Neuropathological features of Covid-19
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Brain Autopsy Series in Patients with Covid-19 Eighteen brains of patients who died 0 to 32 days after the onset of symptoms of SARS-CoV-2 infection showed hypoxic–ischemic changes but no encephali...
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A neuropathological study of 18 adults aged 53-75 who died from COVID-19 revealed neither CT-informed macrostructural abnormalities nor microstructural damage ascribable to the virus, but only mild hypoxia-related modifications with limited evidence of viral presence in the brain.
“a study carried out on the brains of 18 adults between the ages of 53 and 75 fallen victim to the virus revealed neither CT-informed macrostructural abnormalities, nor microstructural damage ascribable to the virus, but only mild hypoxia-related modifications with, importantly, limited evidence of viral presence in the brain (34).”
From The impact of COVID-19 infection and enforced prolonged social isolation on neuropsychiatric symptoms in older adults with and without dementia: A review (2020) · cites this paper as [34]
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ResultLessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic
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“A substantial number of COVID-19 patients exhibit neurological symptoms, which may be further influenced by different host factors such as age, sex, comorbidities, disease progression, and others (Helms et al., 2020; Puelles et al., 2020; Solomon et al., 2020).”
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“Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons.”
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“Although there still appears to be a paucity of neuropathological research (33), a study carried out on the brains of 18 adults between the ages of 53 and 75 fallen victim to the virus revealed neither CT-informed macrostructural abnormalities, nor microstructural damage ascribable to the virus, but only mild hypoxia-…”
BackgroundPersistent Brainstem Dysfunction in Long-COVID: A Hypothesis
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“Although SARS-CoV-2 primarily affects the respiratory system, an increasing number of studies have started to report neurological symptoms, including headache, smell and taste disorders, dysexecutive syndrome, confusion, seizure, and encephalopathy (Giacomelli et al., 2020; Helms et al., 2020; Lechien et al., 2020; Ma…”
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“A range of neurological manifestations of COVID-19 have been reported [32]; however, we were unable to obtain brain tissue in our study.”
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“Furthermore, contrary to a recent report (10) and according with some other studies (7,8), we did not detect any signs of meningitis or encephalitis in any brain areas.”
BackgroundResultPeripheral Nervous System Manifestations Associated with COVID-19
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Histopathological observations in COVID-19: a systematic review
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“23], a recent autopsy series of patients that died with COVID-19—all of whom experienced altered mental status—did not find immunohistochemical evidence of encephalitis or viral invasion into brain tissue [24].”
BackgroundCOVID-19 associated cognitive impairment: A systematic review
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“Viral RNA was detected at low levels, possibly due to in situ viral RNA from the bloodstream (30).”
BackgroundTropism of SARS-CoV-2 for human cortical astrocytes
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Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease
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“Although encephalopathy has been reported in COVID-19 patients at all ages, patients beyond the sixth decade of life and those with preexisting neurologic conditions (stroke, dementia, Parkinson’s disease) are most affected, particularly in the context of severe respiratory illness.(45,47) While encephalopathy in the…”
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What can we learn from brain autopsies in COVID-19?
Mukerji, S. S., & Solomon, I. H. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135528 · Cited by 156 · see citing works
Neurologic manifestations associated with COVID-19: a multicentre registry
Meppiel, E., Peiffer‐Smadja, N., Maury, A., Bekri, I., Delorme, C., Desestret, V., Gorza, L., Hautecloque-Raysz, G., Landre, S., Lannuzel, A., et al. (2020) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2020.11.005 · Cited by 155 · see citing works
Effect of COVID-19 on the Organs
Jain, U. (2020) · Cureus · doi:10.7759/cureus.9540 · Cited by 155 · see citing works
“Brains of dead patients demonstrate hypoxic changes but encephalitis or other changes due to the virus are rare [40].”
BackgroundCOVID ‐19: immunopathology, pathophysiological mechanisms, and treatment options
van Eijk, L. E., Binkhorst, M., Bourgonje, A. R., Offringa, A. K., Mulder, D. J., Bos, E. M., Kolundžić, N., Abdulle, A. E., van der Voort, P. H. J., Rikkert, M. G. M. O., et al. (2021) · The Journal of Pathology · doi:10.1002/path.5642 · Cited by 153 · see citing works
Interactions of SARS-CoV-2 with the Blood–Brain Barrier
Erickson, M. A., Rhea, E. M., Knopp, R. C., & Banks, W. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052681 · Cited by 150 · see citing works
SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation
Keyhanian, K., Umeton, R. P., Mohit, B., Davoudi, V., Hajighasemi, F., & Ghasemi, M. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577436 · Cited by 143 · see citing works
Neuronophagia and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage
Al‐Dalahmah, O., Thakur, K. T., Nordvig, A. S., Prust, M., Roth, W., Lignelli, A., Uhlemann, A., Miller, E. H., Kunnath-Velayudhan, S., Portillo, A. D., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01024-2 · Cited by 136 · see citing works
Jacobs, J. L., Bain, W., Naqvi, A., Staines, B., Castanha, P. M. S., Yang, H., Boltz, V. F., Barratt‐Boyes, S. M., Marques, E. T. A., Mitchell, S. L., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab686 · Cited by 138 · see citing works
“Detection of SARS-CoV-2 RNA in the gastrointestinal tract, endothelium and central nervous system implicates extrapulmonary dissemination as an important contributor to disease manifestations severity [4-12].”
BackgroundMultiple Neuroinvasive Pathways in COVID-19
Bougakov, D., Podell, K., & Goldberg, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02152-5 · Cited by 137 · see citing works
“This possibility is supported by a recent observation of acute neuropathological changes from hypoxia in the brains of 18 consecutive deaths of ventilatordependent COVID-19 patients [71].”
Invited Review: The spectrum of neuropathology in COVID‐19
Al‐Sarraj, S., Troakes, C., Hanley, B. P., Osborn, M., Richardson, M. P., Hotopf, M. H., Bullmore, E. T., & Everall, I. (2020) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12667 · Cited by 148 · see citing works
“Solomon et al., 2020: Brains from 18 patients • Ischaemic changes and reactive changes of Alz- heimer’s type II astrocytes • Immunohistochemical stains for SARS-CoV-2 negative but virus was detected by PCR at low levels in five patients Reichard et al., 2020: Brain from one patient • Widespread…”
BackgroundInfectious agents and Alzheimer's disease
Piekut, T., Hurła, M., Banaszek, N., Szejn, P., Dorszewska, J., Kozubski, W., & Prendecki, M. (2022) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2102073 · Cited by 123 · see citing works
Central Nervous System Manifestations Associated with COVID-19
Divani, A. A., Andalib, S., Biller, J., Napoli, M. D., Moghimi, N., Rubiños, C., Nobleza, C. O., Sylaja, P. N., Toledano, M., Lattanzi, S., et al. (2020) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-020-01079-7 · Cited by 128 · see citing works
Klironomos, S., Tzortzakakis, A., Kits, A., Öhberg, C., Kollia, E., Ahoromazdae, A., Almqvist, H., Aspelin, Å., Martin, H., Ouellette, R., et al. (2020) · Radiology · doi:10.1148/radiol.2020202791 · Cited by 126 · see citing works
Shi, Z., de Vries, H. J., Vlaar, A. P. J., van der Hoeven, J., Boon, R. A., Heunks, L. M. A., Ottenheijm, C. A. C., & Dutch COVID-19 Diaphragm Investigators (2020) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2020.6278 · Cited by 126 · see citing works
COVID-19 and cognitive impairment: neuroinvasive and blood‒brain barrier dysfunction
Chen, Y., Yang, W., Chen, F., & Cui, L. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02579-8 · Cited by 124 · see citing works
Poloni, T. E., Carlos, A. F., Cairati, M., Cutaia, C., Medici, V., Marelli, E., Ferrari, D., Galli, A., Bognetti, P., Davin, A., et al. (2020) · EClinicalMedicine · doi:10.1016/j.eclinm.2020.100490 · Cited by 124 · see citing works
McFarland, A. J., Yousuf, M. S., Shiers, S. I., & Price, T. J. (2021) · PAIN Reports · doi:10.1097/pr9.0000000000000885 · Cited by 124 · see citing works
“currently unclear, however, whether there is brain penetration by SARS-CoV-2, with 18 consecutive brain autopsies of patients with PCR-confirmed COVID-19 finding no neuronal infection.(79) Moreover, a study using single-cell sequencing of BBB and cortical neurons found viral infection in the BBB and choroid”
ResultCOVID‐19‐related neuropathology and microglial activation in elderly with and without dementia
Poloni, T. E., Medici, V., Moretti, M., Visoná, S. D., Cirrincione, A., Carlos, A. F., Davin, A., Gagliardi, S., Pansarasa, O., Cereda, C., et al. (2021) · Brain Pathology · doi:10.1111/bpa.12997 · Cited by 123 · see citing works
Pathophysiology of Post-COVID syndromes: a new perspective
Batiha, G. E., Al-Kuraishy, H. M., Al-Gareeb, A. I., & Welson, N. N. (2022) · Virology Journal · doi:10.1186/s12985-022-01891-2 · Cited by 127 · see citing works
“In this state, post-mortem studies demonstrated that SARSCoV-2 proteins and genes were detected in COVID-19 victims [128, 129].”
BackgroundNeuropathology of COVID-19 (neuro-COVID): clinicopathological update
Lou, J. J., Movassaghi, M., Gordy, D. E., Olson, M. G., Zhang, T., Khurana, M. S., Chen, Z., Perez-Rosendahl, M. A., Thammachantha, S., Singer, E. J., et al. (2020) · Free Neuropathology · doi:10.17879/freeneuropathology-2021-2993 · Cited by 117 · see citing works
Pathological findings in organs and tissues of patients with COVID-19: A systematic review
Peiris, S., Mesa, H. A., Aysola, A. E., Manivel, J. C., Toledo, J., Borges-Sa, M., Aldighieri, S., & Revéiz, L. (2021) · PLoS ONE · doi:10.1371/journal.pone.0250708 · Cited by 113 · see citing works
“Mild meningoencephalitis/encephalitis was found in ~10% of the cases; this may explain the reported neurologic symptoms/mental status changes reported in a subset of critically ill patients [57].”
BackgroundMental Health Issues During and After COVID-19 Vaccine Era
Pandey, K., Thurman, M., Johnson, S., Acharya, A., Johnston, M. P., Klug, E., Olwenyi, O. A., Rajaiah, R., & Byrareddy, S. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.08.012 · Cited by 98 · see citing works
Garcia-Grimshaw, M. A., Ceballos‐Liceaga, S. E., Hernández‐Vanegas, L. E., Núñez, I., Hernández-Valdivia, N., Carrillo-García, D. A., Michel‐Chávez, A., Galnares‐Olalde, J. A., Carbajal‐Sandoval, G., Saniger‐Alba, M. D. M., et al. (2021) · Clinical Immunology · doi:10.1016/j.clim.2021.108786 · Cited by 114 · see citing works
“SARS-CoV-2 has the potential to gain access to the central nervous system [14] and induce the production of proinflammatory cytokines by microglia and astrocytes [15], leading to hyperexcitability and epileptic seizures [16].”
BackgroundHistopathological findings and clinicopathologic correlation in COVID-19: a systematic review
Caramaschi, S., Kapp, M., Miller, S., Eisenberg, R., Johnson, J. E., Epperly, G., Maiorana, A., Silvestri, G., & Giannico, G. A. (2021) · Modern Pathology · doi:10.1038/s41379-021-00814-w · Cited by 111 · see citing works
Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse
Seehusen, F., Clark, J. J., Sharma, P., Bentley, E. G., Kirby, A., Subramaniam, K. S., Wunderlin-Giuliani, S., Hughes, G. L., Patterson, E. I., Michael, B. D., et al. (2022) · Viruses · doi:10.3390/v14051020 · Cited by 112 · see citing works
“4 staining although low levels of viral RNA were detected by RT-PCR in five patients [21].”
BackgroundMethodCOVID-19 and Alzheimer’s Disease
Ciaccio, M., Sasso, B. L., Scazzone, C., Gambino, C. M., Ciaccio, A. M., Bivona, G., Piccoli, T., Giglio, R. V., & Agnello, L. (2021) · Brain Sciences · doi:10.3390/brainsci11030305 · Cited by 111 · see citing works
Fullard, J. F., Lee, H.-C., Voloudakis, G., Suo, S., Javidfar, B., Shao, Z., Peter, C. J., Zhang, W., Jiang, S., Corvelo, A., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00933-8 · Cited by 108 · see citing works
“Brain autopsies and neuroimaging studies have demonstrated acute hypoxic and vascular injury [5, 6], as well as plausible SARS-CoV-2 CNS tropism [7–10].”
BackgroundGuerrero, J. I., Barragán, L. A., Martínez, J. D., Montoya, J. P., Peña, A., Sobrino, F. E., Tovar-Spinoza, Z. S., & Ghotme, K. A. (2021) · BMC Infectious Diseases · doi:10.1186/s12879-021-06185-6 · Cited by 110 · see citing works
“SARS-CoV-2 is a 29,903 bp single-stranded RNA encapsulated virus from the Coronaviridae family, betacoronavirus subfamily, capable of affecting the human brain and other structures of the nervous system [2–4].”
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SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19
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Periodontal tissues are targets for Sars-Cov-2: a post-mortem study
Matuck, B. F., Dolhnikoff, M., Maia, G. V. A., Sendyk, D. I., Zarpellon, A., Gomes, S. C., Duarte‐Neto, A. N., Pinho, J. R. R., Gomes‐Gouvêa, M. S., de Sousa, S. C. O. M., et al. (2020) · Journal of Oral Microbiology · doi:10.1080/20002297.2020.1848135 · Cited by 108 · see citing works
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Infectious disease-associated encephalopathies
Barbosa‐Silva, M. C., Lima, M. N., Battaglini, D., Robba, C., Pelosi, P. P., Rocco, P. R. M., & Maron‐Gutierrez, T. (2021) · Critical Care · doi:10.1186/s13054-021-03659-6 · Cited by 120 · see citing works
COVID-19 and psychosis risk: real or delusional concern?
Watson, C. J., Thomas, R. H., Solomon, T., Michael, B. D., Nicholson, T. R., & Pollak, T. A. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135491 · Cited by 103 · see citing works
COVID-19: Review of a 21st Century Pandemic from Etiology to Neuro-psychiatric Implications
Yamamoto, V., Bolanos, J. F., Fiallos, J., Strand, S. E., Morris, K., Shahrokhinia, S., Cushing, T. R., Hopp, L., Tiwari, A., Hariri, R., et al. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-200831 · Cited by 100 · see citing works
“In a case series, in which autopsies were performed and brain specimens collected, histopathological studies showed only hypoxic changes without evidence of viral encephalitis in SARS-CoV-2- exposed patients [88].”
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- Authors
- Solomon, I. H., Normandin, E., Bhattacharyya, S., Mukerji, S. S., Keller, K., Ali, A. S., Adams, G., Hornick, J. L., Padera, R. F., & Sabeti, P.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Solomon, Isaac H.
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-09-03
- Volume
- 383
- Issue
- 10
- Pages
- 989-992
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC7304421
- OpenAlex
- W3035063822
- Cited by
- 815
- References
- 3
- Citations by year
- 2026: 15 · 2025: 32 · 2024: 75 · 2023: 119 · 2022: 164 · 2021: 267 · 2020: 143
- FWCI
- 75.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (K23MH115812)
- National Institute of Allergy and Infectious Diseases (U19AI110818)
- Topics
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2, neuropathology, brain autopsy, encephalopathy
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Aged, Autopsy, Brain, Female, Humans, Male, Middle Aged, Pneumonia, Viral, Coronavirus Infections, Pandemics
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