Task 8 - What do we know about diagnostics and surveillance?



Which are the sampling methods to determine asymptomatic disease?


Nasopharyngeal and throat swabs and in stool samples [ 4 , 9 ] ) . [COVID-19 virus and children: What do we know?, Archives de Pédiatrie, 2020-04-30]
The proportion of asymptomatic patients described worldwide is very small ( 889 confirmed asymptomatic cases / 45 , 561 confirmed cases in China ; 2 . 0 % [ 5 ] ) , but this could be underestimated because of the diagnostic methods that involved exclusively RNA detection by RT - PCR of secretions ( nasopharyngeal and throat swabs and in stool samples [ 4 , 9 ] ) . RNA in nasopharyngeal and throat swab samples has been shown to become undetectable within 6 - 22 days ( mean : 12 days ) of illness onset in children [ 4 ] . The excretion of the virus could be shorter in asymptomatic patients and there is no systematic sampling series in asymptomatic persons . The age distribution of asymptomatic patients is not detailed in the literature . Do children represent less severe cases , are they less infected , or are they being underdiagnosed as less symptomatic [ 10 ] ?

Our group testing method consists of rst clinically screening out symptomatic individuals . [Analysis and Applications of Non-Adaptive and Adaptive Group Testing Methods for COVID-19, unknown journal, 2020-04-07]
1 Figure 1 . 1 : ( Image credit : Matthew Heidemann ) Our group testing method consists of rst clinically screening out symptomatic individuals . This will lower the prevalence in the test population . Our group testing is especially eective when we can assume the prevalence is uniform over the whole population . Therefore , it is especially applicable to conned or cohesive populations . We split the asymptomatic individuals up into groups for which we mix the samples from each individual and test them . A negative result will conrm many negative cases . We subsequently divide groups and test the mixtures of samples for positive results . This we show , conserves the number of tests and , as a result , the time spent testing . Using numerical experiments , we also show that our methods can be performed without running out of samples from passing through too many rounds .

Dorfman ' s method or divide and test , [Analysis and Applications of Non-Adaptive and Adaptive Group Testing Methods for COVID-19, unknown journal, 2020-04-07]
Rather than considering the application of a level of condence as an idiosyncracy of the method , it is actually a fundamental property of identifying asymptomatic COVID - 19 carriers . Asymptomatic positives cannot be identied without testing them , we can only pick an upper bound on the cases with a high level of certainty . It might seem preferable to then choose a method that instead prescribes a group - size for each level of prevalence , such as Dorfman ' s method or divide and test , but for those methods the possibility that we have misjudged the prevalence still needs to be factored in ! 6 Condence bounds on group testing methods We will apply DT and GBS with groups capped at 4 , 8 , 16 , 32 and 64 samples using two dierent levels of condence .

Nasopharyngeal aspirate ( npa ) had a higher positive rate within 2 weeks of symptom onset , [Which sampling method for the upper respiratory tract specimen should be taken to diagnose patient with COVID-19?, Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery, 2020]
Coronavirus disease 2019 ( COVID - 19 ) is raging in China , especially in Hubei Province , which has resulted great dangers in people ' s life and national economy . According to the guidelines drafted by China ' s Center for Disease prevention and Control ( CDC ) , the positive nucleic acid test is need to the diagnosis of patient with COVID - 19 . Upper respiratory tract specimens are the main sources for nucleic acid detection . However , based on international guidelines of COVID - 19 , no recommended level of upper respiratory tract sampling method is proposed . Therefore , which kind of sampling methods should be chosen to help the COVID - 19 diagnosis and which way is the most secure for doctors and nurses is our concern . In this review , we analyzed a total of 10 literatures on the sampling methods of upper respiratory tract related to infectious diseases such as severe acute respiratory syndrome coronavirus ( SARS ) , middle east respiratory syndrome coronavirus ( MERS ) , and influenza A ( H1N1 ) , which were spread worldwide in past years . Literatures were collected from the three dimensions of sampling method , sampling time , and sampling safety . It was found that among all the upper respiratory sampling methods , nasopharyngeal aspirate ( NPA ) had a higher positive rate within 2 weeks of symptom onset , while combined nasal and oropharyngeal swabs ( NS + OPS ) was the least harmful to medical staff during sampling . We wish this review is helpful for the prevention of COVID - 19 .


What can we do for early detection of disease?


If this approach is not feasible because of widespread community transmission , then community quarantine is also needed with rigorous implementation of social distancing . [Can we contain the COVID-19 outbreak with the same measures as for SARS?, The Lancet Infectious Diseases, 2020-03-05]
The answers to these questions will determine the success . Until those answers are known , the political and medical community needs to persist with containment efforts with the tools that are available at hand for the time being . China should be commended for its political will in implementing what might appear to be extreme measures . Undoubtedly , no other country could enact what China is currently doing . The daily decline in new cases by mid February suggests that China is on the right path , showing that containment could be feasible . Other countries should be aware and reduce the spread of COVID19 . What is already known is that exportations to other countries need not result in rapid largescale outbreaks , if the countries have the political will to rapidly implement early case detection , prompt isolation of ill people , comprehensive contact tracing , and immediate quarantine of all contacts . If this approach is not feasible because of widespread community transmission , then community quarantine is also needed with rigorous implementation of social distancing .

In the early stages of infection spreading in a country , one or two infected persons are usually detected daily . [A cascade of causes that led to the COVID-19 tragedy in Italy and in other European Union countries, unknown journal, 2020-04-04]
With this in mind , let us now look at the Italian and other EU countries ’ reaction to their own epidemic , in view of what Croatia did . In the early stages of infection spreading in a country , one or two infected persons are usually detected daily .

What we can do to deal with an outbreak like covid - 19 would be to ( 1 ) collect information as early as possible , [First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model, Global Health Research and Policy, 2020]
Specifically , what we can do to deal with an outbreak like COVID - 19 would be to ( 1 ) collect information as early as possible , ( 2 ) monitor the epidemic as close as possible just like we do for an earthquake and make preparations for a hurricane and ( 3 ) communicate with the society and use confirmed data appropriately reframed not causing or exacerbating fear and panic in the public , stress and distress among medical and public health professionals , as well as administrators to make right decisions and take the right strategies at the right time in the right places for the right people .

Rt - pcr - based sars - cov - 2 rna detection in respiratory samples provides the only specific diagnostic test at the initial phase of the outbreak . [SARS-CoV-2 and COVID-19: The most important research questions, Cell Biosci, 2020-03-16]
The fifth question concerns how COVID - 19 should be diagnosed and what diagnostic reagents should be made available . RT - PCR - based SARS - CoV - 2 RNA detection in respiratory samples provides the only specific diagnostic test at the initial phase of the outbreak . It has played a very critical role in early detection of patients infected with SARS - CoV - 2 outside of Wuhan , implicating that widespread infection of the virus had occurred in Wuhan at least as early as the beginning of 2020 . This has also pushed the Chinese authority to acknowledge the severity of the situation . Due to difficulties in sampling and other technical issues in this test , at one point in early February clinically diagnosed patients with typical ground glass lung opacities in chest CT were also counted as confirmed cases in order to have the patients identified and quarantined as early as possible . ELISA kits for detection of IgM and IgG antibodies against N and other SARS - CoV - 2 proteins have also been available more recently . This has made specific diagnosis of ongoing and past infection possible . Particularly , seroconversion for IgM antibodies normally occurs a few days earlier than that of IgG . ELISA reagents for detection of SARS - CoV - 2 antigens such as S and N are still in urgent need , and would provide another test highly complementary to viral RNA detection .

Lesions in lobules were detected by chest computed tomographic scans in 28 patients ( 82 . 36 % ) . [Clinical Characteristics of 34 Children with Coronavirus Disease-2019 in the West of China: a Multiple-center Case Series, unknown journal, 2020-03-16]
( which was not peer - reviewed ) The copyright holder for this preprint . https : / / doi . org / 10 . 1101 / / doi . org / 10 . / 2020 3 lesions in lobules were detected by chest computed tomographic scans in 28 patients ( 82 . 36 % ) . The typical feature of ground - glass opacity for adults was rare in paediatric patients ( 2 . 94 % ) . A late - onset pattern of lesions in lobules were also noticed . Stratified analysis of the clinical features were not performed due to relatively limited samples . What did the researchers do and find ?


Is the use of screening of neutralizing antibodies such as ELISAs valid for early detection of disease?


In a study of 623 sars patients , the neutralizing - antibody levels peaked at 20 - 30 days and were sustained for over 150 days . [Pathogenesis of severe acute respiratory syndrome, Current Opinion in Immunology, 2005-08-31]
Detection of serum IgG , IgM and IgA against SARS - CoV using immunofluorescent assays and by ELISA against nucleocapsid antigen occurs around the same time with most patients seroconverted by day 14 after onset of illness [ 48 ] . IgG can be detected as early as 4 days after the onset of illness . The kinetics of neutralization antibodies nearly parallel those for IgG [ 48 ] and most of the neutralizing - antibody activity is attributed to IgG [ 49 ] . In a study of 623 SARS patients , the neutralizing - antibody levels peaked at 20 - 30 days and were sustained for over 150 days . These antibodies can neutralize the pseudotype particles bearing the S protein from different SARS - CoV strains , suggesting that these antibodies are broadly active and that the S protein is highly immunogenic [ 49 ] . Indeed the S protein , among the other structural proteins , such as M , E or N , is the only significant SARS - CoV neutralization antigen and protective antigen [ 50 ] , with amino acids 441 - 700 as the major immunodominant epitope [ 51 ] .

Early antibodies are detected in some patients within two weeks . [Severe acute respiratory syndrome and dentistry A retrospective view, The Journal of the American Dental Association, 2004-09-30]
Enzyme - linked immunosorbent assay , or ELISA , test . From about 20 days after the onset of clinical signs , ELISA tests can be used to detect immunoglobulin , or Ig , M and IgA antibodies in the serum samples of patients with SARS . Early antibodies are detected in some patients within two weeks .

Serologic assays are not useful for early diagnosis as igg antibodies do not appear for 7 - 10 days after onset of symptoms . [SARS: future research and vaccine, Paediatric Respiratory Reviews, 2004-12-31]
Serologic assays are not useful for early diagnosis as IgG antibodies do not appear for 7 - 10 days after onset of symptoms . It has been stated that IgM antibodies typically appear earlier , but detection of IgM antibodies does not appear to permit earlier diagnosis . 1 , 11 Since a few SARS patients have had late seroconversion , it is best to test the convalescent serum collected at least 21 days and preferably 28 days after onset of symptoms , to rule out SARS . 1 At present , the most widely used methods for detection of antibodies against SARS CoV are indirect immunofluorescence assay and ELISA with cell - culture extract , which are difficult to standardise . 25 Therefore , recombinant - antigenbased ELISA assays are being developed using highly immunogenic nucleocapsid protein of SARS CoV , which can be used for a large scale epidemiological study of seroprevalence . 25

Using the three different validated elisas , we found that antibody levels were higher following the severe infection compared to the mild ones ; [SARS-CoV-2 specific antibody responses in COVID-19 patients, unknown journal, 2020-03-20]
The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 18 . 20038059 doi : medRxiv preprint When testing the specificity S1 or its RBD for detecting SARS - CoV - 2 antibodies , none of the sera form the validation cohorts ( A - E ) showed any reactivity ; except for SARS - CoV patients sera . This - not - unexpected - cross - reactivity resulted from the high degree of similarity between the S1 and RBD of the SARS - CoV and SARS - CoV - 2 ( Table 2 ) . However , SARS - CoV has not circulated in the human population since 2003 , i . e . 17 years ago , and an earlier study reported waning of SARS - CoV - specific antibodies which made them undetectable in serum samples of 91 % ( 21 / 23 ) of samples tested 6 years following infection ( 11 ) . It is therefore unlikely that antibodies to this virus are present in the population and thus there could hardly be a chance that false positives result from SARS - CoV - antibodies reactivity . Meanwhile , we made use of the high degree of similarity between the SARS - CoV and SARS - CoV - 2 proteins for the development of our inhouse N ELISA , where we used SARS - CoV N ( 90 % similar to SARS - CoV - 2 ) as an antigen . The N - ELISA could detect SARS - CoV - 2 - specific antibodies with high specificity and sensitivity . Using the three different validated ELISAs , we found that antibody levels were higher following the severe infection compared to the mild ones ; similar findings has been reported earlier for MERS - CoV ( 12 , 13 ) . However , this needs to be confirmed with a larger cohort of patients with varying degrees of severity , while it still highlights the potential need of a sensitive assay to avoid missing those with milder infections in epidemiological studies . Among the 3 inhouse ELISAs tested , the RBD and N ELISAs were more sensitive than S1 ELISA in detecting antibodies in mildly infected patients and showed stronger correlation with PRNT50 titers . Therefore , detecting antibodies against two different antigens might be needed to confirm the findings and avoid false negatives in surveillance studies . However , the sensitivities of the assays need to be further validated with a larger cohort .

Hcov - 229e specific antibodies were infrequently detected in the adult sera screened by hofmann et al . [Seroepidemiology of group I human coronaviruses in children, Journal of Clinical Virology, 2007-11-30]
Since we could not rely on an infected cell lysatesbased ELISAs as a " gold standard , " because of a concern for cross - reactive antibody , we could not test the sensitivity for the recombinant protein - based ELISA . Nonetheless , we demonstrated that the recombinant proteins could be used to specifically detect antibodies for HCoV - 229E and HCoV - NL63 . The high negative predictive value ( 89 % ) indicates that our assay is reliable though may result in an ( albeit small ) underestimation of the true percentage of negatives . However , this negative predictive value was determined for HCoV - 229E ; we could unfortunately not confirm this for HCoV - NL63 , because we could not propagate the HCoV - NL63 virus to sufficient titers . It appears that infection with known group I coronaviruses is common in childhood . Although maternally acquired Ndirected antibodies to both HCoV - 229E and HCoV - NL63 appeared to wane by 4 - 5 months of life , > 30 % of children have serological evidence of infection with either of the two group I human coronaviruses by the age of 12 months . The most likely explanation for this is the exposure and infection with these viruses in the first year of life . Our cross - sectional study revealed that the percentage of seropositive individuals 2 years of age was much greater for HCoV - 229E as compared to HCoV - NL63 suggesting that HCoV - 229E was more prevalent in the 1 - 2 years prior to the acquisition of the serum for these children . Our findings are similar to that of Hofmann et al . who found , with the use of pseudotype virus expressing the S protein , that most sera from adults had HCoV - NL63 - neutralizing antibodies ( Hofmann et al . , 2005 ) . Indeed , the youngest children who had detectable HCoV - NL63 - specific antibodies were ∼1 . 5 years old and by age 8 years , the sera from most of the children screened had HCoV - NL63 - specific antibodies , which are consistent with Table 1 Screening of sera for group I human coronavirus specific antibodies our findings . Furthermore , HCoV - 229E specific antibodies were infrequently detected in the adult sera screened by Hofmann et al . and by our group suggesting that the circulation of the two group I coronaviruses differ . Previous studies of non - SARS human coronaviruses , which focused on HCoV - 229E and HCoV - OC43 , demonstrated that the seroprevalence varies greatly and depends on the age of the population and the method used to detect coronavirus - specific antibodies ( Hambre and Beem , 1972 ; Hasony and Macnaughton , 1982 ; Kaye et al . , 1971 ; McIntosh et al . , 1970 ; Monto and Lim , 1974 ; Pohl - Koppe et al . , 1995 ) . However , these studies used whole virus as antigen and , because of the apparent cross - reactivity of HCoV - 229E antibodies demonstrated in our study , it is likely that the assays used in these studies detected group - specific antibody rather than type - specific antibody . With the discovery of HCoV - NL63 the results of these publications should now be viewed differently : in the studies in which HCoV - 229E antibody was measured , the data likely represents the seroepidemiology of group I coronaviruses . ( The same is likely true for group II coronaviruses with the discovery of HCoV - HKU1 , Woo et al . , 2005a . ) In conclusion , our data indicates that infection with these group I coronaviruses is common in childhood . Application of the recombinant protein - based ELISA will lead to the further understanding of the epidemiology of these viruses .


Which are the existing diagnostic platforms?


The mngs analyses of balf samples were performed on existing samples collected during standard diagnostic tests , posing no extra burden to patients . [RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak, Emerg Microbes Infect, 2020-02-05]
This study was approved by the Ethics Committee of the Zhongnan Hospital of Wuhan University . The mNGS analyses of BALF samples were performed on existing samples collected during standard diagnostic tests , posing no extra burden to patients .

The proteomic analysis of pbmc samples were performed on existing samples collected during standard diagnostic tests , posing no extra burden to patients . [Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis, unknown journal, 2020-04-02]
This study was approved by the Ethics Committee of Shanghai Public Health Clinical Center ( # YJ - 2020 - S052 - 02 ) . The proteomic analysis of PBMC samples were performed on existing samples collected during standard diagnostic tests , posing no extra burden to patients .

Extract rna on more open platforms that enable non - specific reagents and plastics to be used . [Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic, unknown journal, 2020-04-08]
The standard molecular diagnostic test for this virus is a multistep process involving viral RNA extraction and real - time quantitative reverse transcriptase PCR ( qRT - PCR ) . Although many companies have produced PCR kits to amplify the viral RNA , RNA extraction at any scale in a diagnostic laboratory is performed on a limited number of automated platforms that require specific reagents and consumables . This has led to significant effort to build large laboratories with existing research equipment to increase testing capacity , and to extract RNA on more open platforms that enable non - specific reagents and plastics to be used .

Serological antibody detection has the advantage of high sensitivity , so the combination of the two will be a good diagnostic means . [Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing, unknown journal, 2020-03-06]
The disadvantage of nucleic acid detection is the existence of relative high false negative rate , and serological antibody detection has the advantage of high sensitivity , so the combination of the two will be a good diagnostic means . It can be inferred that after the future epidemic situation has been controlled to a certain extent , as a convenient method , antibody detection is still necessary to make differential diagnosis of other respiratory pathogens infection .

A replacement lysis buffer for extraction of viral nucleic acids from respiratory samples was desperately needed by diagnostic laboratories . [Validation of a Lysis Buffer Containing 4 M Guanidinium Thiocyanate (GITC)/ Triton X-100 for Extraction of SARS-CoV-2 RNA for COVID-19 Testing: Comparison of Formulated Lysis Buffers Containing 4 to 6 M GITC, Roche External Lysis Buffer and Qiagen RTL Lysis Buffer, unknown journal, 2020-04-08]
Expansion of PCR testing is critical to gain control over the pandemic spread of COVID - 19 and the world - wide shortage of lysis buffer is a rate limiting step . Here we disseminate details of a lysis buffer formulation that came into existence as a consequence of a rapidly formed multi - centre collaboration . A replacement lysis buffer for extraction of viral nucleic acids from respiratory samples was desperately needed by diagnostic laboratories .


Which are the existing surveillance platforms?


Our findings will support rapid deployment of outbreak surveillance and control capacities in regions at high risk of case importation paired with low surveillance capacity . [Using observational data to quantify bias of traveller-derived COVID-19 prevalence estimates in Wuhan, China, The Lancet Infectious Diseases, 2020-04-01]
Our study will allow better estimates to be produced of the global burden of COVID - 19 , in view of the large underdetection of cases . Our findings will support rapid deployment of outbreak surveillance and control capacities in regions at high risk of case importation paired with low surveillance capacity . Our research implies that existing estimates , which assume perfect detection of cases outside of China , should increase values for infection prevalence in the epicentre of the epidemic and reduce estimates of case - fatality based on our prevalence estimates .

Identified the unusual cluster of pneumonia in wuhan in december 2019 and the rapid deployment of functional studies and genomic tools for pathogen identification and characterization . [Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic, unknown journal, 2020-03-31]
The existing diversity and dynamic process of recombination amongst lineages in the bat reservoir demonstrate how difficult it will be to identify viruses with potential to cause significant human outbreaks before they emerge . This underscores the need for a global network of real - time human disease surveillance systems like that which identified the unusual cluster of pneumonia in Wuhan in December 2019 and the rapid deployment of functional studies and genomic tools for pathogen identification and characterization .

It has strengthened surveillance for undiagnosed severe acute respiratory illnesses . [Epidemiological and Clinical Aspects of COVID-19; a Narrative Review, Arch Acad Emerg Med, 2020-04-01]
Japan ’ s Ministry of Health requested local health governments to be aware of the respiratory illnesses in Wuhan using the existing surveillance system for serious infectious illnesses with unknown etiology . It has strengthened surveillance for undiagnosed severe acute respiratory illnesses . Quarantine and screening measures have been intensified for travelers from Wuhan at the points of entry . Furthermore , National Institute of Infectious Disease ( NIID ) established an in - house PCR assay for COVID - 19 .

Established hospital surveillance systems that are in place for influenza and other diseases in europe may be expanded for this purpose . [First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020, Euro Surveill, 2020-03-05]
With increasing numbers of cases in Europe , data from surveillance and investigations in the region can build on the evidence from countries in Asia experiencing more widespread transmission particularly on disease spectrum and the proportion of infections with severe outcome [ 22 ] . Understanding the infection - severity is critical to help plan for the impact on the healthcare system and the wider population . Serological studies are vital to understand the proportion of cases who are asymptomatic . Hospital - based surveillance could help estimate the incidence of severe cases and identify risk factors for severity and death . Established hospital surveillance systems that are in place for influenza and other diseases in Europe may be expanded for this purpose . In addition , a number of countries in Europe are adapting and , in some cases , already using existing sentinel primary care based surveillance systems for influenza to detect community transmission of SARS - CoV - 2 . This approach will be used globally to help identify evidence of widespread community transmission and , should the virus spread and containment no longer be deemed feasible , to monitor intensity of disease transmission , trends and its geographical spread .

Specifically , we assumed that 130 intensified surveillance led to a reduction in the mean period from symptom onset to 131 hospitalisation , [2019-20 Wuhan coronavirus outbreak: Intense surveillance is vital for preventing sustained transmission in new locations, unknown journal, 2020-01-25]
We then considered the reduction in the probability that an imported case leads to 129 sustained transmission if surveillance is more intense . Specifically , we assumed that 130 intensified surveillance led to a reduction in the mean period from symptom onset to 131 hospitalisation , governed by the parameter ( where = 0 corresponds to no 132 intensification of surveillance , and = 1 corresponds to an implausible scenario in which 133 symptomatic cases are hospitalised immediately ) . We found that , if surveillance is 134 intensified so that the mean time from symptom onset to hospitalisation is halved , the 135 probability that each imported case leads to sustained transmission is reduced to only 136 0 . 005 ( Fig 1D ) . The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 01 . 24 . 919159 doi : bioRxiv preprint Finally , we considered the combined effect if multiple cases arrive in a new location . In 139 that scenario , intense surveillance has the potential to significantly reduce the risk of 140 sustained transmission compared to weak surveillance . For = 0 . 5 , the probability that 141 any of 10 imported cases generate a substantial outbreak is only 0 . 049 ( Fig 2C ) . This to sustained transmission is approximately 0 . 37 ( Fig 1C ) . However , under a higher level 178 of surveillance , the risk of sustained outbreaks is substantially lower ( Fig 1D ) . This result 179 is particularly striking when multiple cases travel to a new location , either simultaneously 180 or in sequence ( Fig 2 ) . In that scenario , intensified surveillance is particularly important . The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 01 . 24 . 919159 doi : bioRxiv preprint collected , and patients may not have been primed to respond quickly to early symptoms . 195


Recruitment, support, and coordination of local expertise and capacity


They can be of timely support to process registrations of the death , permits for burial , etc . [International Committee of the Red Cross (ICRC): General Guidance for the Management of the Dead Related to COVID-19, Forensic Science International: Synergy, 2020-03-31]
Personnel from funeral homes have expertise in the handling and transportation of the dead , though usually without any legal obligation to respond to emergencies , can be considered useful support when capacities are overwhelmed . They can be of timely support to process registrations of the death , permits for burial , etc . They may also offer suitable body storage facilities at their funeral homes should the need arise .

Provide technical support through health promotion , training and training materials , guidelines , coordination , and communication . [The Role of the Global Health Development/Eastern Mediterranean Public Health Network and the Eastern Mediterranean Field Epidemiology Training Programs in Preparedness for COVID-19, JMIR Public Health Surveill, 2020-03-27]
The World Health Organization ( WHO ) declared the current COVID - 19 a public health emergency of international concern on January 30 , 2020 . Countries in the Eastern Mediterranean Region ( EMR ) have a high vulnerability and variable capacity to respond to outbreaks . Many of these countries addressed the need for increasing capacity in the areas of surveillance and rapid response to public health threats . Moreover , countries addressed the need for communication strategies that direct the public to actions for self - and community protection . This viewpoint article aims to highlight the contribution of the Global Health Development ( GHD ) / Eastern Mediterranean Public Health Network ( EMPHNET ) and the EMR ’ s Field Epidemiology Training Program ( FETPs ) to prepare for and respond to the current COVID - 19 threat . GHD / EMPHNET has the scientific expertise to contribute to elevating the level of country alert and preparedness in the EMR and to provide technical support through health promotion , training and training materials , guidelines , coordination , and communication . The FETPs are currently actively participating in surveillance and screening at the ports of entry , development of communication materials and guidelines , and sharing information to health professionals and the public . However , some countries remain ill - equipped , have poor diagnostic capacity , and are in need of further capacity development in response to public health threats . It is essential that GHD / EMPHNET and FETPs continue building the capacity to respond to COVID - 19 and intensify support for preparedness and response to public health emergencies .

We will make existing clinical trial support capacity and trial platforms available . [Global coalition to accelerate COVID-19 clinical research in resource-limited settings, The Lancet, 2020-04-02]
We propose to facilitate COVID - 19 research in LMIC settings by identifying and supporting established local investigators , local manufacturers , and clinical trial sites . We will make existing clinical trial support capacity and trial platforms available . This approach will ensure optimal data gathering , management , security , and analytical capacity , and will support adaptive designs if necessary and feasible . The platform will ensure independent data governance and a controlled and rapid data sharing mechanism . Finally , we will facilitate the establishment and operation of data and safety monitoring boards .

First , the italian decentralisation and fragmentation of health services seems to have restricted timely interventions and effectiveness , and stronger national coordination should be in place . [The Italian health system and the COVID-19 challenge, The Lancet Public Health, 2020-03-25]
In the most affected regions , the National Healthcare Service is close to collapse - the results of years of fragmentation and decades of finance cuts , privatisation , and deprivation of human and technical resources . The National Healthcare Service is regionally based , with local authorities responsible for the organisation and delivery of health services , leaving the Italian Government with a weak strategic leadership . Over the period 2010 - 19 , the National Healthcare Service suffered financial cuts of more than €37 billion , a progressive privatisation of health - care services . Public health expenditure as a proportion of gross domestic product was 6 · 6 % for the years 2018 - 20 and is forecast to fall to 6 · 4 % in 2022 . 2 The Lombardy region has the heaviest burden of the COVID - 19 pandemic , with ( as of March 19 , 2020 ) 19 884 total cases of the disease , 2168 deaths , and 1006 patients requiring advanced respiratory support . At its standard operational level , Lombardy has a capacity of 724 intensive care beds . 3 To tackle the medical equipment shortage , Italian Civil Protection undertook a fast - track public procurement to secure 3800 respiratory ventilators , an additional 30 million protective masks , and 67 000 severe acute respiratory syndrome coronavirus 2 ( SARS - CoV - 2 ) tests . 4 To avert the shortage of health workers produced by decades of inadequate recruitment practices , the Italian Government authorised regions to recruit 20 000 health workers , allocating €660 million for the purpose . 5 There are lessons to be learned from the current COVID - 19 pandemic . First , the Italian decentralisation and fragmentation of health services seems to have restricted timely interventions and effectiveness , and stronger national coordination should be in place . Second , health - care systems capacity and financing need to be more flexible to take into account exceptional emergencies . Third , in response to emergencies , solid partnerships between the private and public sector should be institutionalised . Finally , recruitment of human resources must be planned and financed with a long - term vision . Consistent management choices and a strong political commitment are needed to create a more sustainable system for the long run .

Core expertise in complex symptom management , decision - making in uncertainty , advocacy and education , and ensuring a compassionate response are essential , [Palliative Care Pandemic Pack: a Specialist Palliative Care Service response to planning the COVID-19 pandemic., Journal of Pain and Symptom Management, 2020-04-01]
Abstract : Specialist Palliative Care services ( SPCS ) have a vital role to play in the global COVID - 19 pandemic . Core expertise in complex symptom management , decision - making in uncertainty , advocacy and education , and ensuring a compassionate response are essential , and SPCS are well positioned to take a proactive approach in crisis management planning . SPCS resource capacity is likely to be overwhelmed , and consideration needs to be given to empowering and supporting high - quality primary palliative care in all care locations . Our local SPCS have developed a Palliative Care Pandemic Pack to disseminate succinct and specific information , guidance , and resources designed to enable the rapid up - skilling of non - specialist clinicians needing to provide palliative care . It may be a useful tool for our SPCS colleagues to adapt as we face this global challenge collaboratively .


How states might leverage universities and private laboratories for testing purposes?


No suitable answers found.


Which are the best ways for communications to public health officials and the public?


Standard practices for cold and flu - like illness are the best way to keep you and your community healthy . [The Active Role of a Blood Center in Outpacing the Transfusion Transmission of COVID-19, Transfusion Clinique et Biologique, 2020-03-31]
Standard practices for cold and flu - like illness are the best way to keep you and your community healthy . This includes home quarantine if feeling sick , meticulous hand hygiene either with disinfectants and or with soap and water , adherence to proper cough etiquette and avoiding touching your eyes , nose , or face after touching public surfaces .

Chinese nurses served the sick in the spirit of humanity and charity is the best way to promote the florence [The performance and professionalism of nurses in the fight against the new outbreak of COVID-19 epidemic is laudable, International Journal of Nursing Studies, 2020-03-19]
year of the nurse and midwife which is designated by WHO . Governments and the wider global health community should recognize the potential value of nursing and provide more opportunities to demonstrate the importance of nurses in health care system . In this latest epidemic and threat to those they care for , Chinese nurses showed their courage , wisdom and sense of responsibility amid the novel coronavirus outbreak and won the respect of the Chinese people . Chinese nurses served the sick in the spirit of humanity and charity is the best way to promote the Florence

They also provide timely psychological counselling and support to the community , to counter fears and panic . [Contributions and challenges of general practitioners in China fighting against the novel coronavirus crisis, Fam Med Community Health, 2020-03-23]
GPs are using instant messaging tools such as WeChat , community broadcasts and electronic display boards to disseminate information and mobilise local residents and volunteers in public health duties such as disinfection and sanitisation . GPs also help promulgate public health messages such as reminding the public to avoid social gatherings and visits , personal hygiene awareness , proper ways of using masks , hand washing and the importance of good household ventilation . They also provide timely psychological counselling and support to the community , to counter fears and panic .

The most accurate way of identifying covid - 19 is through the use of reverse transcription polymerase chain reaction or rt - pcr on samples . [Pooling RT-PCR or NGS samples has the potential to cost-effectively generate estimates of COVID-19 prevalence in resource limited environments, unknown journal, 2020-04-06]
Tracking the spread of COVID - 19 is essential to mounting an effective public health response , understanding the current impact of the virus , and ensuring that health systems are prepared . The most accurate way of identifying COVID - 19 is through the use of reverse transcription polymerase chain reaction or RT - PCR on samples . 4 However , facilities for RT - PCR are limited , even in high - income countries , and further , test costs are high both in terms of consumables and trained technicians . Delays in testing have slowed the public health response in Europe and the United States , and challenges to testing in low - and middle - income countries are even greater . Many countries in which transmission of COVID - 19 is occurring in the community are in the acceleration phase and data describing community prevalence of the virus is much needed .

As healthcare professionals with a high public availability , community pharmacists are likely to be many patients ' first option for health information . [Community pharmacists and communication in the time of COVID-19: Applying the health belief model, Research in Social and Administrative Pharmacy, 2020-03-26]
Healthcare professionals across all settings are now caring for and communicating with patients in a context of high uncertainty . The ultimate impact of the COVID - 19 outbreak will not be clear for a long time , but greater adherence to the lifestyle modifications suggested by healthcare and public health organizations will greatly delay the spread of the disease . This , in turn , will keep hospitals and clinics from being overwhelmed . For example , hospitals are overburdened in parts of Italy , which is projected to have approximately 80 % of its total ICU beds occupied by COVID - 19 patients before April 2020 . 6 As healthcare professionals with a high public availability , community pharmacists are likely to be many patients ' first option for health information . Patients may present to community pharmacies for refills or new prescriptions ; prescribers may cancel non - urgent appointments , which would make the community pharmacist a sole point of in - person contact with the healthcare system . It is therefore imperative that community pharmacists be equipped with knowledge and tools to communicate clearly and effectively with patients about ways to limit the impact of COVID - 19 .


What is the speed, accessibility, and accuracy of a point-of-care test?


No suitable answers found.


What is the speed, accessibility, and accuracy of rapid bed-side tests?


No suitable answers found.


Rapid design and execution of targeted surveillance experiments calling for all potential testers using PCR in a defined area to start testing and report to a specific entity


No suitable answers found.


Separation of assay development issues from instruments


Loop - mediated isothermal amplification rt pcr assays ( rt - lamp ) have also been developed for field use given their rapid results with high sensitivity profiles . [MERS coronavirus outbreak: Implications for emerging viral infections, Diagnostic Microbiology and Infectious Disease, 2019-03-31]
MERS - CoV RNA detection kits have been developed . For example , in a recent study 6 commercially available real - time RT - PCR MERS - CoV RNA detection kits based on upE and ORF1a were analyzed and clinically validated on nasopharyngeal swabs taken during the 2015 outbreak in Korea ( Kim et al . , 2016a ) . Results suggested that sensitivity and specificity of all of these assay systems would be sufficient for confirmation of MERS - CoV infection , although use of appropriate internal controls would be important in specimens where PCR inhibition is an issue ( Kim et al . , 2016a ) . In another recent study , a MERS - CoV r - gene ® 32 rRT - PCR assay 33 ( bioMérieux , France ) , targeting the S protein gene , was shown to have comparable accuracy to the WHO recommended in - house rRT - PCR assay targeting upE and ORF1a in a set of 130 respiratory samples ( Lee et al . , 2017 ) . Loop - mediated isothermal amplification RT PCR assays ( RT - LAMP ) have also been developed for field use given their rapid results with high sensitivity profiles . They require minimal instrumentation , thus they can also be used for portable point - of - care testing ( Bhadra et al . , 2015 ) . Other assays targeting small RNA molecules ( leader sequences ) have good sensitivity profiles ( Chan et al . , 2015b ) .

Rt - lamp assays in this study can detect as low as 100 copies of sars - cov - 2 rna . [Development of Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assays Targeting SARS-CoV-2, The Journal of Molecular Diagnostics, 2020-04-07]
Abstract Epidemics of Coronavirus Disease 2019 ( COVID - 19 ) now have more than 100 , 000 confirmed cases worldwide . Diagnosis of COVID - 19 is currently performed by RT - qPCR methods , but the capacity of RT - qPCR methods is limited by its requirement of high - level facilities and instruments . Here , we developed and evaluated RT - LAMP assays to detect genomic RNA of SARS - CoV - 2 , the causative virus of COVID - 19 . RT - LAMP assays in this study can detect as low as 100 copies of SARS - CoV - 2 RNA . Cross - reactivity of RT - LAMP assays to other human Coronaviruses was not observed . We also adapted a colorimetric detection method for our RT - LAMP assay so that the tests potentially performed in higher throughput .

Rt - lamp assays in this study can detect as low as 100 copies of sars - cov - 2 rna . [Development of Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assays Targeting SARS-CoV-2, unknown journal, 2020-03-12]
AbstractEpidemics of Coronavirus Disease 2019 ( COVID - 19 ) now have more than 100 , 000 confirmed cases worldwide . Diagnosis of COVID - 19 is currently performed by RT - qPCR methods , but the capacity of RT - qPCR methods is limited by its requirement of high - level facilities and instruments . Here , we developed and evaluated RT - LAMP assays to detect genomic RNA of SARS - CoV - 2 , the causative virus of COVID - 19 . RT - LAMP assays in this study can detect as low as 100 copies of SARS - CoV - 2 RNA . Cross - reactivity of RT - LAMP assays to other human Coronaviruses was not observed . We also adapted a colorimetric detection method for our RT - LAMP assay so that the tests potentially performed in higher throughput .

The assays developed and validated in this study could be instrumental for patient contact tracing , serosurveillance studies , as well as vaccine evaluation studies . [SARS-CoV-2 specific antibody responses in COVID-19 patients, unknown journal, 2020-03-20]
The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 18 . 20038059 doi : medRxiv preprint Overall , the assays developed and validated in this study could be instrumental for patient contact tracing , serosurveillance studies , as well as vaccine evaluation studies . However , since various studies will be carried out in different labs , it is crucial to calibrate and standardize assays developed by different labs using well defined standard references as a part of diagnostic assay validation . This is not only needed to reduce interassay variability , but to also harmonize the results obtained from different labs using various assays ( 14 ) . This is crucial for better comparison and interpertaion of results from different studies as well as evaluation of vaccine trials , allowing for uniform assessment of immunogenicity , efficacy and better understanding of correlates of immune protection ( 15 ) . Thus , setting up reference panels is a vital element in our preparedness approaches to emerging viruses . All rights reserved . No reuse allowed without permission .

Validated serologic assays are important for contact tracing , identifying the viral reservoir and epidemiological studies . [SARS-CoV-2 specific antibody responses in COVID-19 patients, unknown journal, 2020-03-20]
A new coronavirus , SARS - CoV - 2 , has recently emerged to cause a human pandemic . Whereas molecular diagnostic tests were rapidly developed , serologic assays are still lacking , yet urgently needed . Validated serologic assays are important for contact tracing , identifying the viral reservoir and epidemiological studies . Here , we developed serological assays for the detection of SARS - CoV - 2 neutralizing , spike - and nucleocapsid - specific antibodies . Using serum samples from patients with PCR - confirmed infections of SARS - CoV - 2 , other coronaviruses , or other respiratory pathogenic infections , we validated and tested various antigens in different in - house and commercial ELISAs . We demonstrate that most PCR - confirmed SARS - CoV - 2 infected individuals seroconverted , as revealed by sensitive and specific in - house ELISAs . We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two , with IgA showing higher sensitivity . Overall , the validated assays described here can be instrumental for the detection of SARS - CoV - 2 - specific antibodies for diagnostic , seroepidemiological and vaccine evaluation studies .


Which is the role of the private sector to help quickly migrate assays?


No suitable answers found.


What has been done to track the evolution of the virus?


Since the outbreak of covid - 19 , the government has conducted large - scale medical tracking and quarantine measures . [Prediction of the COVID-19 outbreak based on a realistic stochastic model, unknown journal, 2020-03-13]
Since the outbreak of COVID - 19 , the government has conducted large - scale medical tracking and quarantine measures . These non - negligible measures have a significant impact on the spread of COVID - 19 . The sub - states of E , A and IN in our model are able to reflect such tracking and quarantine measures . Moreover , we also take the latency between medical tracking and quarantine into account . What ' s more , it has been found that the proportion of asymptomatic infected population is considerable . This justifies the introduction of state A . Finally , for an exposed and symptomatic individual , this model describes the complete process from infection to recovery ( or death ) .

The covid19 - track app has been developed in rstudio using the shiny package ( 6 ) . [COVID19-Tracker: A shiny app to produce comprehensive data visualization for SARS-CoV-2 epidemic in Spain, unknown journal, 2020-04-06]
The COVID19 - Track app has been developed in RStudio using the Shiny package ( 6 ) .

How it compares with that of other respiratory diseases such influenza has public health implications . [Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020, Infect Dis Model, 2020-02-29]
Tracking the evolution of the transmission potential of COVID - 19 in different confined settings and how it compares with that of other respiratory diseases such influenza has public health implications . When outbreaks occur in confined settings , it is useful to investigate how the effective reproduction number changes as a result of interventions strategies such as the quarantine that the Japanese government imposed on travelers and crew members aboard the Diamond Princess Ship .

Once the therapy efficacy has been demonstrated , more useful prophylaxis should modify the evolution of this novel pandemic disease . [Any possible role of phosphodiesterase type 5 inhibitors in the treatment of severe COVID19 infections? A lesson from urology, Clinical Immunology, 2020-05-31]
Once the therapy efficacy has been demonstrated , more useful prophylaxis should modify the evolution of this novel pandemic disease .

Genomic epidemiology of emerging viruses has proven to be a useful tool for outbreak investigation and for tracking virus evolution and spread ( 6 , 7 ) . [A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage, unknown journal, 2020-03-30]
Genomic epidemiology of emerging viruses has proven to be a useful tool for outbreak investigation and for tracking virus evolution and spread ( 6 , 7 ) . During the Ebola virus disease epidemic of 2013 - 2016 in West Africa , genomic analyses established that the outbreak had a single zoonotic origin ( 8 ) , that two major viral lineages were circulating ( 9 ) , and that sexual transmission played a role in maintaining some transmission chains ( 10 ) . Viral genome sequencing also uncovered the route that Zika virus traveled from northern Brazil ( 11 ) to other regions , including Central America and Mexico ( 12 ) and the Caribbean and United States ( 13 ) . However , real - time genomic epidemiology data of COVID - 19 to inform public health interventions in California have been lacking .


Latency issues and when there is sufficient viral load to detect the pathogen


There was no obvious difference in viral loads across sex , age groups and disease severity . [Temporal dynamics in viral shedding and transmissibility of COVID-19, unknown journal, 2020-03-18]
A total of 414 throat swabs were collected from these 94 patients ( median = 4 swabs per patient ) , from the day of illness onset up to 32 days after onset . We detected high viral loads soon after illness onset , which gradually decreased towards the detection limit at about 21 days after onset ( Figure 2 ) . There was no obvious difference in viral loads across sex , age groups and disease severity .

At present , the accuracy of hcov detection is hampered by three difficulties . [Human coronavirus NL63: a clinically important virus?, Future Microbiol, 2011-03-02]
At present , the accuracy of HCoV detection is hampered by three difficulties . First , the suitability of the clinical samples examined : a recent study has demonstrated that there are differences between respiratory samples collected by nose / throat swabs , and those collected by nasopharyngeal aspiration , specifically regarding their usefulness in detecting and identifying respiratory pathogens [ 37 ] . The second problem is that diagnostic tests for HCoVs are not frequently used in the routine testing for respiratory viruses , which probably results in the percentage of HCoVs infections being greatly underestimated [ 38 ] . Lastly , over the years several molecular methods of variable sensitivity were used to determine the incidence of the virus [ 39 – 41 ] . Unless sensitive and specific nucleic acid amplification tests are used for the detection of CoVs ( including those infections with low viral load ) as part of a respiratory virus surveillance strategy , the CoVs will always be underdiagnosed [ 42 ] .

One child with hcov - nl63 upper respiratory tract infection had positive results of only the consensus primer pcr , so no viral load could be measured . [Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China, Clin Infect Dis, 2005-06-15]
If we excluded patients for whom the presence of other respiratory pathogens was documented , the HCoV - NL63 load in NPA specimens appears to correlate inversely with the time after onset of symptoms ( r = - 0 . 8 ) ( figure 2 ) . If patients were categorized into those with high viral load ( ⩾1000 copies / reaction ) and low viral load ( < 1000 copies / reaction ) , the mean times ( ±SD ) between onset of symptoms ( defined as onset of fever , if the child was febrile , or as onset of other respiratory symptoms , if the child was afebrile ) and specimen collection were 1 ± 0 . 6 and 2 . 25 ± 0 . 96 days , respectively ( P = . 02 ) . Neither peak temperature nor duration of fever was found to be significantly different between the 2 groups . Six of 10 patients with HCoV - NL63 as the sole identified pathogen had a high viral load , compared with 1 of 4 children infected with multiple viruses ( P not significant ) . One child with HCoV - NL63 upper respiratory tract infection had positive results of only the consensus primer PCR , so no viral load could be measured .

First , the clinical manifestation of covid - 19 ranges from the asymptomatic carrier 19 state to severe pneumonia ; [Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, 2020]
Although information on COVID - 19 has increased rapidly since the emergence of SARS - CoV - 2 , many issues remain unresolved . First , the clinical manifestation of COVID - 19 ranges from the asymptomatic carrier 19 state to severe pneumonia ; however , most early reports only showed the findings of SARS - CoV - 2 pneumonia , in which the ratio of male patients was much larger than that of female patients , there were no pediatric cases , and the mortality rate was high . [ 12 ] [ 13 ] [ 14 ] Subsequent to the publication of the studies of patients with only ARD or mild pneumonia , we found the ratio of male - to - female patients decreased , children or neonates could contract COVID - 19 , and the mortality rate declined compared to that of previous reports . 8 , 11 However , whether children were less susceptible to SARS - CoV - 2 , or their presentation was mostly asymptomatic or difficult to detect , remains unclear . 49 In addition , most studies , especially those with a large patient population , were conducted in China , and the study of asymptomatic carriers was limited . More studies are needed to clarify the epidemiologic characteristics of COVID - 19 and to identify the risk and prognostic factors of patients infected with SARS - CoV - 2 . Second , Zou et al . reported that the viral load detected in asymptomatic patients was similar to that found in symptomatic patients ; however , the viral loads from patients with severe diseases were higher than those in patients with mild - to - moderate presentations . Moreover , higher viral loads were detected in the nose than in the throat . 50 As there is a concern of virus spread due to severe cough 20 induced by performing a throat swab , nasal swab may be a relatively safe and sensitive alternative to collect the respiratory specimen of patients with COVID - 19 . However , this study involved a population of only 18 patients , including one asymptomatic patient . 49 In addition , every test has its own limitation and sensitivity / specificity ; however , the studies investigating the


What is needed in terms of biological and environmental sampling?


No suitable answers found.


Use of diagnostics such as host response markers (e.g., cytokines) to detect early disease or predict severe disease progression


Previous study showed that the mulbsta score can early warn the mortality of viral pneumonia , which included lymphopenia and multilobe infiltration . [Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics, unknown journal, 2020-02-23]
the role of CT to predict disease progression in patients with NCP . Previous study showed that the MuLBSTA score can early warn the mortality of viral pneumonia , which included lymphopenia and multilobe infiltration . 22 Our findings were consistent with theirs but more quantitatively in terms of imaging evaluation of lung involvement . Like SARS and MERS , some NCP patients progressed rapidly at about 10 - 14 days after onset likely dues to the cytokine storm in the body as evidenced by increased plasma proinflammatory cytokines . 11 , 23 Our results further revealed the significant association between inflammatory markers and CT characteristics , especially for C - reactive protein and CT severity score , which indicated the potential value of CT to estimate pulmonary inflammation and lung damage . Furthermore , the predictive significance of NLR and CT severity score was confirmed only in nonimported patients outside Wuhan . Among the imported patients from Wuhan , the elder had higher risk to develop severe illness . However , the reason for this discrepancy between imported and nonimported patients remains to be elucidated .

Saa is a non - specific acute phase protein mainly produced by cytokines il - 1β , il - 6 and tnf - α in liver cells . [SAA is a biomarker to distinguish the severity and prognosis of Coronavirus Disease 2019 (COVID-19), Journal of Infection, 2020-04-08]
Inflammatory factors , such as SAA , CRP , L , PCT , WBC , and PLT are frequently used to predict , diagnose , and evaluate many inflammatory diseases . SAA is a non - specific acute phase protein mainly produced by cytokines IL - 1β , IL - 6 and TNF - α in liver cells . As a marker of inflammation , its clinical value is obtaining more attention recently [ 10 ] [ 11 ] [ 12 ] . Studies report that patients with severe acute respiratory syndrome had significantly increased level of SAA , suggesting SAA could be used as a biomarker to monitor the progression of respiratory diseases 13 . SAA is able to promote inflammatory response through activating chemokine and inducing chemotaxis even at a very low concentration 14 15 SAA / L and elevated L had improved clinical conditions . In addition , the results showed that SAA levels continued to increase in exacerbating and deceased patients , whereas in patients who were discharged and well recovered , SAA fell below 3mg / L . The trend could be described as that patients with progressively decreased SAA are more likely to have a better prognosis than the patients who have continuously high level of SAA , suggesting a significant correlation between SAA dynamic change and prognosis . This phenomenon may be related to the activation of body ' s inflammation response , which stimulates liver cells to produce a large amount of SAA 20 21 .

This model can therefore be used in current pandemic regions to identify patients who are at risk of severe disease at an early enough stage to initialize intensive supportive treatment [Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19, unknown journal, 2020-03-30]
The copyright holder for this preprint . https : / / doi . org / 10 . 1101 / 2020 . 03 . 28 . 20045997 doi : medRxiv preprint hospitals immediately after a positive diagnostic test . Self - referred patients are more likely to have severe symptoms that cause them to seek emergency medical help . Likewise , other hospitals are more likely to test patients who have more pronounced symptoms , thus creating an inherent bias in the patient sample . Therefore , the cohort may not accurately represent patients with mild or asymptomatic COVID - 19 . These results need to be further validated with patients who are hospitalized for different severities of illness . In conclusion , traditional early warning scores and organ injury markers do not help to predict severity and mortality in patients with COVID - 19 . Here , we have developed and validated a clinical prediction model using readily available clinical markers which is able to accurately predict mortality in people with COVID - 19 . This model can therefore be used in current pandemic regions to identify patients who are at risk of severe disease at an early enough stage to initialize intensive supportive treatment and to guide discussions between clinicians , patients and families . It has the potential to be used throughout the world following additional validation . CC - BY - NC - ND 4 . 0 International license It is made available under a is the author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

First , it is better to obtain the outcomes and more detailed therapeutic responses in a cohort study of patients with covid - 19 with gi symptoms . [Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms, Gut, 2020-03-24]
This study has several limitations . First , it is better to obtain the outcomes and more detailed therapeutic responses in a cohort study of patients with COVID - 19 with GI symptoms . Second , although the risk factors for the severe / critical type of COVID - 19 were identified according to patient data on admission , there is still a lack of a predictive model for disease progression . Third , cytokine storm is common in coronavirus28 and reported in a previous SARS - CoV - 2 study5 ; thus , it would be better if we could also detect cytokine changes in this study . Fourth , it will have more clinical relevance to propose an effective strategy for identifying patients with COVID - 19 with GI symptoms who lack the typical symptoms such as fever and cough in the early stage . According to our experience , we should pay more attention to exposure history and family clustering during the screening process . Fifth , it would be meaningful to investigate the correlation between the viral genome and GI symptoms . Finally , since over 50 % of SARS - CoV - 2 was detected in the faeces according to one study , 29 the prevalence of viral RNA from faeces samples in patients with GI symptoms should be compared with those in patients without GI symptoms in the future . Moreover , because of the relatively low detection rate for virus in the stool ( three of nine patients with COVID - 19 positive in our hospital ) and rare stool samples were re - tested for the virus in patients after their recovery in this study , it is difficult to evaluate the implications of faecal - oral transmission , so this needs further investigation .

Development of serological assays would be largely beneficial to detect such types of infection at the population level . [Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study, Chinese medical journal, 2020]
for example , camel is suspected as the intermediate host of MERS - CoV , whereas the palm civet may have contributed to the interspecies transmission of SARS - CoV to humans . [ 25 , 26 ] Bat CoVs may evolve to adapt to using humans as a host during their circulation in a mammalian host , thereby enabling them to effectively infect humans . [ 26 ] However , two of our patients did not have a history of exposure to the seafood market . Therefore , further investigation will be needed to determine the potential of multiple infection sources responsible for this uncommon outbreak . One of the most striking and concerning features of this virus is its ability to cause severe respiratory syndrome . The disease progressed rapidly with a major presentation of lower respiratory pathology . Notably , no obvious upper respiratory tract symptoms such as a sore throat and rhinorrhea were present in these patients . Therefore , further exploration is needed on the distribution of the viral receptor in the organs to potentially account for pathogenesis development . In addition , the possibility of unrecognized mild infections or subclinical infections should be clarified , as identification of such infections is critical to control spread of the disease . Development of serological assays would be largely beneficial to detect such types of infection at the population level .


Policies and protocols for screening and testing


Testing followed a uniform national protocol based on corman et al . [ 3 ] , that was rolled out by two central laboratories in the netherlands . [Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands, March 2020, Euro Surveill, 2020-03-26]
Seven hospitals in the province of Noord - Brabant were approached in the afternoon of Friday 6 March and the morning of Saturday 7 March 2020 with the request to test HCW through Sunday 8 March . Two hospitals indicated that they had already started systematic sampling of HCW as part of their hospital policy . Four hospitals had no systematic sampling policy for HCW but were testing all patients that presented at the emergency ward with respiratory complaints . In addition , two hospitals just outside Noord - Brabant with a large proportion of staff residing in the affected province participated in the assessment ( Figure ) . The participating hospitals were asked to offer screening to HCW and share the results of the testing by 14 : 00 on Monday 9 March 2020 . Upper respiratory tract specimens ( throat and / or nasopharyngeal swab ) were collected from HCW with mild respiratory complaints and without epidemiological link . Testing followed a uniform national protocol based on Corman et al . [ 3 ] , that was rolled out by two central laboratories in the Netherlands . The testing was done either locally or in one of these two central laboratories .

Testing admitted patients only , various rates of community testing of symptomatic cases and active contact - tracing and screening . [Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality., unknown journal, 2020-04-06]
There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid - 19 . A number of explanations have been suggested , but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes , admission policies and other variables . An individual patient simulation model was developed to address this question . Parameters and sensitivity analysis based upon recent international data sources for Covid - 19 and results were averaged over 100 iterations for a simulated cohort of over 500 , 000 patients . Different testing regimes for Covid - 19 were considered ; testing admitted patients only , various rates of community testing of symptomatic cases and active contact - tracing and screening . In the base case analysis , apparent mortality ranged from 10 . 5 % under a policy of testing only admitted patients to 0 . 4 % with intensive contact tracing and community testing . These findings were sensitive to assumptions regarding admission rates and the rate of spread , with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18 % under some circumstances . Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality . Whilst differences in mortality due to health service and demographic factors cannot be excluded , the current international differences in reported mortality are all consistent with differences in practice regarding screening , community testing and admission policies .

By protocol , those in the contactbased group were tested for sars - cov - 2 infection regardless of symptoms , [Epidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts, unknown journal, 2020-03-04]
We define symptom - based surveillance to include symptomatic screening at airport and train stations , community fever monitoring , home observation of recent travellers to Hubei , and testing of hospital patients . Contact - based surveillance is the identification of cases through monitoring and testing of close contacts of confirmed cases . By protocol , those in the contactbased group were tested for SARS - CoV - 2 infection regardless of symptoms , while those in the other categories were tested only if they showed signs or symptoms of disease .

It is proposed that the n gene rt - pcr can be used as a screening assay while the orf1b assay acts as a confirmatory test . [Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review, Journal of Clinical Medicine, 2020]
The Hong Kong University used two monoplex assays which were reactive with coronaviruses under the subgenus Sarbecovirus ( consisting of 2019 - nCoV , SARS - CoV and SARS - like coronavirus ) . Viral RNA extracted from SARS - CoV can be used as the positive control for the suggested protocol assuming that SARS has been eradicated . It is proposed that the N gene RT - PCR can be used as a screening assay while the Orf1b assay acts as a confirmatory test . However , this protocol has only been evaluated with a panel of controls with the only positive control SARS - CoV RNA . Synthetic oligonucleotide positive control or 2019 - nCoV have yet to be tested [ 106 ] .

Testing admitted patients only , various rates of community testing of symptomatic cases and active contacttracing and screening . [Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality., unknown journal, 2020-04-06]
policies and other variables . An individual patient simulation model was developed to address this question . Parameters and sensitivity analysis based upon recent international data sources for Covid - 19 and results were averaged over 100 iterations for a simulated cohort of over 500 , 000 patients . Different testing regimes for Covid - 19 were considered ; testing admitted patients only , various rates of community testing of symptomatic cases and active contacttracing and screening .


Policies to mitigate the effects on supplies associated with mass testing, including swabs and reagents


No suitable answers found.


Technology roadmap for diagnostics


The next generation sequencing ( ngs ) and electron microscope technology play a role in the early diagnosis , [A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version), Military Medical Research, 2020]
The next generation sequencing ( NGS ) and electron microscope technology play a role in the early diagnosis , but their diagnostic values have been weakened by the discovery of specific nucleic acid detection technology . In addition , NGS detection can tell whether the pathogen has mutated or not .

It is possible for scientists and terrorists to be able to apply the same technique to synthesize more complex viruses [ 3 ] 27 , [Prudently conduct the engineering and synthesis of the SARS-CoV-2 virus, Synthetic and Systems Biotechnology, 2020-04-02]
The chemically synthesized SARS - CoV - 2 virus is a part this type of technology , with the benefits mainly including the acceleration of therapeutics and vaccine development , and the protection of human life and health from the virus . However , the risks include the following : ( 1 ) Owing to the fact that SARS - CoV - 2 is a virus with high transmissibility and susceptibility , there exists a biosecurity risk wherein bioterrorists could exploit this characteristic , with potentially hazardous consequences . ( 2 ) By publishing the technology roadmap , it is possible for scientists and terrorists to be able to apply the same technique to synthesize more complex viruses [ 3 ] 27 , or to develop a " super virus " with extremely high infectivity , virulence , or vaccine - resistant . Currently , internet has made it easier to order the related biological materials that could potentially be used to synthesize bioweapons . ( 3 ) Accidental leakage of synthesized virus particles from the laboratory increases biosafety risks , threatening the safety of humans as well as that of the ecological environment .

To develop tools to help control the outbreak , reduce deaths , and minimise damage to economies and the social fabric of communities . [What are the risks of COVID-19 infection in pregnant women?, The Lancet, 2020-03-13]
Fortunately , scientists around the world are working at breakneck speed to figure out how to detect , treat , and control the new coronavirus . On Feb 10 - 12 , 2020 , WHO brought almost 400 scientists together for a research and innovation forum on the new coronavirus . 4 The meeting covered the topics of diagnostics , vaccines , and therapeutics for COVID19 , alongside questions of how to best integrate social science into the response and protection of healthcare workers from infection . The forum generated a research roadmap , due to be published at the end of February , 2020 , to develop tools to help control the outbreak , reduce deaths , and minimise damage to economies and the social fabric of communities .

There are still no rapid , handheld , low - cost , easy - to - use and integrated solutions for the testing of infectious diseases [Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens, unknown journal, 2020-03-25]
Despite the advancement of diagnostic technologies targeting nucleic acids ( NA ) , there are still no rapid , handheld , low - cost , easy - to - use and integrated solutions for the testing of infectious diseases at the Point - of - Need ( PoN ) . This is unfortunately the case for pathogens infecting humans , animals or even plants . This large gap in the diagnostic workflow hampers attempts to contain infectious pathogens from spreading by rapid and early detection . This technological gap has become , once again , evident with the spread of COVID - 19 , the diagnosis of which continues to depend heavily on centralized laboratories with specialized personnel and facilities , which in turn slows down testing and delays treatment .

Over the last decade , advanced sequencing technologies have greatly improved our capacity to detect the causative agents of infectious diseases in clinical samples . [Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV, Journal of Infection, 2020-04-30]
We read with interest recent articles in this journal regarding the utility of next - generation sequencing for the diagnosis bacterial meningitis . 1 , 2 Bacterial meningitis causes substantial morbidity and mortality worldwide . 3 Rapid identification of the microorganisms is essential for early initiation of appropriate antimicrobial therapy , thereby improving clinical outcome . Yet routine diagnostic methods fail to identify the bacteria in the majority of patients . Over the last decade , advanced sequencing technologies have greatly improved our capacity to detect the causative agents of infectious diseases in clinical samples . 4 , 5 Of these , the single molecule real - time sequencing developed by Oxford Nanopore Technologies ( ONT ) is a promising tool for diagnostic setting because of its short turnaround time .


Which are the barriers to developing and scaling up new diagnostic tests?


These tools may not be readily available to implement in many places , and they often require higher expertise or are less accurate than regular pcr tests commonly used . [Efficient and Practical Sample Pooling High-Throughput PCR Diagnosis of COVID-19, unknown journal, 2020-04-07]
The need to scale up diagnostic assays for many thousands of patient samples has been addressed with cutting edge molecular tools such as RNA - Seq with multiplex barcoding 1 and serological test might soon be able to test for the immune status of patients . However , these tools may not be readily available to implement in many places , and they often require higher expertise or are less accurate than regular PCR tests commonly used . A simpler way to scale up diagnostic assays can be found in the method of High - Throughput PCR via sample pooling , used in genetic research as a practical way to reduce the cost of large - scale studies 4 .

This delayed the ability to scale - up testing capacity required for healthcare and population screening . [Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic, unknown journal, 2020-04-08]
The COVID - 19 pandemic placed severe constraints on the availability of laboratory equipment , reagents and consumables required for molecular diagnostics in the UK and Europe . This delayed the ability to scale - up testing capacity required for healthcare and population screening .

Early detection prompts public health actions to prevent and control the spread of pathogens . [Analytical sensitivity and efficiency comparisons of SARS-COV-2 qRT-PCR assays, unknown journal, 2020-04-01]
Accurate diagnostic assays and large - scale testing are critical for mitigating outbreaks of infectious diseases . Early detection prompts public health actions to prevent and control the spread of pathogens . This has been exemplified by the novel coronavirus , known as SARS - CoV - 2 , which was first identified as the cause of an outbreak of pneumonia in Wuhan , China , in December 2019 , and rapidly spread around the world 1 - 3 . The first SARS - CoV - 2 genome sequence was critical for the development of diagnostics 2 , which led to several molecular assays being developed to detect COVID - 19 cases [ 4 ] [ 5 ] [ 6 ] [ 7 ] . The World Health Organization ( WHO ) currently lists seven molecular assays ( i . e . qRT - PCR ) to diagnose COVID - 19 8 ; however , it is not clear to many laboratories or public health agencies which assay they should adopt .

After brief preparation , clinical samples can be loaded directly into the device ; required hands - on time and manual steps are reduced by up to 60 % [Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system, Euro Surveill, 2020-03-05]
Automated solutions for molecular diagnostics can help handle large numbers of samples and can be scaled to keep pace with fluctuating demand [ 10 - 12 ] . The system used in this study fully automates nucleic acid extraction , purification , amplification and detection . We , among others , have previously demonstrated that laboratory - developed tests can be adapted for fully automated PCR platforms such as the cobas 6800 system [ 6 , 13 ] . After brief preparation , clinical samples can be loaded directly into the device ; required hands - on time and manual steps are reduced by up to 60 % ( manual steps reduced from 33 to 14 , hands - on time reduced from 74 min to 14 min ) compared with conventional workflows which usually involve automated extraction and PCR performed as separate procedures [ 13 ] . The inclusion of a full - process control for each reaction further facilitates the handling of results , allowing interpretation by personnel not familiar with RT - PCR diagnostics .

Practitioners have the skills to deliver the recommended care , [Guidelines for preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid review of clinical practice guidelines, unknown journal, 2020-03-26]
☐Purpose and intent of the external review ( e . g . , to improve quality , gather feedback on draft recommendations , assess applicability and feasibility , disseminate evidence ) ☐Methods taken to undertake the external review ( e . g . , rating scale , open - ended questions ) ☐Description of the external reviewers ( e . g . , number , type of reviewers , affiliations ) ☐Outcomes / information gathered from the external review ( e . g . , summary of key findings ) ☐How the information gathered was used to inform the guideline development process and / or formation of the recommendations ( e . g . , guideline panel considered results of ☐Types of facilitators and barriers that were considered ☐Methods by which information regarding the facilitators and barriers to implementing recommendations were sought ( e . g . , feedback from key stakeholders , pilot testing of guidelines before widespread implementation ) ☐Information / description of the types of facilitators and barriers that emerged from the inquiry ( e . g . , practitioners have the skills to deliver the recommended care , sufficient equipment is not available to ensure all eligible members of the population receive mammography ) ☐How the information influenced the guideline development process and / or formation of the recommendations NR 19 . IMPLEMENTATION ADVICE / TOOLS Provide advice and / or tools on how the recommendations can be applied in practice .


How future coalition and accelerator models could provide critical funding for diagnostics?


No suitable answers found.


How future coalition and accelerator models could provide critical funding for opportunities for a streamlined regulatory environment?


No suitable answers found.


New platforms and technology (CRISPR) to improve response times


Compared the diagnostic performance among 79 three different technological platforms : metagenomic sequencing , rt - pcr and crispr . [Development and Evaluation of A CRISPR-based Diagnostic For 2019-novel Coronavirus, unknown journal, 2020-02-23]
The copyright holder for this preprint ( which was not peer - reviewed ) is Here , to address this question and the expanding clinical needs , we developed CRISPR - nCoV , 78 a rapid assay for 2019 - nCoV detection , and compared the diagnostic performance among 79 three different technological platforms : metagenomic sequencing , RT - PCR and CRISPR . To the author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

The diagnostic performance of crispr - ncov was assessed and compared across three technology platforms ( mngs , rt - pcr and crispr ) . [Development and Evaluation of A CRISPR-based Diagnostic For 2019-novel Coronavirus, unknown journal, 2020-02-23]
Background : The recent outbreak of infections by the 2019 novel coronavirus ( 2019 - nCoV ) , the third zoonotic CoV has raised great public health concern . The demand for rapid and accurate diagnosis of this novel pathogen brought significant clinical and technological challenges . Currently , metagenomic next - generation sequencing ( mNGS ) and reverse - transcription PCR ( RT - PCR ) are the most widely used molecular diagnostics . Methods : 2019 - nCoV infections were confirmed in 52 specimens by mNGS . Genomic information was analyzed and used for the design and development of an isothermal , CRISPR - based diagnostic for this novel virus . The diagnostic performance of CRISPR - nCoV was assessed and compared across three technology platforms ( mNGS , RT - PCR and CRISPR ) . Results : 2019 - nCoVs sequenced in our study were conserved with the Wuhan strain , and shared certain genetic similarity with SARS - CoV . A high degree of variation in the level of viral RNA was observed in clinical specimens . CRISPR - nCoV demonstrated a near single - copy sensitivity and great clinical sensitivity with a shorter turn - around time than RT - PCR . Conclusion : CRISPR - nCoV presents as a promising diagnostic option for the emerging pathogen .

Upon the design of aiod - crispr , dual crrnas are introduced to improve the sensitivity and high - concentration . [All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus, unknown journal, 2020-03-21]
In this study , we describe a new CRISPR - Cas12a reaction , AIOD - CRISPR in which all components are incubated in a single reaction system to rapidly , highly sensitively and specifically detect nucleic acids without separate preamplification steps . Upon the design of AIOD - CRISPR , dual crRNAs are introduced to improve the sensitivity and high - concentration . CC - BY - NC - ND 4 . 0 International license author / funder . It is made available under a The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 19 . 998724 doi : bioRxiv preprint ssDNA - FQ reporters are added to strengthen the detection signals . In addition to real - time detection , AIOD - CRISPR assay is also beneficial for point - of - care detection because its detection results can be visually judged based on the fluorescence and color change of reaction solutions . As proof - of - concept assays , AIOD - CRISPR has been successfully developed for SARS - CoV - 2 and HIV - 1 detection .

Collateral cleavage of ssdna - fq reporter by the cas12a is triggered by the binding of crrna to target sites . [All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus, unknown journal, 2020-03-21]
Since RPA amplification reaction is initiated after adding MgOAc , 22 we are interested in knowing if the nucleic acid amplification was initiated at room temperature during sample preparation in our AIOD - CRISPR assay system . We prepared two AIOD - CRISPR solutions ( one positive and one negative ) and allowed them to remain at room temperature for 10 min . As shown in Figure S1 , no significant fluorescence change between positive and negative samples was observed in the AIOD - CRISPR solutions at room temperature . On the contrary , there was an obvious fluorescence increasing after just one - min incubation at 37°C ( Figure S1 ) . The fluorescence signal was eventually saturated at 15 min after incubated at 37°C . Therefore , our AIOD - CRISPR assay system is mainly triggered only after reaction temperature arrives at 37°C . Optimization of AIOD - CRISPR assay . Collateral cleavage of ssDNA - FQ reporter by the Cas12a is triggered by the binding of crRNA to target sites . 13 , 14 Thus , we hypothesized that higher binding opportunities could increase the collateral cleavage activity and eventually improve the detection sensitivity for AIOD - CRISPR . To prove this , we introduced a pair of crRNAs to recognize the corresponding target sites . A pUCIDT - AMP plasmid containing 300 bp HIV - 1 p24 gene cDNA ( p24 plasmid ) was used as the target and three different designs for primers and crRNAs were investigated ( Figure 2A ) . As shown in Figure 2B , AIOD - CRISPR with dual crRNAs ( crRNA1 + crRNA2 ) shows similar fluorescence curve as that with crRNA2 , but was much better than using crRNA1 in real - time detection . Doubling the amount of crRNA1 or crRNA2 actually didn ' t benefit the detection efficiency . On detection sensitivity , Figure 2C shows that AIOD - CRISPR with dual crRNAs was able to detect as low as 1 . 2 copies of the p24 plasmid templates within 40 min , while AIOD - CRISPR with single crRNA2 doesn ' t detect it . Thus , introducing dual crRNAs is beneficial to improve the sensitivity of AIOD - CRISPR assay .

Provide reasonable data - based warnings and risk ratings , and reduce the exposure risk of susceptible people . [Design and preliminary application of regional control and prevention auxiliary information system under the attack of COVID-19 infectious disease, Chinese Journal of Medical Science Research Management, 2020]
Objective To propose the concept of a novel regional control and prevention ( RCP ) system for the outbreak of COVID - 19 infectious disease , design an emergency epidemic prevention information system based on the existing network architecture and information system in the region , and a remote intelligent medical consultation and remote office platform , research and develop the technology of risk assessment and early warning for people in the region , and improve the regions & rsquo ; prevention and control ability facing emergency of major infectious diseases . Methods Taking colleges , affiliated ( teaching ) hospitals , and cloud applications as typical RCP regional units , the existing local area network interaction methods between the cloud and universities and affiliated ( teaching ) hospitals are established to realize remote work in the network environment , remote medical imaging , psychological and ethical consultation and interaction ; applying multi - agent propagation model based on complex network , combining Global Positioning System ( GPS ) , Radio Frequency Identification ( RFID ) , and electronic fence technology , to realize the risk classification and early warning of units and personnel in the area . Results In the RCP , a system architecture combining campus network , affiliated ( teaching ) hospital intranet , and the Internet is used . Dynamic connection is made using distributed technology and cloud storage . The data buffer mechanism of the intermediary database in the network realized telemedicine consultation and telecommuting . Relying on the platform , multi - agent propagation model based on complex network and cellular automaton model are used to realize the score and early warning of population exposure risk in the region by using GPS , RFID and electronic fence technology . Conclusions In the epidemic phase of major infectious diseases , the construction of RCP can improve the response speed of wartime epidemic prevention , provide reasonable data - based warnings and risk ratings , and reduce the exposure risk of susceptible people . The design and development of RCP is a systematic project that needs to combine regional structural and functional characteristics , and the foundation of the early informatization work in the region and the level of the emergency development team determine the development progress , maintenance , and actual application effects . It is recommended to establish a peacetime and wartime combined RCP mode and incorporate it into the government ' s disease control system to improve the national and regional level of prevention and control of major infectious diseases .


New platforms and technology to employ more holistic approaches


Quarantine must be employed with care and compassion . [Lessons from Severe Acute Respiratory Syndrome (SARS): Implications for Infection Control, Archives of Medical Research, 2005-12-31]
There are many lessons from SARS that apply generally to all epidemics . We would summarize by emphasizing the following : the importance of clinicians recognizing a new syndrome , the need for individuals and countries to report epidemics , the role of information technology to communicate , and the key role for the WHO . Quarantine must be employed with care and compassion . The obligation to be interested in the health of all people , the use of assiduous infection control and the need for psychological support of health care workers must be integral components of our approach to SARS and future epidemics .

These challenges can be overcome , however , through an investment of time and effort by staff providers with familiarity with these techniques . [Using Technology to Maintain the Education of Residents During the COVID-19 Pandemic, Journal of Surgical Education, 2020-04-03]
There are a number of limitations to this platform , such as some faculty struggling with novel technology , participants with poor bandwidth connections , and some difficulty reviewing imaging . These challenges can be overcome , however , through an investment of time and effort by staff providers with familiarity with these techniques . Specifically , for imaging , we have had success with recording short video while scrolling through cross - sectional imaging ( making sure to avoid any patient identifiers in the recording ) , then playing this video on a shared display . One approach to mitigating the limitations on technology - savvy staff is to conduct such conferences at a multi - institutional or even regional level with rotating faculty among more than 1 program . This will have the added benefit of increasing the pool of faculty who will invest in these platforms , and adding the unique advantage of learning what other programs are doing . We are actively pursuing this type of experience with nearby institutions .

The platform allows the user to identify and further examine the documents and textual fragments from which the knowledge synthesis signals are derived using the documents and signals applications . [Knowledge synthesis from 100 million biomedical documents augments the deep expression profiling of coronavirus receptors, unknown journal, 2020-03-29]
The platform further leverages statistical inference to calculate " enrichments " based on structured data , thus enabling real - time triangulation of signals from the unstructured biomedical knowledge graph various other structured databases ( e . g . curated ontologies , RNA - sequencing datasets , human genetic associations , protein - protein interactions ) . This facilitates unbiased hypothesisfree learning and faster pattern recognition , and it allows users to more holistically determine the veracity of concept associations . Finally , the platform allows the user to identify and further examine the documents and textual fragments from which the knowledge synthesis signals are derived using the Documents and Signals applications .

In practical applications , several methods are usually combined to avoid the drawbacks of using single method as much as possible . [Recent advances and perspectives of nucleic acid detection for coronavirus, Journal of Pharmaceutical Analysis, 2020-03-01]
To date , considerable efforts have been made to improve the detection of coronavirus and a variety of improved or new approaches have been developed . In practical applications , several methods are usually combined to avoid the drawbacks of using single method as much as possible . In short , with the rapid development of new technologies and methods , we believe that there will be more excellent and efficient detection methods developed in the future , which would provide scientists / clinicians with more choices . At the same time , only by balancing the advantages and disadvantages of various detection assays according to specific purposes can we obtain the most economical and optimal option .

Integrates physicians , psychiatrists , psychologists and social workers into internet platforms to carry out psychological intervention to patients , their families and medical staff . [Recommended psychological crisis intervention response to the 2019 novel coronavirus pneumonia outbreak in China: a model of West China Hospital, Precis Clin Med, 2020-02-18]
The novel coronavirus pneumonia ( COVID - 19 ) epidemic has brought serious social psychological impact to the Chinese people , especially those quarantined and thus with limited access to face - to - face communication and traditional social psychological interventions . To better deal with the urgent psychological problems of people involved in the COVID - 19 epidemic , we developed a new psychological crisis intervention model by utilizing internet technology . This new model , one of West China Hospital , integrates physicians , psychiatrists , psychologists and social workers into Internet platforms to carry out psychological intervention to patients , their families and medical staff . We hope this model will make a sound basis for developing a more comprehensive psychological crisis intervention response system that is applicable for urgent social and psychological problems .


Coupling genomics and diagnostic testing on a large scale


The need to scale up diagnostic assays for many thousands of patient samples has been addressed with cutting edge molecular tools [Efficient and Practical Sample Pooling High-Throughput PCR Diagnosis of COVID-19, unknown journal, 2020-04-07]
The need to scale up diagnostic assays for many thousands of patient samples has been addressed with cutting edge molecular tools such as RNA - Seq with multiplex barcoding 1 and serological test might soon be able to test for the immune status of patients . However , these tools may not be readily available to implement in many places , and they often require higher expertise or are less accurate than regular PCR tests commonly used . A simpler way to scale up diagnostic assays can be found in the method of High - Throughput PCR via sample pooling , used in genetic research as a practical way to reduce the cost of large - scale studies 4 .

Accurate diagnostic assays and large - scale testing are critical for mitigating outbreaks of infectious diseases . [Analytical sensitivity and efficiency comparisons of SARS-COV-2 qRT-PCR assays, unknown journal, 2020-04-01]
Accurate diagnostic assays and large - scale testing are critical for mitigating outbreaks of infectious diseases . Early detection prompts public health actions to prevent and control the spread of pathogens . This has been exemplified by the novel coronavirus , known as SARS - CoV - 2 , which was first identified as the cause of an outbreak of pneumonia in Wuhan , China , in December 2019 , and rapidly spread around the world 1 - 3 . The first SARS - CoV - 2 genome sequence was critical for the development of diagnostics 2 , which led to several molecular assays being developed to detect COVID - 19 cases [ 4 ] [ 5 ] [ 6 ] [ 7 ] . The World Health Organization ( WHO ) currently lists seven molecular assays ( i . e . qRT - PCR ) to diagnose COVID - 19 8 ; however , it is not clear to many laboratories or public health agencies which assay they should adopt .

This has led to significant effort to build large laboratories with existing research equipment to increase testing capacity , [Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic, unknown journal, 2020-04-08]
The standard molecular diagnostic test for this virus is a multistep process involving viral RNA extraction and real - time quantitative reverse transcriptase PCR ( qRT - PCR ) . Although many companies have produced PCR kits to amplify the viral RNA , RNA extraction at any scale in a diagnostic laboratory is performed on a limited number of automated platforms that require specific reagents and consumables . This has led to significant effort to build large laboratories with existing research equipment to increase testing capacity , and to extract RNA on more open platforms that enable non - specific reagents and plastics to be used .

1 . 6 million molecular diagnostic tests identified 1 , 388 sars - cov - 2 infections in guangdong province , china , [Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China, unknown journal, 2020-04-04]
Highlights : 1 ) 1 . 6 million molecular diagnostic tests identified 1 , 388 SARS - CoV - 2 infections in Guangdong Province , China , by 19th March 2020 ; 2 ) Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples . 3 ) Genomic analyses reveal multiple virus importations into Guangdong Province , resulting in genetically distinct clusters that require careful interpretation . 4 ) Large - scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong Summary : COVID - 19 is caused by the SARS - CoV - 2 coronavirus and was first reported in central China in December 2019 . Extensive molecular surveillance in Guangdong , China ' s most populous province , during early 2020 resulted in 1 , 388 reported RNA positive cases from 1 . 6 million tests . In order to understand the molecular epidemiology and genetic diversity of SARS - CoV - 2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches . Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong , although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic . Our results illustrate how the timing , size and duration of putative local transmission chains were constrained by national travel restrictions and by the province ' s large - scale intensive surveillance and intervention measures . Despite these successes , COVID - 19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing .

Here , we present two possible optimized pooling strategies for diagnostic sarscov - 2 testing on large scales , [Efficient and Practical Sample Pooling High-Throughput PCR Diagnosis of COVID-19, unknown journal, 2020-04-07]
Diagnostic assays using quantitative Polymerase Chain Reaction ( qPCR ) most commonly process patient samples one by one . While this is usually an effective and reliable method , the current efforts against the COVID - 19 pandemic demand more efficient measures . Diagnostic assays can be scaled up by the method of High - Throughput qPCR via sample pooling . Pooling , the action of combining multiple samples into one tube , is most effective when the chance of positive detection of the target , SARS - CoV - 2 RNA , is low . In such cases , large groups of samples can be conclusively classified as negative with a single test , with no need to individually test every sample . However , different frequencies of the target - product presence in the samples , require different pool / batch sizes for optimal results . Here , we present two possible optimized pooling strategies for diagnostic SARSCoV - 2 testing on large scales , each one better suited for a different range of target frequency . In the first , we employ a simple information - theoretic heuristic to derive a highly efficient re - pooling protocol : an estimate of the target frequency determines the initial pool size , and any subsequent pools found positive are re - pooled at half - size and tested again . In the range of very rare target ( < 0 . 05 ) , this approach can reduce the number of necessary tests dramatically . For example , this method achieves a reduction of a factor of 50 for a target frequency of 0 . 001 . The second method is a simpler approach of optimized one - time pooling followed by individual tests on positive pools . We show that this approach is just as efficient for moderate target - product frequencies ( 0 . 05 < 0 . 2 ) . For example , it reduces the number of tests needed by half if the frequency of positives samples is 0 . 07 . We show that both methods are comparable to the absolute upper - bound efficiency given by Shannon ' s source coding theorem . Our strategies require no investment at all , and they offer a significant reduction in the amount of equipment and time needed to test large numbers of samples . Both approaches are dynamic ; they can be easily implemented in different conditions with various infection rates and sample numbers . We compare our strategies to the naive way of testing and also to alternative matrix methods . Most importantly , we offer practical pooling instructions for laboratories that perform large scale qPCR assays to diagnose SARS - CoV - 2 viral particles .


What is needed for rapid sequencing and bioinformatics to target regions of the genome that will allow specificity for a particular variant?


Target these regions using crispr - cas13d for viral genome degradation and viral gene inhibition . [Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza, unknown journal, 2020-03-14]
In this work , we developed a Prophylactic Antiviral CRISPR in huMAN cells ( PAC - MAN ) strategy as a form of genetic intervention to target SARS - CoV - 2 , IAV , and potentially all sequenced coronaviruses . We created a bioinformatic pipeline to define conserved regions across the SARS - CoV - 2 genomes and target these regions using CRISPR - Cas13d for viral genome degradation and viral gene inhibition . At the time of paper submission , there is no widely available laboratory strains of SARS - CoV - 2 . Therefore , we tested our approach using synthesized fragments of SARS - CoV - 2 , as well as with live H1N1 IAV . We designed and screened a panel of crRNA pools targeting conserved viral regions and defined the most effective crRNAs . We demonstrated the ability of our approach to cleave SARS - CoV - 2 fragments and to reduce the replication of IAV in human lung epithelial cells . Our bioinformatics author / funder . All rights reserved . No reuse allowed without permission .

Detection of viral antigens and / or viral genomes is critical for rapid diagnosis of respiratory viral infections , followed by an appropriate treatment . [Differentiation between Human Coronaviruses NL63 and 229E Using a Novel Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay Based on Specific Monoclonal Antibodies, Clinical and Vaccine Immunology, 2010-11-17]
Detection of viral antigens and / or viral genomes is critical for rapid diagnosis of respiratory viral infections , followed by an appropriate treatment . Currently , reverse transcription - PCR is the major technique used for diagnosis of HCoV infection ( 2 , 12 , 16 ) . However , this method has some disadvantages , such as possible contamination , instability of the RNA samples , and the need for special equipment that in some cases , in particular , in undeveloped countries , is not available . Other rapid tests are needed in order to facilitate diagnosis . The antigen - capture ELISA using MAbs allows rapid diagnosis of viral infections , and it can be used as an alternative to PCR . On the basis of the low degree of homology among the amino acid sequences of the N proteins of different coronaviruses , together with the high immunogenicity of this protein , the N protein appeared to be a suitable antigenic marker for diagnosis of coronavirus infection . In the work reported here , we described the production and characterization of several species - specific MAbs against the N proteins of human coronaviruses NL63 and 229E and the subsequent development of a differential ELISA that allowed their detection .

Detection of viral antigens and / or viral genomes is critical for rapid diagnosis of respiratory viral infections , followed by an appropriate treatment . [Differentiation between Human Coronaviruses NL63 and 229E Using a Novel Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay Based on Specific Monoclonal Antibodies, Clinical and Vaccine Immunology, 2010-11-17]
Detection of viral antigens and / or viral genomes is critical for rapid diagnosis of respiratory viral infections , followed by an appropriate treatment . Currently , reverse transcription - PCR is the major technique used for diagnosis of HCoV infection ( 2 , 12 , 16 ) . However , this method has some disadvantages , such as possible contamination , instability of the RNA samples , and the need for special equipment that in some cases , in particular , in undeveloped countries , is not available . Other rapid tests are needed in order to facilitate diagnosis . The antigen - capture ELISA using MAbs allows rapid diagnosis of viral infections , and it can be used as an alternative to PCR . On the basis of the low degree of homology among the amino acid sequences of the N proteins of different coronaviruses , together with the high immunogenicity of this protein , the N protein appeared to be a suitable antigenic marker for diagnosis of coronavirus infection . In the work reported here , we described the production and characterization of several species - specific MAbs against the N proteins of human coronaviruses NL63 and 229E and the subsequent development of a differential ELISA that allowed their detection .

Specific pcr reactions were designed to fill in gaps and to sequence regions with low - quality sequence data . [Identification of a new human coronavirus, Nat Med, 2004-03-21]
To determine whether the HCoV - NL63 genome organization shares these characteristics , we constructed a cDNA library with purified virus stock as input material . A total of 475 genome fragments were analyzed , with an average coverage of seven sequences per nucleotide . Specific PCR reactions were designed to fill in gaps and to sequence regions with low - quality sequence data . We combined this with 5 ′ and 3 ′ rapid amplification of cDNA ends to resolve the complete HCoV - NL63 genome sequence .

Further development of accurate and rapid methods to identify unknown respiratory pathogens is still needed . [A Novel Coronavirus from Patients with Pneumonia in China, 2019, N Engl J Med, 2020-02-20]
Further development of accurate and rapid methods to identify unknown respiratory pathogens is still needed . On the basis of analysis of three complete genomes obtained in this study , we designed several specific and sensitive assays targeting ORF1ab , N , and E regions of the 2019 - nCoV genome to detect viral RNA in clinical specimens . The primer sets and standard operating procedures have been shared with the World Health Organization and are intended for surveillance and detection of 2019 - nCoV infection globally and in China . More recent data show 2019 - nCoV detection in 830 persons in China . 17


What is needed for sequencing with advanced analytics for unknown pathogens?


No suitable answers found.


What is needed for distinguishing naturally-occurring pathogens from intentional?


The astute , frontline health care worker is the first defense against spread of an emerging pathogen . [Lessons from Severe Acute Respiratory Syndrome (SARS): Implications for Infection Control, Archives of Medical Research, 2005-12-31]
mortality for the usual causes of community - acquired pneumonias ( approximately 2 - 4 % ) , the 50 % mortality for patients over age 60 also distinguished this pathogen ( 10 ) . Diarrhea and dyspnea were common among populations studied with SARS ( 11 ) , but each was not highly predictive of infection in any single patient with the novel coronavirus . Thus , the high transmissibility to nurses and physicians and the higher than expected mortality were key features strongly suggesting a new pathogen . Furthermore , SARS to many clinicians appeared to have a biphasic course , with cough and fever initially followed in 3 - 5 days with a normal temperature and increasing hypoxia . The point is that physicians and nurses need to be trained to be alert to the unusual , the unexpected , and the variant clinical presentation . The astute , frontline health care worker is the first defense against spread of an emerging pathogen .

One strong predictor of disease progression that distinguishes pathogenic hiv infection and non - pathogenic siv infection is the activation of host antiviral defence [A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses, Emerg Microbes Infect, 2020-03-14]
SIVs are non - pathogenic in their natural hosts , but their transmission to a new host , such as humans for HIV - 1 and HIV - 2 as well as macaques for SIVmac , enable them to become highly pathogenic . HIV - 1 and HIV - 2 share 40 – 60 % nucleotide sequence homology . The transmission rate of HIV - 2 is lower because the viral load is generally lower in infected individuals . The natural history of HIV - 2 infection is quite different from that of HIV - 1 . Although clinical symptoms of acquired immunodeficiency syndrome ( AIDS ) caused by HIV - 1 and HIV - 2 are indistinguishable , most people infected with HIV - 2 do not progress to AIDS . One strong predictor of disease progression that distinguishes pathogenic HIV infection and non - pathogenic SIV infection is the activation of host antiviral defence including a prominent stimulation of T cells in the former but not the latter . Another possibility is that the natural hosts of SIVs might be the survivors of ancient SIV pandemics . One prediction is that HIVs and humans will eventually adapt to each other just like SIVs and their natural hosts . In this regard , AIDS might be considered an accident in which HIVs fail to adapt to humans or humans fail to adapt to HIVs . In support of this view , species - specific features in host restriction factors , such as TRIM5α and tetherin , can prevent SIV infection of humans . On the other hand , adaptive mutations and accessory genes such as Vpu , Nef , and Vif in HIVs have been found to counteract host restriction factors , which constitute the antiviral defence , in a host - specific manner . For example , a five - codon deletion in the cytoplasmic domain of human restriction factor tetherin results in the prevention of its interaction with SIVcpz Nef in humans [ 45 ] . On the side of the virus , some HIV - 1 strains use their Vpu protein to degrade tetherin [ 45 ] .

The novel coronavirus outbreak raises questions about how such pathogens evolve and what makes infections mild or severe [How Coronaviruses Cause Infection—from Colds to Deadly Pneumonia, unknown journal, 2020]
The novel coronavirus outbreak raises questions about how such pathogens evolve and what makes infections mild or severe

The time of processing samples and the availability of reliable diagnostic tests is a challenge during an outbreak . [Accurate Identification of SARS-CoV-2 from Viral Genome Sequences using Deep Learning, unknown journal, 2020-03-14]
Being able to reliably identify SARS - CoV - 2 and distinguish it from other similar pathogens is important to contain its spread . The time of processing samples and the availability of reliable diagnostic tests is a challenge during an outbreak . Developing innovative diagnostic tools that target the genome to improve the identification of pathogens , can help reduce health costs and 330 time to identify the infection , instead of using unsuitable treatments or testing .

Additional research is needed to elucidate viral and host factors in the pathogenesis of severe and fatal infections . [Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis, Travel Medicine and Infectious Disease, 2020-03-13]
Infection with COVID - 19 is associated with significant morbidity especially in patients with chronical medical conditions . At least onefifth of cases require supportive care in medical intensive care units , which is especially limited in most developing countries . Despite the implementation of optimal supportive interventions , case fatality rate among hospitalized patients is more than 10 % . Similar to other viral respiratory pathogens , COVID - 19 presents in the majority of cases with a rapidly progressive course of fever , cough and dyspnea . Important distinguishing factors are leukopenia and the rapid progression to ARDS . Eliciting a history of recent travel to areas with ongoing outbreaks of this emerging pathogen or contact with a confirmed case of COVID - 19 , should prompt clinicians to initiate isolation precautions and obtain laboratory confirmation . Additional research is needed to elucidate viral and host factors in the pathogenesis of severe and fatal infections .


What is known about One Health surveillance of humans and potential sources of future spillover or ongoing exposure for this organism and future pathogens?


One health approaches attempt to strategize the coordinated efforts of multiple overlapping disciplines [ 19 ] , including environmental surveillance and environmental health . [The novel Coronavirus (SARS-CoV-2) is a one health issue, One Health, 2020-02-14]
One Health approaches attempt to strategize the coordinated efforts of multiple overlapping disciplines [ 19 ] , including environmental surveillance and environmental health . Primary components of the approach lie in animal health and environmental aspects . At the time of writing , the host from which the SARS - CoV - 2 entered the human population is unknown although the suspicion is that food markets are likely sources for the original spillover . While the search for the natural host highly implicates bats [ 21 ] , search for the intermediary host , if any , is ongoing with the suggestions of the pangolin as a host far from certain . While it is premature to implicate any one particular urban source or natural host , the ensuing search will give insight into pathogens with potential to cross over into human transmission . This approach of environmental surveillance forms part of the PREDICT strategy [ 20 ] for detecting viruses with potential for spillover into human .

The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas . [Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments, Vet Q, 2020-02-08]
Coronaviruses are the well - known cause of severe respiratory , enteric and systemic infections in a wide range of hosts including man , mammals , fish , and avian . The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus ( SARS - CoV ) outbreaks in 2002 - 2003 followed by Middle East Respiratory Syndrome CoV ( MERS - CoV ) . This decade ’ s first CoV , named 2019 - nCoV , emerged from Wuhan , China , and declared as ‘ Public Health Emergency of International Concern ’ on January 30 ( th ) , 2020 by the World Health Organization ( WHO ) . As on February 4 , 2020 , 425 deaths reported in China only and one death outside China ( Philippines ) . In a short span of time , the virus spread has been noted in 24 countries . The zoonotic transmission ( animal - to - human ) is suspected as the route of disease origin . The genetic analyses predict bats as the most probable source of 2019 - nCoV though further investigations needed to confirm the origin of the novel virus . The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well . The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas .

Very little is known about 2019 - ncov virus , including basic biology , animal source or any specific treatment . [The global spread of 2019-nCoV: a molecular evolutionary analysis, Pathog Glob Health, 2020-02-12]
Very little is known about 2019 - nCoV virus , including basic biology , animal source or any specific treatment . The substantial degree of genetic heterogeneity ( 15 % ) accumulated among human isolates during the past few months of the ongoing epidemic outbreak is not necessarily surprising for an RNA virus that has been shown to be a measurably evolving population over short time spans [ 15 ] . However , our findings underscore the urgent need for further molecular surveillance and the development of appropriate and an in - depth monitoring system capable of investigating viral mutation and transmission capabilities as 2019 - nCoV unfortunately keeps spreading at a regional and potential global level . In other words , given the virus ’ s fast evolutionary rate and population dynamic , tracking the emergence of novel transmission routes and / or patterns should be considered a significant priority .

Many clinical questions remain unresolved at this time and await reporting and future publications . [2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness, Journal of Infection in Developing Countries, 2020]
The number of cases in Wuhan continued to increase due to retrospective testing , new cases , and changes in diagnostic evaluation for etiological agents [ 15 ] . By 28 January 2020 , numerous cases had been identified in throughout China including Taiwan and Hong Kong . As of 28 January 2020 , over 4 , 500 confirmed cases have been reported with > 100 deaths ( National Health Commission of the PRC ) . Human - tohuman transmission was suspected early in the outbreak and has now been confirmed and is the main source of infections [ 14 ] ( National Health Commission of the PRC , update January 22 , 2020 ) . Many clinical questions remain unresolved at this time and await reporting and future publications . Some critical questions include : Do all infected individuals show symptoms ? What is the frequency of asymptomatic infections ? What is the time from exposure to onset of symptoms ? Are asymptomatic individuals infectious ? Is human - to - human transmission linked to specific mutations in the 2019 - nCoV virus ?

Human - to - human transmission of mers - cov has been investigated as a potentially significant route of spread . [Retrospective, epidemiological cluster analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic using open source data, Epidemiol Infect, 2017-10-24]
Human - to - human transmission of MERS - CoV has been investigated as a potentially significant route of spread . Researchers have found that close contact with infected individuals is required to transmit the virus from one human to another , supporting the role of limited human - to - human transmission in the MERS - CoV epidemic and , more specifically , its role in nosocomial and household clusters [ 9 ] . While it is known that the virus can be transmitted through respiratory secretions , the exact routes through which the virus spreads are not well understood [ 9 ] . In an effort to better understand the patterns of transmission , a retrospective analysis of epidemiological clusters identified throughout the ongoing MERS - CoV epidemic was conducted using open - source data .