Pulmonology27(2021)345---380 9.ArtifoniM,Danic G, Gautier G, GicquelP, BoutoilleD,Raffi
F,etal.Systematicassessmentofvenousthromboembolismin COVID-19patientsreceivingthromboprophylaxis:incidenceand roleofd-dimeraspredictivefactors.JThrombThrombolysis. 2020;50:211---6.
10.Zhang L, Feng X, Zhang D, Jiang C, Mei H, Wang J, et al. Deepvein thrombosis inhospitalizedpatientswithCOVID-19 inWuhan,China:prevalence,riskfactors,andoutcome. Circu-lation.2020;142:114---28.
11.Songur Yücel Z, Metin Aksu N, Akkas¸M. The combined use ofend-tidalcarbon dioxideand alveolardeadspacefraction valuesinthediagnosis ofpulmonary embolism.Pulmonology. 2020;26:192---7.
V.Bunela,d,g,L.Sakerb,d,g,N.Ajzenbergc,d,g,J.F.Timsite,d,g, S.Najema,d,g,B.Lortat-Jacobf,d,g,J.Gayc,d,g,
G.Weisenburgera,d,g,H.Mala,d,g,∗,A.Khalilb,d,g aServicedepneumologieB,HôpitalBichat,Assistance Publique-HôpitauxdeParis,InsermUMR1152,Université Paris7DenisDiderot,75018Paris,France
bServicederadiologie,hôpitalBichat,Assistance Publique-HôpitauxdeParis,Paris,France
cServiced’hématologie,hôpitalBichat,Assistance Publique-HôpitauxdeParis,Paris,France
dServicedesmaladiesinfectieusesettropicales,hôpital Bichat,AssistancePublique-HôpitauxdeParis,Paris, France
eServicederéanimationmédicaleetinfectieuse,hôpital Bichat,AssistancePublique-HôpitauxdeParis,Paris, France
fServicederéanimationchirurgicale,hôpitalBichat, AssistancePublique-HôpitauxdeParis,Paris,France gServicedemédecineinterne,hôpitalBichat,Assistance Publique-HôpitauxdeParis,Paris,France
∗Correspondingauthor.
E-mailaddress:herve.mal@bch.aphp.fr(H.Mal). Availableonline8April2021
https://doi.org/10.1016/j.pulmoe.2021.03.007
2531-0437/©2021SociedadePortuguesadePneumologia. PublishedbyElsevierEspa˜na,S.L.U.Thisisanopenaccessarticle undertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
High-resolution
CT
features
in
patients
with
COVID-19
pneumonia
and
negative
nasopharyngeal
and
oropharyngeal
swabs
TotheEditor:
In response to the SARS-CoV-2 outbreak, rapid and accurate diagnosis of COVID-19 pneumonia is essential for controlling the spread of the disease and optimizing patienttreatment.Althoughnasopharyngealand oropharyn-geal(NP/OP)swabtestsarecommonlyusedforlaboratory confirmation of suspected COVID-19 cases, RT-PCR for detection of the virus has been reported to have very high specificity, but sensitivityas low as70---80%. Reasons for initial false-negative NP/OP swab tests may include inadequate sampling techniques and/or low patient viral burden.1
Chestimagingisindicatedforpatientswithmoderateto severesymptomsofCOVID-19infection,regardlessofNP/OP swabresultsand/orforthosewithconfirmeddiagnosisand evidenceofworseningrespiratorystatus.2Recently, ithas beenreportedthatpatientswhoinitiallytestednegativefor COVID-19 byRT-PCR wereless likelytoexhibitpulmonary consolidationbyCT.3
This study aimed to describe the chest CT findings in patientswithCOVID-19pneumoniawhohadinitiallytested negativeby NP/OPswab.The final goalis toassist physi-cians toavoid missed or delayed diagnosesof SARS-CoV-2 infection.
Our study was conductedin accordancewith the Dec-laration of Helsinki and approved by the Padova Hospital ethics committee. De-identified CT scans were assessed by on-site radiologistsat the Departmentof Radiology of PadovaUniversity.AllCTscanswerefrompatientsadmitted totheemergencydepartment(ED)forsuspectedCOVID-19
pneumonia,accordingtoexposurehistoryandclinicaldata, betweenFebruary17andMay5,2020.
The following inclusion criteriawere used:(1) Labora-toryconfirmedSARS-CoV-2infection;(2)Nopreviousknown underlyinglungdisease;(3)CTexaminationperformed1---3 days from admission to the ED. All patients included in the study group initially tested negativefor COVID-19 by NP/OPswabtest. Allresults werecomparedwiththosein thegroupofpatientswhoinitiallytestedpositivefor COVID-19.Tworadiologistswithover5years’experienceanalysed allCTimagesinconsensus.ThefollowingCTfeatureswere assessed:distributionpattern(peripheralorcentral); num-beroflobesinvolved(one,two,ormore);mainradiological feature(ground-glassopacity[GGO],consolidation,orGGO withconsolidation);concomitantlungabnormalities(crazy pavingpattern,fibrousstripes);andextrapulmonary man-ifestations (mediastinal lymph node enlargement, pleural effusion).
Outof453patientsadmittedtotheEDandadministered chestCTduringthestudyperiod,159hadaconfirmed diag-nosisofCOVID-19pneumonia,accordingtoWHOguidance.4 In 28 of theseconfirmed cases (mean age, 64±15 years; male/female, 18/10), the patients initially tested nega-tive by RT-PCR (study group). SARS-CoV-2 infection was confirmedin thesepatientsbyrepeatedNO/OP swabtest (nineteen cases) and bronchoalveolar lavage test (nine cases)overa6-dayduration(range,3---8days).
Unilateral lung involvement wasdetected in 20 out of the28 cases.Radiologicabnormalities hadperipheral dis-tributionin27cases(96%)andinvolvedtwoormorelobes infour cases(14%). UnilateralGGOswithor without con-solidationsorcrazypavingweresignificantlymorecommon among patients in the study group compared with those whoinitially tested positive (19/28 vs. 6/131; p<0.0001)
(Table1)(Fig.1).Fibrousstripesonthebasalregionswere
presentinsevenpatients.Finally, mediastinallymphnode
LETTERTOTHEEDITOR
Table 1 CT features of patients with initially negative or positive NP/OP swab test. (GGO=ground-glass opacity; NP=nasopharyngeal;OP=oropharyngeal).
CTfeature Ptswithinitiallynegative NP/OPswabtest(n=28)
Ptswithinitiallypostive NP/OPswabtest(n=131)
p-Value GGO -Unilateral 19 6 <0.0001 -Bilateral 8 110 <0.0001 Consolidation -Unilateral 15 3 <0.0001 -Bilateral 3 89 <0.0001 Crazypaving -Unilateral 4 0 0.0008 -Bilateral 4 65 0.0008 Fibrousstripes -Unilateral 3 0 0.005 -Bilateral 3 40 0.0353
Figure1 CTscanofa74-year-oldwomanshowingunilateralground-glassopacitiesintherightupperlobe(A),anda47-year-old manshowingunilateralcrazypavingintherightlowerlobe(B).BothpatientshadinitiallytestednegativebyNP/OPswab.
enlargementandpleuraleffusionweredetectedinsixand twocases,respectively.
OurstudydescribeschestCTscanfindingsinagroupof patientswithCOVID-19pneumoniawhoinitiallytested nega-tivebyNP/OPswabtests.Todate,onlyasmallcaseseries, consisting of fivepatients, by Xieetal.5 hasinvestigated the relationship betweennegativeRT-PCR testsand chest CTscans andconcludedthat GGOswere themost typical findinginthiscontext.Thedatapresentedheresuggestthat unilateralGGOswithorwithoutconsolidationarethemost frequentabnormalitiesinthispatientpopulation.
Wehypothesizethatpredominantunilaterallung involve-mentcouldbeduetoarelativelylowviralload.Similarly, Zhaoetal.examinedtherelationshipbetweenCTfindings andtheclinicalcoursesofpatientswithCOVID-19 pneumo-niaandconcludedthatviralloadmayinfluencetheextentof lunginvolvement.6Arelativelylowviralloadhasalsobeen suggested tobe a possible causeof false-negative NP/OP swabtestsinsymptomaticpatientswithpulmonarylesions suspectedofCOVID-19pneumonia.7Onthisbasis,weargue thatourstudy grouppatients couldrepresenta‘low-dose phenotype’, characterised by negative NP/OP swab tests andunilaterallunglesions.
Quantitativedeterminationofviralloadcouldhave con-firmedourhypothesis, butthistest isnotavailable inour hospital.
Becausefalse-negativeNP/OPswabtestshaveimportant implicationsfortimelyCOVID-19diagnosis,earlytreatment, andtheriskofspreadingthedisease,we recommendthat clinicianscontinuetomonitorfor COVID-19whenpatients presentwithunilateralGGOsandhaveinitiallytested nega-tivebyNP/OPswabtests.Acombinationoftestsisurgently neededtominimizetherisksoffalse-negativeresults.
Declarations
of
interest
None.
References
1.HeJL,LuoL,LuoZD,LyuJX,NgMY,ShenXP,etal.Diagnostic performancebetweenCTandinitialreal-timeRT-PCRfor clin-icallysuspected 2019 coronavirus disease (COVID-19) patients outside Wuhan, China. Respir Med. 2020;168(July):105980, http://dx.doi.org/10.1016/j.rmed.2020.105980.
2.Rubin Gd, Ryerson Cj,Haramati Lb, Sverzellati N, Kanne Jp, RaoofS,etal.Theroleofchestimaginginpatientmanagement duringtheCOVID-19pandemic:amultinationalconsensus state-mentfrom theFleischnerSociety.Chest. 2020;158(1):106---16, http://dx.doi.org/10.1016/j.chest.2020.04.003.
Pulmonology27(2021)345---380 disease (COVID-19)? AJR Am J Roentgenol. 2020;(May):1---5,
http://dx.doi.org/10.2214/AJR.20.23012.
4.WHO,March 13Clinicalmanagementof severeacute respira-toryinfection(SARI)whenCOVID-19diseaseissuspected.Interim guidance;2020.
5.Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology. 2020;296(2):E41---5, http://dx.doi.org/10.1148/radiol.2020200343.
6.ZhaoW,ZhongZ,XieX,YuQ,LiuJ.RelationbetweenchestCT findingsand clinicalconditionsofcoronavirus disease (COVID-19) pneumonia: a multicenter study. AJR Am J Roentgenol. 2020;214(5):1072---7,http://dx.doi.org/10.2214/AJR.20.22976. 7.Suo T, Liu X, Feng J, Guo M, Hu W, Guo D, et al. ddPCR:
a more accurate tool for SARS-CoV-2 detection in low viral load specimens. Emerg Microbes Infect. 2020;9(1):1259---68, http://dx.doi.org/10.1080/22221751.2020.1772678.
EmilioQuaiaa,ElisaBaratellab,FilippoCrimia, LucaCancianc,PaolaCrivellid,AndreaVianelloe,∗ aDepartmentofRadiology,UniversityofPadova,Padova, Italy
bDepartmentofRadiology,UniversityofTrieste,Trieste, Italy
cUnitofRadiology,AziendaULSS6Euganea,Cittadella, Italy
dUnitofRadiology,DepartmentofClinicaland
ExperimentalMedicine,UniversityofSassari,Sassari,Italy eRespiratoryPathophysiologyDivision,Departmentof Cardiac,Thoracic,VascularSciencesandPublicHealth, UniversityofPadova,Padova,Italy
∗Correspondingauthorat:U.O.FisiopatologiaRespiratoria, Azienda Ospedaliera di Padova, Via Giustiniani, 2, 35128 Padova,Italy.
E-mailaddress:andrea.vianello@aopd.veneto.it
(A.Vianello). 4August2020
Availableonline21October2020
https://doi.org/10.1016/j.pulmoe.2020.10.001
2531-0437/©2020SociedadePortuguesadePneumologia. PublishedbyElsevierEspa˜na,S.L.U.Thisisanopenaccessarticle undertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Reversibility
of
venous
dilatation
and
parenchymal
changes
density
in
Sars-Cov-2
pneumonia:
toward
the
definition
of
a
peculiar
pattern
DearEditor,InSARS-CoV-2infectionthemild-to-moderatephaseofthe diseaseshowstypeIIpneumocyteshyperplasiawithout hya-line membranes, inflammatory interalveolar infiltrates.1-4 Vascular changes like hyperplasia/dilatation of alveolar capillaries, new angiogenesis, endothelialitis, thrombotic microangiopathy have been also reported.3 Froma radio-logic point of view,Lang etal.5 usingthe dual-energy CT scan technology, described peculiar vascular enlargement andmosaicattenuationasapatternofdisordered vasoregu-lationcharacterizedbyapronouncedvasculardilatation(in 85%ofthepatients)intheaffectedregions,besidethe typ-icalaspectsofgroundglassattenuationandconsolidations. Thesefeatureswerelabeledas‘‘hyperemichalo’’pattern.5 Here we describeCT findingsof five patients affected by COVD-19intheearlyphaseofthediseaseemphasizingthe vascularandalveolarchangesmodifiedbythegravity.
Five subjects with a diagnosis of COVID-19 based on nasal swabtest underwentCT scaninsupine andlater in thesamesessiontheproneposition.CTprotocolconsisted of twoconsecutive acquisitionsrespectivelyin supineand proneposition,thelatterduringadministrationofcontrast medium, with a protocol able to opacify pulmonary both arteriesandpulmonaryveins.
Clinical and laboratory profiles are summarized in
Table1.
Inallthefivecases,pulmonaryveinswerepatent.Other radiologicalfeaturesforeachpatientwereasfollows:
Case 1: 78 years-old male. In the supine position, focal pure ground glass opacities were present in both upper lobes, and some peripheral part-solid ground glass areas with a coexisting crazy paving attenuation in both costophrenicangles.Furthermore,theperipheralbranches of the pulmonary veins of the lower lobes appeared enlarged. In the prone position a significant decrease in diameterofveinsandakind ofparenchymal ground glass attenuationinboth lowerlobes. Moreover,a rapid reduc-tionofthedensitywasobservedinthe‘‘formercrazypaving component’’thatchangedintopuregroundglass
attenua-tion(Fig.1).
Case 2: 64-year-old male. Subsegmental pulmonary arteriesdefectswerepresentintherightlowerlobe. Pul-monaryveinsshowedarelativereductionincaliberinthe pronepositioning.
Case3:52yearoldfemale.Bilateralcentraland periph-eralgroundglassattenuationandvesselenlargement.Inthe rightupperlobeandintheleftlowerlobetheconsolidative aspectpresentinsupinepositionreducedsignificantlyinthe prone.Moreover,veinsdecreasedincaliber(Fig.2).
Case4:57yearsoldfemale.Bilateral, extensiveareas ofgroundglassattenuationwithcentralandperipheral dis-tribution,someperipheralconsolidationinupperandlower lobesandbilateralvenousenlargement.Intheprone posi-tionasignificantreductionincaliberoftheenlargedveinsis associatedwithrelativeincreaseindensityofthepulmonary infiltratesintheanteriorsegmentsofbothupperlobes.
Case 5: 58 years old female. Part-solid ground glass attenuationin supine position with band-like opacities in left lower lobe. Vessel enlargement was present in both lowerlobes,mainlyontheleft.Withthepronepositioning thegroundglassattenuationredistributedinthemedullary portionofthelung,withaconcomitantreductionindensity attenuation.Caliberoftheveinsreduced(1.2vs2.8mm).