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