Limiteddataareavailableforclinicalcharacteristicsofpatientswithcoronavirusdisease
2019(COVID-19)outsideWuhan.Thisstudyaimedtodescribetheclinicalcharacteristicsof
COVID-19andidentifytheriskfactorsforsevereillnessofCOVID-19inJiangsuprovince,
China.ClinicaldataofhospitalizedCOVID-19patientswereretrospectivelycollectedin8
hospitalsfrom8citiesofJiangsuprovince,China.ClinicalfindingsofCOVID-19patientswere
describedandriskfactorsforsevereillnessofCOVID-19wereanalyzed.ByFeb10,2020,202
hospitalizedpatientswithCOVID-19wereenrolled.Themedianageofpatientswas44.0years
(interquartilerange,33.0-54.0).55(27.2%)patientshadcomorbidities.Attheonsetofillness,
thecommonsymptomswerefever(156[77.2%])andcough(120[59.4%]).66(32.7%)patients
hadlymphopenia.193(95.5%)patientshadabnormalradiologicalfindings.11(5.4%)patients
wereadmittedtotheintensivecareunitandnoneofthepatientsdied.23(11.4%)patientshad
severeillness.SevereillnessofCOVID-19wasindependentlyassociatedwithbodymass
index(BMI)≥28kg/m2(oddsratio[OR],9.219;95%confidenceinterval[CI],2.731to31.126;
P<0.001)andaknownhistoryoftype2diabetes(OR,4.326;95%CI,1.059to17.668;P=
0.041).InthiscaseseriesinJiangsuProvince,COVID-19patientshadlessseveresymptoms
andhadbetteroutcomesthantheinitialCOVID-19patientsinWuhan.TheBMI≥28kg/m2
andaknownhistoryoftype2diabeteswereindependentriskfactorsofsevereillnessin
patientswithCOVID-19.
Coronavirusdisease2019(COVID-19)isaninfectiousdiseasecausedbyanovelstrainof
coronavirus,severeacuterespiratorysyndromecoronavirus2(SARS-CoV-2),thatappearedin
ChinainDecember2019andspreadglobally,evolvingintothecurrentlyobservedpandemic.
•ThelaboratorydiagnosisofSARS-CoV-2infectioniscurrentlybasedonreal-timereverse
transcriptase-polymerasechainreaction(RT-PCR)testing,andimagingcannotreplace
genetictestinginpatientssuspectedofCOVID-19.However,withpredominantrespiratory
manifestationsofCOVID-19,particularlyinmoreseverecases,chestimagingusingcomputed
tomography(CT)playsamajorroleindetectingvirallunginfection,evaluatingthenatureand
extentofpulmonarylesions,andmonitoringthediseaseactivity.TheroleofchestCTasa
diagnostictoolmaybeincreasedwhenthelaboratorytestingcapacitiesusingRT-PCRprove
inaccurateorinsufficientduringamajoroutbreakofthedisease.Inthesesettings,arapid
presumptivediagnosisofCOVID-19potentiallyofferedbyCTmightbeanadvantageous.
•TherecentSARS-CoV-2outbreakhasplacedimmensepressureonsupplychains,including
shortagesinnasopharyngeal(NP)swabs.
•BackgroundChestradiography(CXR)mayplayanimportantroleintriageforCOVID-19,

particularlyinlow-resourcesettings.PurposeToevaluatetheperformanceofanartificial
intelligence(AI)systemfordetectionofCOVID-19pneumoniaonchestradiographs.Methods
AnAIsystem(CAD4COVID-Xray)wastrainedon24,678CXRimagesincluding1,540usedonly
forvalidationwhiletraining.ThetestsetconsistedofasetofcontinuouslyacquiredCXR
images(n=454)obtainedinpatientssuspectedforCOVID-19pneumoniabetweenMarch4th
andApril6th2020inasinglecenter(223RT-PCRpositivesubjects,231RT-PCRnegative
subjects).TheradiographswereindependentlyanalyzedbysixreadersandbytheAIsystem.
Diagnosticperformancewasperformedbyreceiveroperatingcharacteristiccurveanalysis.
ResultsForthetestset,themeanageofthepatientswas67.3(+/-14.4)years(56%male).
UsingRT-PCRtestresultsasthereferencestandard,theAIsystemcorrectlyclassifiedCXR
imagesasCOVID-19pneumoniawithanAUCof0.81.Thesystemsignificantlyoutperforms
eachreader(p<0.001usingMcNemartest)attheirhighestpossiblesensitivities.Attheir
lowestsensitivities,onlyonereadercansignificantlyoutperformtheAIsystem(p=0.04).
ConclusionsAnAIsystemfordetectionofCOVID-19onchestradiographswascomparableto
sixindependentreaders.
ThePublicHealthAgencyofSwedenhasanalysedhowmanypregnantandpostpartum
womenwithSARS-CoV-2infectionhavebeentreatedinintensivecareunits(ICU)inSweden
betweentheMarch19andApril20,2020,comparedwithnon-pregnantwomenofsimilarage.
CaseswereidentifiedinaspecialreportingmodulewithintheSwedishIntensiveCareRegistry
(SIR).Fifty-threewomenaged20-45yearswithSARS-CoV-2werereportedinSIR,andthirteen
(n=13)ofthesewomenwereeitherpregnantorpostpartum(<1week).Theresultsindicate
thattheriskofbeingadmittedtoICUmaybehigherinpregnantandpostpartumwomenwith
laboratory-confirmedSARS-CoV-2inSweden,comparedtonon-pregnantwomenofsimilar
age.
Theantimalarials,ChloroquineandHydroxychloroquine(HCQ),andtheantivirals
Lopinavir/Ritonavirhavebeenrecentlyrecordedashavinganti-severeacuterespiratory
syndromecoronavirus2(SARS-CoV-2)effects.1Inparticular,regardingItaly,oneofthe
countriesmostaffectedbythepandemic,theItalianSocietyofInfectiousandTropical
disease(Lombardysection)hasrecommendedtheuseofHCQfortreatmentofcoronavirus
disease2019(COVID-19).
FinallydemonstratedthatthecrystalstructureofMproprovidesabasisfordesigningofa
potentinhibitortotheproteasewithamarkedtropismtothelungandwitheaseof
administrationthroughinhalation.
LStudyingthecrystalstructureoftargetsfortreatmentisverycrucialtoknowthemechanism
ofactionofprospectivedrugs.Astructuralstudyonthecoronavirusmainprotease3CLpro
inhibitorcomplexestablisheddesigningofbroad-spectrumhalomethylketoneinhibitorstothe
Coronaviridaefamilyanddemonstratedthattheseinhibitorsformathioetherlinkagewithhigh
affinitytothetarget3.Hilgenfeld’sgroupreportedearlierthatastructure-baseddesignof
peptidomimeticα-ketoamidesarealsoeffectivebroad-spectruminhibitorstothemainand3Cproteaseofcoronavirusesandenterovirusesasdemonstratedbycrystalstructureofinhibitor￾proteasecomplex4.The3CLproteaseofcoronavirusesfacilitatesviralassemblybycleaving
polyproteinsandmostactivecompoundspreventdiseaseprogressionbyinhibitingviral
proteases5.Instudy,Zhangetal.modifiedthepreviouslydesignedbestinhibitor(11r)to
increaseitshalf-lifeinplasma,increaseitssolubilityandreduceitsbindingtoplasma
proteins1.Here,theauthorshidetheP2-P3amidebondintoapyridoneringtopreventitfrom
cleavagebycellularproteasessothatitsplasmahalf-lifeisincreased.Toincreasesolubility
oftheinhibitorandreduceitsbindingtoplasmaproteins,theauthorsreplacedthe
hydrophobiccinnamoylmoietywithalesshydrophobicBocgroup.
Theintroducedpyridoneringshouldbecompatiblewiththethree-dimensionalstructureofthe
targetwhichhasacrucialroleforeffectiveinhibition.Inordertoconfirmthis,theauthors
solvedthecrystalstructureofMproofSARS-CoV-2at1.75 Åresolutionandfoundthatthe
crystalstructureishighlysimilartothatofSARS-CoVMproonlywitha0.53 År.m.sdifference
betweenthetwofreeenzymes.SARS-CoV-2Mproformsatightdimerandhasacontact
interfacemainlybetweendomainIIofmoleculeAandtheNH2-terminalresiduesofmolecule
Bwherethisdimerizationisimportantforcatalyticactivity.UnlikeSARS-CoV-2,SARS-CoV
MprodimerhasapolarinteractionbetweenthetwodomainsIIIinvolvinga2.60 Åhydrogen
bondbetweenthesidechainhydroxylgroupsofThr285ofeachprotomerwhichisalso
supportedbyahydrophobicinteractionbetweenthesidechainofIle286andThr285.InSARS￾CoV-2Mpro,threonineisreplacedwithalanineandisoleucinewithleucine.Assuggestedby
authors,Alaninereplacementschangetheenzymedynamicsandincreaseitscatalyticactivity
byallowingthetwodomainsIIItobeinaclosecontact;although,thecatalyticactivityofSARS
-CoV-2MprowasonlyslightlyhigherwithsimilarKdofdimerdissociation(~2.5 μM).
Comparedto11r,13ahasa3foldincreaseinplasmahalf-lifeinmice,highlysolubleinplasma
witha19foldincreaseinsolubilityin-vitroanda13foldincreaseinthermodynamicsolubility.
Furtherthebindingof13awithplasmaproteinswasreportedtodecreaseto97%as
comparedto11rwhichshowed99%bindingactivitywithplasmaproteins.Providedthese
improvements,thestructuralmodificationresultedinlossofsomeinhibitoryactivitiesagainst
themainproteaseofSARS-CoV-2and3C
proteasesofenterovirusesasevidencedby
increasedIC50value.Theauthorsincreasetheantiviralactivityof13bagainstbeta
coronavirusesofcladebbysacrificingthebroad-spectrumnatureof13athroughreplacing
theP2cyclohexylmoietyin13awithasmallcyclopropylin13b.TheauthorsdeterminedtheX￾raystructureofα-ketoamide13bandSARS-CoV-2Mprocomplexat1.95and2.20 Åresolution.
Inoneofthestructures,theauthorsfoundthatthekeyresidue,Glu166,formsinactive
conformationinprotomerBwhilethe13bcompoundisboundinthesamefashionasin
moleculeA.Authorsalsofoundthattheinhibitorbindstotheshallowsubstrate-bindingsiteat
thesurfaceofprotomersbetweendomainsIandIIintheinhibitedSARS-CoV-2Mpro.
TheBocgroupwasremovedincompound14bresultingininactiveformwhichmeanstheBoc
groupisnecessarytocrossthecellularmembraneandevenmorehydrophobicmoietymaybe
advantageousprovidedthatitmayresultinincreasedplasmaproteinbinding.Hilgenfeld’s.

groupassessedthepharmacokineticsof13aand13bandfoundthattheabsorption￾distribution-metabolism-excretionofbothcompoundswassimilarwitha90%bindingto
humanplasmaproteins.The13bshowedlessclearancecomparedto13aandgoodtropism
tothelungswithawell-toleratedadministrationthroughinhalationinmice.Takentogether,
theauthorsdesignedα-ketoamideinhibitorswithimprovedinhibitionefficiencyagainst
recombinantSARS-CoV-2Mprotosuppressdiseaseprogress.Their workprovides
insightsintothedevelopmentofmorepotentpyridonecontaininganti-coronaviraldrugs.
Futurestructural-functionalstudiesarerecommendedtoimprovetheefficacyoftargeted
therapiestotackletheemergingpandemicsduetocoronaviruses.