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Table 1 List of included studies and data extraction

From: Lung histopathological findings in COVID-19 disease – a systematic review

Author (year) Country Patients (n) Mean age (years) Sex (M/F) Comorbidities Hyaline membranes Endothelial cells alteration (ECA), interstitial cells involvement (ICI) Alveolar cells: Type I pneumocytes/ Type II pneumocytes involvement Hemorrhage Sampling methods Detection methods (Micro)thrombi Inflammatory cells Fibrin deposits Interstitial/ alveolar edema Viral detection methods
Li et al. (2020) [22] China 69 51 M/F 40/29 Diabetes (8), hypertension (17), coronary disease (4), chronic liver disease (7), chronic respiratory system disease (7), malignancy (1) Reported (2) ICI DAD, pneumocyte hyperplasia, desquamation of pneumocytes NA Biopsy H&E, Masson’s trichrome stain, IHC, EM NA CD68+ macrophages, neutrophils, CD4 +  and CD8+ T cells NA Focal exudative edema Yes, EM, ISH
Buja et al. (2020) [41] USA 23 55 M/F 12/7 Obesity, hypertension, myotonic dystrophy, type II diabetes Absent ICI Type I,II pneumocytes hyperplasia Reported Autopsy RT-PCR Formation of microthrombi in arterioles Neutrophils, lymphocytes, macrophages Intra-vascular and intra-vascular edema Reported Yes, EM
Menter et al. (2020) [45] Switzerland 21 76 M/F 17/4 Hypertension (21), cardiovascular disease (15), diabetes mellitus (7), COPD (3), chronic neurological conditions (5), malignancy (3), chronic liver disease (2), chronic kidney disease (4), acquired immunosuppression (1) Reported Capillary congestion (21), vasculitis (1) Syncytial cells of pneumocytes II origin (11), DAD (8) Reported (3) Autopsy IHC for fibrin, 360x, H&E, IHC Microthrombi of alveolar capillaries (5) Prominent lymphoid infiltrate (3) NA Interstitial edema Yes, SARS-CoV-2 specific RT–qPCR, viral genome detected with the TaqMan 2019-nCoV Assay Kit v1 (Thermo Fisher Scientific) targeting three different viral genomic regions (ORFab1,S Protein, N Protein)
Lax et al. (2020) [35] Austria 11 81 M/F 8/3 Diabetes mellitus, cardiovascular disease Reported (11) ICI, fibroblast proliferation (9) Pneumocytes proliferation (9) Reported (8) Resection H&E Reported (11) Macrophages, lymphocytes, plasma cells, neutrophils Reported Reported (10) Yes, RT-PCR results positive in the right and left bronchus ´10/10)
Fox et al. (2020) [29] USA 10 61 NA At least one comorbidity, the most common: hypertension, type II diabetes, obesity Reported (2) ICI, CD61+ megakaryocytes with nuclear hypercromasia and atypia DAD (10), desquamation Foci of hemorrhage (9) Autopsy H&E Reported (11) CD4+ and CD8+ lymphocytes Reported Reported (2) DRAQS and SYTO RNASelect fluorescent staining
Schaller et al. (2020) [39] Germany 10 79 M/F 7/3 Hypertension, hypothyroidism, diabetes Reported ICI, fibroblastic cells Pneumocytes hyperplasia NA Autopsy IHC Microthrombireported Lymphocytes Reported Alveolar edema Yes, RT-PCR, IHC
Martines et al. (2020) [40] USA 8 74 M/F 4/4 Hypertension, chronic kidney disease, diabetes, obesity NA NA Type II pneumocytes hyperplasia Reported Autopsy IHC, H&E Microthrombi observed Macrophages, neutrophils, leukocytes Reported Alveolar edema Yes, IHC (rabbit polyclonal antibody), RT-PCR
Ackermann et al. (2020) [46] Germany 7 73 M/F 5/2 NA NA ECA Type II pneumocytes hyperplasia Reported Autopsy IHC, scanner election microscopy Fibrin thrombi T lymphocytes Intra-alveolar fibrin Mild interstitial edema No
Cai et al. (2020) [27] China 7 60 M/F 5/2 Interstitial lung disease (1), coronary atherosclerosis (3), chronic obstructive pulmonary disease (2), hyperlipidemia Absent (1) ICI, fibrous connective tissue proliferation No evident pneumocytes hyperplasia (1) NA Biopsy H&E NA Plasma cells and macrophages (1) NA NA No
Magro et al. (2020) [34] USA 5 55 M/F 3/2 Coronary heart disease, diabetes, hepatitis C Reported ICI Type II Reported Biopsy IHC,RT-PCR Reported AP and LP of complement Reported Reported Yes, using NUANCE software
Tian et al. (2020) [47] China 4 73 M/F 3/1 Chronic lymphocytic leukemia, cirrhosis, variceal rupture bleeding, diabetes, hypertension, status post renal transplantation for 3 months Reported (3) ICI, fibrinoid necrosis of the small vessels DAD, type II hyperplasia, syncytial giant cells formation pneumocytes Reported Biopsy H&E, IHC NA scanty inflammatory cells Reported NA Yes, RT-PCR positive only in case 2
Varga et al. (2020) [20] Switzerland 3 66 M7F 2/1 Coronary heart disease, hypertension, diabetes, obesity NA ECA NA NA Biopsy IHC NA Mononuclear cells, apoptotic bodies NA Reported Yes, EM in kidney and small bowel tissue but no obvious viral particles in the lung tissue
Barton et al. (2020) [48] USA 2 60 M/F 2/0 Hypertension, remote deep veins thrombosis, myotonic dystrophy Reported Congestion of septal capillaries DAD in the acute stage (only in one case) NA Autopsy IHC, H&E Microthrombi reported CD3+ T lymphocytes, rare CD20+ lymphocytes, CD8+ T lymphocytes, macrophages, non appreciated neutrophils oreosinophils NA Reported Bilateral lung parenchymal swabs positive only in one case
Tian et al. (2020) [26] China 2 79 M/F 1/1 Lung adenocarcinoma Not prominent ICI, proliferating fibroblasts 1 case) NA, type II pneumocytes hyperplasia (1 case) NA Autopsy H&E NA Mononuclear inflammatory cells Focal fibrin exudates Alveolar edema No
Sekulic et al. (2020) [42] USA 2 68 M/F 2/0 Diabetes mellitus relates renal disease … left ventricular hypertrophy, atherosclerotic coronary artery disease, hypertension, congestive splenomegaly, sinusoidal congestion of the liver Reported (2) fibroblastic proliferation DAD, scattered multinucleated giant cells, squamous metaplasia features of type II pneumocytes viral infection NA Autopsy H&E, EM NA Relative paucity of chronic inflammatory cells Intra-alveolar fibrin deposition Interstitial edema Yes, PCR (2)
Yao et al. (2020) [18] China 1 78 M/F 0/1 NA Reported ICI Type II; DAD with desquamation or proliferative type II cells NA Biopsy PCR(X3), IHC, H&E Hyaline thrombi in micro vessels Macrophages, CD8+ and CD4+ T cells, CD20+ cells Reported No pulmonary edema Yes, EM, IHC with monoclonal anti-nucleoprotein antibody
Lacy et al. (2020) [49] China 1 58 M/F 0/1 Type II diabetes, obesity, hypertension Reported ICI, no fibroblastic foci NA, pneumocyte hyperplasia, no viral inclusion or specific cytopathic changes,focal multinucleated cells Reported Autopsy RT-PCR NA Macrophages Reported Diffuse proteinaceous edema No viral inclusion or cytopathic changes identified
Xu et al. (2020) [19] China 1 50 M/F 1/0 NA Reported NA Desquamation, early ARDS, atypical enlarges pneumocytes with large nuclei, amphophilic granular cytoplasm and prominent nucleoli. No obvious intranuclear or intracytoplasmic viral inclusion identified NA Biopsy NA NA Lymphocytes NA Reported No obvious viral inclusion identified
Karami et al. (2020) [33] Iran 1 27 M/F 0/1 NA Reported NA Pneumocyte proliferation, multinucleation and nuclear atypia, metaplastic changes NA Autopsy NA NA Lymphocytes and macrophages NA NA Yes, RT-PCR confirmed SARS-CoV-2 infection in the lungs
Harkin et al. (2020) [21] USA 1 34 M/F 1/0 NA Absent NA Type II pneumocytes hyperplasia NA Autopsy RT-PCR NA Lymphocytes, hystiocytes Intra-alveolar fibrin deposits NA Yes, RT-PCR positive in BAL
Shao et al. (2020) [50] China 1 65 M/F 1/0 Absent Reported ICI, proliferating fibroblasts, dilated pulmonary capillaries DAD, type II pneumocyte multinucleation, hyperplasia and increased nuclear size, hypercromasia, hyperplasia of alveolarepithelial cells NA Biopsy IHC, GMS Reported (11) Lymphocytes, neutrophils, macrophages Intra-alveolar fibrin exudate NA No, IHC staining for anti-SARS-Cov-2 N Protein was negative
Adachi et al. (2020) [36] Japan 1 84 M/F 0/1 NA Reported ICI, vascularcongestion Type II pneumocytes hyperplasia, squamous metaplasia, desquamation Intra-alveolar hemorrhage Autopsy H&E, IHC NA Plasma cells NA NA Yes, rabbit polyclonal antibodies
Yan et al. (2020) [37] USA 1 44 M/F 0/1 Obesity Reported Non necrotizing lymphocytic vasculitis DAD, desquamation, pneumocytes with ample cytoplasm and enlarged nuclei NA Autopsy EM Not identified Lymphocytes Fibrin aggregates within blood vessels NA No
Pernazza et al. (2020) [51] Italy 1 61 M/F 1/0 Lung adenocarcinoma Absent ICI Pneumocytes desquamation, reactive hyperplasia with focal nuclear inclusion Diffuse hemorrhage Biopsy H&E, IHC NA inflammatory infiltrate mainly composed by cytotoxic (CD8+) T lymphocytes, neutrophilic vascular margination, macrophages Scanty fibrin deposited on the alveolar surface Interstitial edema No
Aguiar et al. (2020) [43] Switzerland 1 31 M/F 0/1 Obesity, hypertension, myotonic dystrophy, type II diabetes Reported Vascular stasis, reported megakaryocytes DAD, type II pneumocytes hyperplasia neither viral inclusion nor giant multinucleated giant cells Hemorrhagic edema, alveolar hemorrhage Autopsy H&E, IHC Absence of hyaline thrombi in microvessels intra-alveolar macrophages, PMN, T (CD3+) lymphocytes Intra-alveolar fibrin deposition Reported Yes, rRT-PCR in the lower respiratory tract
Konopka et al. (2020) [44] USA 1 37 M/F 1/0 Asthma, type II diabetes Scattered hyaline membranes ECA DAD, mucous plugs, mucous glands, hyperplasia, type II pneumocytes hyperplasia NA Autopsy H&E Rare within small vessels scattered neutrophils Fibrin-airspace exudate Reported No
Zeng et al. (2020) [28] China 1 55 M/F 0/1 Pulmonary node Not observed ICI Type II pneumocytes hyperplasia NA Lobectomy H&E NA Monocytes, T (CD3+), B (CD20 +  and PAX5+) lymphocytes, (MUM1+) plasma cells, CD4+ helper and CD8+ cytotoxic lymphocytes, natural killer (CD56+) macrophages, (CD163+) M2 macrophages Not observed Reported Yes, PCR, in situ hybridization technology