Table 3:

Pathological findings in autopsy specimens submitted to the CDC for the evaluation of suspected EVALI

	Weeks from illness onset to death*	Pathological diagnosis in lung tissue	Intra-alveolar macrophages in lung tissue	Other pathological findings in lung tissue	CDC tissue-based infectious disease testing	Major findings in other organs	Findings from initial chest or abdomen CT or x-ray†	Age group, years	E-cigarette or vaping product use	Medical comorbidities at autopsy‡ and smoking history	Surveillance case definition classification §
Autopsies with evidence of acute lung injury and no alternative cause
Case 11	2 weeks	Diffuse alveolar damage (exudative and proliferative), diffuse	Pigmented macrophages (pigment not otherwise specified) and non-pigmented macrophages, multifocal	Multifocal moderate anthracosis; mild haemorrhage; mild oedema	PCR for influenza A, B, RSV, and PIV1–4 negative; Gram stain negative; Streptococcus spp IHC negative, Streptococcus pyogenes, select Gram-negative bacteria:¶ IHC negative in the lung, liver, and kidney	Extensive glomerular fibrin thrombi in the kidney; multifocal arteriolosclerosis; mild oedema in the brain	Not done	<35	THC, nicotine	Conventional cigarette smoking	Confirmed
Case 12	2 weeks	Acute fibrinous and organising pneumonia, diffuse	Abundant pigmented macrophages (pigment not otherwise specified) and non-pigmented macrophages	Multifocal moderate anthracosis; bronchoaspiration; haemorrhage	PCR for PIV1–4; positive for PIV1 in trachea, negative in the bronchus and lung; PCR for influenza A, B, and RSV negative in the trachea, bronchus, and lung	Diffuse small droplet steatosis in the liver; subcapsular cortical atrophy with chronic interstitial nephritis and glomerulosclerosis in the kidney; multifocal contraction band necrosis and interstitial haemorrhage (attributed to resuscitation) in the heart; mild multifocal perivascular haemorrhage in the brain; mild tracheobronchitis in the upper airway	Diffuse patchy ground glass opacities and consolidation, more prominent on the right lung and in the lung bases	<35	THC, nicotine	Conventional cigarette smoking	Probable
Case 13	4 weeks	Diffuse alveolar damage (proliferative)	Multifocal abundant foamy macrophages, non-pigmented macrophages, and pigmented macrophages (pigment not otherwise specified)	Multifocal moderate anthracosis; intravascular leukocytosis; neutrophilic inflammation, focal	Not done	Glomerulosclerosis, mononuclear interstitial nephritis in the kidney	Diffuse ground glass opacities superimposed on paraseptal and centrilobular emphysema	≥35	THC	Immunosuppression; chronic kidney disease; hypertension; conventional cigarette smoking	Confirmed
Case 14	4 weeks	Diffuse alveolar damage (proliferative)	Multifocal non-pigmented macrophages; occasional pigmented macrophages (pigment not otherwise specified)	Anthracosis, rare; haemorrhage, focal; extensive intravascular leukocytosis	Gram stain and GMS non-contributory in the lung	Haemophagocytosis, sinus histiocytosis in the lymph node; fibrin thrombi, acute tubular necrosis in the kidney; central venous congestion in the liver	Moderate extensive patchy bilateral lower lobe consolidation, mediastinal and hilar lymphadenopathy	<35	THC	Conventional cigarette smoking	Confirmed
Case 15	6–8 weeks	Patchy diffuse alveolar damage (exudative); and geographic (proliferative)	Abundant foamy macrophages and pigmented macrophages (haemosiderin-laden and subset of pigmented macrophages not otherwise specified)	Abundant anthracosis; squamous metaplasia; mild haemorrhage; emphysema; septal oedema	Gram stain, GMS, and AFB negative; Streptococcus spp and select Gram-negative bacteria: IHC negative in the lung	Glomerulosclerosis in the kidney; central venous congestion in the liver	Multifocal extensive bilateral patchy airspace disease	≥35	THC, nicotine	Chronic respiratory disease; chronic pain; conventional cigarette smoking	Confirmed
Case 16	6–8 weeks	Diffuse alveolar damage (organising), diffuse	Moderate foamy macrophages and pigmented macrophages (predominantly haemosiderin-laden macrophages, also pigment not otherwise specified)	Anthracosis, rare; bronchiolitis, neutrophilic and mononuclear; squamous metaplasia; necrosis in airways; inspissated mucus; pulmonary haemorrhage; alveolar oedema and necrosis; honeycomb cyst formation	Gram and GMS negative; PCR for influenza A, B, RSV, PIV1–4 negative in the lung	Neutrophils and mononuclear cells in the trachea; immunoblasts and neutrophils in red pulp in the spleen	Diffuse bilateral ground glass opacities, mediastinal and hilar lymphadenopathy	<35	THC, nicotine	Not reported	Confirmed
Case 17	9–11 weeks	Diffuse alveolar damage (organising)	Foamy macrophages, rare; multifocal pigmented macrophages (haemosiderin-laden and pigment not otherwise specified)	Anthracosis, rare; squamous metaplasia; smooth muscle hyperplasia; bronchopneumonia; bronchiectasis or restructuring	Not done	Central venous necrosis in the liver; acute tubular kidney necrosis; heart congestion; tracheitis, neutrophilic	Ground glass opacities and right-sided pneumonia	≥35	THC, nicotine	Diabetes; obesity; chronic respiratory disease; chronic pain; hypertension; chronic liver disease; conventional cigarette smoking	Confirmed
Case 18	9–11 weeks	Diffuse alveolar damage (organising)	Multifocal moderate foamy macrophages; multifocal moderate pigmented macrophages (haemosiderin-laden)	Multifocal rare anthracosis; squamous metaplasia; mononuclear interstitial inflammation; bronchiectasis or restructuring; extensive haemorrhage	Not done	Liver steatosis and cirrhosis; myocyte loss and fibrosis in the heart	Extensive bilateral ground glass opacities	≥35	THC	Conventional cigarette smoking; chronic liver disease	Confirmed
Autopsies with no evidence of acute lung injury or with acute lung injury due to an alternative cause
Case 19	3 weeks	Multifocal bronchopneumonia	Rare foamy macrophages and pigmented macrophages (haemosiderin-laden); moderate non-pigmented macrophages	Anthracosis, rare; erythrophagocytosis; eosinophilic bronchiolitis; intravascular leukocytosis	Gram-variable cocci in pairs in the lung; Streptococcus spp IHC: positive in the lung, negative in the kidney; PCR for Streptococcus pneumoniae: positive in the lung	None seen	Multiple opacified bronchi in both lungs (greatest in lower lobe), patchy consolidation, nodular and ground glass opacities throughout the lungs (greatest in lower lobes)	<35	Nicotine	Conventional cigarette smoking	Probable
Case 20	4 weeks	Increased alveolar macrophages, fibrin, haemorrhage, and bronchoaspiration	Multifocal rare foamy macrophages; locally extensive pigmented macrophages (haemosiderin-laden)	Multifocal rare anthracosis; multifocal bronchoaspiration; haemorrhage locally extensive and multifocal; intravascular leukocytosis	Streptococcus spp, select Gram-negative bacteria: IHC negative in the lung, liver, and kidney; PCR for influenza A, B, RSV, PIV1–4 negative in the trachea	Liver cirrhosis; myocardial fibrosis; necrotising tracheitis in the trachea	Extensive bilateral lung opacities on chest x-ray (no CT done)	≥35	THC, nicotine, CBD	Chronic respiratory disease; obesity; cardiac disease; chronic liver disease; conventional cigarette smoking	Probable
Case 21	12 weeks or more	Chronic interstitial lung disease (non-specific interstitial pneumonia), diffuse; mild bronchiolitis	Rare foamy macrophages; extensive pigmented macrophages (haemosiderin-laden)	Multifocal mild anthracosis; inspissated mucus, macrophages, and neutrophils in airways; squamous metaplasia; haemorrhage; honeycomb cysts	Gram stain and GMS: negative in the lung	Not submitted	Diffuse interstitial thickening with ground glass opacities	≥35	THC	Obesity; obstructive sleep apnoea; diabetes; chronic pain; conventional cigarette smoking	Confirmed
Case 22	2 weeks	Multifocal diffuse alveolar damage (exudative); mild focal bronchopneumonia	Rare foamy macrophages; abundant pigmented macrophages (haemosiderin-laden)	Multifocal moderate anthracosis; mild haemorrhage; septal oedema; intravascular leukocytosis; fibrin thrombi	Gram-negative rods in the kidney; Escherichia coli IHC positive in the kidney, negative in the liver, lung, heart, spleen	Severe kidney pyelonephritis; passive congestion and small droplet steatosis in the liver	Bilateral ground glass opacities and consolidative opacities with areas of peripheral clearing, air bronchograms, areas of superimposed interlobular septal thickening; abdominal ascites with mesenteric oedema and body wall anasarca	<35	Unknown	Obesity; hypertension; conventional cigarette smoking	Not a case
Case 23	5 weeks	Pulmonary oedema and intra-alveolar haemorrhage	Extensive pigmented macrophages (haemosiderin-laden)	None noted	Not done	Myocardial fibrosis with myocyte injury	Not done	<35	THC	Not reported	Not a case

AFB=acid-fast bacilli. CBD=cannabidiol. CDC=Centers for Disease Control and Prevention. EVALI=e-cigarette, or vaping, product use-associated lung injury. GMS=Grocott methenamine silver stain. IHC=immunohistochemistry. PIV=parainfluenza virus. RSV=respiratory syncytial virus. THC=tetrahydrocannabinol.

^*Weeks from illness onset to autopsy are defined as 1 week meaning less than 7 days, 2 weeks meaning 7–13 days, etc.

^†Based on imaging findings reported to the CDC.

^‡Includes reported history of one or more of the following: obesity, chronic pain, chronic respiratory disease, obstructive sleep apnoea, chronic kidney disease, immune suppression, chronic liver disease, diabetes, or hypertension; or autopsy findings consistent with chronic respiratory disease, chronic kidney disease, or cirrhosis. Nine (69%) of 13 individuals had a reported mental health diagnosis and six had a reported history of use or abuse of other substances, excluding marijuana; these data are not included at an individual level in this table.

^§The CDC 2019 lung injury primary or out-of-hospital death surveillance case definition (appendix p 3).²

^¶Details to clarify cross-reactivity of the select Gram-negative IHC assay are in the appendix p 2.