Table 1.
Summary of Published COVID-19 Reports with Autopsy Brain Findings.
| Reference | No. Cases Included; autopsy type | Macroscopic Evaluation | Microscopic Evaluation | SARS-CoV-2 Protein | SARS-CoV-2 RNA |
|---|---|---|---|---|---|
| Puelles et al. 2020 [41] Wichmann et al. 2020 [49] Matschke et al. 2020 [35] |
43; subset full autopsy with brain findings | Edema (n = 23), fresh territorial infarct (n = 6) | Fresh ischemic infarct (n = 6), astrocytosis, microgliosis, perivascular, parenchymal, and leptomeningeal T cells (n = 43) | Viral spike or nucleocapsid IHC positive in 16/40 cases (rare cells in medulla; 2 cases with vagus or glossopharyngeal nerves) | qRT-PCR positive (13/27; median 4700 viral E gene copies/cell; range <1000 to 162,000) in frontal lobe and/or medulla |
| Solomon et al. 2020 [37] | 18; brain-only findings | No specific findings | Mild to moderate acute hypoxic injury (n = 18); rare foci of perivascular and leptomeningeal inflammation (n = 3) | Viral nucleocapsid IHC negative in all cases | qRT-PCR positive (n = 5; 5.0–59.4 N1/N2 copies/μL) |
| Remmelink et al. 2020 [32] | 11; full autopsy with brain findings | Recently drained subdural hematoma (n = 1); cerebral hemorrhage (n = 1) | Cerebral hemorrhage or hemorrhagic suffusion (n = 8), focal ischemic necrosis (n = 3), edema and/or vascular congestions (n = 5), diffuse or focal spongiosis (n = 10) | N.A. | qRT-PCR positive (n = 9; viral E gene; Ct: 28.67–35.11) |
| Schurink et al. 2020 [38] | 11; full autopsy with brain findings | No specific findings | Hypoxic changes, activation/clusting of microglia, astrogliosis, perivascular cuffing of T cells most prominent in olfactory bulbs and medulla (n = 11); neutrophilic plugs (n = 3) | Viral nucleocapsid IHC negative in 11 cases | N.A. |
| Fabbri et al. 2020 [31] | 10; full autopsy with brain findings | Edema and meningeal congestion (n = 10), cerebral infarction (n = 3), uncal herniation (n = 2), purulent leptomeninges (n = 1), subarachnoid hemorrhage (n = 1) | Global hypoxic-ischemic injury (n = 10), acute hypoxic injury (all), intravascular microthrombi (n = 10), macro and/or microinfarcts (n = 10); perivascular microhemorrhage (n = 10), microglial activation (n = 5), perivascular/leptomeningeal lymphocytic inflammation (n = 1) | N.A. | qRT-PCR positive in olfactory nerve and brain tissue in (n = 1; RdRp, E, and N genes) |
| Schaller et al. 2020 [50] | 10; full autopsy with brain findings | No specific findings | No specific findings | N.A. | N.A. |
| Hanley et al. 2020 [34] | 9; full autopsy with brain findings | Hemorrhagic conversion of middle cerebral artery stroke (n = 1) | Moderate to intense microglial activation; mild T- cell infiltrate around blood vessels and capillaries, and ischemic changes of variable extent in the neurons of the cortex and the white matter (n = 5) | N.A. | qRT-PCR positive (n = 4; 101 to 104 viral E gene copies per μg total RNA); Subgenomic viral RNA positive (n = 1; Ct ∼32) |
| Deigendesch et al. 2020 [36] Menter et al. 2020 [26] * |
7; full autopsy with brain findings | Moderate global brain edema without cerebral mass displacement (n = 1) | Microglial activation in pons, medulla, and olfactory bulb; sparse perivascular and leptomeningeal infiltrates of lymphocytes; mild acute hypoxic-ischemic encephalopathy (n = 3) | N.A. | qRT-PCR positive in olfactory bulb (n = 4), optic nerve (n = 2); not detected in brainstem or cerebellum (ORFab1, S, and N genes) |
| von Weyham et al. 2020 [27] | 6; full autopsy with brain findings | Massive hemorrhage and herniation (n = 2); petechial bleedings (n = 4) | Hypoxic alterations (n = 6); lymphocytic meningitis and encephalitis (n = 6); brainstem neuronal cell loss in (n = 4), axon degeneration (n = 3) | N.A. | N.A. |
| Bradley et al. 2020 [28] | 5; full autopsy with brain findings | Scattered punctate subarachnoid hemorrhages (n = 1) | Rare microhemorrhages in the brainstem (n = 1) | N.A. | N.A. |
| Kantonen et al. 2020 [30] | 4; full autopsy with brain findings | Mild brain swelling, discoloration of watershed areas, lacunar infarcts, and microhemorrhages in cerebral and cerebellar white matter, deep gray matter, and brain stem (n = 1) | High density acute microhemorrhages, severe hypoxic-ischemic injury, scattered T lymphocytes, and axonal spheroids (n = 1); mild to moderate hypoxic-ischemic injury (n = 3) | Viral spike IHC negative in brain, olfactory mucosa, and carotid body | qRT-PCR negative in brain and olfactory mucosa (RdRp, N. and E genes) |
| Bussani et al. 2020 [51] | 3; fill autopsy with brain findings | N.A. | Gliosis, neuronal loss, vascular rarefaction | N.A. | N.A. |
| Barton et al. 2020 [52] | 2; full autopsy with brain findings | No gross abnormalities | N.A. | N.A. | N.A. |
| Jaunmuktane et al. 2020 [29] | 2; brain-only findings | Large acute and subacute infarcts (n = 1); white matter microhemorrhages and microinfarcts (n = 1) | Hemorrhages and infarcts (n = 2); mild leptomeningeal inflammation (n = 1) | N.A. | N.A. |
| Kirschenbaum et al. 2020 [39] | 2; brain-only findings | N.A. | Perivascular leukocytic infiltrates in basal ganglia and intravascular microthrombi (n = 2); prominent leukocytic infiltrates in olfactory epithelium (n = 2) | N.A. | N.A. |
| Al-Dalahmah et al. 2020 [33] | 1; full autopsy with brain findings | Cerebellar hemorrhage, acute infarcts in the dorsal pons and medulla, tonsillar herniation | Global hypoxia; numerous microglial nodules and neuronophagia in the inferior olives and cerebellar dentate nuclei; mild perivascular and sparse parenchymal and leptomeningeal lymphocytes; perivascular hemorrhages; chronic active inflammation in olfactory epithelium; red neurons in olfactory bulb and normal tract | Viral nucleocapsid IHC negative | qRT-PCR positive in nasal epithelium (Mean Ct 31.75, 278 copies/μL RNA), olfactory bulb (Ct 36.70, 11 copies/μL); Cerebellar clot (Ct 33.0, 559 copies/μL), and cerebellum (Ct 37.17, 8 copies/μL); Viral ISH negative |
| Craver et al. 2020 [53] | 1; full autopsy with brain findings | No CNS lesions identified | No CNS lesions identified | N.A. | N.A. |
| Dolhnikoff et al. 2020 [54] | 1; full autopsy with brain findings | N.A. | Microglial reactivity | N.A. | N.A. |
| Lax et al. 2020 [55] | 1: full autopsy with brain findings | No acute alterations | No acute alterations | N.A. | N.A. |
| Paniz-Mondolfi et al 2020 [12] | 1; brain-only findings | N.A. | N.A. | TEM showed viral like particles in frontal lobe sections | qRT-PCR positive (four different assays targeting ORF1/a and E-gene, N1, N2, N3, N2 and E-gene, and ORF1ab and S genes) |
| Reichard et al 2020 [14] | 1; brain-only findings | Mild brain swelling and hemorrhagic white matter lesions | Focal hemorrhage, ADEM-like lesions, microinfarcts, damaged axons, hypoxic-ischemic injury | N.A. | N.A. |
Abbreviations: ADEM, acute disseminated encephalomyelitis; Ct, cycle threshold; qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; E gene, SARS-CoV-2 envelope gene; ORF1ab, open reading frame 1ab; IHC, immunohistochemistry; ISH, in-situ hybridization; RdRp, RNA-dependent RNA polymerase gene; N.A., not available or evaluated; TEM, transmission electron microscopy.
*
Provided data on angiotensin converting enzyme – 2 (ACE2) IHC in brain tissue and olfactory bulb.