key: cord-0852058-beqx5am6 authors: Bando, Tomohiro; Takei, Reoto; Mutoh, Yoshikazu; Sasano, Hajime; Yamano, Yasuhiko; Yokoyama, Toshiki; Matsuda, Toshiaki; Kataoka, Kensuke; Kimura, Tomoki; Kondoh, Yasuhiro title: Acute Exacerbation of Idiopathic Pulmonary Fibrosis after SARS-CoV-2 Vaccination date: 2022-02-09 journal: Eur Respir J DOI: 10.1183/13993003.02806-2021 sha: 657965d97bcbde649d17ba2ff6194a6da0761fc4 doc_id: 852058 cord_uid: beqx5am6 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and coronavirus disease 2019 remains a top health concern. Several SARS-CoV-2 vaccines have been produced and are playing great roles in the prevention of infection and worsening to a severe state, and in improving mortality [1]. However, some concerns about adverse effects related to SARS-CoV-2 vaccination have been raised. Recently, various adverse effects have been reported, but there is little data on adverse effects on the lungs [2]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and coronavirus disease 2019 remains a top health concern. Several SARS-CoV-2 vaccines have been produced and are playing great roles in the prevention of infection and worsening to a severe state, and in improving mortality [1] . However, some concerns about adverse effects related to SARS-CoV-2 vaccination have been raised. Recently, various adverse effects have been reported, but there is little data on adverse effects on the lungs [2] . We treated a patient with fibrotic interstitial lung disease (f-ILD) who needed hospitalization for acute respiratory failure and newly arising bilateral ground-glass opacities (GGO) on chest high-resolution computed tomography (HRCT) within nine days after his second mRNA SARS-CoV-2 vaccination. A full inpatient evaluation was performed and the patient was diagnosed with acute exacerbation (AE) of f-ILD (AE-f-ILD), raising a question on the relationship between SARS-CoV-2 vaccination and AE. Since recent studies have reported high mortality among f-ILD patients with SARS-CoV-2 infection [3, 4] , this case has potential clinical significance and we present the clinical course below with some discussion. An 84-year-old male was previously diagnosed with f-ILD ( Figure 1A ) and regularly followed at another hospital from October 2020. He was not receiving any medication. He had a former smoking history of 34 pack-years, and no significant past medical history. In mid-May 2021, he received his first BNT162b2 vaccine (BioNTech/Pfizer), which produced no adverse effects. In June 2021, he received his second vaccine and gradually developed malaise and loss of appetite from the day following the vaccination. The symptoms persisted without improvement for nine days after he received the second vaccine, and he visited a nearby hospital. His chest HRCT revealed diffuse GGO with basal and subpleural honeycomb and reticulation ( Figure 1B Treatment with intravenous corticosteroids (two cycles of methylprednisolone 1000 mg/day for three days followed by 1 mg/kg/day) was initiated, after which methylprednisolone was gradually titrated from 60 mg to 10 mg, by 10 mg each every three or four days. After steroid pulse treatment, the GGO on chest HRCT improved but subpleural reticulation remained and progressed ( Figure 1C ). His respiratory condition stabilized without supplemental oxygen. After two weeks of rehabilitation, he was discharged to a care medical facility while receiving 10 mg of oral corticosteroids on the 71st day from admission. We treated a patient with ILD who had acute respiratory failure and new GGO soon after receiving the SARS-CoV-2 vaccine. Even though he did not undergo a full evaluation for ILD when it was revealed at his former hospital, we retrospectively diagnosed him with IPF. This case met the criteria of AE defined in an international working group report [5] . We diagnosed the condition as AE-IPF, of which the AE could have been triggered by SARS-CoV-2 vaccination. The etiology of AE-ILD remains unknown, but causes such as bacterial/viral infection, certain procedures or surgeries, and drug toxicity have been reported to trigger the pathogenesis of AE [6] . Some vaccinations have also been reported to be a potential cause of AE. Previous case reports showed possible triggering of AE of IPF by influenza A vaccination [7] [8] . A case of AE of connective tissue disease-associated f-ILD resulting from an influenza vaccine was also reported [9] . These three cases were diagnosed as f-ILD (two IPF and one CTD-ILD) before vaccination. Their HRCT showed bilateral GGO and they had respiratory failure several days after vaccination. All of them were treated with corticosteroid pulse therapy and their respiratory condition and CT findings improved after initial treatment. Although the relationship between ILD and vaccination has not been fully elucidated, these findings suggest that vaccination could trigger AE-ILD. No firm conclusion can be reached from this small number of case reports, but those earlier cases and our case share a similar clinical course and radiological features. Therefore, it is reasonable to conclude that our patient experienced AE-IPF triggered by SARS-CoV-2 vaccination. No previous study on AE-f-ILD triggered by SARS-CoV-2 vaccine has been reported. Park et al. has reported a case of SARS-CoV-2 vaccine-related ILD [10] , and the WHO global pharmacovigilance database (VigiAccess) showed 464 cases of suspected ILD, 87 cases of suspected organizing pneumonia, eight cases of acute lung injury and two cases of acute interstitial pneumonitis and idiopathic interstitial pneumonia from the BNT162b2 vaccine. However, no AE-f-ILD cases were seen [11] , nor was AE-f-ILD reported in a clinical trial [2] . Therefore, to our knowledge, this is the first report of AEf-ILD that could have been triggered by SARS-CoV-2 vaccination. The pathogenesis of AE triggered by vaccination remains unclear. SARS-CoV-2 vaccination has been revealed to induce T cell responses reflected in production of some cytokines, such as interferon-gamma and interleukin-2 [12] . Since a high percentage of the population that receives SARS-CoV-2 vaccination experiences fatigue and fever as side effects, some sort of immune response likely occurs in the body, possibly provoking AE in f-ILD patients. However, AE-f-ILD occurs with a certain probability in patients with f-ILD, with an incidence rate reported to be around 5-10% per year [5] [6] . In this case, we cannot prove whether this event just happened to overlap with the timing of vaccination, or was triggered by the vaccination itself. Further study of the possible association between SARS-CoV-2 vaccination and AE is needed, by evaluating numbers of vaccinated patients with ILD and the incidence of AE among those patients. In conclusion, this is the first case report describing AE-f-ILD after SARS-CoV-2 vaccination. Unquestionably, vaccination is a very effective method of preventing al; C4591001 Clinical Trial Group. 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