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What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

This could account for the fact that while IL-6 mRNA expression is up-regulated during the early stages of coronavirus infection, insubstantial increase in IL-6 protein expression was observed [132] . The inhibition of host protein synthesis through the interaction between coronavirus spike protein and eIF3f may therefore have a significant impact on the modulation of coronavirus pathogenicity. Host proteins are also known to play a role in the virus life cycle, especially during viral RNA replication and transcription (Figure 4) .

What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

Expressed only in minute amounts, the induction of IRF7, via virus-induced activation of ISGF3, results in either homo-dimerization or hetero-dimerization with IRF3 and is subsequently followed by nuclear translocation for the activation of both IFN and IFN genes [92, 93] . Coronaviruses and arteriviruses have evolved multiple strategies to avoid elimination from the host. These tactics range from the prevention of detection to inhibition of antiviral responses mounted by the host immune system.

What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

With respect to their significance to the economy, vaccines have also been developed for many of these viruses in a bid to prevent localized infections from progressing into serious outbreaks. This has, however, proven to be a hard battle as the vaccines are unable to provide complete cross-protection among the various serotypes of each virus [19] . During infection, the virus replicates in the host cytosol amidst a myriad of host signaling pathways and systems such that interaction between the virus and the host systems is inevitable.

What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

Sub-genomic sized mRNAs are translated by host ribosomes into viral structural (S, E, M, N) and accessory proteins. The N protein packages the positive-sense genomic RNA into a ribonucleocapsid and is assembled into the virus particles with the help of -actin. The newly formed virus particles undergo maturation when passing through the Golgi and exit the host cell via exocytosis.

What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

Host proteins are also known to play a role in the virus life cycle, especially during viral RNA replication and transcription (Figure 4) . The most well studied host protein that interacts with the coronavirus genome is heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a nuclear protein, whose biological function is to regulate alternative splicing of cellular RNAs [162, 163] . The hnRNP A1 has been shown to bind to both negative-sense leader sequence and negative-sense intergenic (IG) sequence of MHV [164] .

What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

During infection, the virus replicates in the host cytosol amidst a myriad of host signaling pathways and systems such that interaction between the virus and the host systems is inevitable. Virus infection and the consequent host cell response also involve complicated interaction between various host cellular and viral networks. Virus-host interplay occurs at multiple points during the virus replication cycle, from entry to exit.

What is the structure of a coronavirus?

These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis. Text: Coronaviruses, together with arteriviruses and toroviruses, belong in the order Nidovirales, a group of large, non-segmented, positive sense and single stranded RNA animal viruses that produce an extensive 3'-nested set of subgenomic mRNAs for transcription during infection [1] (Table 1) . Nidoviruses such as avian infectious bronchitis coronavirus (IBV), human coronavirus 229E (HCoV-229E), equine arteritis virus (EAV) and the porcine reproductive and respiratory syndrome arterivirus (PRRSV) are important pathogens of both human and animals [2] [3] [4] , and are commonly associated with mild respiratory and enteric diseases, although they are also known to cause more OPEN ACCESS critical lower respiratory tract illness, such as the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic that occurred in 2003 [5] .

Coronaviruses encode many proteins (see yellow boxes) that target multiple steps in the innate immune response mounted by the host cells, ensuring its successful replication in the host. In vitro activation of chicken splenocytes and peripheral blood leukocytes with IBV has also resulted in an increase in chicken interferon gamma (chIFN-γ) production as a form of cell-mediated immune response [124] . This appears to be a polyclonal, non-specific stimulation as chIFN-γ production levels are also elevated in IBV-stimulated chicken splenocytes which lack prior exposure to IBV, when compared to control un-stimulated cells, as well as in cells exposed to inactivated IBV [124] .

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057).

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred. Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] .

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

In early January, the outbreak began to escalate rapidly with hundreds of cases now confirmed along with the presence of a few household clusters [4] [5] [6] [7] . As of 24 January 2020, the cumulative incidence in China is 830 cases, of which 549 cases were diagnosed in Hubei, 26 in Beijing, 20 in Shanghai, and 53 in Guangdong. Additionally, twenty-six deaths have been linked to the outbreak [6, 8] , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] . Although early reports from Wuhan [3] stated that (i) there were only tens of cases in the cluster and (ii) no human-to-human transmission was directly observed, the scientific community was alert to the possibility that the novel coronavirus would spread to other geographic locations-including other countries-via direct human-to-human transmission. In early January, the outbreak began to escalate rapidly with hundreds of cases now confirmed along with the presence of a few household clusters [4] [5] [6] [7] .

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases (95% CI: 350, 3000) as of 17 January 2020 [28] and a University of Hong Kong group estimated 1343 cases (95% CI: 547, 3446) as of 17 January 2020 [29] . The former study from the United States assumes that the catchment area population is 10 million (we use 11.1 million). The number of reported 2019-nCoV infections continues to grow as surveillance and detection methods improve.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

The estimated cumulative incidence has grown as additional cases have been reported. As of 24 January 2020, with reports of thirteen exportation events, the cumulative incidence in China is estimated at 5502 cases (95% confidence interval: 3027, 9057). Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London (ICL) on their own homepage on 22 January 2020 [26] that estimated the incidence based on three importation events at 4000 cases (95% CI: 1000, 9700).

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Table 1 also shows the estimated incidence in China. The first exportation event in Thailand suggests 423 cases with the upper confidence limit of 1863 cases. The estimated cumulative incidence has grown as additional cases have been reported.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Such exposures are expected to include human-to-human transmission, but the levels of transmissibility have yet to be quantified. It is still plausible that a substantial number of human infections arose from animal-to-human exposures, such as was the case during the first outbreak of highly pathogenic influenza (H7N9) in China, 2013, and the human-to-human transmissibility has yet to be quantified in an explicit manner. Despite initially restricting what information on the outbreak was shared publicly, the Chinese government has begun to respectfully provide updates on the situation on a daily basis.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London (ICL) on their own homepage on 22 January 2020 [26] that estimated the incidence based on three importation events at 4000 cases (95% CI: 1000, 9700). Possible reasons for the slight difference include (i) the number of travelers in the previous study was derived from airline passenger data [27] and (ii) the assumed length of T was different. Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases (95% CI: 350, 3000) as of 17 January 2020 [28] and a University of Hong Kong group estimated 1343 cases (95% CI: 547, 3446) as of 17 January 2020 [29] .

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Additionally, twenty-six deaths have been linked to the outbreak [6, 8] , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020. Considering that enhanced surveillance has been underway in these importing countries, case ascertainment has been perhaps better in exported case data. Using a spatial back-calculation method and analyzing exported cases, we estimate the cumulative incidence of 2019-nCoV cases in China in real time, allowing us to update and discuss the extent of transmission at the source.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel. As we already know from elsewhere [11] [12] [13] , given the observed cumulative count of c exported cases, we have a balance equation of the cumulative risk of infection: where T is the sum of incubation and infectious periods, and here is assumed to be 3.2 and 9.3 days [14] , respectively, assuming that these periods are similar to those of other coronaviruses, and thus, T = 12.5 days. The estimated incidence in China is then given bypn.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Using a spatial back-calculation method and analyzing exported cases, we estimate the cumulative incidence of 2019-nCoV cases in China in real time, allowing us to update and discuss the extent of transmission at the source. Table 1 shows the incidence of exported cases by date of hospitalization and report. Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

The number of reported 2019-nCoV infections continues to grow as surveillance and detection methods improve. Our estimate and others [26, 28, 29] agree that the actual number of cases is likely in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than that of the originally linked seafood market in Wuhan have occurred. Such exposures are expected to include human-to-human transmission, but the levels of transmissibility have yet to be quantified.

When was the a cluster of pneumonia cases were first reported ?

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London (ICL) on their own homepage on 22 January 2020 [26] that estimated the incidence based on three importation events at 4000 cases (95% CI: 1000, 9700). Possible reasons for the slight difference include (i) the number of travelers in the previous study was derived from airline passenger data [27] and (ii) the assumed length of T was different. Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases (95% CI: 350, 3000) as of 17 January 2020 [28] and a University of Hong Kong group estimated 1343 cases (95% CI: 547, 3446) as of 17 January 2020 [29] .

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Table 1 also shows the estimated incidence in China. The first exportation event in Thailand suggests 423 cases with the upper confidence limit of 1863 cases. The estimated cumulative incidence has grown as additional cases have been reported.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

The estimated cumulative incidence has grown as additional cases have been reported. As of 24 January 2020, with reports of thirteen exportation events, the cumulative incidence in China is estimated at 5502 cases (95% confidence interval: 3027, 9057). Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London (ICL) on their own homepage on 22 January 2020 [26] that estimated the incidence based on three importation events at 4000 cases (95% CI: 1000, 9700).

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Additionally, twenty-six deaths have been linked to the outbreak [6, 8] , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020. Considering that enhanced surveillance has been underway in these importing countries, case ascertainment has been perhaps better in exported case data. Using a spatial back-calculation method and analyzing exported cases, we estimate the cumulative incidence of 2019-nCoV cases in China in real time, allowing us to update and discuss the extent of transmission at the source.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel. As we already know from elsewhere [11] [12] [13] , given the observed cumulative count of c exported cases, we have a balance equation of the cumulative risk of infection: where T is the sum of incubation and infectious periods, and here is assumed to be 3.2 and 9.3 days [14] , respectively, assuming that these periods are similar to those of other coronaviruses, and thus, T = 12.5 days. The estimated incidence in China is then given bypn.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

In early January, the outbreak began to escalate rapidly with hundreds of cases now confirmed along with the presence of a few household clusters [4] [5] [6] [7] . As of 24 January 2020, the cumulative incidence in China is 830 cases, of which 549 cases were diagnosed in Hubei, 26 in Beijing, 20 in Shanghai, and 53 in Guangdong. Additionally, twenty-six deaths have been linked to the outbreak [6, 8] , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

The estimated incidence in China is then given bypn. With an ad-hoc assumption that the data are generated following the binomial sampling process among travelers from Wuhan, the cumulative incidence is then estimated using a maximum likelihood method. Table 1 also shows the estimated incidence in China.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred. Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] .

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057).

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Using a spatial back-calculation method and analyzing exported cases, we estimate the cumulative incidence of 2019-nCoV cases in China in real time, allowing us to update and discuss the extent of transmission at the source. Table 1 shows the incidence of exported cases by date of hospitalization and report. Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases (95% CI: 350, 3000) as of 17 January 2020 [28] and a University of Hong Kong group estimated 1343 cases (95% CI: 547, 3446) as of 17 January 2020 [29] . The former study from the United States assumes that the catchment area population is 10 million (we use 11.1 million). The number of reported 2019-nCoV infections continues to grow as surveillance and detection methods improve.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

The number of reported 2019-nCoV infections continues to grow as surveillance and detection methods improve. Our estimate and others [26, 28, 29] agree that the actual number of cases is likely in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than that of the originally linked seafood market in Wuhan have occurred. Such exposures are expected to include human-to-human transmission, but the levels of transmissibility have yet to be quantified.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Such exposures are expected to include human-to-human transmission, but the levels of transmissibility have yet to be quantified. It is still plausible that a substantial number of human infections arose from animal-to-human exposures, such as was the case during the first outbreak of highly pathogenic influenza (H7N9) in China, 2013, and the human-to-human transmissibility has yet to be quantified in an explicit manner. Despite initially restricting what information on the outbreak was shared publicly, the Chinese government has begun to respectfully provide updates on the situation on a daily basis.

What is the number of inbound passengers from China?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

The estimated incidence in China is then given bypn. With an ad-hoc assumption that the data are generated following the binomial sampling process among travelers from Wuhan, the cumulative incidence is then estimated using a maximum likelihood method. Table 1 also shows the estimated incidence in China.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London (ICL) on their own homepage on 22 January 2020 [26] that estimated the incidence based on three importation events at 4000 cases (95% CI: 1000, 9700). Possible reasons for the slight difference include (i) the number of travelers in the previous study was derived from airline passenger data [27] and (ii) the assumed length of T was different. Two other estimates have also been published: a preliminary study by a Northeastern University group estimated 1250 cases (95% CI: 350, 3000) as of 17 January 2020 [28] and a University of Hong Kong group estimated 1343 cases (95% CI: 547, 3446) as of 17 January 2020 [29] .

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred. Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] .

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Table 1 also shows the estimated incidence in China. The first exportation event in Thailand suggests 423 cases with the upper confidence limit of 1863 cases. The estimated cumulative incidence has grown as additional cases have been reported.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel. As we already know from elsewhere [11] [12] [13] , given the observed cumulative count of c exported cases, we have a balance equation of the cumulative risk of infection: where T is the sum of incubation and infectious periods, and here is assumed to be 3.2 and 9.3 days [14] , respectively, assuming that these periods are similar to those of other coronaviruses, and thus, T = 12.5 days. The estimated incidence in China is then given bypn.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

The estimated cumulative incidence has grown as additional cases have been reported. As of 24 January 2020, with reports of thirteen exportation events, the cumulative incidence in China is estimated at 5502 cases (95% confidence interval: 3027, 9057). Our latest estimate is comparable to a preliminary report posted by a research group at Imperial College London (ICL) on their own homepage on 22 January 2020 [26] that estimated the incidence based on three importation events at 4000 cases (95% CI: 1000, 9700).

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Text: Since the announcement of a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China, was made on 31 December 2019, many rapid virological, clinical, and epidemiological research responses have taken place [1, 2] . The causative agent of the pneumonia is suggested to be a novel coronavirus (2019-nCoV) of the same lineage (but genetically distinct) from the coronavirus causing severe acute respiratory syndrome (SARS) [1] . Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] .

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Additionally, twenty-six deaths have been linked to the outbreak [6, 8] , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020. Considering that enhanced surveillance has been underway in these importing countries, case ascertainment has been perhaps better in exported case data. Using a spatial back-calculation method and analyzing exported cases, we estimate the cumulative incidence of 2019-nCoV cases in China in real time, allowing us to update and discuss the extent of transmission at the source.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

In early January, the outbreak began to escalate rapidly with hundreds of cases now confirmed along with the presence of a few household clusters [4] [5] [6] [7] . As of 24 January 2020, the cumulative incidence in China is 830 cases, of which 549 cases were diagnosed in Hubei, 26 in Beijing, 20 in Shanghai, and 53 in Guangdong. Additionally, twenty-six deaths have been linked to the outbreak [6, 8] , and thirteen cases were exported to Japan, Singapore, South Korea, Taiwan, Thailand, Vietnam and the United States as of 22 January 2020.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Cases in the initial cluster reported a common exposure-a seafood market in Wuhan where wild animals were served at a restaurant-indicating that a point-source zoonotic (animal-to-human) route was likely the main mode of transmission for those cases [2] . Although early reports from Wuhan [3] stated that (i) there were only tens of cases in the cluster and (ii) no human-to-human transmission was directly observed, the scientific community was alert to the possibility that the novel coronavirus would spread to other geographic locations-including other countries-via direct human-to-human transmission. In early January, the outbreak began to escalate rapidly with hundreds of cases now confirmed along with the presence of a few household clusters [4] [5] [6] [7] .

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Using a spatial back-calculation method and analyzing exported cases, we estimate the cumulative incidence of 2019-nCoV cases in China in real time, allowing us to update and discuss the extent of transmission at the source. Table 1 shows the incidence of exported cases by date of hospitalization and report. Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

The number of reported 2019-nCoV infections continues to grow as surveillance and detection methods improve. Our estimate and others [26, 28, 29] agree that the actual number of cases is likely in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than that of the originally linked seafood market in Wuhan have occurred. Such exposures are expected to include human-to-human transmission, but the levels of transmissibility have yet to be quantified.

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057).

What percent of inbound passengers from China were from Wuhan?

Due to the initial difficulty of diagnosis in the absence of established primer for polymerase chain reaction testing, the time lag between hospitalization and reporting was longer for early cases compared with that of more recent cases. Among the seven locations reporting importation, the total volume of inbound passengers from China was m = 63.1 million per year in 2017 [9] , of which 100q = 2.1% were from Wuhan [10] , a home of n = 19.0 million people as the catchment population of Wuhan airport. Two other locations with confirmed cases, i.e., Macau and Hong Kong, were excluded from the analysis, because it is commutable by land transporation and the first case in Hong Kong was indeed not via airtravel.

Such exposures are expected to include human-to-human transmission, but the levels of transmissibility have yet to be quantified. It is still plausible that a substantial number of human infections arose from animal-to-human exposures, such as was the case during the first outbreak of highly pathogenic influenza (H7N9) in China, 2013, and the human-to-human transmissibility has yet to be quantified in an explicit manner. Despite initially restricting what information on the outbreak was shared publicly, the Chinese government has begun to respectfully provide updates on the situation on a daily basis.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats. Text: Ebolaviruses (EBVs), according to Kuhn et al. classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] .

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

This scenario would be more indicating of a change in the evolutionary trajectory of the pathogen (as moving from Step 4 to 5 in Figure 1 of Wolfe et al. [88] ) than of the natural maintenance of ebolaviruses that is considered here. In order for these protocols to be efficient and well designed, insights from behavioural ecology, plant phenology, and molecular biology (amongst other disciplines) will be necessary.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

How does one puzzle out? Since recent studies have revealed that several bat species have been exposed to ebolaviruses, the common denominator to these hypotheses is that within the epidemiological cycle, some bats species must be exposed to the viruses and infected by these potential alternative hosts. Under this constraint, and given the peculiar ecology of bats (roosting behaviour, habitat utilisation, and flight mode), we review the hosts and transmission pathways that can lead to bat exposure and infection to ebolaviruses.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

As warned above, the EBOV multi-host maintenance system could include a complex network of interacting bat species ( Figure 1A2 ) and to proceed by elimination of alternative hypotheses may be a way to zoom-in on the maintenance community. The hypothesis of human playing a role in ebolavirus maintenance has not been addressed here, even if persistence of EBOV in previously infected humans has been recently proven [51] . This scenario would be more indicating of a change in the evolutionary trajectory of the pathogen (as moving from Step 4 to 5 in Figure 1 of Wolfe et al.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

(A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone. Currently this is logically the most investigated hypothesis given the available data, and represents the maintenance mechanism for another filovirus, the Marburg virus, as currently understood. (A2) Several bat species are needed to create a maintenance community for Zaire ebolavirus (EBOV); each bat species cannot complete EBOV maintenance alone, as it requires interactions with the other species.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

This could be one or more alternative hosts involving possibly bat species. By definition, if such an alternative host exists, there are infectious transmission pathways from this host towards bats that are reviewed here (red arrows). Proving that a bat species maintains EBOV (e.g., [44, 45] ), or that interconnected populations of different bat species create the cradle for EBOV maintenance in a specific ecosystem, is a difficult task.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

(A1) Main maintenance hypothesis: there is one bat Figure 1 . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow). (C) The maintenance community hypothesis, in which several hosts are needed to maintain ebolaviruses (ellipses represent different scenarios of community maintenance). This could be one or more alternative hosts involving possibly bat species.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

A few monkey and bat individuals serologically positive to EBV antigen represent the only exceptions [12] . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species. Despite intense research, the main bat-maintenance hypothesis has not been confirmed yet. The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] . Moreover, Swanepoel et al. showed that EBOV replicated in three species of experimentally infected bats (Tadarida condylura, Tadarida pumila, and Epomophorus wahlbergi), including virus isolated from faeces 21 days after experimental infection [22] .

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

(A2) Several bat species are needed to create a maintenance community for Zaire ebolavirus (EBOV); each bat species cannot complete EBOV maintenance alone, as it requires interactions with the other species. (B) Alternate non-bat maintenance host hypothesis: if it exists, it is known that it can transmit ebolaviruses to some bat species. In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow).

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

What is the structure of the Ebolavirus?

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

Given the number of species already involved/exposed to EBOV, the ecology of EBOV and its maintenance system can be expected to be complex, ecosystem dependent [46] , and dynamic, due to global changes [90] . The Ebola maintenance system, once isolated in the forests, is now interacting with humans and their modified environments and will adapt to it. Aiming at this moving target will require out-of-the-box thinking and interdisciplinary collaboration.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

The maintenance of EBV in equatorial forests is yet to be understood. Some mammal species played a major role in triggering human outbreaks: apes such as chimpanzees (Pan troglodytes troglodytes and P. t. verus) and western lowland gorillas (Gorilla gorilla gorilla) were at the origin of several human outbreaks [10] [11] [12] , but have been found to be highly susceptible to EBV with potential drastic impact for their populations [12, 19] . EBOV PCR positive duiker carcasses (Cephalophus sp.)

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] . Moreover, Swanepoel et al. showed that EBOV replicated in three species of experimentally infected bats (Tadarida condylura, Tadarida pumila, and Epomophorus wahlbergi), including virus isolated from faeces 21 days after experimental infection [22] .

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats. Text: Ebolaviruses (EBVs), according to Kuhn et al. classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] .

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

This scenario would be more indicating of a change in the evolutionary trajectory of the pathogen (as moving from Step 4 to 5 in Figure 1 of Wolfe et al. [88] ) than of the natural maintenance of ebolaviruses that is considered here. In order for these protocols to be efficient and well designed, insights from behavioural ecology, plant phenology, and molecular biology (amongst other disciplines) will be necessary.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

As warned above, the EBOV multi-host maintenance system could include a complex network of interacting bat species ( Figure 1A2 ) and to proceed by elimination of alternative hypotheses may be a way to zoom-in on the maintenance community. The hypothesis of human playing a role in ebolavirus maintenance has not been addressed here, even if persistence of EBOV in previously infected humans has been recently proven [51] . This scenario would be more indicating of a change in the evolutionary trajectory of the pathogen (as moving from Step 4 to 5 in Figure 1 of Wolfe et al.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species. Despite intense research, the main bat-maintenance hypothesis has not been confirmed yet. The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

How does one puzzle out? Since recent studies have revealed that several bat species have been exposed to ebolaviruses, the common denominator to these hypotheses is that within the epidemiological cycle, some bats species must be exposed to the viruses and infected by these potential alternative hosts. Under this constraint, and given the peculiar ecology of bats (roosting behaviour, habitat utilisation, and flight mode), we review the hosts and transmission pathways that can lead to bat exposure and infection to ebolaviruses.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

This does not mean that they can automatically inform on "what maintains ebolaviruses". When looking for the maintenance host, investigations should also target the same and other alternative hosts during inter-outbreak periods with ecologically driven hypotheses. This is what is currently done for bats following the main maintenance hypothesis (e.g., [30] ), but not often for alternative hosts.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

This could be one or more alternative hosts involving possibly bat species. By definition, if such an alternative host exists, there are infectious transmission pathways from this host towards bats that are reviewed here (red arrows). Proving that a bat species maintains EBOV (e.g., [44, 45] ), or that interconnected populations of different bat species create the cradle for EBOV maintenance in a specific ecosystem, is a difficult task.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

(A2) Several bat species are needed to create a maintenance community for Zaire ebolavirus (EBOV); each bat species cannot complete EBOV maintenance alone, as it requires interactions with the other species. (B) Alternate non-bat maintenance host hypothesis: if it exists, it is known that it can transmit ebolaviruses to some bat species. In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow).

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

(A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone. Currently this is logically the most investigated hypothesis given the available data, and represents the maintenance mechanism for another filovirus, the Marburg virus, as currently understood. (A2) Several bat species are needed to create a maintenance community for Zaire ebolavirus (EBOV); each bat species cannot complete EBOV maintenance alone, as it requires interactions with the other species.

When was the West African Ebolavirus outbreak?

The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] . Disentangling the complexity of maintenance hosts or communities in multi-host systems at the wildlife/livestock/human interface is a difficult task [16] [17] [18] . The maintenance of EBV in equatorial forests is yet to be understood.

In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow). (C) The maintenance community hypothesis, in which several hosts are needed to maintain ebolaviruses (ellipses represent different scenarios of community maintenance). This could be one or more alternative hosts involving possibly bat species.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

(A2) Several bat species are needed to create a maintenance community for Zaire ebolavirus (EBOV); each bat species cannot complete EBOV maintenance alone, as it requires interactions with the other species. (B) Alternate non-bat maintenance host hypothesis: if it exists, it is known that it can transmit ebolaviruses to some bat species. In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow).

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow). (C) The maintenance community hypothesis, in which several hosts are needed to maintain ebolaviruses (ellipses represent different scenarios of community maintenance). This could be one or more alternative hosts involving possibly bat species.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species. Despite intense research, the main bat-maintenance hypothesis has not been confirmed yet. The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

This does not mean that they can automatically inform on "what maintains ebolaviruses". When looking for the maintenance host, investigations should also target the same and other alternative hosts during inter-outbreak periods with ecologically driven hypotheses. This is what is currently done for bats following the main maintenance hypothesis (e.g., [30] ), but not often for alternative hosts.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

The EBOV susceptibility and exposure (tested by virology, serology and/or PCR) of many other potential forest hosts, including invertebrates, birds, bats, monkeys, rodents, and other small mammals, have been tested in the field or experimentally with an interestingly large amount of negative results (e.g., [12, [21] [22] [23] [24] [25] [26] ). A few monkey and bat individuals serologically positive to EBV antigen represent the only exceptions [12] . Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

As warned above, the EBOV multi-host maintenance system could include a complex network of interacting bat species ( Figure 1A2 ) and to proceed by elimination of alternative hypotheses may be a way to zoom-in on the maintenance community. The hypothesis of human playing a role in ebolavirus maintenance has not been addressed here, even if persistence of EBOV in previously infected humans has been recently proven [51] . This scenario would be more indicating of a change in the evolutionary trajectory of the pathogen (as moving from Step 4 to 5 in Figure 1 of Wolfe et al.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

It would be tedious to quantitatively estimate probabilities in the case of ebolavirus maintenance given the current lack of information, but trying to define the components of this probability could help. Hence, instead of proving that bats are the maintenance host for EBOV, what if we consider that "bats are not the (only) maintenance host for EBOV"? Here, we consider the scenario presented in Figure 1B ,C, namely, that bats are not the maintenance host for EBOV or that bat species are involved with alternative host(s) in the EBOV maintenance community.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

A list of these pathways is provided, along with protocols to prioritise and investigate these alternative hypotheses. In conclusion, taking into account the ecology of bats and their known involvement in ebolaviruses ecology drastically reduces the list of potential alternative maintenance hosts for ebolaviruses. Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

(A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone. Currently this is logically the most investigated hypothesis given the available data, and represents the maintenance mechanism for another filovirus, the Marburg virus, as currently understood. (A2) Several bat species are needed to create a maintenance community for Zaire ebolavirus (EBOV); each bat species cannot complete EBOV maintenance alone, as it requires interactions with the other species.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

A few monkey and bat individuals serologically positive to EBV antigen represent the only exceptions [12] . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts.

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

One would not expect such a high mortality (relative to their population density) of EBOV in maintenance hosts. However, these data indicate their possible involvement in the transmission function of EBOV, bridging the maintenance host with human populations during a spillover event [18] (Figure 1 ). The EBOV susceptibility and exposure (tested by virology, serology and/or PCR) of many other potential forest hosts, including invertebrates, birds, bats, monkeys, rodents, and other small mammals, have been tested in the field or experimentally with an interestingly large amount of negative results (e.g., [12, [21] [22] [23] [24] [25] [26] ).

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

classification [1] ) are single-strand RNA filoviruses that can induce a high mortality in some hosts, including apes and humans [2, 3] . The different ebolaviruses have caused localised but dramatic human outbreaks, mainly in Central Africa, in the last 40 years. The recent West African outbreak in 2013-2016 gave an outline of the pandemic potential of these pathogens [4, 5] .

What animals are considered to be maintenance hosts to the Ebolavirus?

Today, African bats are considered by many as the best candidates for acting as maintenance hosts for EBOV. Partial vRNA was sequenced from living specimens of three different bat species in Central Africa [23] , and antibodies against ebolavirus antigen have been detected in 9 bat species (8 frugivorous and 1 insectivorous) [3, 23, [27] [28] [29] [30] . Recently, a new ebolavirus species with an unknown pathogenic risk has also been isolated from two insectivorous bat species roosting inside a house [31] .

Here, we consider the scenario presented in Figure 1B ,C, namely, that bats are not the maintenance host for EBOV or that bat species are involved with alternative host(s) in the EBOV maintenance community. Current data and knowledge support both scenarios. Some bats are sometimes in contact with the virus and experience waves of exposure during outbreaks [27] .

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat Figure 1 .

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

(A1) Main maintenance hypothesis: there is one bat Figure 1 . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

A few monkey and bat individuals serologically positive to EBV antigen represent the only exceptions [12] . Potential maintenance mechanisms of ebolaviruses in wildlife, according to current knowledge. Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

This could be one or more alternative hosts involving possibly bat species. By definition, if such an alternative host exists, there are infectious transmission pathways from this host towards bats that are reviewed here (red arrows). Proving that a bat species maintains EBOV (e.g., [44, 45] ), or that interconnected populations of different bat species create the cradle for EBOV maintenance in a specific ecosystem, is a difficult task.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

In this article, we review the potential hosts and associated transmission pathways that link this host to bat species (red arrow). (C) The maintenance community hypothesis, in which several hosts are needed to maintain ebolaviruses (ellipses represent different scenarios of community maintenance). This could be one or more alternative hosts involving possibly bat species.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

From the biodiversity of African forest and the full web of interactions between species, a set of secondary hypotheses indicated in Table 1 can be tested through protocols presented to further investigate the role of different maintenance host candidates for EBOV. The observation of this limited number of hosts calls for testing them, even if only to exclude them from the list of hypotheses and strengthen the main hypothesis. As warned above, the EBOV multi-host maintenance system could include a complex network of interacting bat species ( Figure 1A2 ) and to proceed by elimination of alternative hypotheses may be a way to zoom-in on the maintenance community.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

This means that if bats are not the maintenance hosts for EBOV, then there is only a limited number of candidate species to play the role of alternative maintenance hosts. This limited number of alternative maintenance hosts is defined by the ecology of bats that imposes on those alternative maintenance hosts only a few possible EBOV transmission pathways towards bats. From the biodiversity of African forest and the full web of interactions between species, a set of secondary hypotheses indicated in Table 1 can be tested through protocols presented to further investigate the role of different maintenance host candidates for EBOV.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

These experimental approaches should consider the specific environmental conditions occurring in the tree canopy and cave roofs in terms of substrate, temperature, humidity and light properties. One particular mechanism that has been put forward in the literature is the fruit-borne route concerning frugivorous bats in the tree canopy. The availability of fruits attracts fruit-eating animals, including birds, tree-dwelling mammals, and invertebrates.

What do circles indicate in Figure 1?

Circles (plain or dotted) indicate a maintenance function play by the host(s); arrows represent infectious transmission pathways between hosts. Humans, non-human primates, and duikers are examples of known non-maintenance hosts, exposed occasionally to ebolavirus directly or indirectly through the main maintenance host. (A1) Main maintenance hypothesis: there is one bat species maintaining each ebolavirus alone.

Here, we consider the scenario presented in Figure 1B ,C, namely, that bats are not the maintenance host for EBOV or that bat species are involved with alternative host(s) in the EBOV maintenance community. Current data and knowledge support both scenarios. Some bats are sometimes in contact with the virus and experience waves of exposure during outbreaks [27] .