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Co-infection of SARS-CoV-2 and dengue virus: a clinical challenge

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brazjinfectdis2020;24(5):452–454

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Case

report

Co-infection

of

SARS-CoV-2

and

dengue

virus:

a

clinical

challenge

Naira

Bicudo

a,∗

,

Eliana

Bicudo

a

,

Julia

Duarte

Costa

b

,

Julliana

Alline

Leite

Porto

Castro

a

,

Gustavo

Barcelos

Barra

c

aHOMEHospital,DepartmentofInfectiousDiseases,Brasília,DF,Brazil bHOMEHospital,DepartmentofInternalMedicine,Brasília,DF,Brazil cSabinMedicinaDiagnóstica,Brasília,DF,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received15May2020

Accepted19July2020

Availableonline26August2020

Keywords: Dengue COVID-19 SARS-CoV-2 Co-infection

a

b

s

t

r

a

c

t

Manyregionsoftheworldwheredengueepidemicsareseasonalarealsofacingthe

COVID-19pandemic.Thisisamedicalconcernbecausebothdiseasesaredifficulttodistinguish

sincetheyhavesimilarclinicalsymptomsandlaboratoryfindings,andbecausetheyhave

differentclinicalmanagement.Sofar,co-infectionofSARS-CoV-2anddenguevirus(DENV)

hasnot beenstudied. Hereinwereportthefirstcase ofapatient with co-infectionof

COVID-19anddengue.Bothinfectionsweresimultaneouslylaboratoryconfirmedby

pos-itiveRT-qPCRforSARS-CoV-2andRT-qPCRforDENV,NS1,IgMandIgGantibodytestsfor

dengue.Thepatienthadafavorableclinicalimprovement,withoutseveresymptoms.This

caseemphasizethat,inpandemicera,havingadiagnosticofoneinfectiondoesnotrule

outthepossibilityofhavinganotherinfectionconcomitantly.Inaddition,underscoresthe

importanceofanaccurateandtimelydiagnosistopreventthespreadofCOVID-19.

©2020SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis

anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/

licenses/by-nc-nd/4.0/).

Introduction

SARS-CoV-2,thenovelcoronavirus thatcausesCoronavirus

Disease 2019 (COVID-19), was firstly detected in Brazil on

February25,2020.Sincethen,202,918caseshad been

con-firmedasofMay14,2020.1Inthesameperiod,thecountry

wasalsofacingadenguevirus(DENV)epidemic.Accordingto

theBrazilianMinistryofHealth,theincidenceofdenguecases

showedanupwardtrend,resultingin676,928casesuntilnow.2

Correspondingauthor.

E-mailaddress:[email protected](N.Bicudo).

Brazil’sFederalDistrict,locatedintheCentral-Westregionof

thecountry,hasahighincidenceofDENVin2020sofar(841.9

cases/100,000inhabitants)2andSARS-CoV-2isco-circulating

leadingtoauniqueanddistincthealthscenarioforthe

popu-lation(Fig.1).Co-infectionofSARS-CoV-2andDENVhavenot

beenstudiedneitherdescribedindetailuntilnow.Here,we

describethefirstcasewherebothvirusesinfectedthesame

personsimultaneously.

Case

report

Apreviouslyhealthy56-year-oldwoman,withnotravel

his-tory,residentinanurbanareainBrasíliacity,FederalDistrict,

https://doi.org/10.1016/j.bjid.2020.07.008

1413-8670/©2020SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC

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brazj infect dis.2020;24(5):452–454

453

0 500 1000 1500 2000 2500 3000 3500 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Ca ses

Epidemiological Week

Dengue COVID-19

Fig.1–NumberofdengueandCOVID-19casesperepidemiologicalweek,inFederalDistrict,Brazil,2020.1,3.

Fig.2–Chestcomputedtomography(CT)imageinfirstday ofhospitalization.Theimagedemonstratestwoground glassopacitiesinperipheralareaofleftupperlobe.The patienthadfewbilateral,peripheralgroundglassopacities.

Brazil,wasadmittedtoalocalhospitalonApril14,2020.The

patientcomplained ofsorethroat,anosmiaand ageusiafor

thepast12days,andfrontalheadache,fever,drycough,mild

dyspneawithoutneedforsupplementaryoxygenandSpO2

94% on roomair forfive days. IgMand IgG antibodytests

forDENV (SERIONELISAclassicDengueVirusIgMandIgG,

SerionInc.,Brazil)wereinitiallynegative,whereasreal-time

reversetranscription–polymerasechainreaction(RT-qPCR)

forSARS-CoV-2(in-houselaboratorydevelopedtesttargeting

N1andEgenes4performedonanasopharyngealspecimen)

waspositive.Bloodsamplesshowedleukopenia(2260/mm3),

lymphopenia (497/mm3), thrombocytopenia (143,000/mm3),

and elevated D-dimer (3986ng/mL), C-Reactive Protein-CRP

(16mg/L),serumalanineaminotransferase(ALT60U/L),

aspar-tateaminotransferase(AST40U/L),andferritin(559ng/mL).

Chestcomputedtomography(CT)imagesdemonstratedfew

bilateral,peripheralgroundglassopacities(Fig.2).Thepatient

Fig.3–Denguediffuseitchyerythemato-papularrash, mainlylocatedonthelimbsandtrunkregions,onseton thirddayofhospitalization.

startedtherapywithchloroquine,azithromycinand

anticoag-ulation.

Three days after hospitalization, the patient developed

a diffuse itchy erythemato-papular rash, mainly located

in the limbs and trunk regions (Fig. 3), gastrointestinal

symptoms such as diarrhea and nausea, worsening of

leukopenia (1820/mm3), newonsetofatypical lymphocytes

(9%),thrombocytopenia(92.000/mm3)andprogressive

eleva-tionofaminotransferases(ALT546U/L,AST433U/L).Anew

laboratory investigationfordengueand COVID-19was

per-formedturningoutpositiveforNS1(SDBioLineDengueNS1

Ag from Alere Inv., USA), DENV RT-qPCR (in-house

labora-torydevelopedtesttargetingUTRsequence common toall

fourdenguevirusgenotype5),andIgMandIgGantibodytests

fordengue.SARS-CoV-2RT-qPCRwasagainpositive.

Further-more,dengueviruswasconfirmedasserotypeDENV-1(CDC

DENV1–4genotypingprotocol6).Allmedicationswere

discon-tinuedandthepatienthadprogressiveclinicalimprovement,

withoutcomplications,andwasdischargedonday6of

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454

braz j infect dis.2020;24(5):452–454

consecutivenegativetestsforSARS-CoV-2atday26ofonset

ofsymptoms.

Discussion

This was the first case report of a human co-infection of

SARS-CoV-2andDENV,inwhichbothvirusesweredetectedby

RT-qPCRatthesametime.Webelievethatthepatientwasfirst

infectedbySARS-CoV-2,presentingamilddisease,andone

weeklater,duringtheillnessofCOVID-19,shewasinfectedby

DENV.Despitetheco-infection,thepatientdidnothavesevere

respiratorydiseasenorseveredengue.Recently,twopatients

diagnosedwithCOVID-19 bySARS-CoV-2RT-PCRhad

posi-tiveserologicalantibodytestsfordenguebutnegativeDENV

RT-PCRweredescribedinSingapore,suggestingfalse-positive

serologicaltestresultsfordengueorcross-reaction.7

Dengue and COVID-19 could be difficult to distinguish

becausetheyhavesimilarclinicalsymptomsandlaboratory

findings,suchasfever,headache,myalgiaandfatigue,

mak-ingdifferentialdiagnosischallenging.8,9Althoughinfrequent,

COVID-19casescanpresentskinrash10andlowplateletcount,

meaningthat onedisease canbeinitially misdiagnosedas

theother.Moreover,apositivedengueserologymayappear

onafalse-positivetest,alsoinco-infectionwithSARV-CoV-2

andDENV.Theincorrectordelayeddiagnosiscanhave

seri-ousconsequences,becauseeachdiseasehasdifferentclinical

management, suchas venous hydration,use of

anticoagu-lants,corticosteroids,andearlymechanicalventilation.11

Conclusion

Thisreport confirmthat, inpandemic era, diagnosing one

infectiondoesnotruleoutthepossibilityofhavinganother

infectionconcomitantly.Inaddition,itunderscoresthe

impor-tanceofanaccurateandtimelydiagnosis,withacomplete

laboratoryinvestigationforbothdengueandCOVID-19,in

ter-ritorieswherethereisapossibilityofdengueinfection,since

each infection has different clinical management. Beyond

that,wealertforthispublichealthconcern,especially

high-lightingtheneedinobtainingthecorrectcontactanddroplet

precautions in health services and communities, helping

reducinghuman-to-humantransmission,preventoutbreaks

anddelaythespreadofCOVID-19pandemic.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

WethankClaraWandenkolckSilvaAragãoforthelanguage

help,TicianeHenriquesSantaRitaandPedroGóesMesquita

forthelaboratorycontributions.

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1.BrazilianMinistryofHealth,Availableat:

https://covid.saude.gov.br/.[Accessed14May2020]PAINEL

COVID-19;2020.

2.BrazilianMinistryofHealth,2020.BoletimEpidemiológico

no

19.Monitoramentodoscasosdearbovirosesurbanas

transmitidaspeloAedesAegypti(dengue,chikungunyaezika),

SemanasEpidemiológicas1a18,2020.Volume51.Abril2020.

MinistériodaSaúde.Availableat:

https://portalarquivos.saude.gov.br/images/pdf/2020/May/08/ Boletim-epidemiologico-SVS-19.pdf.[Accessed14May2020].

3.BrazilianMinistryofHealth,Availableat:

http://sinan.saude.gov.br/.[Accessed14May2020]Sistemade

Informac¸ãodeAgravosdeNotificac¸ão–SINAN;2020.

4.BarraGB,SantaRitaTH,MesquitaPG,JácomoRH,NeryLFA. AnalyticalsensibilityandspecificityoftwoRT-qPCRprotocols forSARS-CoV-2detectionperformedinanautomated workflow.MedRxiv.2020.

5.DrostenC,GöttigS,SchillingS,etal.Rapiddetectionand

quantificationofRNAofEbolaandMarburgviruses,Lassa

virus,Crimean-Congohemorrhagicfevervirus,RiftValley

fevervirus,denguevirus,andyellowfevervirusbyReal-Time

ReverseTranscription-PCR.JClinMicrobiol.2002;40:2323–30,

http://dx.doi.org/10.1128/jcm.40.7.2323-2330.2002.

6.SantiagoGA,VergneE,QuilesY,CosmeJ,VazquezJ,Medina JF,etal.AnalyticalandclinicalperformanceoftheCDCreal timeRT-PCRassayfordetectionandtypingofdenguevirus. PLoSNeglTropDis.2013;7:e2311.

7.YanG,LeeCK,LamLT,YanB,ChuaYX,LimAY,etal.Covert COVID-19andfalse-positivedengueserologyinSingapore. LancetInfectDis.2020:10–016.

8.WorldHealthOrganization.ReportoftheWHO-ChinaJoint

MissiononCoronavirusDisease2019(COVID-19).16-24

February2020.Availableat:

https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf.[Accessed6

May2020].

9.SimmonsCP,FarrarJJ,VinChauN,BridgetW.Dengue.NEnglJ Med.2012;366:1423–32.

10.JoobB,WiwanitkitV.Covid-19canpresentwitharashandbe mistakenfordengue.JAmAcadDermatol.2020;82:e177.

11.WorldHealthOrganization.Clinicalmanagementofsevere

acuterespiratoryinfection(SARI)whenCOVID-19diseaseis

suspected:Interimguidance.13March2020.

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