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Initial workup revealed blood eosinophilia &#40;23&#46;8&#37;&#59; 3250&#47;&#956;L&#41; without neutrophilia and increased C-reactive protein &#40;37&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; and total IgE &#40;420&#41;&#46; A course of Levofloxacin was started&#46; Of note&#44; symptoms initiated two weeks after COVID-19 vaccination&#46; Physical examination was unremarkable&#46; PCR for SARS-CoV-2 was negative&#46; Chest radiography showed airspace consolidation in the right upper lobe&#46; Chest HRCT revealed multiple ground glass opacities and interlobular septal thickening &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; Flexible bronchoscopy with BAL analysis revealed eosinophilia &#40;13&#37;&#41; and lymphocytosis &#40;15&#37;&#41;&#46; All microbiological and immunological tests were negative&#46; Rearrangement of PDGFRA was assessed and not found&#46; CT-guided transthoracic lung biopsy was suggestive of eosinophilic pneumonia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Deflazacort 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day was started&#44; with both clinical and radiological resolution&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 2</span>&#58; Forty-seven-year-old caucasian female&#44; non-smoker&#44; with history of psoriasis &#40;treated with ustecinumab since 2019&#41; and depression &#40;treated with fluoxetine 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; She had a history of nonresolving pneumonia in 2009&#44; at that time with documented blood eosinophilia&#59; diagnostic work-up was non-conclusive and spontaneous resolution of symptoms and radiological changes were observed&#46; Regular follow-up did not show clinical&#47;radiological recurrence&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In July 2021&#44; she presented at the emergency department complaining of fatigue and troublesome dry cough for the last 3 weeks&#46; A course of claritromicin was completed&#44; with no symptomatic improvement&#46; Physical examination revealed crackles in the upper lung fields&#46; Initial workup revealed peripheral eosinophilia &#40;10&#46;1&#8211;820&#47;&#956;L&#41;&#44; with no leukocytosis and normal C-reactive protein&#46; Patient was administered with SARS-COV-2 vaccine four weeks before symptoms appeared&#46; Chest HRCT revealed peripheral and subpleural areas of linear parenchymal densification &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Flexible bronchoscopy with BAL analysis revealed eosinophilia &#40;11&#37;&#41;&#46; All microbiological and immunological studies were normal&#44; with exception of positive antinuclear antibodies 1&#47;320 with speckled pattern&#46; CT-guided transthoracic lung biopsy was consistent with eosinophilic pneumonia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; The patient was started on prednisolone 40<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; with clinical and radiological resolution at the end of 14 days&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Acute eosinophilic pneumonia &#40;AEP&#41; is a rare disease that can be idiopathic or secondary to innumerous agents&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The type of T-helper immune response induced by vaccination depends on the antigen &#40;e&#46;g&#46; immunization with inactivated SARS-CoV-1&#59; Immunization with the whole spike &#40;S&#41; protein&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> In the past SARS-CoV-1 vaccines have been shown to induce pulmonary eosinophilia in animals after viral challenge<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and eosinophil-associated type 2 inflammation in reinfection in monkeys&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Eosinophil associated pulmonary disease was also seen subsequently to infection after RSV vaccination<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and a case of AEP related to influenza vaccination has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Moreover&#44; cases of AEP in patients with COVID-19<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> or expressed as a recurrence of respiratory symptoms after COVID-19 recovery were documented&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Since SARS-CoV-1 and SARS-CoV-2 share more than 80&#37; identity&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> it would be no surprise if SARS-CoV-2 vaccines could cause a similar vaccine-associated immunopathology&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In both cases&#44; possible causes of eosinophilic pneumonia&#44; including parasitic infestation&#44; drug-induced eosinophilia&#44; and dust or toxic substance exposure were excluded&#44; therefore the positive temporal relationship between SARS-CoV-2 vaccination and symptoms&#8217; emergence lead the authors to believe that vaccination might be the potential cause of AEP&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">With this report&#44; the authors intend to highlight the potential development or recrudescence of eosinophilic lung disease in association with SARS-CoV-2 vaccination&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Case Report
Eosinophilic Pneumonia Associated to SARS-CoV-2 Vaccine
Neumonía eosinofílica asociada a la vacuna por SARS-CoV-2
Margarida Costa e Silvaa,1,
Corresponding author
mm.costasilva@gmail.com

Corresponding author.
, Marta Sá Marquesa,1, David Joãob, Sérgio Campainhaa
a Pulmonology Department, Centro Hospitalar Vila Nova de Gaia e Espinho, Portugal
b Pathology Department, Centro Hospitalar Vila Nova de Gaia e Espinho, Portugal
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Initial workup revealed blood eosinophilia &#40;23&#46;8&#37;&#59; 3250&#47;&#956;L&#41; without neutrophilia and increased C-reactive protein &#40;37&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; and total IgE &#40;420&#41;&#46; A course of Levofloxacin was started&#46; Of note&#44; symptoms initiated two weeks after COVID-19 vaccination&#46; Physical examination was unremarkable&#46; PCR for SARS-CoV-2 was negative&#46; Chest radiography showed airspace consolidation in the right upper lobe&#46; Chest HRCT revealed multiple ground glass opacities and interlobular septal thickening &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; Flexible bronchoscopy with BAL analysis revealed eosinophilia &#40;13&#37;&#41; and lymphocytosis &#40;15&#37;&#41;&#46; All microbiological and immunological tests were negative&#46; Rearrangement of PDGFRA was assessed and not found&#46; CT-guided transthoracic lung biopsy was suggestive of eosinophilic pneumonia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Deflazacort 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day was started&#44; with both clinical and radiological resolution&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 2</span>&#58; Forty-seven-year-old caucasian female&#44; non-smoker&#44; with history of psoriasis &#40;treated with ustecinumab since 2019&#41; and depression &#40;treated with fluoxetine 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; She had a history of nonresolving pneumonia in 2009&#44; at that time with documented blood eosinophilia&#59; diagnostic work-up was non-conclusive and spontaneous resolution of symptoms and radiological changes were observed&#46; Regular follow-up did not show clinical&#47;radiological recurrence&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In July 2021&#44; she presented at the emergency department complaining of fatigue and troublesome dry cough for the last 3 weeks&#46; A course of claritromicin was completed&#44; with no symptomatic improvement&#46; Physical examination revealed crackles in the upper lung fields&#46; Initial workup revealed peripheral eosinophilia &#40;10&#46;1&#8211;820&#47;&#956;L&#41;&#44; with no leukocytosis and normal C-reactive protein&#46; Patient was administered with SARS-COV-2 vaccine four weeks before symptoms appeared&#46; Chest HRCT revealed peripheral and subpleural areas of linear parenchymal densification &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Flexible bronchoscopy with BAL analysis revealed eosinophilia &#40;11&#37;&#41;&#46; All microbiological and immunological studies were normal&#44; with exception of positive antinuclear antibodies 1&#47;320 with speckled pattern&#46; CT-guided transthoracic lung biopsy was consistent with eosinophilic pneumonia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; The patient was started on prednisolone 40<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; with clinical and radiological resolution at the end of 14 days&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Acute eosinophilic pneumonia &#40;AEP&#41; is a rare disease that can be idiopathic or secondary to innumerous agents&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The type of T-helper immune response induced by vaccination depends on the antigen &#40;e&#46;g&#46; immunization with inactivated SARS-CoV-1&#59; Immunization with the whole spike &#40;S&#41; protein&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> In the past SARS-CoV-1 vaccines have been shown to induce pulmonary eosinophilia in animals after viral challenge<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and eosinophil-associated type 2 inflammation in reinfection in monkeys&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Eosinophil associated pulmonary disease was also seen subsequently to infection after RSV vaccination<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> and a case of AEP related to influenza vaccination has also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Moreover&#44; cases of AEP in patients with COVID-19<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> or expressed as a recurrence of respiratory symptoms after COVID-19 recovery were documented&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Since SARS-CoV-1 and SARS-CoV-2 share more than 80&#37; identity&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> it would be no surprise if SARS-CoV-2 vaccines could cause a similar vaccine-associated immunopathology&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In both cases&#44; possible causes of eosinophilic pneumonia&#44; including parasitic infestation&#44; drug-induced eosinophilia&#44; and dust or toxic substance exposure were excluded&#44; therefore the positive temporal relationship between SARS-CoV-2 vaccination and symptoms&#8217; emergence lead the authors to believe that vaccination might be the potential cause of AEP&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">With this report&#44; the authors intend to highlight the potential development or recrudescence of eosinophilic lung disease in association with SARS-CoV-2 vaccination&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Chest HRCT&#58; multiple ground glass opacities and interlobular septal thickening&#59; &#40;B&#41; Histopathological findings of transthoracic needle biopsy&#58; On hematoxylin and eosin staining there is lung tissue with alevoli filled by histiocytes and eosinophils&#44; forming &#8220;eosinophilic microabscesses&#8221;&#46; &#40;Original magnification&#58; 100&#215;&#41;&#46;</p>"
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ISSN: 03002896
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