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DHS SCIENCE AND TECHNOLOGYMaster Question List forCOVID-19 (caused bySARS-CoV-2)Weekly Report18 March 2020For comments or questions related to the contents of this document, please contact the DHS S&THazard Awareness & Characterization Technology Center at HACTechnologyCenter@hq.dhs.gov.DHS Science and Technology Directorate MOBILIZING INNOVATION FOR A SECURE WORLDCLEARED FOR PUBLIC RELEASE
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2 (COVID-19)Updated 3/18/2020FOREWORDThe Department of Homeland Security (DHS) is paying close attention to the evolving CoronavirusInfectious Disease (COVID-19) situation in order to protect our nation. DHS is working very closely withthe Centers for Disease Control and Prevention (CDC), other federal agencies, and public health officialsto implement public health control measures related to travelers and materials crossing our bordersfrom the affected regions.Based on the response to a similar product generated in 2014 in response to the Ebolavirus outbreak inWest Africa, the DHS Science and Technology Directorate (DHS S&T) developed the following “masterquestion list” that quickly summarizes what is known, what additional information is needed, and whomay be working to address such fundamental questions as, “What is the infectious dose?” and “Howlong does the virus persist in the environment?” The Master Question List (MQL) is intended to quicklypresent the current state of available information to government decision makers in the operationalresponse to COVID-19 and allow structured and scientifically guided discussions across the federalgovernment without burdening them with the need to review scientific reports, and to preventduplication of efforts by highlighting and coordinating research.The information contained in the following table has been assembled and evaluated by experts frompublicly available sources to include reports and articles found in scientific and technical journals,selected sources on the internet, and various media reports. It is intended to serve as a “quickreference” tool and should not be regarded as comprehensive source of information, nor as necessarilyrepresenting the official policies, either expressed or implied, of the DHS or the U.S. Government. DHSdoes not endorse any products or commercial services mentioned in this document. All sources of theinformation provided are cited so that individual users of this document may independently evaluate thesource of that information and its suitability for any particular use. This document is a “living document”that will be updated as needed when new information becomes available.iCLEARED FOR PUBLIC RELEASE
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2(COVID-19)Infectious dose – how much agent willmake a normal individual ill?What do we know? The human infectious dose of SARSCoV-2, which causes coronavirusdisease 19 (COVID-19) is currentlyunknown via all exposure routes.Animal data are used as surrogates. Rhesus macaques are infected withSARS-CoV-2 via the ocularconjunctival and intratracheal routeat a dose of 700,000 PFU (106TCID50).51 A total dose of 700,000 plaqueforming units (PFU) of SARS-CoV-2infected cynomolgus macaques via acombination intranasal andintratracheal exposure (106 TCID50total dose).109 Macaques did notexhibit clinical symptoms, but shedvirus through the nose and throat.109 Nonhuman primate infection may notrepresent human infection. Initial experiments suggest that SARSCoV-2 can infect genetically modifiedmice containing the human ACE2 cellentry receptor. Infection via theintranasal route (dose: 105 TCID50,approximately 70,000 PFU) causeslight infection, however no virus wasisolated from infected animals, andpolymerase chain reaction (PCR)primers used in the study do not alignwell with SARS-CoV-2, casting doubton this study.14 The infectious dose for SARS in miceis estimated to be between 67-540PFU (average 240 PFU, intranasalroute).49-50 Genetically modified mice exposedintranasally to doses of MERS virusbetween 100 and 500,000 PFU showsigns of infection. Infection withhigher doses result in severesyndromes.7, 41, 81, 150Transmissibility – How does it spreadfrom one host to another? How easilyis it spread? Pandemic COVID-19 has caused214,894 infections and 8,732 deaths72in at least 173 countries andterritories (as of 3/18/2020).27, 114, 135 There are 7,769 SARS-CoV-2 casesacross 50 US states, with 118 deaths.(as of 3/18/2020)72; there is sustainedcommunity transmission of COVID-19in the US.17 High-quality estimates of humantransmissibility (R0) range from 2.2 to3.193, 98, 106, 142, 149 Early estimates ofthe attack rate in China range from3%-10%, mainly in households.137 SARS-CoV-2 is believed to spreadthrough close contact and droplettransmission,31 with fomitetransmission73, i.e., germs left onsurfaces, and close-contact aerosoltransmission also plausible.22 SARS-CoV-2 replicates in the upperrespiratory tract (e.g., throat), andinfectious virus is detectable in throatand lung tissue for at least 8 days.138 Pre-symptomatic151 orasymptomatic12 patients can transmitSARS-CoV-2; between 12%54 and 23%90 of infections may be caused byasymptomatic or pre-symptomatictransmission. SARS-CoV-2 is present in infectedpatient saliva,124 lower respiratorysputum,131 and feces. 86 Social distancing and behavioralchanges are estimated to havereduced COVID-19 spread by 44% inHong Kong,47 and a combination ofnon-pharmaceutical interventions(e.g., school closures, isolation) arelikely required to limit transmission.59 Up to 86% of early COVID-19 cases inChina were undiagnosed, and theseinfections were the source for 79% ofdocumented cases.84SARS-CoV-2 (COVID-19)Host range – how many species does itinfect? Can it transfer from species tospecies? Early genomic analysis indicatessimilarity to SARS,154 with asuggested bat origin.5,42, 154 Analysis of SARS-CoV-2 genomessuggests that a non-bat intermediatespecies is responsible for thebeginning of the outbreak.108 Theidentity of the intermediate hostremains unknown.85, 87-88 Positive samples from the SouthChina Seafood Market stronglysuggests a wildlife source,33 though itis possible that the virus wascirculating in humans before thedisease was associated with theseafood market.18, 43, 144, 148 Experiments suggest that SARS-CoV2 Spike (S) receptor-binding domainbinds the human cell receptor (ACE2)stronger than SARS,141 potentiallyexplaining its high transmissibility;the same work suggests thatdifferences between SARS-CoV-2 andSARS-CoV Spike proteins may limitthe therapeutic ability of SARSantibody treatments.141 Modeling between SARS-CoV-2 Spikeand ACE2 proteins suggests thatSARS-CoV-2 can bind and infecthuman, bat, civet, monkey and swinecells.129 There is currently no experimentalevidence that SARS-CoV-2 infectsdomestic animals or livestock,though it is expected that someanimal species could be infected.CLEARED FOR PUBLIC RELEASEUpdated 3/18/2020Incubation period – how long afterinfection do symptoms appear? Arepeople infectious during this time? The best current estimate of theCOVID-19 incubation period is 5.1days, with 99% of individualsexhibiting symptoms within 14 daysof exposure.79 Fewer than 2.5% ofinfected individuals show symptomssooner than 2 days after exposure.79 The reported range of incubationperiods is wide, with high-endestimates of 24,60 11.3,11 and 18days.83 Individuals can test positive forCOVID-19 despite lacking clinicalsymptoms.12, 35, 60, 120, 151 Individuals can be infectious whileasymptomatic,31, 110, 120, 151 andasymptomatic individuals can havesimilar amounts of virus in their noseand throat as symptomaticindividuals.155 Infectious period is unknown, butpossibly up to 10-14 days 5, 84, 114 On average, there are approximately454 to 7.583 days between symptomonset in successive cases of a singletransmission chain. Most individuals are admitted to thehospital within 8-14 days ofsymptom onset.153 Patients are positive for COVID-19via PCR for 8-37 days after symptomonset.153 Individuals may test positive via PCRfor 5-13 days after symptomrecovery and hospital discharge.77The ability of these individuals toinfect others is unknown. According to the WHO, there is noevidence of re-infection with SARSCoV-2 after recovery.78 Experimentally infected macaqueswere not capable of being reinfectedafter their primary infectionresolved.131
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2(COVID-19)Infectious dose – how much agent willmake a normal individual ill?What do we needto know? Human infectious dose by aerosolroute Human infectious dose by surfacecontact (fomite) Human infectious dose by fecal-oralrouteWho is doingexperiments/hascapabilities in thisarea?Capable of performing work- DHS National Biodefense Analysis andCountermeasures Center (NBACC)Transmissibility – How does it spreadfrom one host to another? How easilyis it spread? Capability of SARS-CoV-2 to betransmitted by contact with fomites(doorknobs, surfaces, clothing, etc.)– see also Experimental Stability Superspreading capacity needs to berefined Updated person to persontransmission rates (e.g., R0) ascontrol measures take effect What is the underreporting rate?71 Can individuals become re-infectedwith SARS-CoV-2? What is the difference intransmissibility among countries? Is the R0 estimate higher inhealthcare or long-term carefacilities?Performing work:- Christian Althaus (Bern)- Neil Ferguson (MRC)- Gabriel Leung, Joseph Wu (Universityof Hong Kong)- Sara Del Valle (Los Alamos)- Maimuna Majumder (BostonChildren’s Hospital)- Trevor Bedford (Fred HutchinsonCancer Center)- Sang Woo Park (Princeton)SARS-CoV-2 (COVID-19)Updated 3/18/2020Host range – how many species does itinfect? Can it transfer from species tospecies? What is the intermediate host(s)? What are the mutations in SARS-CoV2 that allowed human infection andtransmission? What animals can SARS-CoV-2 infect(e.g., pet dogs, potential wildlifereservoirs)?Incubation period – how long afterinfection do symptoms appear? Arepeople infectious during this time? What is the average infectious periodduring which individuals can transmitthe disease? Are individuals infectious afterhospital discharge and clinicalrecovery, or are positive PCR testsonly detecting non-infectious virus? Can individuals become re-infectedafter recovery? If so, how long after?Capable of performing work:- Vincent Munster (Rocky MountainNational Laboratory)- Matthew Frieman (University ofMaryland Baltimore)- Ralph Baric (University of NorthCarolina)- Stanley Perlman (University of Iowa)- Susan Baker (Loyola UniversityChicago)- Mark Denison (Vanderbilt University)- Vineet Menachery (University of TexasMedical Branch)- Jason McLellan, Daniel Wrapp,Nianshuang Wang (University ofTexas)- David O’Conner (U. Wisconsin,Madison)Performing work:- Chaolin Huang (Jin Yin-tan Hospital,Wuhan, China)- The Novel Coronavirus PneumoniaEmergency Response EpidemiologyTeamCLEARED FOR PUBLIC RELEASE2
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2(COVID-19)What do we know? Clinical presentation – what are thesigns and symptoms of an infectedperson?The majority of COVID-19 cases aremild (81%, N 44,000 cases)120Initial COVID-19 symptoms includefever (87.9% overall, but only 43.8%present with fever initially60), cough(67.7%60), fatigue, shortness of breath,headache, reduction in lymphocytecount.32, 38, 68 Headache37 and diarrheaare uncommon68, 82Complications include acuterespiratory distress (ARDS observed in17-29% of hospitalized patients,40, 67which leads to death in 4-15% ofcases40, 68, 130), pneumonia,96 cardiacinjury, secondary infection, kidneyfailure, arrhythmia, sepsis, andshock.60,68,130, 153Approximately 15% of hospitalizedpatients were classified as severe,60, 120and approximately 5% of patientswere admitted to the ICU.60, 120Most deaths are caused by respiratoryfailure or respiratory failure combinedwith myocardial (heart) damage.111The case fatality rate (CFR) depends oncomorbidities; cardiovascular disease,hypertension, diabetes, andrespiratory conditions all increase theCFR.120, 153The CFR increases with age; individualsolder than 60 are at higher risk ofdeath,120, 153 and 60% of confirmedfatalities have been male.120Children of all ages are susceptible toCOVID-19,53 though generally presentwith milder symptoms.39 Severesymptoms in children, however, arepossible.89In the US, 34% of hospitalizations havebeen individuals less than 44 yearsold.4 Based on one patient, aproductive immune response isgenerated and sustained for at least 7days.121 Clinical diagnosis – are there tools todiagnose infected individuals? Whenduring infection are they effective?PCR protocols and primers have beenwidely shared among internationalresearchers26, 45, 83, 116, 132, 136 thoughPCR-based diagnostic assays do notdifferentiate between active andinactive virus.A combination of pharyngeal (throat)RT-PCR and chest tomography are themost effective diagnostic criteria(correctly diagnosing 91.9% ofinfections).104 Single throat swabsalone detect 78.2% of true infections,while duplicate tests identify 86.2% ofinfections.104Nasal and pharyngeal swabs may beless effective as diagnostic specimensthan sputum and bronchoalveolarlavage fluid.131RT-PCR tests are able to identifyasymptomatic cases; SARS-CoV-2infection was identified in 2/114individuals previously cleared byclinical assessment.66The FDA released an Emergency UseAuthorization enabling laboratories todevelop and use tests in-house forpatient diagnosis.58Updated tests from the US CDC areavailable to states.26, 31US CDC has expanded patient testingcriteria to include symptomaticpatients at clinician discretion.16Several rapid or real-time test kitshave been produced by universitiesand industry, including the WuhanInstitute of Virology,48 BGI,19 andCepheid.128The US CDC is developing serologicaltests to determine what proportion ofthe population has been exposed toSARS-CoV-2.74Machine learning tools are beingdeveloped to predict severe and fatalCOVID-19 cases based on CT scans.117SARS-CoV-2 (COVID-19)Updated 3/18/2020Medical treatment – are there effectivetreatments? Vaccines?Environmental stability – how long doesthe agent live in the environment? Treatment for COVID-19 is primarilysupportive care, including mechanicalventilation and antibiotics to preventsecondary infection as appropriate.60 Preliminary reports from two clinicaltrials in China suggest that favipiravirimproves lung function and reducesrecovery time in COVID-19 patients.126 Early results suggest that tocilizumabmay be effective at treating severeCOVID-19 cases.145 Press reports of a small clinical trialsuggest that chloroquine is effective atreducing symptom duration.1 Combination lopinavir and ritonavirwith standard care was no moreeffective than standard care alone.24 Corticosteroids are commonly given toCOVID-19 patients153 at risk ofARDS,146 but their use is notrecommended by the US CDC.29 Multiple entities are working toproduce a SARS-CoV-2 vaccine,8including NIH/NIAID,63, 80 ModernaTherapeutics and Gilead Sciences, 2-3, 94and Sanofi with HHS.21 Moderna hasbegun phase 1 clinical vaccine trials inhumans in WA state.107 Regeneron Pharmaceuticals hasdeveloped potential SARS-CoV-2antibody therapies.99 The development of a coronavirusfusion inhibitor in the lab suggestsefficacy across multiple humancoronaviruses.143 Takeda Pharma (Japan) is working tocreate antibody treatments based oninfected patient plasma.62SARS-CoV-2 Data SARS-CoV-2 can persist on plastic andstainless steel surfaces for up to 3 days(at 21-23oC, 40% RH), with a half-life of13-16 hours.125 SARS-CoV-2 has an aerosol half-life of2.7 hours (particles 5 μm, tested at21-23oC and 65% RH).125Surrogate Coronavirus data: Studies suggest that othercoronaviruses can survive on nonporous surfaces up to 9-10 days (MHV,SARS-CoV)25, 36, and porous surfaces forup to 3-5 days (SARS-CoV)56 in airconditioned environments (20-25oC,40-50% RH) Coronavirus survival tends to be higherat lower temperatures and lowerrelative humidity (RH),25, 36, 102, 127though infectious virus can persist onsurfaces for several days in typicaloffice or hospital conditions127 SARS can persist with trace infectivityfor up to 28 days at refrigeratedtemperatures (4oC) on surfaces.25 Beta-coronaviruses (e.g., SARS-CoV)may be more stable than alphacoronaviruses (HCoV-229E).102 No strong evidence for reduction intransmission with seasonal increase intemperature and humidity.92 One hour after aerosolizationapproximately 63% of airborne MERSvirus remained viable in a simulatedoffice environment (25oC, 75% RH)100 The aerosol survival of related humancoronavirus (229E) was relatively high,(half-life of 67 hours at 20oC and 50%RH), indicating 20% of infectious virusremained after 6 days.70 Both higherand lower RH reduced HCoV-229Esurvival; lower temperatures improvedsurvival.70CLEARED FOR PUBLIC RELEASE3
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2(COVID-19)What do we needto know?Who is doingexperiments/hascapabilities in thisarea?Clinical presentation – what are thesigns and symptoms of an infectedperson? How long does it take for infectedindividuals to recover outside of ahealthcare setting? Is the reduction in CFR through timean indication of better treatment, lessovercrowding, or both?Clinical diagnosis – are there tools todiagnose infected individuals? Whenduring infection are they effective? False positive/negative rates for tests Eclipse phase of infection (timebetween infection and detectabledisease) in an individual- Jin Yin-tan Hospital, Wuhan, China- China-Japan Friendship Hospital,Beijing, China- Peking Union Medical College, Beijing,China- Capital Medical University, Beijing,China- Chinese Academy of Medical Sciencesand Peking Union Medical College,Beijing, China- Huazhong University of Science andTechnology, Wuhan, China- The Central Hospital of Wuhan, TongjiMedical College, Huazhong University ofScience and Technology, Wuhan, China- Tsinghua University School of Medicine,Beijing, China- Zhongnan Hospital of Wuhan University,Wuhan, China- Peking University First Hospital, Beijing,China- Peking University People's Hospital,Beijing, China- Tsinghua University-Peking UniversityJoint Center for Life Sciences, Beijing,China- The Fifth Medical Center of PLA GeneralHospital, Beijing, ChinaPerforming work:- CDC- Wuhan Institute of Virology- Public Health Agency of Canada- Doherty Institute of Australia- Cepheid- BGI- Fudan UniversitySARS-CoV-2 (COVID-19)Updated 3/18/2020Medical treatment – are there effectivetreatments? Vaccines?Environmental stability – how long doesthe agent live in the environment? Is GS-5734 (remdesivir) effective invivo (already used in clinical trialsunder Emergency UseAuthorization)?115 Is the GLS-5000 MERS vaccine147cross-reactive against SARS-CoV-2? Efficacy of antibody treatmentsdeveloped for SARS46, 119 and MERS34 What is the efficacy of various MERSand SARS Phase I/II vaccines and othertherapeutics? Are viral replicase inhibitors such asbeta-D-N4-hydroxycytidine effectiveagainst SARS-CoV-2?15 Stability of SARS-CoV-2 in aerosol,droplets, and other matrices(mucus/sputum, feces) Particle size distribution (e.g., droplet,large droplet and true aerosoldistribution) Duration of SARS-CoV-2 infectivity viafomites and surface (contact hazard)? Stability of SARS-CoV-2 on PPE (e.g.,Tyvek, nitrile, etc.)Performing work:Peter Doherty Institute for Infectionand Immunity- Academy of Military Medical Sciences,Beijing, China- Tim Sheahan (University of NorthCarolina)- Takeda Pharma. (Japan)- Regeneron Pharmaceuticals- CureVac (Germany)Capable of performing work:- Ralph Baric (University of NorthCarolina)- Matthew Frieman (University ofMaryland Baltimore)- Sanofi, with BARDA- Janssen Pharma and BARDA64Funded work:CEPI ( 24 million to seven groups):NIAID/NIH:- Moderna and Kaiser Permanente formRNA vaccine Phase I trial.3- University of Nebraska Medical CenterTrial (multiple therapeutics includingGilead’s Remdesivir).2Capable of performing work:- Mark Sobsey (University of NorthCarolina)- DHS National Biodefense Analysis andCountermeasures Center (NBACC)- Defence Science and TechnologyLaboratory (Dstl)- Public Health Agency of Canada- CDC- EPA- NIH-CLEARED FOR PUBLIC RELEASE4
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2(COVID-19)What do we know?Decontamination – what are effectivemethods to kill the agent in theenvironment?SARS-CoV-2 Twice-daily cleaning with sodiumdichloroisocyanuratedecontaminated surfaces in COVID19 patient hospital rooms.95 Alcohol-based hand rubs areeffective at inactivating SARS-CoV-2in liquid.75 EPA has released a list of SARS-CoV-2disinfectants, but solutions were nottested on live virus.6Other Coronaviruses Chlorine-based134 and ethanolbased44 solutions recommended. Heat treatment at 56oC is sufficientto kill coronaviruses,102, 152 thougheffectiveness depends in part onamount of protein in contaminatedmedia102 70% ethanol, 50% isopropanol,sodium hypochlorite [bleach, 200ppm], and UV radiation are effectiveat inactivating several coronaviruses(MHV and CCV)112 Ethanol-based biocides are effectivedisinfectants against coronavirusesdried on surfaces, including ethanolcontaining gels similar to handsanitizer.69, 139 Surface spray disinfectants such asMikrobac, Dismozon, and Korsolexare effective at reducing infectivity ofthe closely related SARS-CoV after 30minutes of contact.101 Coronaviruses may be resistant tothermal inactivation for up to 7 dayswhen stabilized in stool.122-123 Additionally, coronaviruses are morestable in matrixes such as respiratorysputum.55 Hydrogen peroxide vapor is expectedto be effective at repeateddecontamination of N95 respiratorsbased on other pathogens.105SARS-CoV-2 (COVID-19)Updated 3/18/2020PPE – what PPE is effective, and whoshould be using it?Forensics – natural vs intentional use?Tests to be used for attribution.Genomics – how does the disease agentcompare to previous strains? PPE effectiveness for SARS-CoV-2 iscurrently unknown; SARS is used as asurrogate. Healthcare worker illnesses (over1,000120) demonstrates human-tohuman transmission despite isolation,PPE, and infection control.113 US CDC does not recommend the useof facemasks for healthy people.Facemasks should be used by peopleshowing symptoms to reduce the riskof others getting infected. The use offacemasks is crucial for healthworkers and people in close contactwith infected patients (at home or ina health care facility).28 “Healthcare personnel entering theroom [of SARS-CoV-2 patients] shoulduse standard precautions, contactprecautions, airborne precautions,and use eye protection (e.g., gogglesor a face shield)”30 WHO indicates healthcare workersshould wear clean, non-sterile, longsleeve gowns as well as gloves.133 Respirators (NIOSH-certified N95,EUFFP2 or equivalent) arerecommended for those dealing withpossible aerosols134 Additional protection, such as aPowered Air Purifying Respirator(PAPR) with a full hood, should beconsidered for high-risk procedures(i.e., intubation, ventilation)23 SARS-CoV-2 transmission has occurredin hospitals inside130 and outside ofChina,61 including the US.20 Porous hospital materials, includingpaper and cotton cloth, maintaininfectious SARS-CoV for a shortertime than non-porous material.76 Despite extensive environmentalcontamination, air sampling in patientrooms did not detect SARS-CoV-2.95 Genomic analysis places SARS-CoV-2into the beta-coronavirus clade, withclose relationship to bat viruses. TheSARS-CoV-2 virus is distinct from SARSand MERS viruses.52 Genomic analysis suggest that SARSCoV-2 is a natural variant, and istherefore unlikely to be humanderived or otherwise created by“recombination” with other circulatingstrains of coronavirus.9, 154 Some genomic evidence indicates aclose relationship with pangolincoronaviruses140; data suggests thatpangolins may be a natural host forbeta-coronaviruses 87-88. Additionalresearch is needed. Genomic data support at least twoplausible origins of SARS-CoV-2: “(i)natural selection in a non-humananimal host prior to zoonotic transfer,and (ii) natural selection in humansfollowing zoonotic transfer.”9 Eitherscenario is consistent the observedgenetic changes found in all knownSARS-CoV-2 isolates. Additionally, “[ ] SARS-CoV-2 is notderived from any previously used virusbackbone,” reducing the likelihood oflaboratory origination,9 and “[ ]genomic evidence does not supportthe idea that SARS-CoV-2 is alaboratory construct, [though] it iscurrently impossible to prove ordisprove the other theories of itsorigin.”9 There have been no documented casesof SARS-CoV-2 prior to December 2019 Preliminary genomic analyses,however, suggest that the first humancases of SARS-CoV-2 emerged between10/19/2019 – 12/17/2019.10, 18, 103 The mutation rate of SARS-CoV-2 isestimated to be similar to other RNAviruses (e.g., SARS, Ebola, Zika), and iscurrently calculated to be 1.04x10-3substitutions per site per year (N 116genomes).65 Preliminary phylogenetic analysisidentified a very close genetic similaritybetween SARS-CoV-2 and a Batcoronavirus (RaTG13) isolated fromYunnan Province, China; suggestingthat SARS-CoV-2 originated frombats.97 Pangolin coronaviruses are closelyrelated to both SARS-CoV-2 and theclosely related Bat coronavirus(RaTG13); phylogenetic analysissuggested that SARS-CoV-2 is of batorigin, but is closely related to pangolincoronavirus.87-88 The Spike protein of SARS-CoV-2,which mediates entry into host cellsand is the major determinant of hostrange, is very similar to the Spikeprotein of SARS-CoV.91 The rest of thegenome is more closely related to twoseparate bat 91 and pangolin88coronavirus. Analysis of SARS-CoV-2 sequences fromSingapore has identified a largenucleotide (382 bp) deletion in ORF-8that may result in an attenuated (lessvirulent) phenotype.118CLEARED FOR PUBLIC RELEASE5
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2(COVID-19)What do we needto know?Who is doingexperiments/hascapabilities in thisarea?Decontamination – what are effectivemethods to kill the agent in theenvironment? What is the minimal contact time fordisinfectants? Does contamination with humanfluids/waste alter disinfectant efficacyprofiles? How effective is air filtration atreducing transmission in healthcare,airplanes and public spaces?Capable of performing work:- DHS National Biodefense Analysisand Countermeasures Center(NBACC)SARS-CoV-2 (COVID-19)Updated 3/18/2020PPE – what PPE is effective, and whoshould be using it?Forensics – natural vs intentional use?Tests to be used for attribution.Genomics – how does the disease agentcompare to previous strains? Mode of aerosol transmission?Effective distance of spread viadroplet or aerosol? How effective are barriers such asN95 respirators or surgical masks? What is the appropriate PPE for firstresponders? Airport screeners? Proper procedures for reducingspread in medical facilities /transmission rate in medical settingsGenerating recommendations:- WHO- CDC- Pan-American Health Organization What tests for attribution exist forcoronavirus emergence? What is the identity of theintermediate species? Are there closely related circulatingcoronaviruses in bats or other animalswith the novel PRRA cleavage sitefound in SARS-CoV-2? Are there similar genomic differencesin the progression of coronavirusstrains from bat to intermediatespecies to human? Are there different strains or clades ofcirculating virus? If so, do they differ invirulence?Performing genomic investigations:- Kristian Andersen, Andrew Rambaut,Ian Lipkin, Edward Holmes, RobertGarry (Scripps, University ofEdinburgh, Columbia University,University of Sydney, Tulane, ZalgenLabs [Germantown, MD])Capable of performing work:- Pacific Northwest National Laboratory- DHS National Biodefense Analysis andCountermeasures Center (NBACC)Performing work:- Trevor Bedford (Fred HutchinsonCancer Research Center)- Ralph Baric, UNC- National Institute for Viral DiseaseControl and Prevention, ChineseCenter for Disease Control andPrevention- Shandong First Medical University andShandong Academy of MedicalSciences- Hubei Provincial Center for DiseaseControl and Prevention- Chinese Academy of Sciences- BGI PathoGenesis PharmaceuticalTechnology, Shenzhen, China- People's Liberation Army GeneralHospital, Wuhan, China- Wenzhou Medical University,Wenzhou, China- University of Sydney, Sydney, NSW,Australia- The First Affiliated Hospital ofShandong First Medical University(Shandong Provincial QianfoshanHospital), Jinan, ChinaCLEARED FOR PUBLIC RELEASE6
REQUIRED INFORMATION FOR EFFECTIVE INFECTIOUS DISEASE OUTBREAK RESPONSESARS-CoV-2 (COVID-19)Updated 3/18/2020Table 1. Definitions of commonly-used acronymsAcronym/TermDefinitionDescriptionAttack RateProportion of “at-risk”individuals who developinfectionDefined in terms of “at-risk” population such as schools or households, defines the proportion ofindividuals in those populations who become infected after contact with an infectious individualSARS-CoV-2Severe acute respiratorysyndrome coronavirus 2Official name for the virus previously known as 2019-nCoV.COVID-19Coronavirus disease 19Official name for the disease caused by the SARS-CoV-2 virus.CFRCase Fatality RateNumber of deaths divided by confirmed patientsPFUPlaque forming unitMeasurement of the number of infectious virus particles as determined by plaque forming assay. Ameasurement of sample infectivity.TCID5050% Tissue Culture InfectiousDoseThe number of infectious units which will infect 50% of tissue culture monolayers. A measurement ofsample infectivity.HCWHealthcare workerDoctors, nurses, te
DHS Science and Technology Directorate MOBILIZING INNOVATION FOR A SECURE WORLD CLEARED FOR PUBLIC RELEASE DHS SCIENCE AND TECHNOLOGY Master Question List for COVID-19 (caused by SARS-CoV-2) Weekly Report 18 March 2020. For comments or questions related to the contents of this document, please contact the DHS S&T
