Epistemic_Statements  

CORD-19:00a0ab182dc01b6c2e737dfae585f050dcf9a7a5 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T1 446-676 Epistemic_statement denotes That first case was a 60 year old man from Bisha in the KSA and, thanks to the email, the rapid discovery of a second case of the virus, this time in an ill patient from Qatar, was transferred to the United Kingdom for care ( Fig.
T2 1011-1261 Epistemic_statement denotes First known as novel coronavirus (nCoV), the following two to three years were a slow discovery process revealing a virus that appears well established among dromedary camels (DC; Camelus dromedarius) across the Arabian Peninsula and parts of Africa.
T3 1262-1340 Epistemic_statement denotes From infected DCs, the virus is thought to infrequently infect exposed humans.
T4 1341-1501 Epistemic_statement denotes Concern was raised early on that patenting of the first viral isolate would lead to restricted access to the virus and to viral diagnostics (Sciencemag, 2014) .
T5 1502-1674 Epistemic_statement denotes However, sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics were available (Abdel-Moneim, 2014) almost immediately.
T6 1816-2007 Epistemic_statement denotes In search of an animal host, bats were implicated in August 2013 but in that same month a DC link was reported (Reusken et al., 2013c) and that link has matured into a verifiable association.
T7 2537-2719 Epistemic_statement denotes The spread of MERS-CoV among humans has often been associated with outbreaks in hospitals, which in 2012-2014 usually commenced in March (Mackay, 2014; Maltezou and Tsiodras, 2014) .
T8 2720-2898 Epistemic_statement denotes This spread may be linked to some seasonal environmental changes, change in host animal behaviour, or perhaps simple coincidence between season and successive hospital outbreaks.
T9 3428-3686 Epistemic_statement denotes An engaged world has helped understand how the virus has affected the KSA and its neighbouring countries and allowed outsiders to view science musings take shape, collaborations form, local news and commentary trend and new results be discussed in real time.
T10 3901-4088 Epistemic_statement denotes This degree of engagement was not possible in 2002/2003 when the SARS global outbreak began its rise to 8100 human cases including 770 deaths (proportion of fatal cases, or PFC, of 9.5%).
T11 4089-4308 Epistemic_statement denotes The ubiquity of social media appears to have changed what the public expects from a State when it communicates about new or existing infectious disease outbreaks and epidemics, and how quickly they expect that to occur.
T12 4905-5162 Epistemic_statement denotes MERS-CoV may be identified in patients with severe hypoxaemic respiratory failure and extrapulmonary organ dysfunction which can precede death in over a third of infections (Arabi et al., 2014; Assiri et al., 2013a; Hijawi et al., 2013; Zaki et al., 2012) .
T13 5608-5844 Epistemic_statement denotes On occasion, fever and gastrointestinal upset may form a prodrome, after which symptoms decline to be are later followed by more severe systemic and respiratory signs and symptoms (Kraaij-Dirkzwager et al., 2014; Mailles et al., 2013) .
T14 5845-5952 Epistemic_statement denotes Rarely, MERS-CoV has been detected in a person with fever but no respiratory or gastrointestinal symptoms .
T15 5953-6054 Epistemic_statement denotes The extent to which infection by other gastrointestinal pathogens affect this variability is unknown.
T16 6854-7018 Epistemic_statement denotes The relative speed of disease progression may relate to MERS-CoV reaching earlier peak viral loads and infecting different cells than the SARS-CoV (Drosten, 2013) .
T17 7019-7108 Epistemic_statement denotes Nonetheless, it is also apparent that MERS is not restricted to those with comorbidities.
T18 7346-7477 Epistemic_statement denotes This demonstrates that MERS, like most respiratory viruses, is associated with a wide spectrum of symptoms and degrees of severity.
T19 7853-8185 Epistemic_statement denotes The first WHO case definition (World Health Organization, 2014a) defined probable cases of MERS based on the presence of febrile illness, cough, requirement for hospitalization with suspicion of LRT involvement and included roles for contact with a probable or confirmed case or for travel or residence within the Arabian peninsula.
T20 8186-8360 Epistemic_statement denotes If strictly adhered to, only the severe syndrome would meet the case definition and be subject to laboratory testing, which was the paradigm early on (Assiri et al., 2013a) .
T21 8830-9062 Epistemic_statement denotes MERS can progress to an acute respiratory distress syndrome (ARDS) requiring external ventilation and then to multiorgan failure (Devi et al., 2014; Reuss et al., 2014; Zaki et al., 2012) similar to severe influenza and SARS cases .
T22 9063-9183 Epistemic_statement denotes Acute renal failure can occur in MERS patients, doing so sooner than it did among SARS patients (Eckerle et al., 2013) .
T23 9184-9421 Epistemic_statement denotes Progressive impairment of renal function and acute kidney injury can start 9-12 days after symptom onset among MERS patients, compared to a median of 20 days for SARS patients (Chu et al., 2005; Eckerle et al., 2013; Zaki et al., 2012) .
T24 9422-9527 Epistemic_statement denotes This may be due to direct infection of renal tissue by MERS-CoV (Arabi et al., 2014; Zaki et al., 2012) .
T25 9792-9915 Epistemic_statement denotes Monocyte numbers are often normal (Assiri et al., 2013a) while neutrophils may be raised or normal (Assiri et al., 2013a) .
T26 9916-9992 Epistemic_statement denotes As a group, children have rarely been reported to be positive for the virus.
T27 10170-10502 Epistemic_statement denotes In Amman, Jordan, 1005 samples from hospitalised children under the age of 2-years with fever and/or respiratory signs and symptoms were tested but none were positive for MERS-CoV RNA, despite being collected at a similar time to the first known outbreak of MERS-CoV in the neighbouring town of Al-Zarqa (Khuri-Bulos et al., 2013) .
T28 10503-10721 Epistemic_statement denotes A second trimester stillbirth occurred in a pregnant woman during an acute respiratory illness and while not RT-rtPCR positive, the mother subsequently developed antibodies to MERS-CoV, suggestive of recent infection .
T29 10922-11184 Epistemic_statement denotes The virus associated with MERS was initially identified as the "novel coronavirus" or nCOV; a problematic choice given that other novel coronaviruses could be discovered and were being discovered with regularity prior to and since the identification of MERS-CoV.
T30 12161-12400 Epistemic_statement denotes This permitted a predictive calculation of the time to most recent viral ancestor (tMRCA) for most of the variants, which suggested MERS-CoV first appeared around March 2012 (ranging from December 2011 to July 2012) (Cotten et al., 2014) .
T31 12912-13033 Epistemic_statement denotes Open reading frames are indicated as yellow rectangles bracketed by terminal untranslated regions (UTR; grey rectangles).
T32 13129-13308 Epistemic_statement denotes Predicted papain-like proteinase cleavage sites are indicated with orange arrows resulting in ∼16 cleavage non-structural protein products (based on (van Boheemen et al., 2012) ).
T33 14430-14572 Epistemic_statement denotes While the error rate can be higher than for traditional Sanger sequencing, the near-complete genomic length covered by just a single run (e.g.
T34 14747-14968 Epistemic_statement denotes Subgenomic sequencing, a mainstay of viral genotyping and molecular epidemiology to this point, has been used rarely for MERS-CoV identification or confirmation, despite assays having been suggested early on Corman et al.
T35 16046-16200 Epistemic_statement denotes There is as yet no study which attaches clinical relevance to the clades or smaller groupings of MERS-CoV nor any of the genomic variation noted to date .
T36 16201-16447 Epistemic_statement denotes It is interesting that Clade A contains only the African green monkey kidney (Vero; innate immune deficient cells) cell-culture passaged EMC/2012 variant and two variants of the Jordan-N3 variant from 2012, but no camel-derived MERS-CoV genomes .
T37 17106-17238 Epistemic_statement denotes A very divergent MERS-CoV variant originated from an Egyptian DC likely imported from Sudan was identified as NRCE-HKU205|Nile|2013.
T38 17239-17383 Epistemic_statement denotes It constructs a lineage outside the current clades, perhaps comprising the first occupant of Clade C Cotten et al., 2013b; Smits et al., 2015) .
T39 17384-17521 Epistemic_statement denotes This lineage may represent additional diversity of MERS-CoV variants remaining to be discovered in DC from outside the Arabian peninsula.
T40 17522-17736 Epistemic_statement denotes A virus sequenced from a Neoromicia capensis bat was more closely related to MERS-CoV than previous bat sequences had been, providing a link between human, camel and bat viruses as members of the same CoV species .
T41 18013-18174 Epistemic_statement denotes This process of molecular epidemiology can also imply some physical direction to the movement of MERS-CoV around the region and over time (Cotten et al., 2014) .
T42 18666-18829 Epistemic_statement denotes Studies are needed to determine whether there any functional outcomes on virus replication and transmission due to these and future changes (Cotten et al., 2014 ).
T43 19367-19411 Epistemic_statement denotes Antibody testing of human sera remains rare.
T44 19455-19833 Epistemic_statement denotes were quickly recommended by the WHO having been shown to be sensitive The genetic relationship between all near-complete and complete MERS-CoV genome nucleotide sequences (downloaded from GenBank using the listed accession numbers; England2 was obtained from http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/MERSCoV/respPartialgeneticsequenceofnovelcoronavirus/%5D).
T45 20533-20677 Epistemic_statement denotes The target sequences of the recommended screening assays remained conserved among genomes until at least mid-2014 when last checked by IMM (Fig.
T46 21083-21255 Epistemic_statement denotes This may reflect the absence of MERS-CoV, no LRT testing (Memish et al., 2014d) or that 61% of pilgrims were arriving from countries without any known MERS-CoV circulation.
T47 22377-22637 Epistemic_statement denotes Given the proportion of deaths among those infected with MERS-CoV, it is not a virus that should reasonably be described as a "storm in a teacup", however to date it has been given many "opportunities" for worldwide spread and it has not yet taken any of them.
T48 22638-22859 Epistemic_statement denotes Data have shown one or more RT-rtPCR negative URT samples from clinically suspect MERS cases may be contradicted by further URT sampling or the preferred use of LRT samples (Bermingham et al., 2012; Omrani et al., 2013) .
T49 23030-23181 Epistemic_statement denotes Since the majority of disease symptoms appear to have been manifesting as systemic and LRT disease, this may not be surprising (Assiri et al., 2013a) .
T50 23182-23375 Epistemic_statement denotes However at writing, no human data exist to define whether the virus replicates solely in the LRT, the URT, has a preference for one over the other, or replicates in other human tissues in vivo.
T51 23376-23722 Epistemic_statement denotes Sampling of the URT has been frequently noted from the largest human MERS-CoV investigative studies (Gautret et al., 2013 ; Health Protection Agency (HPA) UK Novel Coronavirus Investigation Team, 2013; Memish et al., 2014b,d) and, if noted, for other smaller investigative MERS-CoV testing (Kraaij-Dirkzwager et al., 2014; Memish et al., 2013b) .
T52 23821-23935 Epistemic_statement denotes In a human case, throat swabs were positive for six days, and again after a gap (Kraaij-Dirkzwager et al., 2014) .
T53 25070-25245 Epistemic_statement denotes Fresh samples yield better diagnostic results than refrigerated material and if delays of ≥72 h are likely, samples (except for blood) should be frozen at −70 • C (CDC, 2014).
T54 25246-25345 Epistemic_statement denotes Lung biopsy or autopsy tissues can also be tested if available (World Health Organization, 2013b) .
T55 25346-25504 Epistemic_statement denotes From the URT, which is a less invasive and convenient sampling site, a combined nose and throat swab or a nasopharyngeal aspirate is recommended (CDC, 2014) .
T56 25709-25976 Epistemic_statement denotes Urine has been found to contain MERS-CoV RNA 12 and 13 days after symptom onset and stool samples were RT-rtPCR positive up to 16 days after onset Kraaij-Dirkzwager et al., 2014) ; both sample types should be considered (CDC, 2014; World Health Organization, 2013b) .
T57 26336-26514 Epistemic_statement denotes RNAaemia may also correlate with disease severity; signs of virus cleared from serum in one recovered human case while lingering until the death of another (Faure et al., 2014) .
T58 28377-28540 Epistemic_statement denotes Other bacterial testing has been conducted but the impact of bacterial copresence is also unclear Devi et al., 2014; Memish et al., 2013b; Tsiodras et al., 2014) .
T59 28719-28968 Epistemic_statement denotes Testing for other respiratory pathogens is strongly recommended (World Health Organization, 2013b) but limited data address the occurrence of co-infections or alternative viral diagnoses among both cases and contacts suspected of MERS-CoV infection.
T60 28969-29162 Epistemic_statement denotes Little is known of other causes of MERS-like pneumonia in the KSA or of the general burden of disease due to the known classical respiratory viruses including endemic other human coronaviruses.
T61 29163-29348 Epistemic_statement denotes Despite widespread use in elucidating the role of DCs as a source for MERS-CoV, no strategic and widespread sero-surveys have been conducted in humans using samples collected post-2012.
T62 29349-29586 Epistemic_statement denotes The development of robust serological assays hinges on the accessibility of a reliable panel of well-characterised animal or human sera including those positive for antibodies specific to MERS-CoV and to likely agents of cross-reaction .
T63 29587-29724 Epistemic_statement denotes Obtaining these control materials has been problematic and has slowed the development and commercialization of assays for human testing .
T64 29982-30119 Epistemic_statement denotes Serosurveys are essential to determine a baseline of animal and community exposures to MERS-CoV among countries in the Arabian Peninsula.
T65 30754-30881 Epistemic_statement denotes Eight of 226 slaughterhouse workers were positive by IFA, but those results could not be confirmed by neutralization (NT) test.
T66 30882-30997 Epistemic_statement denotes The study indicated that HCoV-HKU1 was a likely source of cross-reactive antigen by IFA (Aburizaiza et al., 2014 ).
T67 30998-31394 Epistemic_statement denotes An absence of MERS-CoV antibodies among slaughterhouse workers may reflect the killing of older DCs which are less often MERS-CoV positive (see Table 1 ), the rarity of infected animals, a limited transmission risk associated with slaughtering DCs (Aburizaiza et al., 2014) , a weak immune response by humans who do not get severe MERS, or an overall low risk of MERS-CoV transmission by contact.
T68 31395-31540 Epistemic_statement denotes IFA also suffered from some cross-reactivity with convalescent SARS patient sera which could not be resolved by an NT test (Chan et al., 2013b) .
T69 31541-31824 Epistemic_statement denotes The need for well-validated assays was further emphasised when publicly released MERS-CoV antibody test results indicated that a handshake and two face-to-face meetings were sufficient for MERS-CoV transmission between two people in the USA (CDC Newsroom, 2014; Sampathkumar, 2014) .
T70 32411-32679 Epistemic_statement denotes A pseudo particle neutralization (ppNT) assay has seen widespread use in animal studies and is at least as sensitive as the microneutralization (MNT) test (Hemida et al., 2013 (Hemida et al., , 2014a (Hemida et al., , 2015 Perera et al., 2013; Reusken et al., 2013b) .
T71 32680-32986 Epistemic_statement denotes In a study of sera collected at the King Fahd Hospital, Eastern region of the KSA (158 from children with LRT infections between May 2010 and May 2011 and 110 from 19 to 52 year old male blood donors) no evidence of MERS-CoV neutralising antibody could be found using the ppNT assay (Gierer et al., 2013) .
T72 33428-33613 Epistemic_statement denotes MERS-CoV does not appear to be easily transmitted from DCs to humans, or perhaps it does not trigger a detectable immune response if only mild disease or asymptomatic infection results.
T73 33723-34071 Epistemic_statement denotes A Jordanian outbreak of acute LRT disease in a hospital in Al-Zarqa in 2012, which predated the first KSA case of MERS, was retrospectively found to have been associated with MERS-CoV infection, initially via RT-rtPCR, but subsequently, and on a larger scale, using positivity by ELISA and IFA or MNT test Hijawi et al., 2013; Payne et al., 2014) .
T74 34760-35088 Epistemic_statement denotes Detection of MERS-CoV infection using ELISA or S1 subunit protein microarray (Reusken et al., 2013a) has usually been followed by confirmatory IFA and/or a plaque-reduction neutralization (PRNT) test (Aburizaiza et al., 2014; Drosten et al., 2013; Reusken et al., 2013c) or MNT test Perera et al., 2013; Reusken et al., 2013c) .
T75 35089-35466 Epistemic_statement denotes The confirmatory methods ensure the antibodies detected using more subjective screening methods that may also employ a spectrum of potentially cross-reactive antigens, are able to specifically neutralise the intended virus and are not more broadly reactive to other coronaviruses found in DCs (bovine CoV, BCoV) or humans (HC0V-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, SARS-CoV).
T76 37913-38031 Epistemic_statement denotes When ACE2 was expressed in otherwise non-permissive BHK cells, only SARS-CoV could infect them (Muller et al., 2012) .
T77 38032-38217 Epistemic_statement denotes Additionally, blockade of ACE2 by antibodies only prevented SARS-CoV infection of cells otherwise permissive to that virus while MERS-CoV could still infect them (Muller et al., 2012 ).
T78 38785-39082 Epistemic_statement denotes Anti-DPP4 antibodies also blocked human and DC MERS-CoV variants from infecting otherwise permissive human bronchial epithelial cells or Huh-7 cells respectively while inhibitors of the DPP4 function did not, indicating that structure, rather than function, was important for MERS-CoV attachment .
T79 40397-40838 Epistemic_statement denotes Because of the high affinity of MERS-CoV for human DPP4, similar to that for animal DPP4 molecules, it is possible that the MERS-CoV which was detected in humans in 2012 was already modestly adapted to humans and that both DCs and horses, and to a lesser extent goats, should all be considered as sources for intrusion of the virus into human populations because of their degree of binding affinity (Barlan et al., 2014; Raj et al., 2014a) .
T80 40839-40969 Epistemic_statement denotes To date, no sign of natural MERS-CoV infection has been found in goat, sheep, cow or alpaca, despite small seroprevalence studies.
T81 40970-41120 Epistemic_statement denotes However, the DPP4 data suggest the possibility and these animals should be further examined as potential animal hosts (see Table 1 for detail on DCs).
T82 41174-41434 Epistemic_statement denotes DPP4 secretion may decrease in proportion to the level of cellular inflammation and the molecule has a role in T-cell activation and hence immune regulation (Boonacker and Van Noorden, 2003) , which may be important for asthmatic airway and MERS-CoV infection.
T83 41435-41744 Epistemic_statement denotes While few studies have looked at DPP4 in the URT and none did so in relation to MERS-CoV, relevant enzymatic activity has been identified there and shown to decrease in the nasal mucosa of patients with rhinitis (inflammation), returning to normal after treatment and/or improvement (Grouzmann et al., 2002) .
T84 41745-42000 Epistemic_statement denotes To date, the RBD of MERS-CoV have not undergone noteworthy genetic change, which could indicate that the RBD is not a crucial factor for species adaptation (Barlan et al., 2014) , or that time spent in humans has been too short to see such change develop.
T85 42344-42572 Epistemic_statement denotes Autopsy material is not available from fatal MERS cases however such material reflects mostly late stage disease in patients who received numerous therapies and have spent time under mechanical ventilation (Chan et al., 2013c) .
T86 42573-42754 Epistemic_statement denotes Therefore a disease model system is essential to study pathogenesis without the confounding influence of a raft of supportive medical procedures and of pre-existing chronic disease.
T87 43700-43992 Epistemic_statement denotes A report of a mouse model for infection by a MERS-CoV close relative, batCoV HKU5, noted that vaccine designs for any emerging CoV should include elements from that particular virus since different members of the same genus are insufficiently similar to elicit immunological crossprotection .
T88 44308-44495 Epistemic_statement denotes IFN␣2b given with ribavirin improved clinical status and virological control in macaques, in association with reduced systemic and local levels of proinflammatory markers and viral load .
T89 44660-44817 Epistemic_statement denotes The mouse model has shown that immune-deficient mice succumbed to more severe disease, as do humans with comorbidities that may affect their immune function.
T90 45238-45411 Epistemic_statement denotes This resulted in a transient mild-to-moderate clinical disease, including a leucocytosis, with acute localised-to-widespread radiographic changes consistent with pneumonia .
T91 46797-47032 Epistemic_statement denotes While the viral dosage and spread of delivery may be unrealistic, we have since learned that much milder disease is not uncommon among MERS-CoV-positive humans, especially those who are younger and do not have underlying comorbidities.
T92 47165-47350 Epistemic_statement denotes The direct LRT component of virus delivery in this model likely reflects some proportion of the human route of virus acquisition and some of the notable human disease involving the LRT.
T93 47351-47544 Epistemic_statement denotes However, it may also bias against study of any potential URT response to first contact between virus and host and therefore overlook routes of ingress and the length and nature of the prodrome.
T94 47545-47685 Epistemic_statement denotes While MERS-CoV is believed to the cause of MERS in humans, such causality can only be extrapolated from these studies in the macaque model .
T95 47972-48123 Epistemic_statement denotes This system aimed to recreate the main epithelial lining which is possibly the site of first contact between host and MERS-CoV (Kindler et al., 2013) .
T96 48830-49120 Epistemic_statement denotes However, MERS-CoV was perhaps a better replicator in these tissues than SARS-CoV and it's targeting of Type I and Type II alveolar cells within the lungs indicated its potential to hinder lung regeneration after infection, since Type II cells are important for repair (Chan et al., 2013c) .
T97 49121-49314 Epistemic_statement denotes By comparison, HCoV-229E, a generally more mild pathogen, did not replicate in lung tissue while influenza A(H5N1) virus, known to be associated with viral pneumonia, did (Chan et al., 2013c) .
T98 49450-49692 Epistemic_statement denotes MERS-CoV is also a very weak inducer of IFN, most likely through an immune dampening effect that both it and SARS-CoV mediate via retention of interferon regulatory factor 3 (IRF-3) in the cytoplasm of infected cells (Zielecki et al., 2013) .
T99 49693-49897 Epistemic_statement denotes MERS-CoV was again shown to be more sensitive to IFN␤, although this was based on pre-treatment of cells, a situation that does not mimic clinical reality for human cases of MERS (Zielecki et al., 2013) .
T100 49913-50191 Epistemic_statement denotes noted that the comparatively limited transcriptional response after infection of HAE cultures by any CoV, with no induction of IFN␤ and only mild induction of proinflammatory cytokines, may mean that MERS-CoV is already adapted to growing in these cells (Kindler et al., 2013) .
T101 50192-50377 Epistemic_statement denotes Professional cytokine-producing cells such as plasmacytoid and conventional dendritic cells and macrophages were lacking in the HAE system but were present in the ex vivo tissues above.
T102 52409-52642 Epistemic_statement denotes The increased relative growth of SARS-CoV in Calu-3 cells compared to using HAE cultures above might reflect the latter's variable expression of the SARS-CoV receptor (Josset et al., 2013 (Josset et al., 2013; Kindler et al., 2013) .
T103 52856-53145 Epistemic_statement denotes Because of the rapidity of MERS-CoV host cell expression changes, post-infection treatment with a kinase inhibitor was not as effective as pre-treatment (Josset et al., 2013) , reinforcing the challenges faced in treatment of MERS cases who present once disease processes are well engaged.
T104 53146-53381 Epistemic_statement denotes MERS-CoV has been shown to infect and replicate within primary human monocyte-derived macrophages and produce considerable virus, in contrast to SARS-CoV which could enter, but not propagate within dendritic cells (Zhou et al., 2014) .
T105 53382-53516 Epistemic_statement denotes Interestingly, MERS-CoV antigens were not found to co-localise with macrophages in infected ex vivo lung tissue (Chan et al., 2013c) .
T106 54541-54803 Epistemic_statement denotes These immune studies raise questions about whether age and immune status or genetic disorders which affect IFN signalling and production could be a risk factor for severe MERS or whether the actions of MERS-CoV itself are sufficient to interfere with signalling.
T107 55019-55244 Epistemic_statement denotes While unclear at that time, approximately 12 MERS-CoV detections from a community outbreak in Hafr Al-Batin between June and August 2013 were possibly triggered by the index case having had DC contact (Memish et al., 2014g) .
T108 55245-55378 Epistemic_statement denotes Today, animal MERS-CoV infections must be reported to the world organization for animal health (OIE) as an emerging disease (2014f) .
T109 55820-55992 Epistemic_statement denotes Providing some support for a droplet transmission route, one report identified viral RNA in an air sample collected in a barn housing an infected DC (Azhar et al., 2014b ).
T110 55993-56061 Epistemic_statement denotes The precise route by which humans acquire MERS-CoV remains unproven.
T111 56062-56498 Epistemic_statement denotes From early on and continuing throughout the MERS epidemic in the KSA, older human males have featured prominently, especially among index cases, implying behavioural factors may play a role (Penttinen et al., 2013) , and these factors may provide important clues as to why so few human cases report DC contact and are reported to have had contact with an infected human, leaving this group without any obvious route of acquisition (Fig.
T112 56504-56627 Epistemic_statement denotes Whether the above definition of animal contact is sufficient to capture exposure to this respiratory virus remains unclear.
T113 56628-56789 Epistemic_statement denotes Cases are sometimes listed in WHO disease notices as being in proximity to camels or farms, but individuals may have denied coming into contact with the animals.
T114 56874-57038 Epistemic_statement denotes Fewer than half of human cases have reported camel contact (Gossner et al., 2014) but what constitutes a definition of "contact" during these interviews is unclear.
T115 57039-57262 Epistemic_statement denotes In a May 2014 WHO update and risk assessment, specific wording focused on consumption of camel products while equivalent wording was not used to ascribe risk to a potential droplet route for acquisition of MERS-CoV from DC.
T116 57263-57275 Epistemic_statement denotes For example:
T117 57276-57524 Epistemic_statement denotes "Until more is understood about MERS, people at high risk of severe disease (those with diabetes, renal failure, chronic lung disease, and immunocompromised persons), should take precautions when visiting farms and markets where camels are present.
T118 57525-57718 Epistemic_statement denotes These precautions include: avoiding contact with camels; not drinking raw camel milk or camel urine; and not eating meat that has not been thoroughly cooked" (World Health Organization, 2014c).
T119 57719-57871 Epistemic_statement denotes Despite the early evidence of DC contact, the diversity of coronaviruses known to exist among bats made them a more widely discussed initial focus (Fig.
T120 58422-58587 Epistemic_statement denotes Unfortunately further sequence from this sample could not be obtained because the cold chain was broken when samples shipped to the USA for study thawed and decayed.
T121 58588-58694 Epistemic_statement denotes The role of bats as the natural host of MERS-CoV or the host of a MERS-CoVlike virus remains to be proven.
T122 59031-59241 Epistemic_statement denotes Near the KSA, Yemen has the highest density of camels, and within the country the Ha'il region is most densely populated with DCs (Gossner et al., 2014) despite there being no human MERS cases from this region.
T123 59242-59309 Epistemic_statement denotes Contact may be commonplace and could occur in variety of ways (Fig.
T124 59607-59762 Epistemic_statement denotes However, MERS-CoV infection frequency appears much lower than does the more widespread and frequent habit of eating, drinking and preparing camel products.
T125 60086-60401 Epistemic_statement denotes DC urine is also consumed or used for supposed health benefits including a belief that it will keep hair parasite-free and has reported application as an aspirin-like anti-platelet-aggregation substance (Alhaidar et al., 2011) and as a specific anti-cancer and immune modulation substance (Al-Yousef et al., 2012) .
T126 61061-61295 Epistemic_statement denotes A neutralising antibody assay found that 10% of strongly seropositive Canary Island DC sera could neutralise the virus while all of the Omani DC sera had high levels of specific MERS-CoV neutralising antibody (Reusken et al., 2013c) .
T127 61296-61451 Epistemic_statement denotes This indicated that DCs had in the past been infected by MERS-CoV, or a very similar virus, but its spread to camels beyond these borders remained unclear.
T128 61452-61618 Epistemic_statement denotes Since this study, a host of peer-reviewed reports have looked at DCs, and other animals, and the possibility that they may play host to MERS-CoV infection (Table 1 ).
T129 61895-62260 Epistemic_statement denotes Many of these animals have only been tested in small numbers and rats, mice, cats, and baboons (wide-ranging in Saudi Arabia and known to come into contact with humans and travel to caves possibly frequented by bats) have yet to be tested at all (Alagaili et al., 2014; Alexandersen et al., 2014; Meyer et al., 2014b; Perera et al., 2013; Reusken et al., 2013b,c) .
T130 63478-63623 Epistemic_statement denotes These are identified as such by screening sera against likely viral culprits, for example BCoV or HCoV-OC43 (as an antigenic facsimile for BCoV).
T131 63624-63825 Epistemic_statement denotes It is possible that other MERS-CoV-like viruses also reside within camels, but this would in no way detract from the current definitive characterization of identical MERS-CoV sequences found in camels.
T132 63826-64130 Epistemic_statement denotes Camel screening studies have shown that juvenile DCs are more often virus or viral RNA positive while older DCs are more likely to be seropositive and RNA or virus negative or if RNA positive in the process of sero-converting, indicative of recent infection (Hemida et al., 2013 (Hemida et al., , 2014a .
T133 64131-64279 Epistemic_statement denotes In adults, MERS-CoV RNA has been detected among animals with pre-existing antibody suggesting re-infection is also possible (Hemida et al., 2014a) .
T134 64280-64616 Epistemic_statement denotes Viral loads among positive camels can be very high (Alagaili et al., 2014; Hemida et al., 2013 Hemida et al., , 2014a Nowotny and Kolodziejek, 2014) and camels have been found positive both when ill with URT respiratory signs (Adney et al., 2014; Azhar et al., 2014a; Hemida et al., 2014a; Memish et al., 2014f) or not obviously unwell.
T135 64617-64685 Epistemic_statement denotes These findings indicate camels can host natural MERS-CoV infections.
T136 64845-65169 Epistemic_statement denotes Older sera have not been tested and so precisely how long camels have been afflicted by MERS-CoV, whether the virus is enzootic among them, only introduced to them 20-years ago from bats, or they are the subject of regular but short-lived viral incursions perhaps occasionally from humans themselves, cannot yet be answered.
T137 65625-65796 Epistemic_statement denotes These results indicated a recent outbreak had occurred in this herd; the first indication of MERS-CoV RNA found within DCs with a temporal association to human infections.
T138 66870-66964 Epistemic_statement denotes A rise in titre theoretically begins 10-21 days after camel infection (Memish et al., 2014f) .
T139 66965-67390 Epistemic_statement denotes While samples were few, the authors of this and a subsequently published study of the same farmer and camel herd in which samples were collected a few days earlier, suggested that the rise in titre in camel sera which occurred alongside a declining RNA load, while the patient was actively ill and hospitalised, indicated that the camels were infected first followed by the owner (Azhar et al., 2014a; Memish et al., 2014f) .
T140 67391-67584 Epistemic_statement denotes Bovine coronavirus (BCoV) antibodies were also present and rising in one of the two RT-rtPCR positive animals but no animal's antibodies could neutralise BCoV infection (Memish et al., 2014f) .
T141 67585-67743 Epistemic_statement denotes These studies show that DCs, but perhaps not one of the other animal species tested, are a reservoir for the MERS-CoV by which they seem to be often infected.
T142 67821-67952 Epistemic_statement denotes It remains unknown whether isolating the reservoir would stop sporadic transmission of MERS-CoV to humans (Nishiura et al., 2014) .
T143 68416-68553 Epistemic_statement denotes URT shedding of infectious virus continued for seven days after inoculation while viral RNA could be detected for 35 days in nasal swabs.
T144 68554-68811 Epistemic_statement denotes Small quantities of viral RNA, but not culturable virus, were detected in exhaled breath but no virus or viral RNA was detected in serum or whole blood and no viral RNA could be detected in faeces or urine for 42 days post inoculation (Adney et al., 2014) .
T145 68910-69101 Epistemic_statement denotes We also do not know whether camels are essential to maintaining chains of human infection which subsequently amplify into more apparent clusters and outbreaks by spreading from humanto-human.
T146 69102-69299 Epistemic_statement denotes Parturition in DCs occurs in the winter months (early in the Gregorian calendar year) which may be a driver of the subsequent spike in human cases seen during 2013 and 2014 (Memish et al., 2014f) .
T147 69300-69585 Epistemic_statement denotes Juvenile camels appear to host active infection more often than adult camels and this may help explain why the slaughter of camels, which must be five years of age or older, does not contribute to significantly to exposure among slaughterhouse workers (Nowotny and Kolodziejek, 2014) .
T148 69586-69867 Epistemic_statement denotes Small numbers of tested DCs from Australia were not seropositive, but expanded virological investigations of Australian (a source of export) and African camels as well as bats may lead to findings of a more ancestral viral variant or more seropositive animals and geographic areas.
T149 70001-70227 Epistemic_statement denotes The MERS-CoV genome does not appear to have changed significantly during its movement through humans in 2012-2014, nor during human and camel spillovers; human variants show very little divergence from camel MERS-CoV variants.
T150 70228-70405 Epistemic_statement denotes This implies that the major source for human acquisition is the camel, rather than another animal, but more testing of other animal species is needed to support that conclusion.
T151 70406-70689 Epistemic_statement denotes Over a month, a DC virus sequenced on different occasions, did not change at all genetically, indicating a high level of genomic stability and supporting the possibility that DCs might be the natural, rather than intermediate, host for MERS-CoV we know today (Hemida et al., 2014a) .
T152 70690-70828 Epistemic_statement denotes The precise role for camels and the route(s) of human acquisition of MERS-CoV from camels in sporadic infections remains to be determined.
T153 70829-71152 Epistemic_statement denotes Nonetheless in the absence of any other likely animal source and in the interest of public health, risk reduction activities now recommend reducing contact with camels, especially when ill, and limiting contact with camel secretions and excretions including the handling of camel milk and meat and the butchering of camels.
T154 71153-71358 Epistemic_statement denotes The potential for aerosol-generation by all these procedures, yet to be defined, described or studied, has not been acknowledged in plain language as a risk to date (see Section 9.1 for aerosols and risk).
T155 71359-71524 Epistemic_statement denotes Thus, camels develop signs of URT disease, shed infectious virus in high quantities in URT secretions and the possibility exists that they may aerosolise that virus.
T156 71525-71644 Epistemic_statement denotes Transmission of MERS-CoV has been defined as sporadic, intrafamilial and healthcare associated (Memish et al., 2014e) .
T157 71813-72142 Epistemic_statement denotes Spread of MERS-CoV within families Omrani et al., 2013) and between people has been well documented ; Health Protection Agency (HPA) UK Novel Coronavirus Investigation Team, 2013; MERS, 2014b; Puzelli et al., 2013) however the first known MERS outbreak was one of acute LRT disease in a healthcare setting (Hijawi et al., 2013) .
T158 72143-72307 Epistemic_statement denotes This occurred in Al-Zarqa, Jordan and was retrospectively linked to the MERS-CoV after some detailed laboratory and epidemiological analyses (Hijawi et al., 2013) .
T159 72488-72716 Epistemic_statement denotes Further investigations deployed an ELISA employing the genetically and antigenically similar btHKU5.2 recombinant nucleocapsid antigen (Chan et al., 2013c) , a MERS-CoV Hu/Jordan-N3/2012 infected Vero cell IFA, and an MNT test .
T160 74241-74586 Epistemic_statement denotes Historically, such rises are consistent with changing definitions and laboratory and clinical responses to, and understanding of, a newly discovered virus that was first noted among the severely ill. As adjustments to testing occurred, more cases of milder disease and those with subclinical infections were noted among MERS-CoV positive people.
T161 74587-74704 Epistemic_statement denotes Over time there has been an apparent cyclical pattern to the average weekly age of people positive for MERS-CoV (Fig.
T162 74705-74855 Epistemic_statement denotes 9A ) however the age distribution changed most notably after the Jeddah-2014 outbreak during which a shift towards younger people became evident (Fig.
T163 75110-75258 Epistemic_statement denotes This is explainable because to date, each spike has been intimately associated with healthcare-facility related outbreaks (Penttinen et al., 2013) .
T164 75420-75650 Epistemic_statement denotes Healthcare facilities have therefore been a regular target for suggested improvements aimed at bolstering weaknesses in infection prevention and control (IPC) procedures (Penttinen et al., 2013; World Health Organization, 2014f) .
T165 76033-76247 Epistemic_statement denotes The outbreak was mostly (>60% of cases) associated with human-to-human spread within hospital environments, and was thought to have resulted from a lack of, or breakdown in, IPC (Brown, 2014; Zumla and Hui, 2014) .
T166 76335-76515 Epistemic_statement denotes Genome sequences indicate viral change, and if the virus is well characterised, such changes may flag alterations to transmissibility, replication, lethality and response to drugs.
T167 77046-77212 Epistemic_statement denotes Those genomes from the Jeddah-2014 outbreak indicated no outstanding genetic or possibly replicative changes from earlier variants World Health Organization, 2014c) .
T168 77297-77373 Epistemic_statement denotes How the index case(s) for either outbreak acquired MERS-CoV remains unknown.
T169 77374-77588 Epistemic_statement denotes Genomic sequence can also be used to define the boundaries of a cluster or outbreak based on the similarity of the variants present among the infected humans and animals and at different healthcare facilities (Fig.
T170 78529-78758 Epistemic_statement denotes Tracing usually identifies dozens of potential cases per confirmed case and while it is a time consuming and expensive process it is essential for understanding transmission and for containing a virus about which little is known.
T171 78759-79056 Epistemic_statement denotes Eighty-three symptomatic or asymptomatic contacts of a case imported to Germany from the United Arab Emirates (UAE) harboured no sign of virus or antibody (Reuss et al., 2014) and similar examples of very limited to no onward transmission have been the hallmark of contact tracing results to date.
T172 79057-79357 Epistemic_statement denotes In a study of 123 contacts of a case imported to France, only seven matched the definition for a possible case and were tested; one who had shared a 20 m 2 room while in a bed 1.5 m apart from the index case was positive and this was determined to be a nosocomial acquisition (Mailles et al., 2013) .
T173 79358-79487 Epistemic_statement denotes It is possible that further mild yet positive cases may have been identified had all contacts been tested regardless of symptoms.
T174 80130-80337 Epistemic_statement denotes One example identified the likely role of a mild or asymptomatic case, present in a hospital during their admission for other reasons, as the likeliest index case for a family cluster (Omrani et al., 2013) .
T175 80562-80746 Epistemic_statement denotes Infectious MERS-CoV added to camel, goat or cow milk and stored at 4 • C could be recovered at least 72 h later and, at 22 • C, for up to 48 h afterwards (van Doremalen et al., 2013) .
T176 81504-81690 Epistemic_statement denotes By comparison, influenza A virus A/Mexico/4108/2009 (H1N1) could not be recovered in Madin-Darby canine kidney (MDCK) cells beyond 4 h under any conditions (van Doremalen et al., 2013) .
T177 81954-82349 Epistemic_statement denotes MERS-CoV survival is inferior to that previously demonstrated by SARS-CoV (Chan et al., 2011) however for context, pathogenic bacteria can remain viable for 45 min in a coughed aerosol and can spread 4 m, thus MERS-CoV's ability to remain viable over long time periods gives it the capacity to thoroughly contaminate a room occupied by an infected and symptomatic patient (Knibbs et al., 2014) .
T178 82350-82619 Epistemic_statement denotes Such findings expand our understanding of the risks associated with bioaerosols for transmission of respiratory viruses in many settings, including hospital waiting rooms, emergency departments, treatment rooms, open intensive care facilities and private patient rooms.
T179 82979-83344 Epistemic_statement denotes By extrapolation, aerosol-generating events involving camels (urination, defecation, and the processes of preparation and consumption of camel products) should be factored into risk measurement and reduction efforts and the need to define whether a more stringent level of personal protective equipment should be worn by HCWs and animal handlers remains a priority.
T180 83345-83705 Epistemic_statement denotes When the MERS-CoV detection tally sat below 120, analyses of the basic reproduction number (R 0 ) -the average number of infections caused by one infected individual in a fully susceptible population -returned values below 1, indicating that a pandemic was not likely (Bauch and Oraby, 2013; Breban et al., 2013; Cauchemez et al., 2014; Poletto et al., 2013) .
T181 83814-83998 Epistemic_statement denotes These analyses reflected charting of small public data sources and indicated that while cases could climb suddenly, such as during the Al-Ahsa outbreak , the climb was not logarithmic.
T182 83999-84175 Epistemic_statement denotes Methods used in these studies vary but some make allowance for more extensive case numbers than may have been publicly reported (Cauchemez et al., 2014; Poletto et al., 2013) .
T183 84176-84242 Epistemic_statement denotes If R 0 was greater than 1, sustained case climb would be expected.
T184 84243-84487 Epistemic_statement denotes The impact of incomplete case contact tracing, limited community testing and clinically defined cases in the absence of laboratory confirmation might affect some R 0 calculations and make it difficult to identify patterns among case occurrence.
T185 84488-84657 Epistemic_statement denotes The implication is that more positives among these population groups could have occurred and thus a greater transmission efficiency and higher R 0 value may be possible.
T186 84658-84944 Epistemic_statement denotes When narrowing an analysis to index cases (the case with the earliest onset date of a cluster) and inferring secondary case numbers, one study predicted that the R 0 could be slightly above 1.0 (0.8-1.3 with an upper bound of 1.2-1.5 depending on method used) (Cauchemez et al., 2014) .
T187 85122-85325 Epistemic_statement denotes Most cases of MERS have resulted from human-to-human transmission, however that transmission was inefficient Memish et al., 2013b; Omrani et al., 2013) and defined as sporadic rather than sustained (Fig.
T188 85410-85639 Epistemic_statement denotes Relevant data are scant but it appears that the majority of human cases of MERS-CoV do not transmit to more than one other human and to date, the localised epidemic of MERS-CoV has not been selfsustaining (Poletto et al., 2013) .
T189 86323-86537 Epistemic_statement denotes older and it has yet to be established whether infections thought to have been acquired from an animal source produce a more severe outcome than those spread between humans (The WHO MERS-CoV Research Group, 2013) .
T190 86538-86679 Epistemic_statement denotes Strategic sero-assays have yet to investigate the extent to which milder or asymptomatic cases contribute to the MERS-CoV transmission chain.
T191 87022-87386 Epistemic_statement denotes It is impossible to predict whether a MERS-CoV vaccine for human use will fall victim to a lack of commercial interest or remain relevant in the time it will take to be developed, however a vaccine for use in camels is a more practical option given the identity shared between human and camel viral variants and the apparent rarity of MERS-CoV spillover to humans.
T192 87387-87519 Epistemic_statement denotes If applied to young camels ahead of their first virus acquisition, such a vaccine may be capable of eradicating MERS-CoV from herds.
T193 87520-87707 Epistemic_statement denotes But if the source of camel infections is bats, newly imported camels or other herds, any vaccine would need to be used in an ongoing manner and be able to reach feral camel herds as well.
T194 87708-87832 Epistemic_statement denotes Care of hospitalised patients remains supportive, with vigilance for complications (The WHO MERS-CoV Research Group, 2013) .
T195 88214-88269 Epistemic_statement denotes However, research advances in this area have been made.
T196 89039-89325 Epistemic_statement denotes A novel molecule, K22, showed promise both directly and as an example that it was possible to target and specifically disrupt very conserved viral replication processes such as double membrane vesicle-associated RNA replication, without causing cellular toxicity (Lundin et al., 2014) .
T197 89326-89526 Epistemic_statement denotes Another approach has been to target the interface between the MERS-CoV RBD and the receptor by employing competitive substrates or inhibitors of the enzymatic function of DPP4 (Kawalec et al., 2014) .
T198 89527-89786 Epistemic_statement denotes DPP4 inhibitors, in their role as anti-diabetes drugs, already exist, are tolerated and are not associated with adverse events (Kawalec et al., 2014) although it is unclear whether they may already be in use among MERS patients with underlying kidney disease.
T199 89787-89994 Epistemic_statement denotes Additionally, targeting the viral MERS-CoV 3C protease, important for replicase polyprotein maturation, may be a viable strategy in the future because it has so far remained conserved (Cotten et al., 2014) .
T200 90246-90443 Epistemic_statement denotes MERS-4, MERS-27 and 3B11) directed towards the S protein are capable of neutralising infection by the MERS-CoV and hold future promise for use as a therapeutic and prophylactic Tang et al., 2014) .
T201 90444-90724 Epistemic_statement denotes A replication-competent, propagation-deficient E gene-deleted mutant of MERS-CoV variant EMC/2012 (rMERS-CoV-E) may also prove to be a useful vaccine candidate while a truncated RBD of MERS-CoV has been shown to elicit antibodies in mice (Almazán et al., 2013; Du et al., 2013a) .
T202 90725-90891 Epistemic_statement denotes A conserved peptide in the RdRp of all HCoVs was also identified, and that may provide the basis for an epitope-directed universal vaccine (Sharmin and Islam, 2014) .
T203 91756-91860 Epistemic_statement denotes Since MERS seems to be a prolonged disease that is well engaged (Mackay, 1997) and blog (Mackay, 2013) .
T204 91861-91993 Epistemic_statement denotes upon presentation for medical help, it is unclear how this drug cocktail could be delivered early enough to moderate severe disease.
T205 92185-92350 Epistemic_statement denotes When used as a primary treatment of an infected physician and as prophylaxis for his wife, it was unclear whether the cocktail had any effect (Khalid et al., 2014) .
T206 92873-93085 Epistemic_statement denotes However there were often delays in the posting of such information, most notably during the Jeddah-2014 outbreak when no new case details were confirmed by the WHO as originating from KSA for more than six weeks.
T207 93086-93467 Epistemic_statement denotes Cases announced via the KSA Ministry of Health website have often had data inconsistencies including errors, format variations, have often lacked key information including dates, have presented deaths with insufficient information to permit linkage with the announced case and over one hundred cases remain devoid of all key data, excluding them from most epidemiological analyses.
T208 93468-93584 Epistemic_statement denotes This was a particular problem during periods when rapid case accumulation became a concern for the global community.
T209 93585-93937 Epistemic_statement denotes When available, WHO DONs fill in vital missing detail, with additional important demographic data like age, sex or essential dates permitting improved understanding of when illness onset occurred, when cases were hospitalised, whether they were asymptomatic and if the newly announced case was a contact of another case, an animal or an animal product.
T210 93938-94019 Epistemic_statement denotes However DONs are only effective when the underlying data is forwarded to the WHO.
T211 94020-94286 Epistemic_statement denotes Such comprehensive data permits other calculations, for instance the likely laboratory turnaround time, the possibility for nosocomial spread occurring and the location of cases as a determining factor in whether a cluster has become an outbreak or a local epidemic.
T212 94287-94393 Epistemic_statement denotes WHO data can be viewed by the public but are also relied upon by WHO Member States' epidemiology analysts.
T213 94564-94799 Epistemic_statement denotes The decisions which follow may include the need to raise alert levels, prepare laboratory capacity, create educational materials, free specific response funds, ramp up messaging, manage and alter border controls or issue travel alerts.
T214 95194-95597 Epistemic_statement denotes Their social media unit strove to answer questions posed by everyone and anyone through Twitter, which in turn allowed users to take control of further disseminating the information they found most interesting, informative, relevant or concerning to others in their social networks; a process that can also be informative to public health bodies who seek to provide their clients the detail they desire.
T215 95841-96004 Epistemic_statement denotes Their role is to advise the WHO Director-General on the need for action and, as yet, no Public Health Emergency of International Concern (PHEIC) has been declared.
T216 96163-96506 Epistemic_statement denotes Gregory Härtl, Coordinator of the Department of Communications for the WHO, noted that "the more answers public health experts can provide now, the greater the public's trust in these institutions will be if and when the virus should become easily transmissible between humans and cause more widespread morbidity and mortality" (Hartl, 2013) .
T217 96915-97250 Epistemic_statement denotes Despite data in the scientific literature strongly indicating that camels harboured MERS-CoV or a very closely related virus, communication about camels posing a risk to humans as the zoonotic sources for infections did not became a mainstream public health message until late April of 2014; two years after the discovery of the virus.
T218 97251-97475 Epistemic_statement denotes This shift correlated with a change in the KSA Minister of Health, requests for help in containing the Jeddah-2014 outbreak and a new WHO risk assessment, which included mention of camels (World Health Organization, 2014e) .
T219 97646-97833 Epistemic_statement denotes However, the message to date, underpinned as it is by a paucity of understanding about how and from where the virus transmits, may not yet capture or adequately communicate all the risks.
T220 97834-97922 Epistemic_statement denotes Much of what is considered social media is a volatile resource, yet a very valuable one.
T221 98087-98325 Epistemic_statement denotes Tweets can disappear to search after a short period, blog pages can come and go and be untraceably altered while online mainstream news stories, in some countries more than others, may suffer similar fates as they rapidly become old news.
T222 98326-98484 Epistemic_statement denotes Despite that, internet-driven information has played a vital role in rapidly tracking and unearthing cases, clusters and outbreaks of disease in recent years.
T223 98485-98526 Epistemic_statement denotes This has been the case for MERS globally.
T224 99310-99499 Epistemic_statement denotes The public audience may not spend the time and mostly do not have the background expertise to interpret the densely presented, often slow to appear, scientific and public health literature.
T225 99500-99753 Epistemic_statement denotes The space between the scientific literature and mainstream media is occupied by those science communicators who may, sometimes with and sometimes without relevant scientific training, be as up-to-date on their topics as the best academic epidemiologist.
T226 99754-100050 Epistemic_statement denotes The President John F. Kennedy quote, "One person can make a difference, and everyone should try" seems an apt one to describe these dedicated people who, often without any paid incentives, devote their personal time, effort and money to better understand and communicate about infectious disease.
T227 100051-100432 Epistemic_statement denotes Frequently updated data repositories such as the small FluTrackers group constantly compile, actively curate and condense worldwide news sources into threads of information that often assemble into patterns that can predict emerging infectious disease events well before they reach the mainstream media, and their line list of MERS-CoV detections (Ministry of Health, Saudi Arabia.
T228 102210-102332 Epistemic_statement denotes Each resource is as distinct yet complimentary source of information that together are sometimes referred to as flublogia.
T229 102333-102687 Epistemic_statement denotes While it is often overlooked and perhaps underestimated by some professional scientists and clinicians, flublogia compiles or uses publicly available, deidentified data and adds publicly relevant interpretation which is greatly appreciated, much more widely read and far, far more often cited than anything seen in the professional scientific literature.
T230 102760-102869 Epistemic_statement denotes The MERS-CoV appears to be an entrenched camel virus infecting the URT which may have its origins among bats.
T231 102870-102936 Epistemic_statement denotes Human infection may result from rare zoonotic spillover to humans.
T232 102937-103201 Epistemic_statement denotes Many potential animal, human and environmental sources await further testing but thanks to quick action, the sensitive and rapid molecular diagnostic tools required to achieve this goal have been in place and available since the virus was made known to the public.
T233 103347-103517 Epistemic_statement denotes Commercial unavailability remains an issue for more widespread use and so collaboration with the relevant research groups must be the immediate option for future studies.
T234 103518-103666 Epistemic_statement denotes The MERS-CoV can spread from human-to-human but seems to do so only sporadically and sustained chains of transmission have not been evident to date.
T235 103667-103786 Epistemic_statement denotes There is also no evidence that MERS-CoV is a virus of pandemic concern, despite many opportunities for it to become so.
T236 103787-103886 Epistemic_statement denotes But vigilance is key for a virus with a genetic makeup that has only been observed for three years.
T237 104040-104344 Epistemic_statement denotes While whole genome sequencing has been used extensively to study MERS-CoV, it remains a tool for experts and collaborations have again been key for less equipped or experienced researchers to decode the MERS-CoV as it moves through people, over time and across distance in the KSA and beyond its borders.
T238 104456-104651 Epistemic_statement denotes Nonetheless, figures modelling efficiency of transmission will need confirmation once better serological and RT-rtPCR-based studies of humans, covering more of the community, have been conducted.
T239 104652-104805 Epistemic_statement denotes It has become very clear that the MERS-CoV may spread poorly from human-to-human, but that spread is at its most effective around a hospital environment.
T240 104806-104940 Epistemic_statement denotes Indications are that this can be traced back to poor IPC practices and protocols (Brown, 2014; Editorial, 2014; Zumla and Hui, 2014) .
T241 104941-105178 Epistemic_statement denotes The virus has its greatest impact on those with underlying diseases and such cases, sometimes suffering multiple comorbidities, are likely to visit hospital for treatment, creating a perfect storm of exposure, transmission and mortality.
T242 105336-105921 Epistemic_statement denotes Characteristics including the higher PFC among MERS cases (above 50% in 2013 and currently at 30-40%; well above the 9.5% of SARS), the association between fatal disease and older males with underlying comorbidities, the very broad tropism of MERS-CoV, its rapid in vitro growth, rapid induction of cytopathogenic change, robust yet distinct transcriptional responses, use of a different receptor, its induction of a more proinflammatory but reduced and delayed innate antiviral response and its sensitivity to external IFN␣ or IFN␤ all signal differences from SARS-CoV to some degree.
T243 106061-106273 Epistemic_statement denotes From those studies conducted thus far that screen people beyond the most severely ill, there appears to be a 2-3% prevalence of MERS-CoV in the KSA with a 5% chance of secondary transmission within the household.
T244 106771-106816 Epistemic_statement denotes Much remains unknown about MERS-CoV and MERS.
T245 106817-106908 Epistemic_statement denotes Further cooperative data-sharing and research is needed to address questions which include:
T246 106909-106953 Epistemic_statement denotes • What is the natural host for the MERS-CoV?
T247 106954-107098 Epistemic_statement denotes • Are camels the source of sporadic human infections and if so, why is MERS-CoV seroprevalence among humans working closely with camels, so low?
T248 107099-107247 Epistemic_statement denotes • What is the route of transmission to humans and between humans and what is the best personal protective equipment to be adopted by frontline HCWs?
T249 107248-107519 Epistemic_statement denotes • Which hospital IPC measures are insufficient or insufficiently employed to halt the transmission of MERS-CoV and what is the extent of transmission and clinical impact of, and nosocomial infection by, other co-occurring respiratory viruses in these settings in the KSA?
T250 107571-107642 Epistemic_statement denotes Are there differences in activity and exposure that could explain this?
T251 107643-107706 Epistemic_statement denotes What is the prevalence of underlying disease between the sexes?
T252 107952-108044 Epistemic_statement denotes If not, might MERS-CoV be a rare, seasonal and endemic infection of humans like other HCoVs?
T253 108184-108355 Epistemic_statement denotes • March and April seem to be when human outbreaks of MERS begin-what are the events occurring in and around this time of year that may increase human exposure to MERS-CoV?
T254 108571-108771 Epistemic_statement denotes • What proportion of acute respiratory tract disease cases continue to go untested because they do not manifest as severe disease and could these clarify gaps in the transmission chains of some cases?
T255 109037-109256 Epistemic_statement denotes The localised MERS-CoV epidemic reminds us of the importance of communication at all levels and perhaps the need to rethink how stakeholders are informed of the progress of chasing down and studying new disease threats.
T256 109942-110435 Epistemic_statement denotes This case highlighted the effectiveness of social media in communicating digestible information to expectant stakeholders compared to the use of a generally slower and more elite peer-reviewed scientific publication pipeline which is often better suited to detailed research description over the long haul, but with some exceptions, a process unsuited for informing a concerned global and always-online public of potential threats to its immediate health or providing context to those threats.
T257 110436-110671 Epistemic_statement denotes However, while MERS-CoV is not a rapidly spreading global contagion, it may evolve further to become that or another may emerge in the future and vigilance and rapid communication will be key to a timely response and early containment.
T258 110773-110920 Epistemic_statement denotes One constant in all this however is the human; it is we who fan the flames of a disease cluster until it becomes an outbreak, epidemic or pandemic.
T259 111008-111174 Epistemic_statement denotes MERS highlighted that some paradigms can be stumbling blocks to seeking and communicating knowledge and containing and understanding the spread and nature of a virus.
T260 111175-111388 Epistemic_statement denotes It also served as yet another reminder to us that global human and animal health, politics, agriculture and economies are all intimately interwoven and it takes just a single tiny virus to tip a very fine balance.