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 |