COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes

Abstract

Background There is a growing need for information regarding the recent coronavirus disease of 2019 (Covid-19). We present a comprehensive report of Covid-19 patients in Iran.
Methods One hundred hospitalized patients with Covid-19 were studied. Data on potential source of exposure, demographic, clinical, and paraclinical features, therapy outcome, and post-discharge follow-up were analyzed.
Results The median age of the patients was 58 years, and the majority of the patients (72.7%) were above 50 years of age. Fever was present in 45.2% of the patients on admission. The most common clinical symptoms were shortness of breath (74%) and cough (68%). Most patients had elevated C-reactive protein (92.3%), elevated erythrocyte sedimentation rate (82.9%), lymphocytopenia (74.2 %) on admission. Lower lobes of the lung were most commonly involved, and ground-glass opacity (81.8%) was the most frequent finding in CT scans. The administration of hydroxychloroquine improved the clinical outcome of the patients. Lopinavir/ritonavir was efficacious at younger ages. Of the 70 discharged patients, 40% had symptom relapse, (8.6%) were readmitted to the hospital, and 3 patients (4.3%) died.
Conclusions This report demonstrates a heterogeneous nature of clinical manifestations in patients affected with Covid-19. The most common presenting symptoms are non-specific, so attention should be made on broader testing, especially in age groups with the greatest risk and younger individuals who can serve as carriers of the disease. Hydroxychloroquine and lopinavir/ritonavir (in younger age group) can be potential treatment options. Finally, patients discharged from the hospital should be followed up because of potential symptom relapse.

Full text

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Preprint:Pleasenotethatthisarticlehasnotcompletedpeerreview.
COVID-19inIran,acomprehensiveinvestigationfrom
exposuretotreatmentoutcomes
CURRENTSTATUS:UND ERREVI EW
MohammadAliAshraf
ShirazUniversityofMedicalSciences
NasimShokouhi
TehranUniversityofMedicalSciences
ElhamShirali
TehranUniversityofMedicalSciences
FatemeDavari-tanha
TehranUniversityofMedicalSciences
OmeedMemar
AcademicDermatologyandSkinCancerInstitute,Chicago,IL
AlirezaKamalipour
UniversityofCaliforniaSanDiego
AyeinAzarnoush
AlborzUniversityofMedicalSciences
AvinMabadi
IranUniversityofMedicalSciences
AdeleOssareh
ShahidBeheshtiUniversity
MiladSanginabadi
TehranUniversityofMedicalSciences
TalatMokhtariAzad
TehranUniversityofMedicalSciences
LeilaAghaghazvini
TehranUniversityofMedicalSciences

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SaraGhaderkhani
TehranUniversityofMedicalSciences
TaherehPoordast
ShirazUniversityofMedicalSciences
AliehPourdast
TehranUniversityofMedicalSciences
PershangNazemi
TehranUniversityofMedicalSciences
nazemipershang@gmail.comCorrespondingAuthor
ORCiD:https://orcid.org/0000-0003-2991-7923
10.21203/rs.3.rs-26339/v1
SUBJECTAREAS
InfectiousDiseases
KEYWORDS
Coronavirusdisease2019(COVID-19);2019-nCoV;SARS-CoV-2;Iran;clinical
characteristics;treatmentoutcomes

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Abstract
BackgroundThereisagrowingneedforinformationregardingtherecentcoronavirusdiseaseof2019
(Covid-19).WepresentacomprehensivereportofCovid-19patientsinIran.
MethodsOnehundredhospitalizedpatientswithCovid-19werestudied.Dataonpotentialsourceof
exposure,demographic,clinical,andparaclinicalfeatures,therapyoutcome,andpost-discharge
follow-upwereanalyzed.
ResultsThemedianageofthepatientswas58years,andthemajorityofthepatients(72.7%)were
above50yearsofage.Feverwaspresentin45.2%ofthepatientsonadmission.Themostcommon
clinicalsymptomswereshortnessofbreath(74%)andcough(68%).MostpatientshadelevatedC-
reactiveprotein(92.3%),elevatederythrocytesedimentationrate(82.9%),lymphocytopenia(74.2%)
onadmission.Lowerlobesofthelungweremostcommonlyinvolved,andground-glassopacity
(81.8%)wasthemostfrequentfindinginCTscans.Theadministrationofhydroxychloroquine
improvedtheclinicaloutcomeofthepatients.Lopinavir/ritonavirwasefficaciousatyoungerages.Of
the70dischargedpatients,40%hadsymptomrelapse,(8.6%)werereadmittedtothehospital,and3
patients(4.3%)died.
ConclusionsThisreportdemonstratesaheterogeneousnatureofclinicalmanifestationsinpatients
affectedwithCovid-19.Themostcommonpresentingsymptomsarenon-specific,soattentionshould
bemadeonbroadertesting,especiallyinagegroupswiththegreatestriskandyoungerindividuals
whocanserveascarriersofthedisease.Hydroxychloroquineandlopinavir/ritonavir(inyoungerage
group)canbepotentialtreatmentoptions.Finally,patientsdischargedfromthehospitalshouldbe
followedupbecauseofpotentialsymptomrelapse.
Introduction
Coronavirusesarethesecondcauseofthecommoncoldafterrhinoviruses.1Humancoronavirus
pathogenscancauseawiderangeofdiseasesfromthecommoncoldtoseverepneumonia.Two
previouslarge-scalepandemicsofcoronavirusinfectionsin2002–2003[coronavirus-severeacute
respiratorysyndrome(SARS)]and2012[coronavirus-MiddleEastrespiratorysyndrome(MERS)]had
severeglobalhealthimpacts.2,3Therecentcoronavirusdiseaseof2019(COVID-19)hasstrickenthe

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globalhealthandtheeconomyevenmorethanthepreviousones.Ithasspreadtomorethan209
countries/territoriesandhasinfectedmorethanamillionpeoplearoundtheworld.Iranhasbeenone
ofthemostseverelyaffectedcountriesbythevirus.4,5
Previousstudiesdescribedtheclinicalanddemographiccharacteristicsofthedisease.Information
regardingthetransmissionpatternismostlyrelatedtoChina.Thereisalso,alackofinformation
aboutthepotentialtreatmentoutcomes,andpost-hospitalizationfollow-upintheliterature.6–9
ThisstudyisoneofthefirstreportsofCOVID-19patientsfromIran.Wereporteddetailedinformation
aboutthepotentialsourceofexposure,householdcontactinformation,outcomesofpotential
therapies,andpost-dischargefollow-up,aswellasdemographic,clinical,andparaclinical
characteristics.
Methods
Patientsandstudyoverview
MedicalrecordsofsuspectedcasesofCOVID-19fromFebruary22,2020,toMarch5,2020,admitted
totheYAShospitalaffiliatedtoTehranUniversityofMedicalSciences,werereviewed.Ourhospital
wasthefirstcenterinTehrantocareforadultCOVID-19patients.Asuspectedcasewasdefinedasa
flu-likesyndrome/orsymptomaticpatientalongwithradiologicpulmonaryfindings.Dataofpatients
forwhomtheresultsofreverse-transcriptase-polymerase-chain-reaction(RT-PCR)werenotavailable
wasexcludedfromthestudy.COVID-19wasconfirmedusingRT-PCRofnasopharyngealspecimens.
ThisstudywasapprovedbytheTehranUniversityofMedicalSciences(TUMS)ethicscommittee
(IR.TUMS.VCR.REC.1398.1036).Informedconsentwasobtainedfromallpatientsortheirfirst-degree
relativesinunconsciouspatients.
Datasources
Patientswhocametothehospitalwereexaminedbyaninfectious-diseasespecialist,andclassified
intothreegroupsaccordingtodiseaseseveritybasedonIran’snationalguidelineforthediagnosis
andtreatmentofCOVID-19inoutpatientsandinpatients(Fig.1).10Patientsassignedtomoderateor
severeinfectiongroupwereadmittedtothehospital.
Patients’occupation,travelhistorywithinthepast14days,householdcontactinformation,

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demographiccharacteristics,potentialsourceofexposure,influenzavaccinationhistory,currentlist
ofmedications,pastmedicalhistory,socialhistory,andtheuseofpreventivemeasureswere
determined.
Historyofpresentillnessandcomprehensivereviewofsystemsweretaken,andacompletephysical
examinationwasdone.Clinicallaboratorystudiesandchestcomputedtomography(CTscan)were
requestedonthefirstdayofadmissionaccordingtoinfectiousdiseasespecialistrecommendations.
Wecollectedhospitalizationdatausingpatients’papermedicalrecords.
AvailableCTscanswerereportedbyaradiologistandscoredforseverityandlocationofinvolvement.
Thefinalreportswerereviewedbyaninfectiousdiseasespecialistandapulmonologist.
Themaintreatmentmedicationsincludedoseltamivir(75mgtwicedaily),hydroxychloroquine
(200mgtwicedaily/400mgsingledosewhencombinedadministrationwithLopinavir-Ritonavir),
Lopinavir-Ritonavir(400mgLopinavir-100mgRitonavirtwicedaily),andRibavirin(1200mgtwice
daily)accordingtothenationalguideline.10
Also,weconductedatelephonesurveyofpatientswhoweredischargedfromthehospital.A
questionnairewasdevelopedtofollowpatientsfor14dayspost-discharge.Weaskedpatientsabout
theepisodesofsymptomrelapse,theneedforhospitalreadmission,andwhethertheycompleted14
daysofhomequarantineafterdischarge.DischargedpatientswerefolloweduptoMarch19,2020.
Studyoutcomes
Thecriticalsituationofthepatients,whichwasdefinedasadmissiontoanintensivecareunit,theuse
ofmechanicalventilation,ordeath,wasconsideredasaprimarycompositeendpoint.Wecompared
demographiccharacteristics,hospitalizationdata,andpotentialtreatmentoutcomesincriticallyill
andnon-criticallyillpatients.Post-dischargefollow-upwasreportedfromthedischargedpatients.
Studydefinitions
IndexpatientwasdefinedasthefirstpersoninahouseholddiagnosedwithCovid19usingRT-PCR.
Theincubationperiodwascalculatedfromthetimebetweenthelastpotentialexposureandthetime
showingthefirstdiseasesymptoms.
Lunglobarscoreswerecalculatedusingascoringsystemgivingeachfivelobesascoregradedfrom

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0–4accordingtotheseverityoftheinvolvedlobe.(0 = notinvolved;1 = upto25%involvement;2 =
26–50%involvement;3 = 51–75%involvement;4 = 76–100%involvement).Thesumofalllobar
scorescombinedisdefinedasthetotallungscore,whichestimatestheseverityoftheentirelung
involvement(providesascorebetween0–20).Lowerlobesscorewasdefinedasthesumsofright
lowerlobeandleftlowerlobescores(providesascorebetween0–8).Themiddlelobescorewas
definedastherightmiddlelobescore(providesascorebetween0–4).Upperlobesscorewasdefined
asthesumsofrightupperlobeandleftupperlobescores(providesascorebetween0–8).
Laboratoryconfirmation
LaboratoryconfirmationofSARS-CoV2wasperformedintheNationalInfluenzaCenterlocatedatthe
SchoolofPublicHealth,TehranUniversityofMedicalSciences.Nasopharyngealswabspecimenswere
collectedfromhospitalizedpatientsusingDacronsterileswabsandplacedin2ccviraltransport
mediaandsenttothelaboratoryincoldcondition.AllsamplesweresubjectedtoRNAextractionwith
HighPureViralNucleicAcidKit(Roche,Germany)accordingtothemanufacturer’sinstructions.Real-
Time(RT)-PCRwasusedtodetectthepresenceofSARS-CoV2withkits(ModularDxKit,WuhanCoVE
&RdRPgenes)providedbyWHOtargetingtheEregionforscreeningandRNAdependentRNA
polymeraseforconfirmation.InvitrogenSuperScriptIIIOne-StepRT-PCRSystemwithPlatinumTaq
DNAPolymerasewasusedforPCR.Foreachreaction,12.5µlreactionmix,1µlRTenzyme,0.5µl
primer,probemixand5.6µlPCRgradewaterwasaddedto5µlRNAtemplate.Cyclingconditionsfor
amplificationofEandRdRPgeneswere50°Cfor30min,95°Cfor2minthen45cyclesof95°Cfor
15secand58°Cfor30sec.Acyclethresholdvalueoflessthan36Ctwasdefinedasapositivetest
result.11
Statisticalanalysis
Non-parametrictests(includingFisher’sexacttest,Mann-WhitneyUtest,andFriedmantest)were
usedtoanalyzedata.CrosstabulationandFisher’sexacttestwereusedtoinvestigatetherelation
betweenthebinaryvariables.Mann-WhitneyUtestwasappliedtocomparethequantitativevariables
betweenthetwogroups,andthemedianandinterquartilerange(IQR)werepresentedwiththe
results.IntheCTscananalysis,theFriedmantestwasusedtocomparebetweendifferentlunglobes

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involvementandcomparisonoftripleaccumulativescores.Inaddition,logisticregressionwasusedto
estimatetheeffectofthetreatmentonanoddsratio(OR)scaleusingthebackwardWaldelimination
ofvariables.Intheregressionmodel,theresponsevariablewasconsideredasabinaryvariablewith
either0or1(1incaseofdischargeandrecovery,and0incaseofdeath).Alloftheadministered
medications(hydroxychloroquine,lopinavir/ritonavir,ribavirin,andantibiotics)wereenteredintothe
regressionmodelasbinaryandindependentvariables.Patients’ageandcoexistingdisorders
(includinghypertension,diabetes,andCOPD/asthma)wereconsideredascovariatevariables,andthe
interactionbetweenageandpatient’scondition(criticallyillvs.non-criticallyill),andmedications
(hydroxychloroquine,lopinavir/ritonavir,andribavirin)wereincludedinthemodel.Also,inorderto
examinethesimultaneouseffectofhydroxychloroquineandazithromycin,theinteractionofthese
twovariableswasconsideredinthemodel.AllanalysiswasperformedusingSPSSsoftware,version
23(IBM).
Results
Inthisstudy,weincluded100hospitalizedpatientsoutof185admittedpatientsfromFebruary22,
2020,toMarch5,2020.Figure1showsthedistributionoftheindexpatientsin22districtsofTehran
andthesurroundingareas/cities.District2wasthemostaffecteddistrictinTehran,followedby
district12,5,8,and3.Findingsshowthat37%ofthepatientseitherlivedinorvisitedthese
neighboringareaswithinthe14dayspriortoadmission.Fiveofthesepatientswerelinkedtothecity
ofQom,theepicenterofthediseaseinIran.12Recentpotentialexposures,householdcontact
information,demographics,clinicalcharacteristics,laboratory,andradiologicfindings,andpatients’
outcomeswereextractedasshowninTable1.
Pre-hospitalizationanddemographicinformation
Themedianageofthepatientswas58years(range,26–93).Themajorityofthepatients(72.7%)
wereabove50yearsofage.Criticallyillpatientswereolderthanthenon-criticallyillgroup(100%
vs.67.9%;P = 0.005).Malesconstitutedthemajorityofthepatients(64.6%).Themedianoffamily
memberswas2persons(IQR,2–3)inahousehold.Atotalof126familymembers(55%female,45%
male)wereidentifiedtoliveinahouseholdwithindexpatients;63%wereabove50yearsofage.

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Accordingtojobclassification,28patients(28%)hadlowexposureriskoccupations,25(25%)had
highexposureriskoccupations,and5ofthem(5%)weremedicalstaff.Mostpotentialexposures
werecontactwithasuspectedfamilymember(22%)andcontactwithunderagefamilymemberswho
hadupperrespiratoryinfectionsymptoms(8%).Nineteenpatients(19%)wholivedinTehranhada
recenthistoryofdomestictravel,and3(3%)hadrecentoverseastravel.Noneofthepatients
recentlytraveledtoorfromChina(Table1).
Clinicalandparaclinicalfindings
Themedianincubationperiodwas7days(IQR,5–7).Feverwaspresentin45.2%ofthepatientson
admission.Themostcommonclinicalsymptomswereshortnessofbreath(74%),cough(68%),and
myalgia(18%).Decreaselevelofconsciousnesswasevidentin33%amongcriticallyillpatients,as
comparedwith0%amongthenon-criticallyillgroup(P < 0.001).Furthermore,respiratoryratewas
higherincriticallyillpatientscomparedwithnon-criticallyillgroup(medianof25.5vs.19/minutes;P
= 0.02).Thepresenceofacoexistingdisorderwashigherinthecriticallyillgroupbutwasnot
statisticallysignificant(73.3%vs.60%,relativeriskforthecriticallyillgroup,0.59;95%confidence
interval[CI],0.20–1.73;P = 0.25).
Laboratorytestsonadmissionshowthat74.2%ofthepatientshadlymphocytopenia,92.3%had
elevatedC-reactiveprotein,82.9%hadelevatederythrocytesedimentationrate,and75%had
elevatedlactatedehydrogenaselevels.Themedianlevelofwhite-cellcountandmedianneutrophil
countwerestatisticallydifferentintwogroupsofcriticallyandnon-criticallyillpatients.(P = 0.001
andP < 0.001,respectively).Abnormalcreatininelevelpercentagewashigherincriticalpatients
comparedtonon-criticalones(relativeriskforthecriticallyillgroup,4.53;95%confidenceinterval
[CI],1.75–11.73,P = 0.004).
Intotal,55CTscanswerereviewedandscoredbyanexpertradiologist.Non-parametricFriedman
testshowsdifferentinvolvementintermsoflobarpredominance.Rightlowerandleftlowerlobes
werethemostinvolvedlobesfollowedbytherightmiddlelobe,rightupperlobe,andleftupperlobe,
respectively(P < 0.001).Also,thetestshowsadifferenceinthreecumulativescores.MedianLower
lobesscorewasthehighestscorefollowedbymedianupperlobesscoreandmedianmiddlelobe

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score,respectively(P < 0.001).Ground-glassopacitywasthemostcommonradiologyfinding
(81.8%),followedbymixedpattern(ground-glassopacity + consolidation)andcrazypaving
appearance,whichwerefoundequallyintheresults(18.2%).Bothgroups(criticallyillvs.non-
criticallyill)hadsimilarCTscanfindings.
Treatmentandclinicaloutcomes
Allofthepatientsreceivedoseltamivirasarecommendedmedicationaccordingtothenational
guideline.Othermainadministeredmedicationsincludedhydroxychloroquine(94%),
lopinavir/ritonavir(60%),andribavirin(12%)wasadministeredinthepatients.Intravenousantibiotics
werealsoadministeredasshowninTable1.Allpatientsreceivedsupplementaryoxygentherapy
basedonpatients’conditions.Intravenousfluidtherapywasgivenforroutinemaintenance,as
mentionedbysolutiontypeandvolume(Table1).Intotal,19patientswerealreadytakinglosartan
andangiotensin-converting-enzymeinhibitors(ACEinhibitors)duetohypertension,whichcontinued
duringhospitalizationcourse(16%losartanvs.3%ACEinhibitors).Mechanicalventilationwasusedin
13%ofthepatients(2%non-invasiveventilationvs.12%invasiveventilation).
Hydroxychloroquine(OR = 61.859;95%CIforOR,9.009-424.722)andtheinteractionof
lopinavir/ritonavir*age*severity(OR = 0.922;95%CIforOR,0.887–0.958)hadasignificanteffecton
theoddsratio.However,theinteractionofazithromycinbyhydroxychloroquinedidnothavea
significanteffectonthemodel(OR = 0.917;95%CIforOR,0.00-4.34*109).Table2showsthefirst
andthelaststepofthebackwardeliminationinregressionanalysis.ThevalueofNagelkerke’sR2for
thefinalmodelwas0.840,andCoxandSnell’sR2was0.630,whichbothvaluesshowedthegoodness
offitinourmodel.
Ofthe185patientsadmittedtothehospitalduringthestudyperiod,only100patientswereeligible.
Ofthese100,12patients(12%)died,and70patients(70%)dischargedatthedateofdatacutoff.
Thecausesofdeathwereasfollows:fivepatientsduetoacuterespiratorydistresssyndrome,2
patientsdiedofsepticshock,2patientsdiedduetocardiacarrhythmia,and1diedofpneumothorax.
Thetworemainingpatientsdiedofsuddencardiacarrest.
Post-dischargefollow-up

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Seventypatientswerefollowedwithin14daysofdischargedate.Thirty-sixpatients(51.4%)had
observed14daysofhomequarantinepost-discharge.Symptomshadrelapsedin40%ofthepatients.
Shortnessofbreath(13%)andcough(13%)werethemostcommonsymptomsofrelapseafter
discharge.Sixofthepatients(8.6%)werereadmittedtothehospital,and3patients(4.3%)diedpost-
discharge(Table3).
Discussion
OurhospitalwasthefirstcentertocareforthenewCOVID-19casesappearinginTehran,Iran.We
presentedthefirst100casesofCOVID-19patientsinTehran.Weidentifiedthemostcommonsource
ofexposure,detailedclinicalandparaclinicalfindings,theclinicaloutcomeofcommonproposed
antiviraltherapies,andpost-dischargefollow-up.
Themostimportantfindingsconsistedofthepositiveeffectofhydroxychloroquineand
lopinavir/ritonavironthediseaseoutcome.Ourfindingsareinconcordancewithpreviousstudies,
wherehydroxychloroquineshowedefficacyindiseaseoutcome.13,14Furthermore,Caoetal.
concludedthatlopinavir/ritonavirisnotefficaciousforCOVID-19;however,thedatawasnotassessed
inrelationtoindividualpatientparameters.15Ourregressionmodelidentifiedageasadeterminant
inresponsivenesstolopinavir/ritonavir,withefficacybeingrelatedtoyoungerages.Agehasbeen
identifiedasanimportantdeterminantinthemortalityfromCOVID-19,butweshowthatyoungerage
isalsoadeterminantintheresponsivenesstoanti-viraltherapywithlopinavir/ritonavir.Wealsoused
themodeltodeterminetheefficacyofacombinedazithromycin/hydroxychloroquineregimenand
foundthatthecombinationwasnotsignificantinclinicaloutcomes.Thisiscontrarytocurrent
protocolsandapreviousstudy.16
Thesecondmostsignificantfindingwassymptomrelapsein40%ofpatientsafterdischarge.The
mostcommonrelapsedsymptomswerecough(18.6%)andshortnessofbreath(18.6%).Sixpatients
(8.6%)werereadmittedtothehospital,and3patients(4.3%)diedafterdischarge.Thisemphasizes
theneedforaclosefollow-upaftersymptomimprovement.Lanetal.showedthatcertainpatients
couldrecoverandtestnegative,onlytotestpositiveagain.17,18Thisphenomenonmightunderlie

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thesymptomreboundinourpatientsandmightindicatethatpatientsarestillasourceof
transmissionafterrecoveringfromCOVID-19.
ThenextsignificantfindinginourstudywasagreaterprevalenceofCOVID-19inhigher
socioeconomicneighborhoods.WewouldhaveexpectedthelowersocioeconomicsegmentsinTehran
tobemoreimportantintransmission,butinourstudy,wefoundthecontrary.Thismaybeexplained
bythegreaternumberofcrowdedareaslikeshoppingmallsandhospitalsinaffluentareasin
comparisontothelessaffluentareas.
Furthermore,themajorityofthepatientsdidnotfollowWHOpreventivemeasures;only5%used
medicalmasks,9%usedanalcohol-basedhandrub,and37%washedtheirhandsregularly.19This
emphasizestheimportanceofpreventivemeasures.
Feverwaspresentinlessthanhalf(45.2%)ofthepatientsonadmission,whilethemostcommon
clinicalsymptomswereshortnessofbreath(74%)andcough(68%).Ourdataonfeverissimilarto
Guanetal.whoreported43.8%feveronadmissionanddiffersfromChenetal.andWangetal.who
reported83%and98.6%,respectively.6–8Thismightindicatethatfeverisnotaspecificfindingin
COVID-19.However,thecoughhasbeenaconsistentprominentclinicalsymptominCOVID-19.
Theseverityofdiseasewasdirectlyrelatedtopatientsageover50years,higherrespiratoryrate,and
decreasedlevelofconsciousness.Thisisconsistentwithpreviousstudies.20,21Also,therateofco-
existingwashigheramongmorecriticalgroup.Thisfindingisconsistentwithameta-analysisof17
studieswerehypertension,COPD,diabetes,andcardiovasculardiseasewerehigheramongcritically-
illpatients.22
Lymphocytopeniawasacommonlaboratoryfinding.Itmayserveasamorespecificmarkeratthe
beginningofthisinfectionconsideringpreviousstudies.6–8However,itwasabsentin25%ofour
studypopulation.
Abnormalcreatininelevels,higherwhitecellcount,andhigherneutrophilcountwereseeninour
criticallyillpatients.Thismaybeexplainedbydirectrenalinvolvement,orfluidimbalancesecondary
tothecriticallyillstatusofthepatients.23IncreasedWBCcountincriticallyillpatientswiththe

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predominanceofneutrophilscanbeasignofsecondarybacterialinfection.
ChestCTscansanalysisrevealedhigherinvolvementinbothlowerlunglobescomparedwithright
middleandupperlunglobes.Themostcommonfindingwasground-glassopacity(81.8%).24The
presenceofground-glassopacityandbilaterallowerlobeinvolvementisthemostcommon
radiographicfindingsofthesepatients,similartoXuEtal.,andcanbeusedasadiagnosticfactorfor
COVID-19.25
Limitations
First,wedidnothaveaccesstoreviewallCTscanssincesomewereperformedatoutsidereferring
hospitals.Second,thelimitednumberoflaboratorystudieswereduetothehighpatientloadand
limitedresources.Third,manypatientswereexcludedduetothelackofPCRkitsattheonsetofthe
epidemicinTehran.Fourth,somepatientmedicalrecordswerenotcompleteduetotheemergency
situation.Fifth,manyofthepatientswereunabletorememberinitialexposure.Sixth,wecouldnot
determinethecauseofdeathinpatientswhodiedpost-discharged.
Conclusion
COVID-19canpresentwithaheterogeneouspatternofnon-specificfindingsbutaffectsolder
individualsmoreadversely.Thereisahighriskofdiseaserelapseandnecessitatesclosemonitoring
ofdischargedpatients.Therushisontofindaneffectivetherapy.Themedicalcommunityisactively
testingnumerousrepurposedandnoveldrugs.
Declarations
Ethicsapprovalandconsenttoparticipate.
ThisstudywasapprovedbytheTehranUniversityofMedicalSciences(TUMS)ethicscommittee
(IR.TUMS.VCR.REC.1398.1036).
Consentforpublication.
Informedconsentwasobtainedfromallpatientsortheirfirst-degreerelativesinunconscious
patients.
Availabilityofdataandmaterials.
Thedatasetsusedand/oranalysedduringthecurrentstudyareavailablefromthecorresponding
authoronreasonablerequest.

13
Competinginterests.
Theauthorsdeclarethattheyhavenocompetinginterests.
Funding.
Thisprojectwasnotfundedbyanyorganization
Authors’contributions.
MSandLAinterpretedthedataregardingradiologicfindingsinthisstudy.SA,TP,AP,andPNmade
substantialcontributionsinthedesigningandtheconceptofthestudy.AA,AM,andAShad
contributioninacquisitionandanalysisofthedata.TMAhadaroleinwritingthemanuscriptand
interpretationthedataregardingthePCRconfirmationofthepatients.MAhadmajorcontributionin
interpretationofdataandwritingthemainmanuscript.OMandAKhadsubstantiallyrevisedthe
manuscript.NS,ES,FDhadmajorrolesinacquisitionandinterpretationregardinglabfindingsand
post-dischargefollow-updata.
Everyauthorthoroughlyreadtheentiremanuscriptandcheckedfortheaccuracyofthedata,
protocolmethod,andanalysis.
Acknowledgements.Weappreciateallthehospitalstafffortheirsupportanddedicationtopatients
care,andallthepatientswhoconsentedtotheirinformationbeingreported.
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15
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Tables
Table1.Demographiccharacteristicsandparaclinicalfindingsofhospitalizedpatients,Comparedbetweencriticallyillpatientsandnon-criticallyillpatients.
Variable


17
Exposurehistory—no./totalno.(%)
ContactwithsuspectedCOVID-19familymember

Contactwithmedicalstaffinfamilymember

contactwithunderagewithupper
respiratoryinfectionsymptoms
Contactwithanimals
Theuseofpreventingmeasures—no./totalno.(%)a
Usedtowearmedicalmasks
Usedanalcohol-basedhandrub
Usedtowashhandsregularly
Hadpersonalknowledgeabout
thediseasesymptom
Travelhistorywithin14daysbeforetheonsetofthesymptoms—no./totalno.(%)
Domestictravelhistory
Internationaltravelhistory(exceptchina)
Traveltochina
Socialhistory—no./totalno.(%)
Smoker
Vaccinationhistory
IndexpatientsJobclassification—no./totalno.(%)b
Lowexposureriskoccupations

18
Highexposureriskoccupation
Medicalstaff
Demographicinformation
Age
median(IQR)—yr
Distribution—no./totalno.(%)
>50—no.(%)
Malesex—no./totalno.(%)
Medianhospitalizationperiod(IQR)—days
Medianincubationperiod(IQR)—days
Vitalsignsonadmission
Feveronadmission—no./totalno.(%)c
Mediantemperature(IQR)—°C
Distributionoftemperature—no./totalno.(%)
≥37.8°C
Peripheralcapillaryoxygensaturation(SpO2)%—no./totalno.(%)
SpO2<93%
Medianrespiratoryrate(IQR)—/minutes
Medianheartrate(IQR)—/minutes
Bloodpressure
Mediansystolicbloodpressure(IQR)—mmHg
Mediandiastolicbloodpressure(IQR)—mmHg
Clinicalsymptoms—no./totalno.(%)

19
Cough
Sputumproduction
Shortnessofbreath
Myalgia
Headache
Fatigue
Pleuriticchestpain
Rhinorrhea
Sorethroat
Nauseaorvomiting
Diarrhea
Decreaselevelofconsciousness
Coexistingdisorder—no./totalno.(%)
Any
Diabetes
Hypertension
Ischemicheartdisease
Chronicobstructivepulmonarydisease/asthma
Hypothyroidism
Others
Laboratoryfindings
White-cellcount
Median(IQR)—permm3

20
Distribution—no./totalno.(%)
<4000permm3
4000-10000permm3
>10000permm3
Lymphocytecountd
Median(IQR)—permm3
Distribution—no./totalno.(%)
<1500permm3
Neutrophilcount
Median(IQR)—permm3
Distribution—no./totalno.(%)
>1800permm3
1800-7800permm3
<7800permm3
Plateletcounte
Median(IQR)—permm3
<150000permm3
Distributionofotherfindings—no./totalno.(%)
Erythrocytesedimentationratef

21
Median(IQR)—mm/hour
Elevatedmm/hour
C-reactiveprotein
Median(IQR)—mg/liter
>6mg/liter
Lactatedehydrogenase
Median(IQR)—U/liter
>480U/liter
Aspartateaminotransferase
Median(IQR)—U/liter
>40U/liter
Alanineaminotransferase
Median(IQR)—U/liter
>40U/liter
Alkalinephosphatase
Median(IQR)—U/liter
>140U/liter
Creatininekinase
>170U/liter
Creatinine
Median(IQR)—μmol/liter
≥133μmol/liter

22
Prothrombintime
Median(IQR)—second
>13second
Partialthromboplastintime
Median(IQR)—second
>39second
Internationalnormalizedratio
>1.2
Bloodgas—no./totalno.(%)
Metabolicacidosis
Respiratoryacidosis
Metabolicalkalosis
Respiratoryalkalosis
MetabolicacidosisandRespiratoryacidosis
MetabolicacidosisandRespiratoryalkalosis
MetabolicalkalosisandRespiratoryacidosis
MetabolicalkalosisandRespiratoryalkalosis
Minerals
Mediansodium(IQR)—mmol/liter
Medianpotassium(IQR)—mmol/liter
Radiologicfindingsg
Lobarpredominance—no./totalno.(%)

23
Rightupperlobe
Rightmiddlelobe
Rightlowerlobe
Leftupperlobe
Leftlowerlobe
Scoring
Lobarscores
Medianrightupperlobescore(IQR)
Medianrightmiddlelobescore(IQR)
Medianrightlowerlobe(IQR)
Medianleftupperlobescore(IQR)
Medianleftlowerlobescore(IQR)
Cumulativescores
Mediantotalscore(IQR)
Medianlowerlobesscore(IQR)
Medianmiddlelobescore(IQR)
Medianupperlobesscore(IQR)
Anatomicdistribution—no./totalno.(%)
peripheral(subpleural)predominance
Central/perihilarpredominance
Unilateral
Bilateral
Attenuation

24
Ground-glassopacity
Mixed
(ground-glassopacityandconsolidation)
Crazypavingappearance
Othersigns
Reticulation
Cavitation
Bronchiectasis
Pleuraleffusion
Lymphadenopathy
Treatments
Admissiontointensivecareunit—no.(%)
Mechanicalventilation—no.(%)
Non-invasiveventilation
Invasiveventilation
Medications
Oseltamivir—no./totalno.(%)
Hydroxychloroquine—no./totalno.(%)
Lopinavir/Ritonavir—no./totalno.(%)
Ribavirin—no./totalno.(%)
Systemicglucocorticoids—no./totalno.(%)
Losartan—no./totalno.(%)

25
ACEinhibitor—no./totalno.(%)
Levofloxacin—no./totalno.(%)
Vancomycin—no./totalno.(%)
Azithromycin—no./totalno.(%)
Ceftriaxone—no./totalno.(%)
Piperacillin-tazobactam—no./totalno.(%)
Meropenem—no./totalno.(%)
Imipenem—no./totalno.(%)
Ciprofloxacin—no./totalno.(%)
Intravenousfluidtherapy
Solutiontype—no./totalno.
Dextrose3.3%-sodiumchloride0.3%
Sodiumlactate
Sodiumchloride0.9%
Sodiumchloride0.45%
Dextrose5%-saline0.9%
MedianSolutionamount(IQR)—cc/24hours
Clinicaloutcomeathospitalizationdatacutoff—no./totalno.(%)
Stillhospitalized
Dischargedfromhospital
Death
aPreventivemeasuresconsistedofwearingamedicalfacialmaskwhenincontactwiththepublic.2.Touseanalcohol-basedhandrub3.Towashhandsregularlyaccordingtotheworldhealthorganization(WHO)guideline.

26
bThepatient’soccupationriskwasclassifiedintothreegroups.1.Lowexposureoccupationsthatdonotrequireclosecontact(atleastwithin6feet)withthegeneralpublic.2.Highexposureoccupationsthathavefrequentclosecontact(atleastwithin6feet)withthegeneralpublic.3.Medicalstaffoccupationwasdefinedasajobinwhichpeopleworkincloseproximity(atleastwithin6feet)topatientsknownorsuspectedofCOVID-19infection.
cFeverwasdefinedasanaxillarybodytemperatureof37.8°Corabove.
dLymphocytopeniawasdefinedaslymphocytecountlessthan1500.
eThrombocytopeniawasdefinedasaplateletcountoflessthan150000.
fESRnormalrangeisdependentonageandsexofthepatientsanddefinedasfollows:Formaleindividuals50>yearsofage,thenormalrangeisbelow15;for>50and<85yearsofage,thenormalrangeisbelow20;andfor>85yearsofage,thenormalrangeisbelow30.Forfemaleindividuals50>yearsofage,thenormalrangeisbelow20;for>50and<85yearsofage,thenormalrangeisbelow30;andfor>85yearsofage,thenormalrangeisbelow42.AnyvaluesabovethenormallimitsweredefinedaselevatedESRinthetable.
gDataregardingCTscanweremissingfor45patientsduetothefactthattheywereperformedatoutsidereferringhospitals.
Table2.TheResultsofLogisticRegressionUsingaBackwardWaldEliminationofVariables(Response:Outcome)a

 Regressioncoefficient(B) Standarderror(S.E.) Pvalue
Step1   
age -0.006 0.023 0.81
hospitalizationperiod -0.005 0.259 0.98
Hydroxychloroquine(1) 5.138 2.944 0.08
Ribavirin(1) -1.854 4.555 0.68
Lopinavir/Ritonavir(1) 0.858 1.829 0.64
Intravenous
antibiotics(1)
-1.212 3.085 0.69
Hydroxychloroquine(1)
byagebyseverity(1)
0.332 758.358 1.00
Lopinavir/Ritonavir(1) -0.639 766.387 1.00

27
byagebyseverity(1)
Ribavirin(1)byageby
severity(1)
0.236 110.643 1.00
Diabetes(1) -2.310 1.750 0.19
Hypertension(1) 2.513 2.062 0.22
Chronicobstructive
pulmonary
disease/asthma(1)
34.177 10895.718 1.00
Azithromycin(1)by
Hydroxychloroquine(1)
-0.087 11.366 0.99
AgebyAzithromycin(1)by
Hydroxychloroquine(1)
0.028 0.207 0.89
Step13   
Hydroxychloroquine(1) 4.125 0.983 <0.001
Lopinavir/Ritonavir(1)
byagebyseverity(1)
-0.081 0.020 <0.001
aComplete13stepsofLogisticRegressionisprovidedintheelectronicsupplementarymaterial(supplementarytable2).
Table3.Post-dischargeFollow-up.
Variable DischargedPatients
Observinghomequarantineafter
discharge—no./totalno.(%)b
36/70(51.4)

28
Post-dischargesymptomrelapse—no./totalno.(%)
Any 28/70(40)
Fever 3/70(4.3)
Sorethroat 3/70(4.3)
Lossofappetite 2/70(2.9)
Dizziness 2/70(2.9)
Shortnessofbreath 13/70(18.6)
Cough 13/70(18.6)
Fatigue 4/70(5.7)
Myalgia 3/70(4.3)
Nauseaorvomiting 4/70(5.7)
Post-dischargeoutcome—no./totalno.(%)
Hospitalreadmission 6/70(8.6)
Deathc3/70(4.3)
Recovery 61/70(87.1)
aOnlydischargedpatientswereeligibleforthetelephonesurvey(N=70).
bThepatientswereaskedwhethertheycompleted14daysofhomequarantineafterdischarge.
cWecouldnotdeterminethecauseofdeathinpatientswhodiedpost-discharged.
Figures

29
Figure1
FlowChartwithanOverviewofStudySteps.Patientswereclassifiedintothreegroupsof
mild,moderate,andseveredisease.Treatmentregimenandadmission/dischargecriteria
wereaccordingtoIran’snationalguidelinefornovelcoronavirusinfection.Thedefinitionof

30
mild,moderate,andseverediseasewasasbelowaccordingtothenationalguideline:
Patientswithaflu-likesyndromewith/withoutfever,whodidnothaveanysignsof
infiltrationinlungimagingwereclassifiedashavingmilddisease.Themoderategroupwas
definedassymptomaticpatientswithpulmonaryinfiltrationoratleastoneoftheadmission
criteria,asexplainedinthefigure.Theseveregroupconstitutedpatientswhohaveatleast
oneofthefollowingcriteria:1.Reducedconsciousness;2.Respiratoryrate(RR)≥30;3.
Bloodpressure(BP)BP<90/60;4.Multilobularinfiltration;5.Hypoxemia.
Figure2
DiseaseDistributionMapinTehranandSurroundingAreas/Cities.Thismapshowsthe
distributionofallRT-PCRconfirmedindexpatientsin22districtsofTehranandsurrounding
areas.Wedidnothaveaccesstotheaddressoftwopatientsinthestudy.*Qomismarked
astheepicenterofCovid-19inIran.
SupplementaryFiles

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Thisisalistofsupplementaryfilesassociatedwiththispreprint.Clicktodownload.
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