Table 3: Reviews describing pathological findings in covid-19 positive case.
AUTHOR |
PROCEDENCE |
TYPE |
CASES |
MALE |
FEMALE |
PROCEDURE |
METHODS |
ORGANS STUDIED |
Main Findings* |
||||||
DAD |
Hyaline membranes |
Pneumocyte hyperplasia |
Congestion of alveolar capillaries |
Thrombosis in small pulmonary vessels |
Lymphocytic interstitial inflammation |
Other findings |
|||||||||
Tian, et al. |
Wuhan, China |
Case Report |
2 |
1 |
1 |
Partial lobectomy |
NS |
Lungs |
X |
|
X |
|
|
|
Suspected viral inclusions, alveolar proteinaceous exudates, spherical secretions or globules, vascular congestion, mild inflammatory infiltrates without significant neutrophils, intraalveolar fibrin with mononuclear and giant multinucleated cells, pneumocyte hyperplasia |
Yao, et al. [13] |
Chongqing, China |
Case Report |
3 |
NE |
NE |
Minimally invasive autopsy |
IHC (CD4, CD8, CD68, TTF-1, 2019-nCoVS1, nucleocapsid protein N), PCR, EM |
Lungs, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, bowel, thyroid, skin |
X |
|
|
X |
X |
X |
Serous alveolar exudates, increase of intraalveolar macrophages, hyperplasia and detachment of type II pneumocytes. Viral particles detected by IHC and EM in type II pneumocytes and bronchiolar epithelia |
Wichmann, et al. [12] |
Hamburg, Germany |
Case Series |
12 |
9 |
3 |
Complete Autopsy |
PCR, IHC (CK) |
Lungs, brain, heart, kidney, spleen, liver, bowel |
X |
X |
|
X |
X |
|
Interstitial edema, moderate inflammatory infiltrates mainly lymphocytic, squamous metaplasia, bacterial bronchopneumonia. Mononuclear infiltration in the myocardium Deep venous thrombosis in 7 of 12 cases High viral titers of viral RNA in liver, kidney and heart |
Barton, et al. [28] |
Oklahoma, US |
Case Report |
2 |
2 |
0 |
Complete Autopsy |
IHC (CD3, CD20, CD4, CD8, CD68) |
Lungs, brain, heart, digestive tube, liver, pancreas, kidneys, thyroid |
X |
X |
|
X |
X |
|
Sparse interstitial lymphocytic infiltration, alveolar and bronchial edema, and mild inflammatory infiltrates in bronchi and bronchioles. T cell infiltrate, with more CD8+ than CD4+ cells. No myocarditis |
Varga, Flammer, et al. [34] |
Zurich, Suiza |
Letter |
3 |
2 |
1 |
Complete Autopsy |
EM, IHC (CaspaSE-3) |
Lungs, heart, kidneys, small bowel, liver |
|
|
|
X |
|
|
Inflammatory endothelitis and apoptotic bodies in lung, heart, small bowel, congestion of small lung vessels; liver cell necrosis. Viral inclusion structures identified by EM in endothelial cells of the kidney. |
Xu, et al. [44] |
Wuhan, China |
Case Series |
10 |
7 |
3 |
Minimally invasive autopsy |
PCR, IHC (CD3, CD20, CD4, CD8, CD21, CD56, CD68); ISH EBV |
Spleen |
- |
- |
- |
- |
- |
- |
Depletion of T and B cells in the spleen, atrophy of lymphoid follicles (white pulp) |
Dohlnikoff , et al. [20] |
Sao Paulo, Brazil |
Letter |
10 |
5 |
5 |
Minimally invasive autopsy, US guided |
NS |
Lungs, kidney, heart, liver, spleen, brain, skin, skeletal muscle |
X |
|
|
|
X |
|
Viral cytopathic changes in alveoli and respiratory epithelia, little lymphocytic infiltration. Endothelial swelling, megakaryocytes in pulmonary capillaries. Few and small foci of alveolar hemorrhage. |
Xu, et al. [21] |
Beijing, China |
Case Report |
1 |
1 |
0 |
Postmortem biopsy |
NS |
Lungs, liver, heart, |
X |
X |
|
|
|
X |
Cellular fibromyxoid infiltrates, desquamation of pneumocytes. Intraalveolar multinucleated syncytial cells and pneumocytes with cytopathic-like changes. Liver with microvesicular steatosis and mild lobular and portal activity (could be direct change or drug-induced). Few interstitial mononuclear infiltrates in heart |
Tian, et al. |
Wuhan, China |
Case Series |
4 |
3 |
1 |
Postmortem biopsy |
PCR, IHC (CD20, CD3, CD5, CD23, CD4, CD8) |
Lungs, liver, heart |
X |
X |
X |
|
|
|
Scan inflammatory infiltrates. Syncytial giant cells. Focal interstitial thickening, Intraalveolar hemorrhage, Intraalveolar fibrin. Fibrinoid necrosis of vessel wall. Mild sinusoidal dilatation and mild lobular lymphocytic infiltration in liver |
Konopka, et al. [24] |
Michigan, US |
Case Report |
1 |
1 |
0 |
Not specified |
NS |
Lungs |
X |
X |
|
|
X |
X |
Patchy fibrinous exudates with mononuclear cells and scattered neutrophils in airspaces. CD4+ > CD8+ cells. |
Fox, et al. [29] |
New Orleans, US |
Case Series |
4 |
NE |
NE |
Autopsy (type not precised) |
IHC (CD61, CD4, CD8), EM |
Lungs, heart |
X |
X |
|
|
X |
|
Atypical pneumocytes, hyperchromatic and atypical megakaryocytes (CD61+) within capillaries and small vessels. Scattered necrotic myocytes with some lymphocytes adjacent to degenerated myocytes. |
Carsana, et al. [22] |
Milan & Bergamo, Italia |
Case Series |
38 |
33 |
5 |
Autopsy (type not precised) |
IHC (CD45, CD3, CD68, CD61, TTF-1, p40, Ki-67), EM |
Lungs |
X |
X |
X |
X |
X |
X |
Focal squamous metaplasia. Myofibroblast proliferation, alveolar granulation tissue and obliterating fibrosis in half of the cases. Four patients with bacterial abscesses. Macrophages in the alveolar lumen, megakaryocytes (CD61+) in lung capillaries. Viral particles in the pneumocytes. |
Su, et al. [45] |
Wuhan, China |
Case Series |
26 |
19 |
7 |
Autopsy (type not precised) |
PAS, Masson trichrome, Jones methenamine silver stains, IHC (CD4, CD8, CD235a, CD61, CD3, ACE2) EM, IF |
Kidney |
- |
- |
- |
- |
- |
- |
ATI with loss of brush border, viral particles on tubular cells and podocytes seen on electron microscopy, peritubular capillary occlusion by erythrocytes |
Santoriello, et al. [46] |
New York, USA |
Case series |
42 |
29 |
13 |
Complete autopsy |
ISH for SARS-CoV-2, EM |
Kidney |
- |
- |
- |
- |
- |
- |
Mild acute tubular injury, No definite identification of virus with EM or ISH |
Menter, et al. [18] |
Basel, Switzerland |
Case series |
21 |
17 |
4 |
Complete autopsy |
NS, IHC (ATTR, CD3, CD4, CD8, CD20, CD68, MUM-1, TTF1) |
Lung, heart, kidney, liver, lymph node, spleen, bone marrow |
X |
|
|
X |
X |
X |
Mucous tracheobronchitis, Large pulmonary capillary congestion, reactive pneumocytes, syncytial cells of pneumocyte origin, some cases with bronchopneumonia and no DAD, ATI with flattened tubular epithelium, probable viral inclusions on podocyte cytoplasm Myocardial hypertrophy, Senile cardiac amyloidosis, atherosclerosis Left-shifted myelopoiesis, congestion of lymph nodes with reactive plasmablasts |
Sadegh, et al. [23] |
Tehran, Iran |
Case series |
31 |
25 |
6 |
Minimally invasive autopsy |
Masson trichrome, PAS, Gram, Ziehl-Neelsen, Gomori methenamine silver, PCR |
Lung and liver |
X |
|
X |
|
|
|
Positive PCR for SARS-Cov-2 in lung and liver, hepatic steatosis, lymphoplasmacytic portal inflammation Intraalveolar organization and fibrin balls, interstitial neutrophilic infiltrate |
Basso, et al. [47] |
Padua and Bologna (IT); Boston and Rochester (USA); Amsterdam (PB); |
Case series |
21 |
15 |
6 |
Complete autopsy |
IHC (CD3, CD4, CD68) |
Heart |
- |
- |
- |
- |
- |
- |
Lymphocytic myocarditis with macrophages, subendocardial coagulative necrosis, left ventricle fibrosis |
Jacobs, et al. [26] |
Antwerp, Belgium |
Case report |
1 |
1 |
0 |
Complete autopsy |
IHC (E06, anti-4-HNE) |
Lung, heart, kidney |
X |
X |
X |
|
X |
X |
Multinucleated cells in lung tissue, no viral inclusions, hypertrophic myocytes with lymphocytic infiltrate (mostly T cells but also B cells), no cardiac fibrosis. Kidney: ATN and inflammatory lymphocytic infiltrate |
Elsoukkary, et al. [31] |
New York, USA |
Case Series |
32 |
22 |
10 |
Autopsy (type not precised) |
IHC (CD61, CD163, ERG, CD3, CD20, C5b-9) |
Lung, heart, kidney, ovary, esophagus, thyroid, trachea |
X |
|
X |
|
X |
|
Alveolar neutrophils, organizing pneumonia, bronchial squamous metaplasia, microthrombi in myocardial vessels and several other organs. Hepatic steatosis, portal lymphocytic inflammation. Tubulointerstitial scarring in kidney biopsies, ATI, C5b-9+ endothelial injury. |
Borczuk, et al. [14] |
New York, USA; Padova, Italy |
Retrospective cohort |
68 |
47 |
21 |
Post mortem biopsy |
EM, IHC (CD61, SARS- CoV-2 viral spike protein) |
Lung |
X |
X |
X |
|
X |
|
Neutrophilic inflammation with mucosal ulceration in large airways. Few cases with organizing pneumonia and squamous metaplasia. Multinucleated syncytial pneumocytes. Suspected viral inclusions. SARS- CoV-2 viral spike protein and viral RNA in tracheal epithelium, hyaline membranes and atypical pneumocytes. |
Wang, et al. [35] |
Beijing, China |
Case series |
3 |
1 |
2 |
Postmortem percutaneous biopsy |
Masson trichrome stain, IHC (CD21, CD10, CD3, CD4, CD8, LCA), ISH for SARS CoV-2 |
Lung |
X |
|
X |
X |
X |
|
Micro and macrothrombi in pulmonary vessels. Loss of pneumocytes in alveoli, suspected viral inclusion inside pneumocytes, interstitial edema and fibrosis. Heart: Old infarction, fibrosis, no inflammatory cells seen on IHC. Liver: coagulative necrosis, microvesicular steatosis |
De Michele, et al. [32]
|
New York, USA |
Case series |
40 |
28 |
42 |
Autopsy (type non specified) |
IHC(CD61) |
Lung |
X |
|
X |
|
X |
|
Vascular proliferation most frequently found in cases with no signs of acute lung injury(non-ALI), DAD and type II pneumocyte hyperplasia in cases with ALI, intravascular fibrin or platelet aggregates in both groups. |
Nienhold, et al. [48] |
Liestal, Switzerland; Trento, Italy; Zurich, Switzerland; Oxford,UK
|
Cohort |
16 |
13 |
3 |
Post mortem biopsy |
Transcriptomics of Interferon stimulating genes (ISG), IHC (CD3, CD20, CD8, PD1, CD123) |
Lung |
X |
|
|
|
|
|
Two patterns of gene regulation in COVID-19 patients: ISGlow, associated to DAD and downregulation of anti-thrombotic genes; ISGhigh, upregulation of pro inflammatory genes and extensive lung damage |
Duarte-Neto, et al. [25] |
Sao Paulo, Brazil |
Case series |
5 |
2 |
3 |
Minimally invasive autopsy |
EM, PCR, IHC (GFAP, CD45, CD68) |
Heart, lung, liver, spleen, kidneys, brain, quadriceps muscle and skin |
X |
|
|
X |
X |
|
Pediatric patients with MISC-C. SARS Cov-2 in heart and lungs. Desquamation of pneumocytes and cells with suspected viral changes. Interstitial edema in heart, ATN in kidneys. Splenic hemorrhage and lymphoid hypoplasia, Vascular congestion in multiple organs. |
Bryce, et al. [11] |
New York, USA |
Case series |
100 |
NE |
NE |
Autopsy (type non specified) |
EM, IHC (CD3, CD4, CD8, CD34, CD61, CD163, ACE2) |
Lung, spleen, brain, heart |
X |
X |
X |
X |
|
X |
Septal capillary proliferation, multinucleated cells, inflammatory infiltrate consisted of T cells, macrophages and a few B cells. Fibrin thrombi in small lung vessels, capillary proliferation. Bronchioles with squamous metaplasia. Suspected viral particles on EM. Absent germinal centers in spleen and lymph nodes. Red pulp necrosis, Myocyte hypertrophy and fibrosis. |
Damiani, et al. [30] |
Bologna, Italy |
Case series |
9 |
7 |
2 |
Complete autopsy |
IHC (AE1/AE3, TTF-1, p40, CD68, CD4/8, CD31, ERG, CMV, HSV-1 and -2, ACE2, TMPRSS2) |
Lung |
X |
X |
|
|
X |
|
Fibrin balls in early and subacute phases, areas of thick fibrin fibers (> 50% of the sample) in later phases. Shedding of pneumocytes with ACE2 and TMPRSS22 expression. Suspected iral particles inside cells. Hemosiderin macrophages in patients with superimposed bacterial infection. |
Falasca, et al. [10] |
Rome, Italy; London, UK |
Case series |
22 |
15 |
7 |
Complete autopsy |
Masson trichrome stain, PAS, Perls stain, IHC (CD3, CD4, CD8, CD15, CD26, CD183, CD20, CD68) |
Lung, heart, Liver, kidney, spleen, bone marrow |
X |
X |
X |
|
X |
|
Suspected viral cytopathic changes in pneumocytes, alveolar duct fibrosis, granulocytes, macrophages and lymphocytes in alveolar septa. CD26+ pneumocytes. Lymphocytic myocarditis with focal necrosis, fibrinous pericarditis. Interstitial renal fibrosis. Spleen: lymphoid hypoplasia in white pulp and congested red pulp. |
Ferlicot, et al. [16] |
Paris, France |
Case series |
47 |
38 |
9 |
In vivo Biopsy |
PAS, Masson trichrome stain, Methenamine silver, IF, EM |
Kidney |
- |
- |
- |
- |
- |
- |
Collapsing glomerulopathy, deposits of IgM and C3, interstitial lymphocytes. ATI, tubular cells with PAS+ deposits. |
Doglioni, et al. [33] |
Milan, Italy |
Case series |
12 |
7 |
5 |
Post mortem transbronchial biopsy |
IHC (CK7, Ki67, Tubilin-beta-3, CD3, CD4, CD8, CD14, CD20, CD25, CD30, CD61, CD123, GATA3, T-bet, TCF1, MUM-1, PD-1, IDO, PD-L1, Phospho-STAT3, SARS-CoV-2, IL-6) |
Lung |
X |
|
X |
|
|
|
Clusters of hyperplastic type II pneumocytes, syncytial cells of suspected pneumocyte origin, dilated and hyperplastic interstitial capillaries and venules, lymphocytic infiltrate around venules. PD-L1 expression in macrophages inside alveoli. SARS-Cov-2, STAT3, tubulin-beta-3, Ki67 expression in pneumocytes. No STAT3 expression in interstitial cells. STAT3, PD-L1 and IDO expression in endothelial cells of venules and interstitial capillaries. |
Takahashi, et al. [9] |
Okinawa, Japan |
Case report |
1 |
1 |
0 |
Postmortem biopsy |
Azan stain, IHC(SARS-CoV-2) |
Lung, liver |
X |
X |
X |
|
|
|
Alveolar fibrosis in organizing phase, hepatic micro abscesses, negative PCR and IHC for SARS-CoV-2. |
Miao, et al. [17] |
Minnesota, USA |
Case report |
1 |
1 |
0 |
Not specified |
EM, Silver stain, ISH(SARS-Cov-2), IHC(PLA2R) |
Kidney |
- |
- |
- |
- |
- |
- |
No thrombi, necrosis or capillary hypercellularity in glomeruli. ATI, tubular atrophy, interstitial fibrosis. Negative ISH for SARS-Cov-2. Granular dense subendothelial deposits on EM, foot process effacement. |
Meliambro, et al. [17] |
New York, USA |
Case report |
1 |
0 |
1 |
Not specified |
EM, ISH(SARS-Cov2), methenamine silver stain |
Kidney |
- |
- |
- |
- |
- |
- |
SARS-Cov-2 was not found in the samples. Interstitial fibrosis, tubular atrophy. Upregulation of genes associated to cell regeneration. |
Akilesh, et al. [18] |
Washington, USA |
Case series |
17 |
8 |
9 |
Post mortem biopsy |
PCR, ISH(SARS-Cov2) |
Kidney |
- |
- |
- |
- |
- |
- |
Collapsing glomerulopathy, loss of podocyte foot processes in EM, ATN, thrombotic microangiopathy 2 patients had high-risk APOL1 genotypes. |
Flikweert, et al. [27] |
Breda, Netherlands |
Case series |
7 |
5 |
2 |
Post mortem biopsy |
PAS-D |
Lung |
X |
X |
|
|
X |
|
Organizing pneumonia in 5/7 patients. Fibroblastic bodies in alveoli, fibrosis with loss of alveolar architecture. Only one case had DAD with hyaline membranes. |
Suess, et al. [8] |
St Gallen, Switzerland |
Case report |
1 |
1 |
0 |
Complete autopsy |
PAS, IHC (CD68, TTF-1) |
Lung |
X |
X |
X |
|
X |
X |
Proteinaceous exudates, alveolar hemorrhage, intra-alveolar macrophages and fibrin deposition, cells with suspected viral inclusion. Bronchial squamous metaplasia. Non caseous granulomas in lymph nodes. Pericarditis with plasma cells and lymphocytes. |
Wu, et al. [49] |
Shandong, China |
Case report |
1 |
1 |
0 |
Percutaneous biopsy |
IHC (MPO, IgG, IgD, IL-10, TNF-alpha, ACE2) |
Lung |
|
|
|
|
|
|
Alveolar collapse and epithelial hyperplasia, severe fibrinoid necrosis of alveolar structures and small vessels. Expression of IgG, IgD, IL-6, TNF-alpha, MPO, ACE2 in inflammatory infiltrate. |
(*) Other pathological findings, related to preexisting diseases, and not associated with COVID-19 infections, are not included in this table.
EM: Electron Microscopy; IHC: Immunohistochemistry; ISH: In-Situ Hybridization; PCR: Polimerase Chain Reaction in Tissues; NS: Not Specified (Only H&E); IF: Immnunofluorescence; ATI: Acute Tubular Injury