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COVID-19 Vaccine-Related Interstitial Lung Disease: a Case Study

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COVID-19 Vaccine-Related Interstitial Lung Disease: a Case Study Case based discussion COVID-19 vaccine- related interstitial lung disease: a Thorax: first published as 10.1136/thoraxjnl-2021-217609 on 6 August 2021. Downloaded from case study Ji Young Park ,1 Joo- Hee Kim ,1 In Jae Lee,2 Hwan Il Kim,1 Sunghoon Park,1 Yong Il Hwang,1 Seung Hun Jang,1 Ki- Suck Jung1 1Division of Pulmonary, Allergy DR JI YOUNG PARK aspartate aminotransferase, 18 IU/L; and alanine and Critical Care Medicine, Herd immunity through extensive and rapid vaccina- aminotransferase, 11 IU/L. Chest radiograph revealed Department of Internal bilateral reticular opacities. Empirical antibiotics Medicine, Hallym University tion rather than natural immunity acquired by infec- Sacred Heart Hospital, Hallym tion is necessary to control a global pandemic like were administered for 3 days considering a diagnosis University College of Medicine, COVID-19. The development of COVID-19 vaccines of pneumonia; however, the symptoms and chest Anyang, South Korea radiograph findings worsened. Chest CT revealed 2 has been accelerated through government funding Department of Radiology, and the collaborative efforts of the medical–scien- bilateral diffuse ground- glass opacities (GGO) with Hallym University College of 1 2 Medicine, Anyang, South Korea tific institutions and the pharmaceutical industry. focal consolidations, centrilobular micronodules In South Korea, the ChAdOx1 nCoV-19 (Oxford/ and interlobular septal thickening (figure 1A,B). The Correspondence to AstraZeneca) and BNT162b2 (Pfizer/BioNTech) C reactive protein level increased to 11.43 mg/dL. Dr Ji Young Park, Division of vaccines have received emergency approval and are The brain natriuretic peptide level (88 pg/mL) was Pulmonary, Allergy and Critical being used. Although the safety and efficacy of these within the reference range, and serum procalcitonin Care Medicine, Department vaccines were established through interim analysis (0.32 ng/mL) was slightly elevated. of Internal Medicine, Hallym University Sacred Heart Hospital, in global clinical trials, long-term data and reports 1 2 Hallym University College of of rare adverse reactions remain inadequate. We Medicine, Anyang 14068, South report a case of interstitial lung disease (ILD) after DR SUNGHOON PARK Korea; evan007@ naver. com COVID-19 vaccination and review the literature on The results of COVID-19 PCR testing (Real- Q 2019- influenza vaccine-related ILDs. This review is favour- nCoV Detection kit; BioSewoom, Seoul, Korea) of Received 14 May 2021 nasopharyngeal swabs and sputum samples were Accepted 11 July 2021 able as influenza vaccines are widely administered annually among the elderly, and several vaccine- negative, initially and after 3 days. Test results of the related ILDs have been reported. induced sputum samples were negative for other pathogens (seasonal respiratory virus multiplex PCR testing (Real- Q RV Detection kit, BioSewoom), DR HWAN IL KIM bacterial culture, acid–fast bacillus smear, tubercu- In early April 2021, an 86- year- old man presented losis PCR testing and respiratory bacterial multiplex Chest clinic to the emergency department with a 1- day history PCR testing (Allplex PneumoBacter Assay; Seegene, http://thorax.bmj.com/ of weakness, dyspnoea and fever. He had no cough, Seoul, Korea)). He was seronegative for rheuma- expectoration, nasal discharge or sore throat. One day toid factor and anticitrullinated peptide, antineutro- before symptom onset, he had received a COVID-19 phil cytoplasmic, antinuclear, anti-dsDNA, anti- Sm, mRNA vaccine. He had hypertension, diabetes and anti- U1RNP, anti- Scl-70, anti- Ro and anti- La anti- chronic renal disease, which were well controlled bodies. IgE, IgG, IgA and IgM concentrations were with medications (atorvastatin, amlodipine, furo- within the normal range, and 62 allergen-specific semide, linagliptin, metformin and clopidogrel). IgE antibodies using AdvanSure AlloScreen (LG He was a non- smoker with no history of cardiovas- Life Science, Seoul, Korea) were negative. Broncho- on September 28, 2021 by guest. Protected copyright. cular, pulmonary, allergic or connective tissue disease scopic bronchoalveolar lavage and lung biopsy could (CTD). He took an influenza vaccine annually with not be performed because of the patient’s refusal. no adverse events and had no history of adverse COVID-19 vaccine-related ILD was diagnosed based events with other vaccines or drugs. He denied any on the clinical course, radiological features and labo- recent changes in his living environment and expo- ratory results. We discontinued antibiotic therapy and sure to chemicals or organic particles. On admission, initiated intravenous methylprednisolone at 1 mg/kg/ his body temperature was 38.2°C, and peripheral day. His symptoms and chest radiography findings oxygen saturation was 80% on room air. He had no rapidly improved the following day. After 3 days, rash, oedema or clubbing, but bilateral crackles were the steroid dose was reduced. Thirteen days later, he found on auscultation. The partial pressure of oxygen was discharged. Subsequently, the steroid dose was in arterial blood (PaO2)/fraction of inspired oxygen gradually tapered and discontinued with no relapse. © Author(s) (or their ratio (FiO2) was maintained at 248 (50% FiO2; PaO2, The onset was acute after vaccination, and the clin- employer(s)) 2021. No 124.2 mm Hg; PaCO , 21.2 mm Hg) with high- flow ical course was transient with rapid improvement by commercial re- use. See rights 2 and permissions. Published nasal cannula oxygen therapy. An electrocardiograph steroid treatment. by BMJ. showed sinus tachycardia without ST changes. Blood A SARS-CoV -2 serological antibody test performed investigations revealed the following: haemoglobin, 16 days after vaccination showed that both IgM To cite: Park JY, Kim J- H, 136 g/L; white cell count, 11.60×109/L (neutrophils, and IgG were negative (STANDARD Q COVID-19 Lee IJ, et al. Thorax Epub ahead of print: [please 82.8%; eosinophils, 4.1%; lymphocytes, 5.8%); IgM/IgG Plus Test; SD Biosensor, Korea). The test 9 include Day Month Year]. platelets, 340×10 /L; International Normalized was conducted to reconfirm whether the patient doi:10.1136/ Ratio (INR), 1.04; D-dimer , 0.55 µg/mL; blood had a previously undiagnosed COVID-19 before thoraxjnl-2021-217609 urea nitrogen, 22.7 mg/dL; creatinine, 1.85 mg/dL; vaccination and to rule out the hypothesis that a Park JY, et al. Thorax 2021;0:1–3. doi:10.1136/thoraxjnl-2021-217609 1 Case based discussion Thorax: first published as 10.1136/thoraxjnl-2021-217609 on 6 August 2021. Downloaded from Chest clinic http://thorax.bmj.com/ Figure 1 (A) Clinical course and chest radiography findings of a patient with COVID-19 vaccine-related ILD. (B) Chest CT images obtained at 4 days (A) and 18 days after COVID-19 vaccination. (C) Data of 10 previously reported cases of influenza vaccine-related ILD. *One case each of chronic hypersensitive pneumonitis and idiopathic pulmonary fibrosis. #1, Johnston et al5; #2, Heinrichs et al6; #3, Kanemitsu et al7; #4, Bhurayanontachai8; on September 28, 2021 by guest. Protected copyright. #5, Umeda et al9; #6, Kumamoto et al10; #7, Watanabe et al11; #8, Hibino and Kondo12; #9, Hibino and Kondo12; #10, Numata et al.4 BAL, bronchoalveolar lavage; ED, emergency department; FiO2, fraction of inspired oxygen; HFNC, high- flow nasal cannula; ILD, interstitial lung disease; MPD, methylprednisolone; n, no; y, yes. past SARS- CoV-2 infection may have elicited a robust antibody vaccination. The rechallenge test is necessary only when no alter- response after vaccination. Moreover, high- dose steroids might native treatment is available; therefore, the patient was advised not prevent adequate antibody formation after vaccination. However, to take the second dose of the vaccine. Lastly, the ‘exclusion of to date, there are no commercial antibody tests approved for other conditions’ criterion was met as infections and CTDs were the evaluation of immunity following COVID-19 vaccinations, ruled out based on the radiological findings and microbiolog- including the tests we conducted. ical and serological test results. Bronchoalveolar lavage and lung biopsy were not performed. However, their results are usually non- DR YONG IL HWANG specific for the diagnosis of DILD. Drug- induced interstitial lung disease (DILD) has a wide spectrum of clinical presentation, from transient lung infiltration to acute DR SEUNG HUN JANG AND DR IN JAE LEE respiratory distress syndrome, and is a diagnosis of exclusion. The We found 10 published case reports of influenza vaccine- associated ‘identification’ and ‘singularity’ criteria proposed by Camus et al3 ILD.4–12 The clinical characteristics of influenza vaccine-related were met, because other than the routine medications for hyper- ILD cases were similar to those of the current case in the following tension and diabetes, COVID-19 mRNA vaccine was the only drug respects (figure 1c). Symptom onset was acute and occurred at a administered before the onset of ILD. The ‘temporal eligibility’ median of 2 days after vaccination, and fever appeared in most criteria were met as the patient had no respiratory symptoms or patients. In all cases where chest CT findings can be referred fever, and ILD with severe hypoxia occurred on the day after to, bilateral distribution and GGO were confirmed. All patients 2 Park JY, et al. Thorax 2021;0:1–3. doi:10.1136/thoraxjnl-2021-217609 Case based discussion recovered, and most responded well to steroid therapy. Interest- to determine their relevance.14 15 In countries such as South Korea, Thorax: first published as 10.1136/thoraxjnl-2021-217609 on 6 August 2021. Downloaded from ingly, 8 of 10 patients were Asian, underlying ILD in two cases. where vaccine availability is limited, elderly subjects are being Although publication bias is a significant limitation, these might be prioritised for vaccination after healthcare workers. However, risk factors for influenza vaccine-related ILD. There was a vaccine older adults usually have pre- existing comorbidities and are less safety committee’s report of acute deterioration of underlying ILD tolerable of adverse events.
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