Table 1 Summary of systematic review of autopsy findings in COVID-19 deaths

A post-mortem examination of COVID-19 pulmonary pathology in 9 cases

Bloom et al. (2020)

USA

Case-control study

9 cases

5 case study patients with severe COVID-19

4 case-control patients with negative COVID-19

Case study: Microscopic findings on respiratory system include -

1) Multifocal to diffuse alveolar necrosis and bronchiolar respiratory epithelial necrosis.

2) Interstitial mononuclear inflammatory infiltrates, mainly lymphocytes, in a multifocal pattern.

3) Perivascular and peribronchiolar lymphoid infiltrates along with marked congestion.

4) Scattered fibroplasia in the severe cases, extending into alveolar spaces and thickening the alveolar septum.

5) Mild hyaline membrane formation and slight microthrombi formations in small pulmonary vasculature found in one case.

Case control: Characterized by diffuse pulmonary oedema and marked congestion.

Post-mortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction

Menter et al. (2020) 

Switzerland

Autopsy cohort study

21 cases with comorbidity

Hospitalized: median of 7.15 days and mean of 5.7 days

Respiratory system: Lungs heterogeneous, ranging from patchy to diffuse areas of consolidation to severe and extensive suppurative bronchopneumonic infiltrate. Mostly present with exudative diffuse alveolar damage (DAD) and 38% with proliferative DAD.

Cardiovascular system: Myocardial hypertrophy and atherosclerosis at aorta.

Renal system: signs of shock and acute tubular injury.

Other systems: Perihilar and peritracheal lymph nodes congested with increased number of plasmablasts.

Pulmonary and systemic involvement in COVID-19 patients assessed with ultrasound-guided minimally invasive autopsy

Duarte-Neto et al. (2020) 

Sao Paulo, Brazil

Case series study

10 cases

Respiratory system: Exudative-proliferative DAD, fibrinous thrombi in alveolar arterioles and secondary suppurative pneumonia with CD20 positive B cell markers present while proliferative DAD present in longer hospitalized patients.

Other findings:

1) Related to chronic diseases

2) Finding related to shock

3) Finding unascertained etiologies

The spectrum of histopathologic findings in lungs of patients with fatal COVID-19 infection

Roden et al. (2021) 

Rochester, USA

Case study

8 cases with comorbidity: cardio-vascular disease and dementia

Respiratory system: Lung heavier than normal, patchy consolidation, majority serous pleural effusion, one gross thromboemboli at distal pulmonary artery, chronic inflammation mostly at bronchi and bronchioles, majority present with DAD (acute/organizing/acute and organizing), bronchopneumonia and thromboemboli. CT scan showed extensive mixed ground glass opacities, X-ray showed patchy opacities peripheral and basilar.

Post-mortem lung findings in a patient with asthma and COVID-19

 (Konopka et al. 2020)

Michigan, USA

Case report

1 case (COVID-19 symptoms)

Respiratory system: Heavy edematous lungs with microscopic features of DAD and asthma correlates with history.

Post-mortem findings in Italian patients with COVID-19: a descriptive full autopsy study of cases with and without comorbidities

Falasca et al. (2020)

Rome, Italy

Case report

22 cases

Respiratory system: Lungs were heavy, edematous, some have pleural effusion, presence of DAD, cytopathic virus induced changes, thrombi, inflammatory cells infiltrate.

Cardiovascular system: Hypertrophied heart in all patients with comorbidities and some without, active inflammation (myocarditis and pericariditis).

Renal system: Interstitial fibrosis and swollen endothelial cells in patients without comorbidities.

Hepatobiliary system: Sinusoidal congestion & extravasation of red blood cells to space of Disse, microvacuolar and macrovacuolar steatosis.

Other systems: Lymphoid hypoplasia in spleen with congested red pulp in patients without comorbidities. Microscopically showed replacement of red haematopoietic bone marrow with yellow adipocyte-rich marrow in group 1 patients.

Dying with SARS-CoV-2 infection—an autopsy study of the first consecutive 80 cases in Hamburg, Germany

Edler et al. (2020) 

Hamburg, Germany

Case-control study

80 cases

46 males, 34 females

38% overweight or obese

Comorbidity: 85% cardio-vascular disease, 55% lung diseases, 35% central nervous system diseases, 21% diabetes mellitus and 16% carcinomas/haematological diseases

Cause of Death (COD): 57 cases (71%) had pneumonia, with or without evidence of sepsis. Out of ten cases (25%) present with pneumonia, seven cases present with fatal fulminant pulmonary artery embolism while one case each with aortic valve endocarditis, septic encephalopathy, and hepatorenal failure secondary to liver cirrhosis were contributory COD. Total of seven cases (10%) were considered with a competing COD in addition to COVID-19 e.g. aspiration pneumonia, pronounced emphysema without evidence of pneumonia or acute bronchitis.

Respiratory system: Lung findings include-

1) Broad spectrum of macroscopic changes, often overlaid by chronic diseases such as chronic bronchitis and emphysema.

2) A mosaic-like pattern of pale fields and slightly protruding dark purple sections with prominent capillary drawing seen in COVID-19-associated deaths appeared as a purulent respiratory tract infection with abscessed bronchopneumonia.

3) Microscopically, DAD with activated type II pneumocytes, fibroblasts, protein-rich exudate, and hyaline membranes. In advanced stages, squamous metaplasia and fibrosis occurred.

4) Giant cells and megakaryocytes appeared. The small pulmonary arteries often showed a pronounced infiltrate of lymphocytes and plasma cells, whereby the endothelia were not reactively altered in the sense of vasculitis.

Post-mortem examination of patients with COVID-19

Schaller et al. (2020) 

Augsburg, Germany

Case report

12 cases

Comorbidity: Median 4

Respiratory system: Microscopically, DAD present at various stages.

Cardiovascular and hepatobiliary system: Microscopically, lymphocytic infiltration was seen at myocardium, epicardium and periportal liver.

Pathological study of the COVID-19 through post-mortem core biopsies

Tian et al. (2020)

Wuhan, China

Case report

4 cases

Respiratory system: Radiographic findings include bilateral pneumonia with ground glass opacities with/without consolidations. Microscopic findings include features of DAD in all cases with different stages.

COVID-19 Autopsies, Oklahoma, USA

(Barton et al. 2020)

Oklahoma, USA

Case report

2 cases

Case 1: 77 years old male presented with underlying hypertension, deep vein thrombosis, splenectomy, osteoarthritis post total knee arthroplasty, and pancreatitis. COD: COVID-19 and coronary artery disease.

Respiratory system: Radiologically, bilateral pulmonary opacities/. Grossly, bilateral lungs heavy and edematous parenchyma. Microscopically, DAD in acute stage, chronic inflammation in bronchi and bronchioles and mucosal edema.

Case 2: 42 years old male presented with muscular dystrophy. COD: Complications of hepatic cirrhosis.

Respiratory system: Radiologically, bilateral ground glass opacities with consolidations. Grossly, bilateral lungs heavy, red mottled appearance. Microscopically, acute bronchopneumonia with rare, aspirated food particles and no DAD was seen.

Other systems: Liver cirrhosis with gynecomastia and testicular atrophy were seen.

Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series

Bradley et al. (2020)

Washington, USA

Case series

14 cases with comorbidity: hypertension, chronic kidney disease, obstructive sleep apnea, obesity and diabetes

Respiratory system: Microscopically, DAD presented in acute/organizing phases, and chronic interstitial inflammation.

Other systems: Other organs presented with comorbidities changes.

Post-mortem examination of hospital inpatient COVID-19 deaths in Lusaka, Zambia - a descriptive whole-body autopsy series

Himwaze et al. (2021) 

Lusaka, Zambia

Case study

29 cases with comorbidity: HIV infection (28%), hypertension (20%), tuberculosis (10%) and diabetes (10%)

Commonest COD were pulmonary thromboembolism (45%), DAD (31%), and COVID-19 pneumonia (25%).

Representative samples were obtained from the various organs (brain, lungs, heart, liver, spleen and kidneys).

COVID-19 autopsies of Istanbul

Arslan et al. (2021)

Istanbul, Turkey

Case study

348 cases

Respiratory system: Lung findings include-

1) Sticky gelatinous fluid in cavities, firm and swollen lungs with varying degrees of consolidation were most commonly seen.

2) Microscopically, DAD, type-II pneumocyte hyperplasia, hyaline membrane formation, fibrinous exudate, and fibrinous plaques in the alveoli were the most common findings.

3) Lungs were swollen and tight filled the chest cavity in all cases.

4) Patchy or diffuse interstitial lymphocytic infiltration of viral pneumonia and features of DAD in various stages.

Post-mortem kidney pathology findings in patients with COVID-19

Santoriello et al. (2020)

New York, USA

Cohort study

42 cases

69% males 31% females

Comorbidity: 73% hypertension, 57% hispanic

Renal system: Kidney findings include-

1) Acute kidney injury (AKI) developed in 31 of 33 patients (94%), including six with AKI stage 1, nine with stage 2, and 16 with stage 3.

2) The predominant finding correlating with AKI was acute tubular injury.

3) Focal kidney fibrin thrombi in six of 42 (14%) autopsies. A single Black patient had collapsing focal segmental glomerulosclerosis (FSGS).

4) Urine dipstick assessment of proteinuria was positive in 23 of 29 subjects (79%) but yielded a urine protein concentration of 100 mg/dl in 76%.

5) Haematuria was present in 19 of 29 individuals, all of whom had indwelling urinary catheters at the time of collection.

6) Hypophosphataemia (17%), Glucosuria (17%), hypokalaemia (6%) were indicators of possible proximal tubular injury.

Post-mortem diagnosis and autopsy findings in SARS-CoV-2 infection: forensic case series

Keresztesi et al. (2020)

Slobozia, Romania

Autopsy case study

15 cases

11 males, 4 females

Comorbidity: hypertension, coronary artery disease, and history of stroke

Respiratory system: Macroscopically, lungs were congested, firm, heavy lungs with areas of oedematous tissue and patchy involvement, as well as areas of diffuse consolidation. In most cases, the superior airways were mucus free. Microscopically, four cases with bronchopneumonia evidence of DAD with exudative lesions associated with hyaline membranes and oedema.

Renal system: Kidney injury with acute epithelial tubular necrosis were seen.

Autopsy findings in 32 patients with COVID-19: a single-institution experience

Elsoukkary et al. (2021)

New York, USA

Case study

32 cases

Main findings: Total of 27 (84%) patients had macroscopic and/or microscopic thrombi at autopsy.

Respiratory system: Macroscopic pulmonary thrombi were detected in 11 (34%) cases. Most patients (n = 24, 75%) had both exudative and proliferative DAD. Three (9%) patients each showed only acute/exudative DAD or organizing/proliferative DAD. Total of 16 (50%) showed the presence of alveolar neutrophils and 14 (44%) showed evidence of organizing pneumonia. All cases had some degree of type II pneumocyte hyperplasia with reactive atypia and bronchial squamous metaplasia.

Cardiovascular system: Small intramyocardial vessels contained microthrombi in 6 (19%) and contained fibrin, platelets, or a mixture of both. One case showed acute myocardial infarction.

Other systems: Thrombi were also observed in the prostatic venous plexus, trachea, lymph nodes, and kidney. Several organs showed concurrent parenchymal infarction.

Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy

Carsana et al. (2020)

Milan, Italy

Case study

38 cases with comorbidity: 18 hypertension, 11 cardio-vascular disorders, 9 diabetes, 4 malignancy, 3 mild chronic obstructive pulmonary disorders

Respiratory system: Lung findings include-

1) Exudative and proliferative phases of DAD were found.

2) Capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia with platelet-fibrin thrombi were present.

3) Inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstice.

4) Electron microscopy revealed viral particles in the cytoplasm of pneumocytes.

A series of COVID-19 autopsies with clinical and pathologic comparisons to both seasonal and pandemic influenza

McMullen et al. (2021)

Chicago, USA

Comparative case series

28 cases (16 COVID-19 cases, 6 fatal seasonal influenza, 6 fatal pandemic influenza)

COVID-19 case findings:

Respiratory system: Consolidation (diffuse and focal), haemorrhagic parenchyma, pulmonary oedema, DAD in early to organizing phase, interstitial inflammation, superimposed infections (mostly bacterial) and scattered microscopic thrombi in pulmonary capillaries were discovered.

Other systems: Thrombotic micro-angiography, myocytes hypertrophy, and acute tubular injury in kidney were seen.

Influenza case findings:

Most cases showed DAD and haemorrhage in respiratory system.

COVID-19 autopsy reports from the Ga-East Municipal and the 37 Military Hospitals in Accra, Ghana

Attoh et al. (2020)

Accra, Ghana

Case report

20 cases with comorbidity

65% diabetes mellitus type 2 or hypertension

Respiratory system: Macroscopically, lungs were heavy, firm, and severely congested. Microscopically, lungs showed features of DAD.

Cardiovascular system: Heart was enlarged with concentric left ventricle hypertrophy.

Hepatobiliary system: Liver was heavy with fatty changes and severely congested.

Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection

(Copin et al. 2020)

Lille, France

Case report

6 cases

Respiratory system: Lung findings include-

1) One case: Lymphocytic viral pneumonia.

2) Other five cases: Acute fibrinous and organizing pneumonia (AFOP) with an extensive intra-alveolar fibrin deposition called fibrin ball, rather than hyaline membrane, was seen. Vascular injury, whereby endothelial injury with cytoplasmic vacuolization and cell detachment in small to medium-sized pulmonary arteries, was also present.