PMC:7340597 / 6542-12573 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7340597","sourcedb":"PMC","sourceid":"7340597","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7340597","text":"3.1 Clinical features\nDuring the study period, seven patients underwent postmortem needle core biopsy of the lungs. Patients age ranged from 58 to 83 years (median 74 year) and five patients were male. None of the patients had a history of (chronic) pulmonary disease. One patient used immunosuppressive medication before hospital admission, in this case a short course of prednisolone. Median time from hospital to ICU admission was 0 days (interquartile range 0–4). Time from hospital admission to death ranged from 12 to 36 days. Patients deceased at median of 21(range 9–36) ventilated days. In five out of seven patients ICU stay was complicated by pulmonary embolism. Adopting the proposed definition of CAPA by van Arkel et al. [9], six patients were classified as having probable CAPA (Table 1 ), based on a positive GM on BAL fluid. In those patients, combination antifungal therapy with voriconazole and anidulafungin was started. Three out of six patients were on corticosteroids (60 mg prednisolone daily) at the time of CAPA diagnosis and corticosteroid treatment was terminated. Indication for steroid treatment in these patients was a suspicion of an organizing pneumonia on chest CT or signs of progression to fibrosis. Nosocomial infections including signs for pulmonary aspergillosis were excluded by bronchoscopy with BAL before steroid treatment was started. Radiologic findings of chest CT and histologic results of the lungs biopsies of all seven patients are shown in Table 2 .\nTable 1 Patient characteristics and clinical course.\nCase Sex, age (years) Medical history Total hospital days Total ventilated days Berlin classification of ARDS Compliance phenotype PE BAL fluid GM and culture (days post hospital admission) CAPA Chloroquine Prednisolone use during hospital admission Duration of prednisolone treatment\n1 M, 77 None 12 10 Severe Low Yes GM negative No Yes No\n2 F, 73 None 20 16 Severe High Yes GM index 4.4 (day 19) Aspergillus fumigatus Probable No Yes 8 days\n3 F, 58 None 30 26 Severe Low Yes GM index 3.4 (day 20) Probable Yes Yes 5 days\n4 M, 68 None 21 21 Moderate Low Yes GM index 5.7 (day 1) Aspergillus fumigatus Enterococcus faecium Probable Yes No\n5 M, 78 HT, CKI 22 21 Moderate Low No GM index 4.3 (day 20) Enterococcus faecium Probable Yes Yes 2 days\n6 M, 83 HT, DM 13 9 Moderate Low No GM index 1.7 (day 11) Probable Yes No\n7 M, 74 None 36 36 Severe Low Yes GM index 4.4 (day 24) Enterococcus faecalis Probable Yes Yes 4 days\nARDS acute respiratory distress syndrome; BAL broncho-alveolar lavage; CAPA, COVID-19 associated pulmonary aspergillosis; CKI, chronic kidney injury; DM, diabetes mellitus; GM, galactomannan; HT, hypertension; PE pulmonary embolism.\nTable 2 Radiological Chest CT scan and histological findings.\nCase Radiological findings Histological findings description Diagnosis\n1 GGO, crazy paving, non-dependent consolidation, subpleural sparing, segmental and subsegmental PE Intra-alveolar fibromyxoid/fibroblastic bodies (25%), micro-thrombi, thrombi in lager vessels, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae OP\n2 GGO, crazy paving, resolving consolidation, bronchiectasis, segmental and subsegmental PE Extensive fibrosis with destruction of alveolar structures, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae Fibrosis\n3 GGO, large dependent consolidation, bronchiectasis, subsegmental PE Inflammatory infiltrate, hyaline membranes, sporadic intra-alveolar fibroblastic plug, micro-thrombi, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae DAD\n4 GGO, crazy paving, non-dependent consolidation, bronchiectasis, segmental and subsegmental PE Intra-alveolar fibroblastic tissue, with a diffuse component of fibrinous exudate, widening of alveolar septa, micro-thrombi, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae AFOP\n5 GGO, consolidation Intra-alveolar fibromyxoid/fibroblastic bodies (32%), micro-thrombi, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae OP\n6 GGO, consolidation Intra-alveolar fibromyxoid/fibroblastic bodies (80%), widening of alveolar septa, micro-thrombi, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae OP\n7 GGO, crazy paving, consolidation, bronchiectasis, subsegmental PE Intra-alveolar fibromyxoid/fibroblastic bodies (27%), mild widening of alveolar septa, micro-thrombi, hyperplasia with atypia, multinucleated giant cell, intranuclear inclusion bodies, no hyphae OP\nAFOP acute fibrinous and organizing pneumonia, DAD diffuse alveolar damage, GGO, ground glass opacities; OP organizing pneumonia; PE pulmonary embolism.\nTo further investigate histopathologic findings we now present the detailed clinical course of four patients with four different histopathological characteristics. Because of complexity and importance of the distinct patterns and their relation with radiologic findings and treatment, we preferred to discuss them separately in more detail. Chest CT imaging of the four discussed patients are shown in Fig. 1 .\nFig. 1 Chest CT scans of case 1–4. For each patient image A represents chest CT at hospital admission, image B follow up CT-scan (note: chest CT of case 4 was not repeated). 1A: bilateral areas of GGO, patchy subpleural non-dependant consolidations 1B: progression of dens subpleural consolidations with air-bronchograms. 2A GGO in both lungs, combined with crazy-paving pattern, subtle bronchiectasis are present in affected areas. 2B GGO persisted, without progression to consolidations, more pronounced fibrotic reticulation with traction bronchiectasis. 3A diffuse bilateral GGO with large gravity dependant consolidations. 3B persistent GGO and consolidation, newly formed cyst-like lesions in middle and ventral regions. 4A bilateral areas of GGO, patchy non-dependant peripheral consolidations with mild 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