Epidemiological and clinical characteristics of coronavirus disease 2019 in Daegu, South Korea
JiyeonLeea,1,Seung WanHongb,1,MiriHyuna,Jae SeokParkc,Jae HyuckLeed,
YoungSung Suhb,Dae HyunKimb,Seong-Wook Hane,Chi-HeumChof,HyunahKima,*
aDepartmentofInfectiousDisease,KeimyungUniversityDongsanHospital,KeimyungUniversitySchoolofMedicine,Daegu,RepublicofKorea
bDepartmentofFamilyMedicine,KeimyungUniversityDongsanHospital,KeimyungUniversitySchoolofMedicine,Daegu,RepublicofKorea
cDepartmentofPulmonology,KeimyungUniversityDongsanHospital,KeimyungUniversitySchoolofMedicine,Daegu,RepublicofKorea
dDepartmentofFamilyMedicine,DaeguDongsanHospital,Daegu,RepublicofKorea
eDepartmentofCardiology,KeimyungUniversityDongsanHospital,KeimyungUniversitySchoolofMedicine,Daegu,RepublicofKorea
fDepartmentofObstetricsandGynecology,KeimyungUniversityDongsanHospital,KeimyungUniversitySchoolofMedicine,Daegu,RepublicofKorea
ARTICLE INFO
Articlehistory:
Received3June2020
Receivedinrevisedform8July2020 Accepted16July2020
Keywords:
CoronavirusDisease2019(COVID-19) Severeacuterespiratorysyndrome coronavirus2(SARS-CoV-2) Epidemiology
ABSTRACT
Objectives:TwoCoronavirusDisease2019(COVID-19)outbreakssimultaneouslyoccurredatachurchand along-termcarefacilityinDaegu,SouthKorea.Thisstudyaimedtoinvestigatetheepidemiological characteristicsofCOVID-19andfactorsrelatedtosevereoutcomes.
Methods:WeenrolledallinpatientsdiagnosedwithCOVID-19betweenFebruary21andApril2,2020,in Daegu DongsanHospital.Weanalyzedtheirclinicaland demographicdata,laboratoryparameters, radiologicalfindings,symptoms,andtreatmentoutcomes.
Results:Of694patients,severecasesaccountedfor19.7%(137patients).Noseverecasewasobserved amongpatientsaged19years.Hypertensionwasthemostcommoncomorbidity(27%),andcoughwas themostcommonsymptom(59%).Asymptomaticpatientsaccountedfor14.4%ofcases.Lymphopenia, lactatedehydrogenase,C-reactiveprotein,andalbuminwereassociatedwithsevereoutcomes.Thefirst outbreakwasmostlyassociatedwithyoungeragegroups,andasymptomaticpatientsmostlyshowed mildprogression.Inthesecondoutbreakinvolvingalong-termcarefacility,boththenumberofsevere patientsandthemortalityratewerehigher.
Conclusions:TheoverallmortalityinDaeguwaslow,whichmighthaveresultedfromlargescalemass screeningtodetectpatientsandstartingappropriatetreatment,includinghospitalizationforsevere cases,andquarantineforasymptomaticpatients.
©2020TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.
ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc- nd/4.0/).
Introduction
Thecoronavirusdisease2019(COVID-19)isarespiratorytract infectioncausedbyanewemergingcoronavirus,currentlynamed severeacuterespiratory syndromecoronavirus 2 (SARS-CoV-2).
ThefirstcaseofCOVID-19wasreportedinWuhan,HubeiProvince, China,inDecember2019.Now,COVID-19hasspreadtoover200 countrieswithinonlyfourmonths(Huietal.,2020;WorldHealth
Organization,2020a).InSouthKorea,thefirstcaseinfectedwith SARS-CoV-2, a Chinese visitor from Wuhan, was reported on January20,2020(Kimetal.,2020).OnFebruary18,2020,aCOVID- 19outbreakinSouthKoreastartedinDaegu,anditisworthnoting thatthecoronavirushadspreadmainlyamongareligiousgroup called Shincheonji (Park etal., 2020). Asof June 30, 2020, the number of confirmed cases increased rapidly, reaching 12,757 cases,including282deaths(TheKoreaCentersforDiseaseControl
& Prevention, 2020). Daegu was at the hub of the COVID-19 outbreak,withthehighestnumberofcasesinSouthKorea(6906 outof12,757casesnationwide(54.1%).
Investigating the epidemiological characteristics of patients withCOVID-19inDaeguisusefultogaininsightintothesituation and characteristics of the diseasein South Korea. Unlike other regionsnationwide,DaeguwashitbytwoCOVID-19outbreaksat
*Corresponding author at: Department of Infectious Disease, Keimyung University DongsanHospital, Keimyung University School ofMedicine,1035, Dalgubeol-daero,Dalseo-gu,Daegu,RepublicofKorea.
E-mailaddress:[email protected](H.a.Kim).
1Contributedequallytothisworkandarejointfirstauthors.
https://doi.org/10.1016/j.ijid.2020.07.017
1201-9712/©2020TheAuthors.PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
ContentslistsavailableatScienceDirect
International Journal of Infectious Diseases
j o u r n a lh o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / i j i d
thesame time, of which the largestoutbreak was related toa religiousmeetingandtheotheronetoalong-termcarefacility.
Consequently,theepidemiologicalcharacteristicsofCOVID-19in Daegumaydifferfromthose inotherregions. Moreover,SARS- CoV-2 is a newly emerging virus, and its epidemiological characteristics remain inadequately described (Wang et al., 2020a).Therefore,it isvitaltoexaminetheaspectsand factors relatedtosevereoutcomestoenableappropriatetreatmentand prevention.
Methods Patients
Thisstudywas approvedbytheinstitutionalethicsboardof KeimyungUniversityDongsanHospital(No.2020-03-027).After receiving approval, we retrospectively collected data from all inpatientsdiagnosedwithSARS-CoV-2infectionfromFebruary21, 2020,toApril2,2020,inDaeguDongsanHospital.Therequirement forinformedconsentwaswaivedduetotheretrospectivenatureof thestudy.Clinicalmanifestationsandoutcomesofthepatientshad alsobeenmonitoredasofApril2,2020.Duringtheoutbreak,this hospitalwasdesignatedasaspecializedhospitalwith465bedsfor COVID-19patients.
Inthisstudy,weusedreal-timereversetranscriptionpolymer- ase chain reaction (RT-PCR), which has been widely used to diagnose COVID-19. Protocols used to diagnose COVID-19 vary accordingtocountry; inSouth Korea,RT-PCR is used todetect severeacuterespiratoryvirussyndromecoronavirus-2(SARS-CoV- 2)throughtheidentificationofRdRp,E,andNgenes(Cormanetal., 2020).
Datacollection
We collected different types of data, including clinical and demographic information, laboratory parameters, radiological findings, and outcomes from patients’ medical records and attendingdoctors.Symptomsduringhospitalizationwerecollect- eddaily,andalldatawerecollectedretrospectively.
Weinvestigatedwhetheroxygensupply,mechanicalventilation, or extracorporeal membrane oxygenation (ECMO) had been prescribed.Wealsocollectedpatients’treatmentoutcomesusing retrospective chart reviews, i.e., whether they died or were dischargedalive.AsrecommendedbytheWorldHealthOrganiza- tion(WHO),aseverecasewasdefinedasapatientwhometatleast oneofthefollowingcriteria:
(1)Shortnessofbreath,respiratoryrate30breaths/min;
(2)oxygensaturationatrest93%;or
(3)partial pressureofarterialoxygen(PaO2)/fractionofinspira- tionoxygen(FiO2)300mmHgor
(4)a requirement of mechanical ventilation (World Health Organization,2020b).
All the other cases, including those with simple upper respiratory tract disease and pneumonia, were classified into themildgroup.
Data onsymptomswerecollecteddailyduring thepatients’ hospitalstay,andthosewhomanifestedthemostsymptomsona givendaywereselectedforanalysis.
Chestcomputedtomography(CT)findingsweredividedinto two categories: positive and negative CT scans. A patient was classifiedasapositiveCTscanifheorshehadanyconsolidationor ground-glassopacity(GGO)inCTfindingsduringhospitalization.A patient with no consolidations or GGO in his/her CT findings duringthehospitalizationwasclassifiedtohaveanegativeCTscan.
Statisticalanalyses
Categoricalvariables wereanalyzed usingFisher's exact test and presented as frequencies and percentages. Continuous variableswereanalyzedusingtheindependentt-testifthedata werenormallydistributed,otherwisetheMann–Whitneytestwas used. Continuousvariables werethen expressed as means and standarddeviations.Two-sidedpvaluesof0.05wereconsidered to be statistically significant. All statistical analyses were performedusingStatisticalPackagefortheSocialSciences(SPSS) version23.0software(IBMCorp.,Armonk,NY,USA).
Results
Inourstudy,694casesinfectedwithSARS-CoV-2wereenrolled, including137,14,andthreepatientswhorequiredoxygentherapy, ventilationtherapy,andECMOtherapy,respectively,forhypoxia.
Intotal,18patientsdiedduetoCOVID-19,while137patientswere classifiedasseverecases.
Demographicandepidemiologicaldata
Patientsagesrangedfrom19monthsto98years,withtheage group60yearsbeingthemostaffected.Nopatientsagedunder 19yearswereidentifiedasseverecases.Meanwhile,intheage groupofover80years,severecasesconstituted74.5%(41/55)of thecases(Figure1).
Hypertensionwas themost commoncomorbid disease(131 cases).Thenumberofseverecaseswassignificantlyhigheramong patients with hypertension, diabetes, stroke, dementia, and chronickidneydisease; morecomorbid diseases werefoundin theseverecasesgroup.Nopatientsinthegroupofseverecases wereasymptomatic.Coughingwasthemostprevalentsymptom, occurringin328cases.Theproportionsoffever,chill,cough,sore throatanddyspneawerehigherinseverecasesthaninmildcases.
Eightypatientsinthegroupofmildcaseswereasymptomatic.
Themostcommontransmissionsourceconsistedof280cases who were followers of the religious group at the Shincheonji ChurchofJesus.Theproportionofhospital-transmittedSARS-CoV- 2infectionswashigherinseverecases(19.7%)thaninmildcases (4.3%). The actual proportion could have been higher as the transmissionsourcewasnotclearlyidentified(Table1).
Radiologicalandlaboratoryfindings
Thewhitebloodcellcount,neutrophilcount,C-reactiveprotein (CRP),procalcitonin,aspartatetransaminase(AST),alaninetrans- aminase(ALT), lactatedehydrogenase(LDH), and albuminwere correspondingly higher in severe cases than in mild cases.
However, the lymphocyte count and estimated glomerular filtrationrate(eGFR)werecorrespondinglylowerinseverecases thanthoseinmildcases(Table2).
CTscanswereperformedfor369patients.Bothsymptomsand CTscansweresurveyedin300cases.AmongthosewithpositiveCT scans,22.7%and57.3%sufferedfromfeverandcough,respectively, while13.8%didnothaveanysymptoms(Table3).
Discussion
Inourstudy,themortalityrateamongCOVID-19patientswas 2.6%(18cases),whichalmostissimilartothepooledmortalityrate in SouthKorea(2.3%) (TheKoreaCentersfor DiseaseControl&
Prevention,2020).Comparedtotheglobalmortalityrates,thislow mortalityratemighthaveresultedfromlargescalemassscreening to detect patients and starting appropriate treatment. In the beginning, all confirmed cases were hospitalized for medical
treatment,regardlessoftheseverityofthedisease.However,after thelargeoutbreakbegan, onlypatientswhose conditions were severeand, therefore, in direneed of hospitaltreatment, were admitted to the hospital. Meanwhile, to prevent transmission, asymptomaticpatientsormildcaseswerereferredtodormitories,
wheretheyweremanagedingroups.Amongthesepatients,those withseveresymptomswerehospitalizedaftertheywereidentified byusingsimpletestsandquestionnaires.
Inlinewithapreviousstudy(Lietal.,2020),ourstudyfoundno severe case in the pediatric age group. The number of overall patientsandthosewithseriousoutcomesincreasedabovetheage of 45 years. This implies that careful monitoring should be performedamongpatientsinthisolderagegroup.
InDaegu,SouthKorea,mostCOVID-19patientswereidentified asmembersofareligiousgroupcalledShincheonji,afteramass outbreakofCOVID-19occurredinShincheonji,Daegu.ByJune30, 4265(61.8%)patientswerefoundtoberelatedtoShincheonjiout of a total of 6906 confirmed cases in Daegu, while 540(7.8%) patients were related to a long-term care facility. Religious activities in confined spaces may have led to the outbreak of COVID-19inthesamemannerasincruiseshipsorprisons(Kinner etal.,2020;MizumotoandChowell,2020).
The comorbidities contributing to increasingthe severityof COVID-19 in ourstudy includedhypertension,diabetes, stroke, Fig.1.Numberofcoronavirus2019casesbyagegroupsandseverity.
Table1
Generalcharacteristicsofcoronavirus2019cases.
Characteristics Mildcase(n=557) Severecase(n=137) p-value
Age,mean(standarddeviation),years 52.10(18.29) 71.41(13.17) 0.000
Gender Male 155(27.8%) 57(41.6%) 0.003
Female 402(72.2%) 80(58.4%)
Comorbidity Hypertension 86(22.4%) 45(44.6%) 0.000
Diabetesmellitus 48(12.5%) 33(32.7%) 0.000
Coronaryarterydisease 11(2.9%) 6(5.9%) 0.137
Stroke 9(2.3%) 8(7.9%) 0.012
Asthma 13(3.4%) 1(1.0%) 0.319
Chronicobstructivepulmonarydisease 2(0.5%) 2(2.0%) 0.193
Oldtuberculosis 2(0.5%) 0(0.0%) 1.000
Heartfailure 6(1.6%) 4(4.0%) 0.228
Chronickidneydisease 1(0.3%) 4(4.0%) 0.008
Liverdisease 2(0.5%) 3(3.0%) 0.063
Thyroiddisease 6(1.6%) 2(2.0%) 0.674
Dementia 5(1.3%) 5(5.0%) 0.037
Cancer 18(4.7%) 5(5.0%) 1.000
Otherdiseases 20(5.2%) 8(7.9%) 0.336
Totaldiseasecount 0.60(0.85) 1.25(1.10) 0.000
Symptoms Nosymptoms 80(16.8%) 0(0.0%) 0.000
Fever 80(16.8%) 31(38.3%) 0.000
Chill 97(20.4%) 29(35.8%) 0.004
Cough 262(55.2%) 66(81.5%) 0.000
Sputum 244(51.4%) 50(61.7%) 0.092
Rhinorrhea 141(29.7%) 21(25.9%) 0.597
Sorethroat 124(26.1%) 31(38.3%) 0.031
Myalgia 93(19.6%) 22(27.2%) 0.137
Headache 115(24.2%) 25(30.9%) 0.214
Diarrhea 134(28.2%) 32(39.5%) 0.048
Dyspnea 58(12.2%) 33(40.7%) 0.000
Chestpain 75(15.8%) 14(17.3%) 0.744
Symptomscount 2.99(2.31) 4.37(2.29) 0.000
ChestX-rayresults Positive 275(49.5%) 128(93.4%) 0.000
Negative 281(50.5%) 9(6.6%)
CTscanresults Positive 192(68.6%) 81(91.0%) 0.000
Negative 88(31.4%) 8(9.0%)
Exposurehistory WithinFamily 87(15.6%) 13(9.5%) 0.077
Fromaco-workerorfriend 57(10.3%) 5(3.6%) 0.012
AtShincheonjiChurchofJesus 258(46.4%) 22(16.1%) 0.000
In-hospital 24(4.3%) 27(19.7%) 0.000
Overseas 3(0.5%) 1(0.7%) 0.587
Others 3(0.5%) 1(0.7%) 0.587
Unknown 124(22.3%) 68(49.6%) 0.000
All%presenttheproportionsofcharacteristicsinthemildorseverecasegroup,excludingthemissingvalues.Pvalueswereanalyzedusingthet-testorMann–Whitneytest forcontinuousvariablesandFisher'sexacttestforcategoricalvariables.
chronic kidney disease, dementia, and comorbidity counts.
Comorbiditiesare a risk factor forsevere outcomesin patients withCOVID-19(Huangetal.,2020;Wangetal.,2020a).
Coughwasthemostcommonsymptomamongpatientswith COVID-19inourstudy(55.2%amongmildcasesand81.5%among severecases).Theproportionofpatientswithfeverwasnotashigh asthosereportedinChina(20%vs.90%)(Huangetal.,2020;Wang etal., 2020a).Accordingtoa reportfromEurope,thisrate was 45.4%,withheadache(70.3%)andlossofsmell(70.2%)asthemost commonsymptoms(Lechienetal.,2020).
Thepresentstudyincluded80asymptomaticcases,accounting for14.4%ofallcases.Duringeachquarantineday,allasymptomatic patients were checked for the development of symptoms; no patientsshowed symptomsuntiltheirrelease fromquarantine.
Thismighthaveresultedfromthehigherproportionofmildcases beingidentifiedbytherelativelybroad-basedscreeningtestsfor SARS-CoV-2inSouthKorea.ByJune30,intotal,1,273,766PCRtests were conducted for the diagnosis of SARS-CoV-2. Due to the epidemicassociatedwithShincheonji,thegovernmentconducted large-scale screening tests for more than 10,000 Shincheonji church members, regardless of symptoms. Because of this screening,severalconfirmedbutasymptomaticcaseswerefound early and were isolated in facilities and hospitals to suppress transmission.
Asymptomatic patients are crucial factorsin controllingthe COVID-19 outbreak. Furthermore, in the early stage of this outbreak in SouthKorea,everyonewho had closecontactwith confirmedcasesreceivedaSARS-CoV-2test.Therefore,webelieve thattherewerearelativelylargenumberofasymptomaticpatients includedourdatacompared tootherstudies.Itisbelieved that antibody-basedfollow-upstudieswouldbeneededtodetermine theextenttowhichasymptomaticpatientspotentiallycontributed tothetransmissioninthisCOVID-19pandemic.
Inourstudy,patientswithin-hospitalexposuretoSARS-CoV-2 weremorelikelytohavesevereoutcomes,whichmightbebecause they already had a poor general condition, suffered from comorbidities,andbelongedtoolderagegroups.Thishighlights the need for preventing in-hospital transmission. Patients who werenot awareof infectionsources alsoreportedmore severe outcomes, which might have been affected by the time until diagnosis. The efficacy of mass SARS-CoV-2 screening requires furtherresearch.
Morepatientswithlymphopeniawereobservedinthesevere casesgroup.ThismaybeacharacteristicofSARS-CoV-2infection, asthis wasalsoreportedintwoprevious studies(Huang etal., 2020;Wangetal.,2020b).Similarly,lactatedehydrogenase,CRP, and albuminwerealsocorrelatedwithsevereoutcomesinthis study.
We contrastedpatients’ symptomswithCT scan resultsand found that 31 patients wereasymptomatic, although they had positiveCTscanresults(13.8%ofallpatientswithCTscans).These patientsmighthavehadapotentialroleinSARS-CoV-2transmis- sion,asreportedinseveral otherstudies(Baietal.,2020;Chan etal.,2020; Wanget al.,2020c).Therefore,wespeculatethata carefulapproachtowardasymptomaticindividualsisrequiredto preventafurtherupsurgeintheoutbreak.
Thisstudyhasseverallimitationsthatneedtobeaddressed.
First, it was a retrospective study with missing data, possibly leadingtomultivariateanalysiserrors.Second,weonlycollected initial laboratory data; there might be some deviations in laboratory findings due totemporal differences. Finally,certain symptoms might not have been documented because we only collecteddataonsymptomsduringthepatients’hospitalstay.This meansthatifcertainsymptomsoccurredbeforethepatientswere hospitalized,theproportionofasymptomaticpatientsmightnot reflecttheactualone.
Table2
Laboratoryfindingsofcoronavirus2019cases.
Variables Total(n=694) Mildcase(n=557) Severecase(n=137) pvalue
Whitebloodcellcount,103/mL 5.39(2.11) 5.19(1.71) 6.22(3.15) 0.000
Neutrophilcount,103/mL 3.25(1.92) 2.93(1.36) 4.57(3.00) 0.000
Lymphocytecount,103/mL 1.59(0.71) 1.70(0.71) 1.13(0.52) 0.000
Monocytecount,103/mL 0.45(0.17) 0.45(0.16) 0.47(0.24) 0.449
Hemoglobin,g/dL 12.62(1.52) 12.72(1.47) 12.22(1.62) 0.001
Hematocrit,% 37.95(4.28) 38.31(4.10) 36.47(4.66) 0.000
Plateletcount,103/mL 235.65(85.37) 240.46(83.17) 215.87(91.56) 0.003
Glucose,mg/dL 123.37(62.56) 117.36(54.44) 148.09(84.30) 0.000
Creatinephosphokinase,U/L 90.53(121.14) 82.42(118.17) 124.15(127.83) 0.001
C-reactiveprotein,mg/dL 2.00(4.10) 0.86(1.85) 6.66(6.69) 0.000
Procalcitonin,ng/mL 2.00(2.64) 1.62(2.23) 3.31(3.41) 0.000
Aspartatetransaminase,U/L 26.36(16.49) 23.87(11.62) 36.63(26.60) 0.000
Alaninetransaminase,U/L 24.78(18.50) 23.88(17.45) 28.50(22.01) 0.024
Lactatedehydrogenase,U/L 496.29(250.19) 447.55(124.11) 695.19(455.13) 0.000
Albumin,g/dL 4.00(0.48) 4.12(0.39) 3.53(0.50) 0.000
Bloodureanitrogen,mg/dL 14.68(7.00) 13.58(4.83) 19.20(11.40) 0.000
Creatinine,mg/dL 0.78(0.34) 0.74(0.22) 0.96(0.57) 0.000
Estimatedglomerularfiltrationrate,mL/min/1.73m2 94.48(25.59) 99.01(23.82) 75.87(24.24) 0.000
Alldataarepresentedasmeans(standarddeviations).TheestimatedglomerularfiltrationrateiscalculatedusingtheChronicKidneyDisease-EpidemiologyCollaboration equation.Pvaluesareanalyzedusingthet-testorMann–Whitneytest.
Table3
Theproportionofpatientsbysymptomsandcomputedtomographyscanresults.
Symptoms CTnegative(n=75) CTpositive(n=225) p-Value
Nosymptoms 19(25.3%) 31(13.8%) 0.031
Fever 4(5.3%) 51(22.7%) 0.000
Chills 6(8.0%) 56(24.9%) 0.002
Cough 30(40.0%) 129(57.3%) 0.011
Sputum 31(41.3%) 113(50.2%) 0.230
Rhinorrhea 18(24.0%) 63(28.0%) 0.550
Sorethroat 17(22.7%) 52(23.1%) 1.000
Myalgia 4(5.3%) 45(20.0%) 0.002
Headache 9(12.0%) 62(27.6%) 0.007
Diarrhea 18(24.0%) 78(34.7%) 0.115
Dyspnea 4(5.3%) 41(18.2%) 0.005
Chestpain 9(12.0%) 38(16.9%) 0.363
Each%presentstheproportionofpatientswithacertaintypeofsymptomorno symptomsineithertheCTnegativegrouportheCTpositivegroup.Pvaluesare calculatedusingFisher'sexacttest.
