Task 3 - What do we know about virus genetics, origin, and evolution?

Real-time tracking of whole genomes to inform the development of diagnostics

Real-time tracking of whole genomes to inform the development of therapeutics

Real-time tracking of whole genomes to track variations of the virus over time

Mechanism for coordinating the rapid dissemination of whole genomes to inform the development of diagnostics

Mechanism for coordinating the rapid dissemination of whole genomes to inform the development of therapeutics

Mechanism for coordinating the rapid dissemination of whole genomes to track variations of the virus over time

Which geographic and temporal diverse sample sets are accessed to understand geographic differences?

To overcome potential systematic bias resulting from cryptic diversity , where possible , all sequences were generated from the same sample for each species or from the same species collected in the same geographical area as the original sample . All sequences newly generated are deposited into GenBank accession numbers ( KP175738 – KP176371 ) and concatenated with previously published data where possible ( supplementary table S3 , Supplementary Material online ) . In total , 40 species , including A . ornatus , from eight families were analyzed .

• Cluster 4 ( light green ) is one of the smallest clusters but is spread fairly wide temporally . It features 4 samples taken in China and then transitions geographically to Singapore and France .

The close phylogenetic relationship between Rs - BatCoV HKU32 and BatCoV HKU10 may be explained by the geographical proximity of their hosts . Besides Rs - BatCoV HKU32 and Tr - BatCoV HKU33 , diverse alphaCoVs and betaCoVs were also detected in our bat samples . Hi - BatCoV HKU10 and Coronavirus PREDICT CoV - 37 , belonging to alphaCoVs , were detected in bats in Hong Kong , while SARSr - BatCoVs and Ty - BatCoV HKU4 , belonging to lineage B ( Sarbecovirus ) and C ( Merbecovirus ) betaCoVs , respectively , were detected in bats in Guangdong and Guizhou provinces . It is of note that Rs - BatCoV HKU32 and BatCoV HKU10 were detected in bats of different families but captured from the same sampling location at a country park in Hong Kong . This suggests that these viruses may have evolved among geographically close but phylogenetically distant bat populations . We have also previously described interspecies transmission of BatCoV HKU10 between Rousettus leschenaultii and Hipposideros pomona bats which belonged to two different bat families [ 42 ] . Given that the genetic cluster formed by Rs - BatCoV HKU32 , BatCoV HKU10 , BtRs - AlphaCoV and BtMs - AlphaCoV were detected from diverse bat families , this suggests that these alphaCoVs may have a tendency for cross - species transmission . This is in contrast to Tr - BatCoV HKU33 and related viruses which were limited to the family Vespertilionidae . Greater bamboo bats , the host of Tr - BatCoV HKU33 , and other Vesper bats are geographically widespread and able to occupy distinct and diverse habitats [ 43 ] . Interestingly , MERS - CoV - related bat lineage C betaCoVs ( Merbecovirus ) have also been exclusively detected in the family Vespertilionidae [ 10 , 11 , 13 , 14 , 15 , 44 , 45 ] . Further studies are needed to understand the mechanism for host tropism , especially the stringency of host receptor usage by different alphaCoVs , the interspecies transmissibility of coronaviruses among different bats and the contribution of bat ecology to this phenomenon .

. CC - BY - NC 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 . 30 . 015008 doi : bioRxiv preprint Figure 1 . Top : Breakpoints identified by 3SEQ shown by the percentage of sequences ( out of 68 ) that support a particular breakpoint position . Note that breakpoints can be shared between sequences if they are descendants of the same recombination events . The pink , green , and orange bars show breakpoint - free regions ( BFRs ) , with Region A ( nt showing two trimmed segments to yield Region A ' ( nt 13291 - 14932 , 15405 - 17162 , 18009 - 19628 ) . Region B spans nucleotides 3625 - 9150 , and region C spans 9261 - 11795 . The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 03 . 30 . 015008 doi : bioRxiv preprint 0 . 04 Y u n n a n 2 0 1 6 [ Y N 2 0 1 8 A ] Y u n n a n 2 0 1 2 [ R f4092 ] Y u n n a n 2 0 1 3 [ R s4231 ] To avoid artefacts due to recombination , we focused on the non - recombining regions NRR1 , NRR2 , and the recombination - masked alignment NRA3 for inferring time - measured evolutionary histories . Visual exploration using TempEst indicates there is no evidence for temporal signal in these data sets ( Figure S1 ) . This is not surprising for diverse viral populations with relatively deep evolutionary histories . In such cases , even moderate rate variation among long deep phylogenetic branches will significantly impact expected root - to - tip divergences over a sampling time range that represents only a small fraction of the evolutionary history ( Trova et al . , 2015 ) . However , formal testing using marginal likelihood estimation ( Duchene et al . , 2019 ) does not reject the absence of temporal signal in all three data sets ( Table S1 ) , albeit without strong support in favor of temporal signal ( log Bayes factor support of 3 , 10 , and 3 for NRR1 , NRR2 , and NRA3 respectively ) .

This should be unacceptable , since raw read data can be used to uncover viral diversity within individual samples and to evaluate robustness and reliability of the assembly . To demonstrate that such diversity exists , we mapped Illumina reads against COVID - 19 reference ( NC _ 045512 ) and identified sequence variants with frequencies above 5 % while taking into account quality of alternative bases and strand bias . Five percent was selected as a conservative threshold that can be reliably resolved from Illumina data [ 12 ] . Using this threshold , thirty nine single nucleotide variants ( SNVs ) were identified in total across all samples ( Fig . 1 ) . The most prominent sequence variant was observed in sample SRR10903401 . It is an A - to - C substitution with alternate allele frequency of 38 % that causes a Lys 921 Gln amino acid replacement within the spike glycoprotein S ( product of gene S ) . S is a homotrimeric protein containing S1 and S2 subdomains mediating receptor recognition and membrane fusion , respectively [ 13 ] . S2 subdomains contain two heptad repeat ( repeats of units containing seven amino acids ) regions : HR1 and HR2 . The Lys 921 Gln substitution we observed is located in HR1 and forms a salt bridge with Gln 1188 within HR2 . This is one in a series of salt bridges involved in the formation of the HR1 / HR2 hairpin structures [ 14 ] . This site invariably contains Lys in all human SARS - related coronaviruses ( S protein residue 903 ) as well as in many other coronaviruses ( Fig . 2 ) . However , more distantly related coronaviruses The copyright holder for this preprint ( which was not peer - reviewed ) is the . https : / / doi . org / 10 . 1101 / 2020 . 02 . 21 . 959973 doi : bioRxiv preprint the salt bridge with Gln 1188 and may have structural and functional implications for the spike protein structure and , consequently , COVID - 19 virulence . This potentially adaptive change was not observed in the other two samples and lack of raw read data prevented us from identifying it in other geographically and temporally distributed samples .

Which geographic and temporal diverse sample sets are accessed to understand genomic differences?

To further explore the diversity of CoVs in bats and understand the genetic evolution of CoVs , we collected bat samples from Hong Kong and mainland China . Diverse CoVs belonging to alphaCoVs and betaCoVs were detected , including two novel alphaCoVs , as confirmed by complete genome sequencing and characterization , supporting bats as an important reservoir for CoVs . The evolutionary relationship of the two novel alphaCoVs to other known CoVs is also discussed .

To overcome potential systematic bias resulting from cryptic diversity , where possible , all sequences were generated from the same sample for each species or from the same species collected in the same geographical area as the original sample . All sequences newly generated are deposited into GenBank accession numbers ( KP175738 – KP176371 ) and concatenated with previously published data where possible ( supplementary table S3 , Supplementary Material online ) . In total , 40 species , including A . ornatus , from eight families were analyzed .

Of the primer - probe sets without background CT values in the SARS - CoV - 2 - negative mock samples ( E - Sarbeco , RdRp - SARSr , HKU - N , HKU - ORF1 , and 2019 - nCoV _ N1 ) , our results show that none were able to detect SARS - CoV - 2 RNA at 1 ( 10 0 ) virus genome equivalents / μL and mixed detection at 10 ( 10 1 ) virus genome equivalents / μL ( Fig . 3 ) . We found that the two most sensitive primer - probe sets are E - Sarbeco ( Charité ) and HKU - ORF1 , which each detected 6 / 8 ( 75 % ) of the nasopharyngeal swabs spiked with 10 virus genome equivalents / μL ( Fig . 3 ) . At 100 ( 10 2 ) virus genome equivalents / μL , we could detect virus ( CT < 40 ) and differentiate between the negative mocks for all replicates and primers sets , except for the RdRp - SARSr ( Charité ) set , which was negative ( CT > 40 ) for all 10 0 - 10 2 genome equivalents / μL concentrations . Thus , our results show that there are differences in each of the primer - probe sets to differentiate between true negatives and true positives at virus concentrations at or below 10 virus genome equivalents / μL . Fig . 3 : All nine primer - probe sets have a similar lower detection limit of 10 2 SARS - CoV - 2 genome equivalents / μL . We determined the lower detection limit of nine primer - probe sets as well as the human RNase P control for mock samples ( RNA extracted from nasopharyngeal swabs collected in 2017 ) spiked with known concentrations of SARS - CoV - 2 RNA . We performed 6 - 8 technical replicates with mock samples without spiking RNA and mock samples spiked with 10 0 - 10 2 genome equivalent / μL of SARS - CoV - 2 RNA . For each primer - probe set , we show the range of cycle threshold values obtained with mock samples extracted from SARS - CoV - 2 - negative nasopharyngeal swabs , which indicates variation in the lower detection limit of each primer - probe set . ND = not detected . Gray - shaded areas = non - specific amplification .

In order to explore the potential animal origin of MERS - CoV , as well as understanding the host diversity and evolutionary pathway of Merbecovirus , samples from various mammals were collected from China . We discovered a novel member of Merbecovirus from two Amur hedgehogs ( Erinaceus amurensis ) . Genome analysis indicated that the virus belongs to a novel species under Merbecovirus , being most closely related to EriCoV from hedgehogs in Germany . The findings support that hedgehogs are an important reservoir of Merbecovirus .

SARS - CoV . We compiled a set of 69 SARS - CoV genomes including 58 genomes sampled from human and 11 sampled from civets and raccoon dogs . This data set comprises an updated version of the one used in Hon et al ( 2008 ) .

Is there more than one strain in circulation?

The strains GZ43 and GZ60 from two health - care workers affected within the same hospital seem phylogenetically similar ; wherease GZ50 , which is an independent case from the community , is a distinct lineage . This finding suggests that there were multiple lineages of viruses circulating in Guangdong . One of these lineages ( GZ50 ) maintains an outgroup relation to the major cluster of cases in Hong Kong and could represent the precursor virus of the Hong Kong outbreak . Whether some lineages are more transmissible than others is not clear . 1 An analysis of more strains from Guangdong are needed to address this issue . The spread of SARS CoV in Foshan and Zhongshan in November and December , 2002 , did not lead to an outbreak of the same scale as that in Guangzhou in January and February , 2003 . Foshan and Zhongshan , like Guandong , are large urban conurbations of more than 1 million people . One possibility is that the virus was adapting to human beings - ie , human transmission with time . However , spread of the disease might have been promoted by the movement of people during the Chinese New Year holiday season that , in 2003 , occurred at the end of January . Furthermore , Guangzhou , being a premier medical centre , received transfers of several patients with respiratory complications associated with SARS .

Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses ( HCoV ) , including HCoV - 229E and - OC43 and recently described strains ( HCoV - NL63 and - HKU1 ) . By enzyme - linked immunosorbent assay , we measured anti - HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U . S . sites from 105 adults aged 50 years and older ( mean age , 67 ± 9 years ) with chronic obstructive pulmonary disease . Most patients ( 95 [ 90 % ] ) had at least one more chronic disease . More patients had serum antibody to each HCoV strain ( 104 [ 99 % ] had antibody to HCoV - 229E , 105 [ 100 % ] had antibody to HCoV - OC43 , 103 [ 98 % ] had antibody to HCoV - NL63 , and 96 [ 91 % ] had antibody to HCoV - HKU1 ) than had antibody to each HCoV strain in nasal wash specimens ( 12 [ 11 % ] had antibody to HCoV - 229E , 22 [ 22 % ] had antibody to HCoV - OC43 , 8 [ 8 % ] had antibody to HCoV - NL63 , and 31 [ 31 % ] had antibody to HCoV - HKU1 ) , respectively ( P < 0 . 0001 ) . The proportions of subjects with IgA antibodies in nasal wash specimens and the geometric mean IgA antibody titers were statistically higher for HCoV - OC43 and - HKU1 than for HCoV - 229E and - NL63 . A higher proportion of patients with heart disease than not had IgA antibodies to HCoV - NL63 ( 6 [ 16 % ] versus 2 [ 3 % ] ; P = 0 . 014 ) . Correlations were highest for serum antibody titers between group I strains ( HCoV - 229E and - NL63 [ r = 0 . 443 ; P < 0 . 0001 ] ) and between group II strains ( HCoV - OC43 and - HKU1 [ r = 0 . 603 ; P < 0 . 0001 ] ) and not statistically significant between HCoV - NL63 and - OC43 and between HCoV - NL63 and - HKU1 . Patients likely had experienced infections with more than one HCoV strain , and IgG antibodies to these HCoV strains in serum were more likely to be detected than IgA antibodies to these HCoV strains in nasal wash specimens .

is the ( which was not peer - reviewed ) The copyright holder for this preprint . https : / / doi . org / 10 . 1101 / 2020 . 03 . 19 . 20039198 doi : medRxiv preprint population . After establishing the possible transitions between compartments , the 459 system was found to have four equilibrium points : the disease free equilibrium , the 460 existing strain equilibrium , the emergent strain equilibrium , and the endemic 461 equilibrium . Upon examining the conditions for existence and local stability , the 462 disease - free equilibrium was determined to be locally stable when both R v and R 0 are 463 less than one . This is consistent with the reproduction number for this multi - strain 464 model . The existing strain equilibrium surprisingly did not impose that R 0 < 1 , which 465 is the condition for the DFE of a normal SIR model for a single - strain without 466 immunity . This implies that if the original strain is much more contagious than the 467 emergent strain , the emergent strain would still die out eventually regardless of the fact 468 that it would persist in the population if it was on its own . On a similar note , the local 469 stability condition for the emergent equilibrium condition also does not impose that 470 R v < 1 . This means that the state of the system prior to the emergence of the new 471 strain does not matter as long as the emergent strain is more contagious than the 472 existing strain . This leaves a highly restrictive condition for endemic equilibrium to 473 exist : the emergent strain must be able to survive by itself and the original strain must 474 be contagious enough to infect enough people , which is given by Eq 44 . Eq 44 also 475 implies that the two - strain endemic equilibrium will only be locally asymptotically . CC - BY 4 . 0 International license It is made available under a author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

The most prevalent strain detected was closely related to HCoV - OC43 , occurring in patients younger than 10 or older than 40 years of age . The second most prevalent strain detected was closely related to NL63 , which has been related to acute respiratory symptoms , mainly in children and immunocompromised individuals [ 28 , 29 ] . Previous studies ( 2007 and 2009 ) in the US on the prevalence of HCoV in respiratory tract infections of children reported different circulating strains by region . In the Rocky Mountain region , the predominant strains were NL63 , OC43 and 229E , while in the Pacific Northwest , HKU1 was predominant [ 21 , 30 ] . In this study , we surveyed both children and adults and demonstrated that OC43 and NL63 CoVs were the predominant strains . In another study , using samples from Rochester , NY , Nashville , TN and Cincinnati , OH , the findings were similar to our study , in which the OC43 was the most prevalent strain , followed by NL63 and HKU1 , and 229E was the least prevalent [ 31 ] . Prill et al . [ 31 ] reported that OC43 tended to circulate from fall to winter and NL63 from winter to spring , while 229E was not detected in the first four years of the study and only one cluster of HKU1 during a single winter . In a study by Kuypers et al . [ 30 ] , HKU1 was more likely to occur from October to February and 229E from December to June . In a study by Domiguez et al . [ 21 ] , HKU1 was more likely to occur from February to May and 229E from February to June . Based on the distribution of HKU1 and 229E the studies of Kuypers et al . [ 30 ] and Dominguez et al . [ 21 ] , we should have been able to detect both strains if they had circulated with similar seasonality in Arkansas ; however , only one case of 229E and one case of HKU1 were detected .

Is any multi-lateral agreement leveraged such as the Nagoya Protocol?

Is there evidence that livestock could be infected and serve as a reservoir after the epidemic appears to be over?

Has there been any field surveillance to show that livestock could be infected?

Has there been any genetic sequencing to show that livestock could be infected?

Has there been any receptor binding to show that livestock could be infected?

Is there evidence that farmers are infected?

Is there evidence that farmers could have played a role in the origin?

What are the results of the surveillance of mixed wildlife-livestock farms for SARS-CoV-2 and other coronaviruses in Southeast Asia?

What are the results of the experimental infections to test host range for this pathogen?

Which are the animal hosts?

Coronaviruses ( CoVs ) are important pathogens in animals and humans , responsible for a variety of respiratory , enteric , hepatic , and neurological diseases . They are now classified into four genera , Alphacoronavirus , Betacoronavirus , Gammacoronavirus , and Deltacoronavirus , with Betacoronavirus further divided into lineages A to D1 – 4 . Humans are infected by six CoVs , including human CoV 229E ( HCoV - 229E ) and human CoV NL63 ( HCoV - NL63 ) belonging to Alphacoronavirus ; human CoV OC43 ( HCoV - OC43 ) and human CoV HKU1 ( HCoV HKU1 ) belonging to Betacoronavirus lineage A ; Severe Acute Respiratory Syndrome - related CoV ( SARSr - CoV ) belonging to Betacoronavirus lineage B ; and Middle East Respiratory Syndrome CoV ( MERS - CoV ) belonging to Betacoronavirus lineage C5 – 12 . The emergence potential of CoVs is believed to be related to their tendency for mutation and recombination , allowing the generation of new viruses being able to adapt to new hosts3 , 13 – 18 .

An alternative strategy of generating neutralizing antibodies against 2019 - nCoV S protein would be to immunize large animals ( sheep , goat , cow ) with the 2019 - nCoV S protein , and then purifying polyclonal antibodies from the animals 20 . This strategy may serve an expedited service in the setting of an outbreak and has many advantages such as simplifying production and manufacturing , but has limited guarantees that each animal would produce neutralizing antisera , or what the antibody titer would be in each animal 21 . Moreover , there is also the human immune response against foreign immunoglobulins to other species , which would potentially complicate any treatment scenarios 22 . In a truly desperate scenario , this strategy may be viable for a short - term , but would not easily scale in the 2019 - nCoV outbreak , which is already rapidly multiplying .

The copyright holder for this preprint ( which was not peer - reviewed ) is . https : / / doi . org / 10 . 1101 / 2020 . 02 . 21 . 20026146 doi : medRxiv preprint live animals includes the following behaviours : visiting the live poultry or wild animal markets , buying live poultry or wild animals ( i . e . , frequency of purchases , practice of picking up live animals before purchasing , location where the purchased animals were slaughtered ) , eating wild animal products , raising pets , and touching stray animals . To measure behavioural change during the outbreak , each respondent was asked to report exposing behaviours both ( 1 ) prior to the outbreak : before Dec 31 , 2019 when COVID - 19 cases were first released by Wuhan Health Commission and ( 2 ) since the outbreak , between Jan 1 to Feb 10 , 2020 . For live animal consumption habits , where behaviour change cannot be measured in a short period of time , we assessed people ' s intention to : 1 ) buy live poultry or wild animals , and eat wild animal products ( continue to buy / eat as usual , buy / eat less , not buy / eat any more ) and 2 ) continue raising pets and touching stray animals ( continue to raise / touch as usual , temporarily not during the outbreak , try or resolutely not even after the outbreak ) .

The international virology community , which includes many Chinese American virologists residing in North America , is concerned about this virus . It is imperative that animal reservoirs that transmitted the virus to humans be identified as quickly as possible to aid in control of this disease . It is thus urgent that the results of animal testing from the seafood market in Wuhan , where the virus was initially isolated , be released as soon as possible . This is particularly crucial given the rapidly approaching Lunar Chinese New Year , which will take place on 25 January 2020 , during which tens of millions of people will travel , and large amounts of animal meats , some of which may contain this virus , will be consumed . It is noteworthy that recently the local health administration in Wuhan issued guidance regarding the prevention and treatment of the pneumonia caused by this coronavirus [ 9 ] . It is also encouraging that the World Health Organization has issued detailed guidance on the clinical management of the disease in relation to this outbreak [ 10 ] .

As demonstrated with SARS - CoV , the generation of mice expressing human DPP4 may be the most rapid strategy to yield a small animal model . Indeed , when mice were transduced with an adenovirus vector that expressed human DPP4 , they were susceptible to MERS - CoV infection and developed pneumonia , albeit without associated mortality ( 105 ) . Transgenic mice could be generated via traditional methods or using the CRISPR - Cas9 ( 106 ) Under the FDA ' s Animal Efficacy Rule ( " Animal Rule " ) therapeutics against rare , emerging , or virulent agents can achieve regulatory approval provided efficacy is demonstrated in two animal models ( one of which must be a non - rodent species ) . Animal species of interest must first be evaluated for permissiveness to viral replication and presentation of clinical disease .

Is there evidence of continued spill-over to humans from animals?

Coronaviruses , enveloped RNA viruses with surface spikes , infect a wide range of animals and humans . They can cause mild , self - limited upper respiratory infections in humans ( the common cold ) . A few coronaviruses , normally carried by apparently healthy animals , can be lethal if they infect humans . For many viruses that primarily infect animals but can spill over into the human population , humans are dead - end hosts . Examples include the rabies virus and most hantaviruses . With these , transmission to other humans does not occur , or does so rarely .

In humans , overt disease was given the name Middle East respiratory syndrome , with the acronym MERS . From intermittent animal - to - human spill - over events , the MERS - CoV spreads sporadically among people , causing more severe disease among older adults , especially males , with pre - existing diseases . The spread of MERS - CoV among humans has often been associated with outbreaks in hospitals , with around 20 % of all cases to date involving healthcare workers ( HCWs ) .

Considering that animal CoVs spilled over into humans in three different occasions in the short time span of two decades , a more reverent management of the environment will be fundamental to prevent future emergence of pandemic CoVs . Under these circumstances , veterinary medicine should support policy makers to adopt and promote sound and sustainable measures for management of the environment and of animals and advance the global ' One Health ' movement .

In the last 15 years , two outbreaks of previously unknown highly pathogenic coronaviruses , SARS - CoV and MERS - CoV , have demonstrated that CoVs will continue to spill over into human populations , likely facilitated by interaction between infected animals and humans . Reverse genetics approaches have generated pre - emergent BatCoVs from sequence , especially those related to SARS - CoV and MERS - CoV . These particularly novel avenues of research have identified that BatCoV strains with similar pathogenic profiles to SARS - CoV or MERS - CoV continue to circulate within bat populations , indicating a continued vulnerability to highly pathogenic coronavirus emergence . While the next emerging coronavirus may be symptomatically or antigenically similar to SARS - CoV or MERS - CoV , the possibility exists that novel highly pathogenic coronaviruses may be poised for spillover into human populations , with potentially disastrous consequences . Currently , public health measures have been adequate to stymie the spread of SARS - CoV and MERS - CoV primarily due to disease surveillance coupled with viruses with limited person - to - person transmission . However , biological factors that increase cross - species transmission or facilitate person - to - person spread may lead to future coronavirus strains not capable of being contained by timely quarantine of infected individuals . Any increase in highly pathogenic CoV virulence , pathogenesis , or transmission would likely require a targeted medical countermeasure . Without strategic research programs that fill the gaps identified in our literature review , medical countermeasures that target highly pathogenic coronaviruses cannot be brought to market , leaving global public health vulnerable to this emerging threat .

The novel human CoV ( HCoV ) is a betacoronavirus genetically related to Severe acute respiratory syndrome ( SARS ) CoV and only distantly related to Middle East respiratory syndrome CoV ( MERS - CoV ) and it was designated as SARS type 2 CoV ( SARS - CoV - 2 ) . Similar to the other hypervirulent HCoVs , SARS - CoV - 2 has a putative animal origin , likely descended from a related bat CoV that spilled over to humans either directly or after adaptation in another animal species , such as the Malayan pangolin ( Lam et al . , 2020 ) . SARS - CoV - 2 is highly related genetically ( 96 % nt ) to a SARSlike bat CoV The SARS - CoV - 2 induced disease , referred to as CoronaVirus Disease 2019 , affects the respiratory tract , with a number of patients displaying severe pneumonia and requiring hospitalisation and admission to intermediate or intensive care units . Unlike SARS and MERS , J o u r n a l P r e - p r o o f COVID - 19 is characterised by low lethality rates and high frequency of asymptomatic or paucisymptomatic infections that likely favoured the spread of this new pandemic ( Lai et al . , 2020 ) . As SARS - CoV - 2 started spreading globally , between February and March 2020 , potential spill over exposure ( viral RNA ) was noted in companion animals , likely due to their strict social interactions with humans . SARS - CoV - 2 RNA was detected in two dogs and a cat without clinical how CoVs can evolve , changing their tissue tropism and virulence ( Decaro and Lorusso , in press ) .

Which are the socioeconomic and behavioral risk factors for the spill-over to humans from animals?

With COVID - 19 , we need to identify all possible animal sources and routes of transmission as they determine the persistence in animals ranging from infection to disease to being a reservoir . Accidental or continuous spill - over to human beings usually determines the length of exposure and consequent outbreaks . 5 Socio - economic and behavioural risk factors in various societies and geographic regions also play a critical role . Various risk reduction strategies at human , animal and environmental interface need to be studied for defining the high - risk situations .

In humans , overt disease was given the name Middle East respiratory syndrome , with the acronym MERS . From intermittent animal - to - human spill - over events , the MERS - CoV spreads sporadically among people , causing more severe disease among older adults , especially males , with pre - existing diseases . The spread of MERS - CoV among humans has often been associated with outbreaks in hospitals , with around 20 % of all cases to date involving healthcare workers ( HCWs ) .

Considering that animal CoVs spilled over into humans in three different occasions in the short time span of two decades , a more reverent management of the environment will be fundamental to prevent future emergence of pandemic CoVs . Under these circumstances , veterinary medicine should support policy makers to adopt and promote sound and sustainable measures for management of the environment and of animals and advance the global ' One Health ' movement .

For behavioral responses , increases in anxiety levels , perceived risks and harms to body relative to SARS , and confusion about information reliability were significantly associated with higher probability of carrying out all recommended and avoidance behaviors during the outbreak ( Table 3 ) . For increases in frequencies of immediate handwashing behavior when returning home , the factor that exerted the largest impact was having received and read information brochures from the government , followed by having correct perceived efficacy of behaviors ( Table S3 ) . Higher perceived harm to body compared with SARS was the only factor with significant explanatory power for goggles purchase behavior . We found no evidence that perceptions and anxiety levels were associated with changes in frequencies of wearing face masks during the outbreak ( Table S3 ) .

Sustainable risk reduction strategies

In summary , we have examined current and unfolding responses to COVID - 19 and their implications for the Sendai Framework . Core to our argument are strategies for resilience building against biological hazards and pandemic . We reiterate our assertion that there is a lack of early and rapid actions from the DRR - related organisations , despite the SFDRR ' s call for building resilience including from biological hazards . The SFDRR ' s ultimate goal is a substantial reduction of risk and losses , coupled with laying the essential foundations for rapid and sustained recovery and sustainable development . We hope the evidence we have added shows the crisis of COVID - 19 could be used to make 2020 a " super year " of great progress on these goals .

Thus far we have focused on the impacts of shield immunity as a singular strategy , yet in practice , multiple interventions will be used in parallel . Hence , we evaluated the synergistic potential of utilizing shield immunity in combination with social distancing . Social distancing is modeled as a reduction in the transmission rates sustained over the post - intervention period . As is apparent in Figure 4 , shielding can augment social distancing , particularly when social distancing is relatively ineffective . For example , contour lines of reduction in total fatalities suggest that a combination of 10 % reduction in trans - . CC - BY 4 . 0 International license It is made available under a author / funder , who has granted medRxiv a license to display the preprint in perpetuity .

We then considered the reduction in the probability that an imported case leads to sustained transmission if surveillance is more intense . Specifically , we assumed that intensified surveillance led to a reduction in the mean period from symptom onset to hospitalisation , governed by the parameter ρ ( where ρ = 0 corresponds to no intensification of surveillance , and ρ = 1 corresponds to an implausible scenario in which infectious cases are hospitalised immediately ) . We found that , if surveillance is intensified so that the mean time from symptom onset to hospitalisation is halved , the probability that each imported case leads to sustained transmission is reduced to only 0 . 012 ( CrI [ 0 , 0 . 099 ] ; Figure 1D ) . Finally , we considered the combined effect if multiple cases arrive in a new location . In that scenario , intense surveillance has the potential to reduce the risk of sustained transmission significantly compared to weak surveillance . For ρ = 0 . 5 , the probability that any of 10 imported cases generate a substantial outbreak is only 0 . 12 ( CrI [ 0 , 0 . 65 ] ; Figure 2C ) . This highlights the importance of rigorous surveillance , particularly in locations where infected hosts are most likely to travel .

If COVID - 19 containment policies fail and social distancing measures cannot be sustained until vaccines becomes available , the next best approach is to use interventions that reduce mortality and prevent excess infections while allowing low - risk individuals to acquire immunity through natural infection until population level immunity is achieved . In such a situation , allowing some infections to occur in lower - risk groups might lead to an overall greater reduction in mortality than trying to protect everyone equally .

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