Scientific Letter
Acute Eosinophilic Pneumonia Associated With SARS-CoV-2 Infection
Neumonía eosinofílica aguda asociada con la infección por SARS-CoV-2
Vicente Descalzoa, Fernando Salvadora,
, Irene Sansanob, Óscar Persivac, Andrés Antónd, David Clofente, Manuel Lópeze, Benito Almirantea
Corresponding author
a Department of Infectious Diseases, Vall d’Hebron University Hospital, Barcelona, Spain
b Department of Pathology, Vall d’Hebron University Hospital, Barcelona, Spain
c Department of Radiology, Vall d’Hebron University Hospital, Barcelona, Spain
d Department of Microbiology, Vall d’Hebron University Hospital, Barcelona, Spain
e Department of Pulmonology, Vall d’Hebron University Hospital, Barcelona, Spain
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"Department of Microbiology, Vall d’Hebron University Hospital, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Pulmonology, Vall d’Hebron University Hospital, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neumonía eosinofílica aguda asociada con la infección por SARS-CoV-2" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1769 "Ancho" => 1674 "Tamanyo" => 433019 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) CT scan showing ground glass opacities with areas of consolidation, air bronchogram and bronchiectasis; (b) Hematoxylin eosin staining (40× magnification) showing prominent lymphoplasmacytic interstitial infiltrate with numerous eosinophils. Alveoli infiltrate with mixed cellularity (lymphocytes, plasma cells, eosinophils, foamy macrophages, fibroblasts). Note one macrophage with phagocytized eosinophil granules (arrow).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute eosinophilic pneumonia (AEP) is a rare condition characterized by an eosinophil infiltration of pulmonary parenchyma, which leads to an acute respiratory illness. It can be idiopathic or secondary to various agents, including infectious diseases.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> We describe a case of AEP related to SARS-CoV-2 infection, expressed as a recurrence of respiratory symptoms after initial recovery from Covid-19 pneumonia.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 61-year-old man without relevant medical history arrived at the emergency room with dyspnea, having started with fever and cough 2 weeks before. He did not smoke and denied other toxic use. A chest x-ray showed bilateral peripheral opacities and a nasal-oropharynx PCR for SARS-CoV-2 was positive. Mild elevation of ferritin, CRP and IL-6 was observed. The patient was admitted to the hospital with the diagnosis of Covid-19 pneumonia and treatment began with hydroxychloroquine, azithromycin and lopinavir/ritonavir (following the current hospital protocol at that moment), plus oxygen therapy at an initial FiO<span class="elsevierStyleInf">2</span> of 28%. Patient's clinical and respiratory condition progressively improved and he was discharged after 5 days.</p><p id="par0015" class="elsevierStylePara elsevierViewall">He came back to the hospital after one week because of recurrence of dyspnea and mild fever. New bilateral consolidations were observed in the chest X-ray, with no major changes in inflammatory parameters compared to previous admission. Slight elevation of neutrophils was observed, with normal eosinophil count (200<span class="elsevierStyleHsp" style=""></span>cells/ml). The PCR for SARS-CoV-2 at this time was negative. With the suspicion of infectious vs inflammatory complication, ceftriaxone and iv methylprednisolone 60<span class="elsevierStyleHsp" style=""></span>mg per day were started, and the patient was readmitted to the hospital.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The CT scan showed bilateral subpleural ground glass opacities with areas of consolidation, with an air bronchogram sign and associated bronchiectasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). A bronchoscopy for bronchoalveolar lavage (BAL) and transbronchial biopsy was performed on the fifth day after admission. Bacterial cultures and bacilloscopy of BAL, bronchial aspirate and biopsy were negative. SARS-CoV-2 PCR was positive in bronchial aspirate but negative in BAL. The differential cell count in BAL fluid had 50% macrophages, 30% lymphocytes, and 20% polymorphonuclears (including 5% eosinophils). The biopsy showed a prominent mixed infiltrate in interstitium and alveoli with numerous eosinophils, compatible with partially treated AEP (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The patient completed one week of hospitalization, with both clinical and radiological improvement, and he was discharged continuing prednisone at a dose of 30<span class="elsevierStyleHsp" style=""></span>mg per day. During follow up in outpatient consultation the study was completed with HIV and <span class="elsevierStyleItalic">Strongyloides stercoralis</span> serology, as well as ANA and ANCA antibodies, which were all negative. A CT scan was repeated after one month, showing resolution of consolidation areas with persistence of minimum ground glass infiltrates. At this time, complete functional recovery was objectified with a forced vital capacity of 141% with no obstructive espirometric pattern, a carbon monoxide diffusion capacity of 84%, and absence of oxygen desaturation in the six minute walking test.</p><p id="par0030" class="elsevierStylePara elsevierViewall">AEP presents as an acute respiratory illness, whose symptoms appear within days or weeks. Severity can go from mild disease to acute respiratory distress syndrome, with potential progression to death. It can be idiopathic or secondary to inhalational toxics, drugs or infections.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Diagnosis is challenging, especially during the current pandemic situation, since the clinical picture might resemble COVID-19 disease.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Diagnosis is based on clinical and laboratory criteria, with a leading role of cytological analysis of BAL fluid, where eosinophils usually represent more than 25% of the cells. Lung biopsy is not usually required, unless an alternative diagnosis needs to be excluded. Management consists in cessation of exposure to underlying causes when identifiable, and treatment with systemic glucocorticoids in most cases. Clinical and radiological response is usually rapid and complete without any long term sequelae.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnosis of AEP in our patient was established through biopsy which confirmed pulmonary eosinophilia. However, as a main limitation in this case report, the BAL fluid differential count only showed 5% of eosinophils. This low percentage could be related to the fact that bronchoscopy was performed 5 days after initiation of glucocorticoids. As seen in other AEP case reports, eosinophils in BAL fluid return to normal as the illness resolves, in some cases within a few days after initiation of treatment so steroids could have influenced this result.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3,4</span></a> Another feature supporting AEP diagnosis in our patient is the rapid clinical and radiological response, considered an important diagnostic criterion.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding possible etiologies of AEP in this case, SARS-CoV-2 would be suggested as a first option. The infection was confirmed by PCR technique and the initial clinical picture was typical. At readmission, recurrence of symptoms with worsening of pulmonary infiltrates would recall the inflammatory phase in Covid-19 disease, but the biopsy results were unusual. Previous histopathological reviews of Covid-19 pneumonia have not reported the presence of eosinophils as a common finding, and the role of pulmonary eosinophilia does not seem to be relevant in the physiopathology.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5–7</span></a> Therefore, we could suggest our case as a rare eosinophilic complication differentiated from typical Covid-19 disease. Although parasites and fungus are the infectious agents most frequently associated with AEP, other viruses such as Influenza A H1N1 have been reported, so an eventual association with SARS-CoV-2 could also be possible.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Other potential causes of AEP would be related to the treatment that our patient had received. A few cases of drug induced eosinophilic pneumonia have been reported associated to azithromycin and antimalarial drugs, including chloroquine, but none to lopinavir/ritonavir.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10,11</span></a> Against this possibility, there is the fact that patient's clinical condition was improving while on these drugs, whereas symptoms reappeared once the treatment was over.</p><p id="par0055" class="elsevierStylePara elsevierViewall">We finally want to highlight the importance of having a clinical suspicion of AEP when patients affected by Covid-19 pneumonia experience a recurrence or worsening of symptoms, since early glucocorticoid therapy would avoid further complications. In these cases, BAL should be ideally performed before instauration of treatment for proper diagnosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1769 "Ancho" => 1674 "Tamanyo" => 433019 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) CT scan showing ground glass opacities with areas of consolidation, air bronchogram and bronchiectasis; (b) Hematoxylin eosin staining (40× magnification) showing prominent lymphoplasmacytic interstitial infiltrate with numerous eosinophils. Alveoli infiltrate with mixed cellularity (lymphocytes, plasma cells, eosinophils, foamy macrophages, fibroblasts). Note one macrophage with phagocytized eosinophil granules (arrow).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute eosinophilic pneumonia. Causes diagnosis, and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. De Giacomi" 1 => "R. Vassallo" 2 => "E.S. Yi" 3 => "J.H. Ryu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201710-1967CI" "Revista" => array:6 [ "tituloSerie" => "Am. J. Respir. Crit. Care Med." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 2 | 14 |
| 2024 October | 76 | 25 | 101 |
| 2024 September | 93 | 13 | 106 |
| 2024 August | 112 | 48 | 160 |
| 2024 July | 91 | 21 | 112 |
| 2024 June | 130 | 27 | 157 |
| 2024 May | 142 | 27 | 169 |
| 2024 April | 120 | 24 | 144 |
| 2024 March | 93 | 25 | 118 |
| 2024 February | 84 | 32 | 116 |
| 2024 January | 85 | 30 | 115 |
| 2023 December | 82 | 39 | 121 |
| 2023 November | 88 | 34 | 122 |
| 2023 October | 92 | 30 | 122 |
| 2023 September | 88 | 32 | 120 |
| 2023 August | 90 | 32 | 122 |
| 2023 July | 69 | 27 | 96 |
| 2023 June | 74 | 20 | 94 |
| 2023 May | 72 | 18 | 90 |
| 2023 April | 69 | 27 | 96 |
| 2023 March | 98 | 44 | 142 |
| 2023 February | 91 | 18 | 109 |
| 2023 January | 87 | 24 | 111 |
| 2022 December | 135 | 30 | 165 |
| 2022 November | 151 | 41 | 192 |
| 2022 October | 138 | 46 | 184 |
| 2022 September | 140 | 49 | 189 |
| 2022 August | 107 | 36 | 143 |
| 2022 July | 106 | 59 | 165 |
| 2022 June | 148 | 48 | 196 |
| 2022 May | 165 | 41 | 206 |
| 2022 April | 127 | 78 | 205 |
| 2022 March | 170 | 64 | 234 |
| 2022 February | 165 | 71 | 236 |
| 2022 January | 177 | 50 | 227 |
| 2021 December | 167 | 25 | 192 |
| 2021 November | 132 | 31 | 163 |
| 2021 October | 141 | 40 | 181 |
| 2021 September | 153 | 32 | 185 |
| 2021 August | 137 | 36 | 173 |
| 2021 July | 147 | 25 | 172 |
| 2021 June | 195 | 40 | 235 |
| 2021 May | 216 | 44 | 260 |
| 2021 April | 360 | 91 | 451 |
| 2021 March | 128 | 40 | 168 |
| 2021 February | 99 | 35 | 134 |
| 2021 January | 129 | 39 | 168 |
| 2020 December | 0 | 4 | 4 |
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