equipment or personnel; or active evasion of screening by travellers. Previously we estimated the effectiveness of traveller screening for a range of pathogens that have emerged in the past, and found that arrival screening would miss 50–75% of infected cases even under optimistic assumptions (Gostic et al., 2015). Yet the quantitative performance of different policies matters for planning interventions and will influence how public health authorities prioritize different measures as the international and domestic context changes. Here we use a mathematical model to analyse the expected performance of different screening measures for COVID-19, based on what is currently known about its natural history and epidemiology and on different possible combinations of departure and arrival screening policies.\nFirst we assess the probability that any single individual infected with SARS-CoV-2 would be detected by screening, as a function of time since exposure. This individual-level analysis is not a comprehensive measure of program success, but serves to illustrate the various ways in which screening can succeed or fail (and in turn the ways it can or cannot be improved). Further, these analyses emphasize the importance of the incubation period, and the fraction of subclinical cases, as determinants of individual screening outcomes. We define subclinical cases as those too mild to show symptoms detectable in screening (fever or cough) after passing through the incubation period (i.e. once any symptoms have manifested). The true fraction of subclinical COVID-19 cases remains unknown, but anecdotally, many lab-confirmed COVID-19 cases have not shown detectable symptoms on diagnosis (Hoehl et al., 2020; Nishiura et al., 2020; Hu et al., 2020). About 80% of clinically attended cases have been mild (The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020), and clinically attended cases have been conspicuously rare in children and teens (Chen et al., 2020; The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team, 2020; Huang et al., 2020; Li et al., 2020), raising the possibility that subclinical cases may be common.\nNext, we assess the overall effectiveness of a screening program by modeling screening outcomes in a hypothetical population of infected travellers, each with a different time since exposure (and hence a different probability of having progressed through incubation to show detectable symptoms). Crucially, the distribution of times since exposure will depend on the epidemiology of the source population, so this overall measure is not a simple average of the individual-level outcomes. We estimate the fraction of infected travellers detected, breaking down the ways in which screening can succeed or fail. An alternate measure of program success is the extent to which screening delays the first importation of cases into the community, possibly providing additional time to train medical staff, deploy public health responders or refine travel policies (Cowling et al., 2010). To quantify the potential for screening to delay case importation, we estimate the probability that a given screening program would detect the first n or more imported cases before missing an infected person.\nScreening will be less effective in a growing epidemic, due to an excess of recently-exposed and not-yet-symptomatic travellers (Gostic et al., 2015). In the context of COVID-19, we consider both growing and stable epidemic scenarios, but place greater emphasis on the realistic assumption that the COVID-19 epidemic is still growing. Since late January 2020, the Chinese government has imposed strict travel restrictions and surveillance on population centers heavily affected by COVID-19 (BBC News, 2020; Cellan-Jones, 2020), and numerous other countries have imposed travel and quarantine restrictions on travellers inbound from China. Until about Feb. 20, 2020, these measures had appeared to successfully limit community transmission outside of China, but all the while multiple factors pointed to on-going risk, including evidence that transmission is possible prior to the onset of symptoms (Yu et al., 2020; Hu et al., 2020), and reports of citizens seeking to elude travel restrictions or leaving before restrictions were in place (Ma and Pinghui, 2020; Mahbubani, 2020). Now, in the week following Feb. 20, 2020, new source epidemics have appeared on multiple continents (World Health Organization, 2020a), and the the risk of exportation of cases from beyond the initial travel-restricted area is growing.\nAs the epidemic continues to expand geographically, arrival screening will likely be continued or expanded to prevent importation of cases to areas without established spread. At the same time, there is great concern about potential public health consequences if COVID-19 spreads to developing countries that lack health infrastructure and resources to combat it effectively (de Salazar et al., 2020). Limited resources also could mean that some countries cannot implement large-scale arrival screening. In this scenario, departure screening implemented elsewhere would be the sole barrier -- however leaky -- to new waves of case importation. It is also important to recognize that, owing to the lag time in appearance of symptoms in imported cases, any weaknesses in screening would continue to have an effect on known case importations for up to two weeks, officially considered the maximum incubation period (World Health Organization, 2020c). Accordingly, we consider scenarios with departure screening only, arrival screening only, or both departure and arrival screening. The model can also consider the consequences when only a fraction of the traveller population is screened, due either to travel from a location not subject to screening, or due to deliberate evasion of screening.\nOur analysis also has direct bearing on other contexts where symptom screening is being used, beyond international air travel. This includes screening of travelers at rail stations and roadside spot checks, and screening of other at-risk people including people living in affected areas, health-care workers, cruise ship passengers, evacuees and people undergoing quarantine (Hoehl et al., 2020; Japan Ministry of Health, Labor and Welfare, 2020; Nishiura et al., 2020; Schnirring, 2020c). Below, we chiefly frame our findings in terms of travel screening, but these other screening contexts are also in the scope of our analysis. Any one-off screening effort is equivalent to a departure screen (i.e. a single test with no delay), and our findings on symptom screening effectiveness over the course of infection are directly applicable to longitudinal screening in quarantine or occupational settings.\nThe central aim of our analysis is to assess the expected effectiveness of screening for COVID-19, taking account of current knowledge and uncertainties about the natural history and epidemiology of the virus. We therefore show results using the best estimates currently available, in the hope of informing policy decisions in this fast-changing environment. We also make our model available for public use as a user-friendly online app, so that stakeholders can explore scenarios of particular interest, and results can be updated rapidly as our knowledge of this new viral threat continues to expand."}

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