2 1 Accepted 11July2021 Received 14May2021 Korea; Medicine, Anyang 14068, South Hallym UniversityCollegeof University SacredHeartHospital, of InternalMedicine, Hallym Care Medicine, Department Pulmonary, Allergy andCritical Dr Ji Young Park, Divisionof Correspondence to Medicine, Anyang, SouthKorea Hallym UniversityCollegeof Anyang, SouthKorea University CollegeofMedicine, Sacred HeartHospital, Hallym Medicine, HallymUniversity Department ofInternal and CriticalCareMedicine, by BMJ. and permissions. Published commercial re- employer(s)) 2021. No © Author(s) (ortheir Department ofRadiology, Division ofPulmonary, Allergy Lee IJ thoraxjnl-2021-217609 doi:10.1136/ include DayMonth Year]. ahead ofprint: [please To Kim J- cite: Park JY, , et al.Thorax Epub evan007@ ​ ­use ​naver. . Seerights com ​ H, ­ annually amongtheelderly, andseveralvaccine- related ILDshavebeenreported. able asinfluenzavaccinesarewidelyadministered influenza vaccine- vaccination and review the literature on COVID-19 report acaseofinterstitiallungdisease(ILD)after ratio (FiO in arterialblood(PaO found onauscultation.Thepartialpressureofoxygen rash, oedemaorclubbing,butbilateralcrackleswere oxygen saturationwas80%onroomair. Hehadno his bodytemperaturewas38.2°C,andperipheral sure tochemicalsororganicparticles.Onadmission, recent changesinhislivingenvironmentandexpo- events withothervaccinesordrugs.Hedeniedany no adverse events and had no history of adverse (CTD). Hetookaninfluenzavaccineannuallywith cular, pulmonary, allergicorconnectivetissuedisease He wasanon- semide, linagliptin, metformin andclopidogrel). with medications(atorvastatin,amlodipine,furo- chronic renaldisease,whichwerewellcontrolled mRNA vaccine.Hehadhypertension,diabetesand before symptom onset, he had received a COVID-19 expectoration, nasaldischargeorsorethroat.Oneday of weakness, dyspnoea and fever. He had no cough, to theemergencydepartmentwitha1- In earlyApril2021,an86- DR HWAN ILKIM tific institutionsandthepharmaceuticalindustry. and thecollaborativeeffortsofmedical–scien- has been accelerated through government funding vaccines The development ofCOVID-19 COVID-19. tion isnecessarytocontrolaglobalpandemiclike tion ratherthannaturalimmunityacquiredbyinfec- Herd immunitythroughextensiveandrapidvaccina- DR JI YOUNG PARK platelets, 340×10 82.8%; eosinophils,4.1%;lymphocytes, 5.8%); of rareadversereactionsremaininadequate. in globalclinicaltrials,long- vaccines wereestablishedthroughinterimanalysis being used. Although the safety and efficacy of these vaccines havereceivedemergencyapprovalandare AstraZeneca) andBNT162b2(Pfizer/BioNTech) In SouthKorea, theChAdOx1 nCoV-19 (Oxford/ urea nitrogen, 22.7 Ratio (INR),1.04; D- 124.2 136 investigations revealedthefollowing: haemoglobin, showed sinustachycardiawithout STchanges.Blood nasal cannulaoxygen therapy. Anelectrocardiograph Yong IlHwang, Ji YoungPark case study COVID-19 vaccine-

g/L; whitecellcount,11.60×10

mm Hg;P 2 ) wasmaintainedat248(50%FiO Park JY, et al.Thorax 2021;0:1–3. doi:10.1136/thoraxjnl-2021-217609 ­ smoker withnohistoryofcardiovas

aCO related ILDs.Thisreviewisfavour ­ ‍ 1 9 SeungHunJang,

/L; International Normalized /L; InternationalNormalized mg/dL; creatinine, 1.85 ‍ , 2 , 21.2 1 2 )/fraction ofinspiredoxygen Joo- dimer ­

mm Hg)withhigh- ­ year ­Hee Kim term dataandreports ­ , 0.55 - old manpresented ­ 9 /L (neutrophils, /L (neutrophils,

­ related interstitiallungdisease: µ g/mL; blood

­ day history ‍ 1 Ki- ‍ , 2

mg/dL; ; PaO 1 1 2 InJae Lee, ­Suck Jung ­ flow W We 1 2 2 - - ,

­

COVID-19 vaccine- COVID-19 not beperformedbecauseofthepatient’srefusal. scopic bronchoalveolar lavage andlung biopsy could Life Science, Seoul, Korea) were negative. Broncho- IgE antibodiesusingAdvanSure AlloScreen(LG vaccination and to rule out the hypothesis that a vaccination and toruleoutthehypothesis that a before had a previously undiagnosed COVID-19 was conductedtoreconfirm whether thepatient IgM/IgG PlusTest; SDBiosensor, Korea). Thetest and IgGwerenegative(STANDARD QCOVID-19 16 daysaftervaccinationshowed thatbothIgM steroid treatment. ical coursewastransientwithrapidimprovementby The onsetwasacuteaftervaccination,andtheclin- gradually tapered and discontinued with no relapse. was discharged.Subsequently, thesteroiddosewas the steroid dose wasreduced. Thirteen days later, he rapidly improvedthefollowingday. After 3 initiated intravenous methylprednisolone at 1 ratory results.We discontinuedantibiotic therapyand on theclinicalcourse,radiologicalfeaturesandlabo- within thenormalrange,and62allergen- bodies. IgE,IgG,IgAandIgMconcentrationswere day DR SUNGHOONPARK anti- phil cytoplasmic, antinuclear, anti- toid factorandanticitrullinatedpeptide,antineutro- Seoul, Korea)). He wasseronegative for rheuma- PCR testing(AllplexPneumoBacterAssay; Seegene, losis PCR testing and respiratory bacterial multiplex bacterial culture,acid–fastbacillussmear, tubercu- testing (Real- pathogens (seasonalrespiratoryvirusmultiplexPCR induced sputumsampleswere negative for other negative, initiallyandafter3 nasopharyngeal swabs and sputum samples were nCoV Detectionkit;BioSewoom,Seoul,K PCR testing (Real-The results of COVID-19 C reactive protein level increased to 11.43 The brainnatriureticpeptidelevel(88 bilateral diffuseground- radiograph findingsworsened.ChestCTrevealed of pneumonia;however, thesymptomsandchest were administeredfor3 bilateral reticularopacities.Empiricalantibiotics and interlobular septal thickening (figure focal consolidations, centrilobular micronodules aminotransferase, 11 aspartate aminotransferase,18 (0.32 within the reference range, and serum procalcitonin A SARS- . His symptoms and chest radiography findings . His symptoms and chest radiography findings 1 ­ U1RNP 2

ng/mL) wasslightlyelevated. Hwan IlKim, CoV ­ , anti- Q ­ -2 serological antibody test performed -2 serological antibody test performed RV Detection kit, BioSewoom), Scl-70, anti- ­ related ILDwasdiagnosedbased ­

IU/L. Chestradiographrevealed Case baseddiscussion 1 SunghoonPark,

days consideringadiagnosis glass opacities(GGO)with ­

days. T R ­ o andanti-

IU/L; andalanine dsDNA, ­ est results of the est resultsofthe

pg/mL) was

1A,B ­ Q anti- La anti ­ orea) of orea) of 1 a specific ­

mg/dL.

mg/kg/ ). The ). The 2019-

days,

Sm, ­

1 -

­

Thorax: first published as 10.1136/thoraxjnl-2021-217609 on 6 August 2021. Downloaded from from Downloaded 2021. August 6 on 10.1136/thoraxjnl-2021-217609 as published first Thorax: http://thorax.bmj.com/

on September 28, 2021 by guest. Protected by copyright. by Protected guest. by 2021 28, September on Chest clinic Chest clinic fever, and ILD with severe hypoxia occurred on the day after criteria weremet asthepatienthadnorespiratory symptomsor administered beforetheonset of ILD.The‘temporaleligibility’ mRNAvaccine wastheonlydrug tension anddiabetes,COVID-19 were met,becauseotherthanthe routinemedicationsforhyper bronchoalveolar lavage; ED, emergencydepartment; FiO #5, Umedaetal 2 criteriaproposedby Camusetal ‘identification’ and‘singularity’ respiratory distresssyndrome,and isadiagnosisofexclusion. The of clinical presentation, from transient lung infiltration to acute Drug- DR YONG ILHWANG including thetestsweconducted. vaccinations, the evaluation of immunity following COVID-19 to date,therearenocommercialantibodytestsapproved for prevent adequate antibody formation after vaccination. However, response aftervaccination.Moreover, high- past SARS- hypersensitive pneumonitisandidiopathicpulmonaryfibrosis. #1, Johnstonetal (A) and18daysafterCO Figure 1 MPD, methylprednisolone; n, no; y, yes. Case baseddiscussion induced ­

(A) ClinicalcourseandchestradiographyfindingsofapatientwithCO CoV ­ 9 interstitial lung disease (DILD) has a wide spectrum interstitial lung disease (DILD) has a wide spectrum ; #6, Kumamoto etal -2 infection may have elicited a robust antibody -2 infectionmayhaveelicitedarobustantibody VID-19 vaccination. (C)Dataof10previouslyreportedcasesinfluenza vaccine- 10 ; #7,; Watanabe dose steroidsmight ­ et al 2 , fractionofinspiredoxygen; HFNC, high- 11 ; #8, HibinoandKondo 3 -

to, bilateral distribution and GGO were confirmed. All patients to, bilateral distribution and GGO were confirmed. All patients patients. Inall cases wherechestCTfindings canbereferred median of 2 respects (figure ILD casesweresimilar to those of the current case inthefollowing specific forthediagnosisofDILD. biopsy were not performed. However, their results are usually non- ical andserologicaltestresults.Bronchoalveolarlavagelung ruled outbasedontheradiologicalfindingsandmicrobiolog - other conditions’criterionwasmetasinfectionsandCTDswere to taketheseconddoseofvaccine.Lastly, the‘exclusion of native treatment isavailable; therefore, thepatient was advised not vaccination. Therechallengetestisnecessaryonlywhennoalter ILD. We found 10 published case reports of influenza vaccine- DR SEUNGHUNJANG AND DR INJAE LEE 5 ; #2, Heinrichsetal VID-19 vaccine- 4–12 12 ; #9, HibinoandKondo Theclinicalcharacteristicsof influenzavaccine- Park JY, et al. Thorax 2021;0:1–3. doi:10.1136/thoraxjnl-2021-217609

days

1c ­ flow nasalcannula; related ILD ­ ). Symptom onset was acute and occurred at a ). Symptom onset was acute and occurred at a after vaccination, and fever appeared in most after vaccination, and fever appeared in most 6 ; #3, Kanemitsuetal related ILD ­ 12 . (B)ChestCTimagesobtainedat4 ; #10, Numataetal. . *Onecaseeachofchronic ILD, interstitial lungdisease; 7 ; #4, Bhurayanontachai 4 BAL, ­ associated related ­

days 8 ;

-

­

Thorax: first published as 10.1136/thoraxjnl-2021-217609 on 6 August 2021. Downloaded from from Downloaded 2021. August 6 on 10.1136/thoraxjnl-2021-217609 as published first Thorax: http://thorax.bmj.com/ on September 28, 2021 by guest. Protected by copyright. by Protected guest. by 2021 28, September on wide. vaccineworld- people receivedatleastonedoseoftheCOVID-19 surveillance). tions andappropriatestatisticmodelsarenecessary(activesafety onset events,largehealthcaredatabaseswithstandardisedde surveillance. Moreover, for rare adverse reactions and delayed- vidual andnotthroughcaseseriesorreportsfrompassivesafety tive studies that can proactively evaluate every vaccinated indi- factors for adverse reactions should be analysed through prospec- clinical trial. 1273, respectively. Novaccine- (4/21621) and0.04%(6/15181)withBNT162b2mRNA- The rateoftreatment- the seconddoseofBNT162b2andmRNA-1273,respectively. dose. Fever occurred in 16% and 17.4% of young individuals after by approximately one- dose than the first dose. With both vaccines, fatigue was reported were morecommoninyoungindividualsandafterthesecond tion sitewereinfrequent(approximately 6%).Systemicreactions which resolved within 2–3 mRNA-1273, 74% among older participants after the first dose), local reactionwaspainattheinjectionsite(BNT162b2,71%; vaccines showedsimilarreactogenicityprofiles.Themostcommon Park JY, et al.Thorax 2021;0:1–3. doi:10.1136/thoraxjnl-2021-217609 events havebeenreported,although furtheranalysisisnecessary national vaccinationprogramme, anaphylaxisandthrombotic has beenwidelyadministeredto thegeneralpopulation.After the late- confirmed throughphaseII/III trials. However, extremelyrareor The safetyofthemRNA- DR KI-SUCKJUNG AND DRJI YOUNG PARK respectively, in the primary analysis of phase II/III trials. and mRNA-1273(Moderna),showed95%94.1%efficacy, used worldwide under an emergency authorisation, BNT162b2 development andclinicaltrials.Two mRNA- vaccines and protein subunit vaccines, are in different stages of vaccines, viral vector vaccines, nucleic acid(DNAormRNA- Various suchasinactivated candidatevaccinesagainstCOVID-19, DR JOO-HEEKIM vaccine in2009–2010,Japan). Labour andWelfare (19casesfrom22.8 after influenzavaccinationsfromtheJapaneseMinistryofHealth, safety committee’s report of acute deterioration of underlying ILD risk factorsforinfluenzavaccine- Although publication bias is a significant limitation, these might be ingly, 8of10patientswereAsian,underlyingILDintwocases. recovered, andmostrespondedwelltosteroidtherapy. Interest- the drugisinconsistent. and thecausalrelationshipbetweenasuspectedadverseeffect of thisdatabaseisthattheinformationcamefromvarioussources, disease and pulmonaryvasculitis. However, a significantlimitation case eachofacuteinterstitialpneumonitis,immune- pneumonitis, 4 of alveolitis, 2 of eosinophilic pneumonia and 1 haemorrhage, 9oforganisingpneumonia,6hypersensitivity of acute respiratory distress syndrome, 9 of pulmonary alveolar adverse eventsregisteredincluded135casesofpneumonitis,88 Eighty- vaccine- tify individualcasesofsuspectedCOVID-19 (through VigiAccess, summarystatisticsfromVigiBase) toiden- until 6 June 2021. Additional vaccine- cases of COVID-19 Between 14December2020and6June2021,905.89 ­onset adverseeventsmightbeidentified onlyafterthevaccine 13 ­ four We reviewed the WHO global pharmacovigilance database cases of ILD (single diagnosis code) had been reported cases of ILD (single diagnosis code) had been reported 1 2 third oftheelderlysubjectsafterfirst ­ related seriousadverseeventswas0.02% ­ based vaccinescurrentlyinuse has been ­

days. related ILDwasreportedineither ­ 9 However, theevaluationofrisk Redness and swelling at the injec- related ILD.Therewasavaccine ­

million dosesofH1N1 based vaccinesbeing ­ mediated lung ­ related ILD. ­ 1 2

million ­ related based) ­ Both Both fi ni-

­

ratio remainsfirmlyinfavourofvaccination. vaccine,we emphasise that the risk:benefit tion oftheCOVID-19 tolerable ofadverseevents.Acomprehensivereviewwithalong- older adultsusuallyhavepre- prioritised for vaccinationafter healthcare workers. However, where vaccine availability is limited, elderly subjects are being Although vaccine- vaccine- monitoring theadverseeventsshouldbevigilantforCOVID-19 adults is lacking. This report suggests that healthcare professionals term follow- Pr P Joo- Ji Young Park ORCID iDs non- determined byBMJ. You mayuse, download andprintthearticleforanylawful, terms andconditionsfortheduration ofthecovid-19pandemicoruntilotherwise This articleismadefreelyavailable foruseinaccordancewithBMJ’s website Competing interests funding agencyinthepublic, commercialornot- Funding and editing. All authorsreviewedandapprovedthefinalmanuscript. analysis andinterpretation. JYPandKJoversawtheconception, writing, formatting manuscript. ILreviewedtheradiology ofthecase. J- Contributors not representtheopinionofUppsalaMonitoringCentreor WHO. drug andreportedadverseeventmightvary, dependingonthecase. Ourreportdoes collects datafromvarious sources, andthedegreeofassociationbetweenacertain Acknowledgements 15 14 13 12 11 10 olack FP, Thomas SJ, KitchinN, et al. Safetyandefficacy oftheBNT162b2mRNA REFERENCES notices andtr to determine their relevance. 9 8 7 6 5 4 3 2 1 atient consentforpublication ovenance andpeerreview

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­ , ChocronR, et al. Vaccination againstCOVID-19: insightfrom W None declared. ​org/ ​org/ e havedescribeddataretrievedfrom VigiBase, which vaccinations ​ 0000- ​ 0000- ​

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​0002- et al. Influenza vaccine- threatening adversereactiontomonov ­ 14 15 Not required. J ­ anuary 13, 2021. MMWRMorbMortal Wkly Rep existing comorbiditiesandareless ­ 1572- ​ In countries such as South Korea, 6533- ​ Case baseddiscussion . InternMed2018;57:707–11. ​5149 ​4656 ­ for - ­ HK, VID-19 vaccines in older vaccinesinolder VID-19 profit sectors ­ externallypeerreviewed. YIH andSHJcontributedto induced interstitiallung ­ ­ induced pneumonitis . alent H1N1 ​ ­

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on September 28, 2021 by guest. Protected by copyright. by Protected guest. by 2021 28, September on Chest clinic