Cited by 822Long-Term Effects of COVID-19Infectious Encephalopathies and EncephalitisCOVID-19 Clinical Research Studies

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Neuropathological Features of Covid-19

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Solomon, Isaac H., Normandin, Erica, Bhattacharyya, Shamik, Mukerji, Shibani S., Keller, Kiana, Ali, Ahya S., Adams, Gordon, Hornick, Jason L., Padera, Robert F., Sabeti, Pardis·2020·New England Journal of Medicine

DOI 10.1056/nejmc2019373PMC PMC7304421

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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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Lechien, J. R., Chiesa-Estomba, C. M., De Siati, D. R., Horoi, M., Le Bon, S. D., Rodriguez, A., Dequanter, D., Blecic, S., El Afia, F., Distinguin, L., et al. (2020) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-020-05965-1 · Cited by 2,668
Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study
Giacomelli, A., Pezzati, L., Conti, F., Bernacchia, D., Siano, M., Oreni, L., Rusconi, S., Gervasoni, C., Ridolfo, A. L., Rizzardini, G., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa330 · Cited by 1,326

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de Oliveira, M. V. B., Irikura, S., Lourenço, F. H. D. B., Shinsato, M., Irikura, T. C. D. B., Irikura, R. B., Albuquerque, T. V. C., Shinsato, V. N., Orsatti, V. N., Fontanelli, A. M., et al. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100252 · Cited by 27
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“Neurologic manifestations are the combination of non-specific systemic disease complications, direct viral infection effects, and inflammation on the nervous system and vasculature (3-7).”
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Multisystem screening reveals SARS‐CoV ‐2 in neurons of the myenteric plexus and in megakaryocytes
Gray‐Rodriguez, S., Jensen, M. P., Otero‐Jimenez, M., Hanley, B. P., Swann, O. C., Ward, P. A., Salguero, F. J., Querido, N. R., Farkas, I., Velentza‐Almpani, E., et al. (2022) · The Journal of Pathology · doi:10.1002/path.5878 · Cited by 25
“about the possibility of viral protein or RNA in the CNS are conflicting [8,14,16,32,33].”
Background
Organoid Studies in COVID-19 Research
Kim, J., Koo, B., & Clevers, H. C. (2022) · International Journal of Stem Cells · doi:10.15283/ijsc21251 · Cited by 27
“Moreover, viral RNA has been detected in patient brain samples (33-36).”
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Mechanisms of COVID‐19‐associated olfactory dysfunction
Chang, K., Zaikos, T. D., Kilner‐Pontone, N., & Ho, C. (2024) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12960 · Cited by 26
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Neshin, S. A. S., Shahjouei, S., Koza, E., Friedenberg, I., Khodadadi, F., Sabra, M., Kobeissy, F. H., Ansari, S., Tsivgoulis, G. K., Li, J., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.649922 · Cited by 25
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Human placenta-derived amniotic epithelial cells as a new therapeutic hope for COVID-19-associated acute respiratory distress syndrome (ARDS) and systemic inflammation
Babajani, A., Moeinabadi‐Bidgoli, K., Niknejad, F., Rismanchi, H., Shafiee, S., Shariatzadeh, S., Jamshidi, E., Farjoo, M. H., & Niknejad, H. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02794-3 · Cited by 24
Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients
Michael, B. D., Walton, D., Westenberg, E., García‐Azorín, D., Singh, B., Tamborska, A., Netravathi, M., Chomba, M., Wood, G. K., Easton, A., et al. (2021) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.22010002 · Cited by 26
COVID-19 Pathology in the Lung, Kidney, Heart and Brain: The Different Roles of T-Cells, Macrophages, and Microthrombosis
Poloni, T. E., Moretti, M., Medici, V., Turturici, E., Belli, G., Cavriani, E., Visonà, S. D., Rossi, M., Fantini, V., Ferrari, R. R., et al. (2022) · Cells · doi:10.3390/cells11193124 · Cited by 24
Neurological complications of COVID-19
Dai, X., Cao, X., Jiang, Q., Wu, B., Lou, T., Shao, Y., Hu, Y., & Lan, Q. (2022) · QJM · doi:10.1093/qjmed/hcac272 · Cited by 26
The functional and structural changes in the hippocampus of COVID-19 patients
Nouraeinejad, A. (2023) · Acta Neurologica Belgica · doi:10.1007/s13760-023-02291-1 · Cited by 28
SARS-CoV-2 Spike Protein S1 Domain Accelerates α-Synuclein Phosphorylation and Aggregation in Cellular Models of Synucleinopathy
Wang, J., Dai, L., Deng, M., Xiao, T., Zhang, Z., & Zhang, Z. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03726-9 · Cited by 24
New-onset dementia among survivors of pneumonia associated With severe acute respiratory syndrome coronavirus 2 infection
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“Acute hypoxic injury in the cerebrum and cerebellum and loss of neurons in the cerebral cortex, hippocampus, and cerebellar Purkinje cell layer, with foci of perivascular lymphocytes and focal leptomeningeal inflammation, are seen in patients with SARS-CoV-2 infection [26].”
Anosmia and COVID-19: perspectives on its association and the pathophysiological mechanisms involved
Júnior, P. R. D. S., Gomes, A. L. O. R., Coelho, L. E. A., Morais, M. A., de Almeida, P. V. F. C., Neri, W., Mascena, G. V., & Leal, A. A. D. F. (2021) · The Egyptian Journal of Neurology Psychiatry and Neurosurgery · doi:10.1186/s41983-020-00266-0 · Cited by 23
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Septyaningtrias, D. E., & Susilowati, R. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0092 · Cited by 23
“2020) but other autopsies demonstrated lack of immune cell infiltration and cerebrovascular inflammation (Kantonen et al. 2020; Schaller et al. 2020; Solomon et al. 2020).”
BackgroundResult
Postmortem pathological changes in extrapulmonary organs in SARS-CoV-2 rt-PCR–positive cases: a single-center experience
Buğra, A., Daş, T., Arslan, M. N., Ziyade, N., & Büyük, Y. (2021) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-021-02638-8 · Cited by 23
“found acute hypoxic damage in the brain and cerebellum in all cases in a series of 18 cases [14, 34].”
Background
Association of consciousness impairment and mortality in people with COVID‐19
Xiong, W., Lu, L., Zhang, B., Luo, J., Li, W., He, L., Sander, J. W. A. S., Mu, J., Zhu, C., & Zhou, D. (2021) · Acta Neurologica Scandinavica · doi:10.1111/ane.13471 · Cited by 22
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Matos, A. D. M. B., Dahy, F. E., de Moura, J. V. L., Marcusso, R. M. N., Gomes, A. B. F., de Carvalho, F. A. B., Fernandes, G. B. P., Félix, A. C., Smid, J., Vidal, J. E., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.678924 · Cited by 23
“Hypoxia and pro-inflammatory cytokines are possible contributory mechanisms in SARS-CoV-2 encephalopathy (24).”
Background
Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting
Huth, S. F., Cho, S., Robba, C., Highton, D., Battaglini, D., Bellapart, J., Suen, J. Y., Bassi, G. L., Taccone, F. S., Arora, R. C., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.664599 · Cited by 23
Recent Advances in the Impact of Infection and Inflammation on Stroke Risk and Outcomes
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Role of neuroinflammation mediated potential alterations in adult neurogenesis as a factor for neuropsychiatric symptoms in Post-Acute COVID-19 syndrome—A narrative review
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“, 2020) and post-mortem brain studies (Fabbri et al., 2021; Solomon et al., 2020; Thakur et al., 2021) have shown neuropathogenic changes in the hippocampus caused by SARS-CoV-2 infection.”
Background
Neuropathological findings in COVID-19: an autopsy cohort
Eschbacher, K. L., Larsen, R. A., Moyer, A. M., Majumdar, R., & Reichard, R. R. (2022) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlac101 · Cited by 23
Imaging and neuropathological findings in patients with Post COVID-19 Neurological Syndrome—A review
Okrzeja, J., Garkowski, A., Kubas, B., & Moniuszko-Malinowska, A. M. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1136348 · Cited by 23
“Furthermore, atrophy of the hippocampus and cortex (23, 27, 28), ischemic alterations (29), and small vessel disease (SVD) (30) have been demonstrated to develop as a result of inflammatory reactions and oxidative stress during COVID-19 (23, 31).”
Background
Severe COVID-19 induces molecular signatures of aging in the human brainPreprint
Mavrikaki, M., Lee, J. D., Solomon, I. H., & Slack, F. J. (2021) · medRxiv · doi:10.1101/2021.11.24.21266779 · Cited by 23
“Although COVID-19 is primarily a respiratory disease, neurological symptoms are also 34 reported in a subpopulation of infected COVID-19 individuals [1], with substantially higher rates 35 (up to 84%) in severe COVID-19 cases [2].”
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Pensato, U., Muccioli, L., Pasini, E., Tappatà, M., Ferri, L., Volpi, L., Licchetta, L., Battaglia, S., Rossini, G., Bon, I., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.587226 · Cited by 27
“Encephalopathy in the contest of potentially neurotropic virus infection, such as SARS-CoV-2, may raise suspicion of a viral encephalitis; however, CSF and MRI findings in our patient were inconsistent with this hypothesis, in line with the vast majority of COVID-19 patients presenting with central neurological manife…”
BackgroundResult
Brain MR Spectroscopic Findings in 3 Consecutive Patients with COVID-19: Preliminary Observations
Rapalino, O., Weerasekera, A., Moum, S. J., Eikermann‐Haerter, K., Edlow, B. L., Fischer, D. B., Torrado-Carvajal, Á., Loggia, M. L., Mukerji, S. S., Schaefer, P. W., et al. (2020) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6877 · Cited by 24
Mild to Severe Neurological Manifestations of COVID-19: Cases Reports
Melegari, G., Rivi, V., Zelent, G., Nasillo, V., Santis, E. D., Melegari, A., Bevilacqua, C., Zoli, M., Meletti, S., & Barbieri, A. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18073673 · Cited by 22
Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Nath, A. (2021) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000992 · Cited by 24
Identifying cerebral microstructural changes in patients with COVID-19 using MRI
Alhazmi, F. H., Alsharif, W. M., Alshoabi, S. A., Gameraddin, M. B., Aloufi, K. M., Abdulaal, O. M., & Qurashi, A. A. (2023) · Brain Circulation · doi:10.4103/bc.bc_77_22 · Cited by 22
“[40] The hippocampus appears to be particularly exposed to coronavirus infections, thus increasing the chance of postinfection memory impairment and the quickening of neurodegenerative disorders.[39,50-59] It was reported that the hypoxemia brought on by COVID-19 and the Figure 2: Consistent results are displayed in t…”
Result
COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications
Kanberg, N., Grahn, A., Stentoft, E., Bremell, D., Yilmaz, A., Studahl, M., Nilsson, S., Schöll, M., Gostner, J. M., Blennow, K., et al. (2023) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiad395 · Cited by 20
Delayed reemergence of consciousness in survivors of severe COVID-19
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“The clinical manifestations [1, 3], EEG characteristics [1, 15], CT/MRI findings [3, 16, 17] and histopathological hallmarks [18, 19] of these injurious processes, including elevated stroke risk, are just beginning to be recognized.”
Background
Visual Snow-Like Symptoms and Posterior Uveitis following COVID-19 Infection
Braceros, K. K., Asahi, M., & Gallemore, R. P. (2021) · Case Reports in Ophthalmological Medicine · doi:10.1155/2021/6668552 · Cited by 21
Clinical and radiological findings of silent hypoxia among COVID-19 patients
Okuhama, A., Ishikane, M., Hotta, M., Sato, L., Akiyama, Y., Morioka, S., Suzuki, S., Tajima, T., Yamamoto, M., Teruya, K., et al. (2021) · Journal of Infection and Chemotherapy · doi:10.1016/j.jiac.2021.07.002 · Cited by 21
“1538 and cerebellar Purkinje cell layer; SARS-CoV-2 was also detected in several brain sections [10].”
BackgroundResult
Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients
Santinelli, L., Laghi, L., Innocenti, G. P., Pinacchio, C., Vassalini, P., Celani, L., Lazzaro, A., Borrazzo, C., Marazzato, M., Tarsitani, L., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.756177 · Cited by 21
“New findings show that detectable levels of the virus in COVID-19 in the brains are low and do not correlate with histopathological changes (31).”
Background
Olfactory Dysfunction in Patients With Coronavirus Disease 2019: A Review
Wei, G., Gu, J., Gu, Z., Du, C., Huang, X., Xing, H., Li, L., Zhang, A., Hu, X., & Huo, J.-G. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.783249 · Cited by 21
“However, subsequent studies showed that ACE2 was not expressed in olfactory neurons of the olfactory bulb (79, 82).”
Background
Elevation of neural injury markers in patients with neurologic sequelae after hospitalization for SARS-CoV-2 infection
Spanos, M., Shachar, S., Sweeney, T., Lehmann, H. I., Gokulnath, P., Li, G., Sigal, G. B., Nagaraj, R., Bathala, P., Rana, F., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104833 · Cited by 23
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Premeaux, T. A., Mediouni, S., Léda, A. R., O’Brien, R. L. F., Valente, S. T., Fine, H. A., Nixon, D. F., & Ndhlovu, L. C. (2021) · mBio · doi:10.1128/mbio.00680-21 · Cited by 22
Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection
Zhang, T., Li, Y., Pan, L., Sha, J., Bailey, M., Faure-Kumar, E., Williams, C. K., Wohlschlegel, J., Magaki, S., Niu, C., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00730-z · Cited by 20
“However, spatial transcriptomic profiling revealed that most DE genes were in the frontal gray matter and pontine nuclei, compared to white matter tracts (Extended Data subcortical infarcts, intracranial bleeding, hypoxic-ischemic injury and occasional necrotizing encephalitis and vasculitis 15–20 .”
Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses
Riederer, P. F., & ter Meulen, V. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02230-x · Cited by 21
“Only a few publications and sometimes only case reports report on autopsy studies of patients dying from COVID-19 infection (Solomon et al. 2020).”
Background
Neuropathogenesis of acute coronavirus disease 2019
Farhadian, S., Seilhean, D., & Spudich, S. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000944 · Cited by 20
Neuroinflammation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection: Pathogenesis and clinical manifestations
Cárdenas, G., Fragoso, G., & Sciutto, E. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.12.008 · Cited by 21
Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response
Hirzel, C., Grandgirard, D., Surial, B., Wider, M., Leppert, D., Kühle, J., Walti, L. N., Schefold, J. C., Spinetti, T., Suter‐Riniker, F., et al. (2022) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864221080528 · Cited by 20
Deleterious effects of nervous system in the offspring following maternal SARS-CoV-2 infection during the COVID-19 pandemic
Wang, R., Wu, Z., Huang, C., Hashimoto, K., Yang, L., & Yang, C. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01985-z · Cited by 20
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Latorre, D. (2022) · European Journal of Immunology · doi:10.1002/eji.202149475 · Cited by 20
Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study
Ardellier, F.-D., Baloglu, S., Sokolska, M., Noblet, V., Lersy, F., Collange, O., Ferré, J., Maamar, A., Carsin-Nicol, B., Helms, J., et al. (2023) · Journal of Neuroradiology · doi:10.1016/j.neurad.2023.01.005 · Cited by 20
“Proof of direct viral CNS infection are scarce[19, 20], and the low number of positive RT-PCR on CSF in our cohort does not support this mechanism.”
High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection
Normandin, E., Rudy, M. A., Barkas, N., Schaffner, S. F., Levine, Z. C., Padera, R. F., Babadi, M., Mukerji, S. S., Park, D. J., MacInnis, B. L., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-34256-y · Cited by 21
Neuropathological features of SARS-CoV-2 delta and omicron variants
Normandin, E., Valizadeh, N., Rudmann, E. A., Uddin, R., Dobbins, S. T., MacInnis, B. L., Padera, R. F., Siddle, K. J., Lemieux, J. E., Sabeti, P. C., et al. (2023) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlad015 · Cited by 20
Cerebrospinal Analysis in Patients With COVID-19
Miller, E. H., Namale, V. S., Kim, C. F., Dugue, R., Waldrop, G. E., Ciryam, P., Chong, A. M., Zucker, J. E., Miller, E. C., Bain, J., et al. (2020) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofaa501 · Cited by 18
“low viral loads of uncertain clinical significance when reported[27-29].”
Background
Clinical Electroencephalography Findings and Considerations in Hospitalized Patients With Coronavirus SARS-CoV-2
Ayub, N., Cohen, J. M., Jing, J., Jain, A., Tesh, R. A., Mukerji, S. S., Zafar, S. F., Westover, M. B., & Kimchi, E. Y. (2020) · The Neurohospitalist · doi:10.1177/1941874420972237 · Cited by 22
“Autopsy series, however, have been conflicting regarding rates of neuroinvasion,(15) with the largest series suggesting that neuroinvasion is limited.(16) It is therefore unclear whether seizures or encephalopathy in SARS-CoV-2 are due to new CNS injury, reflect increased sensitivity in patients with preexisting vulne…”
Background
Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy
Rapalino, O., Pourvaziri, A., Maher, M. D., Jaramillo‐Cardoso, A., Edlow, B. L., Conklin, J., Huang, S. Y., Westover, M. B., Romero, J. M., Halpern, E. F., et al. (2021) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6966 · Cited by 20
“Review of the current literature suggests possible roles for “silent hypoxia” and/or “cytokine storm” in the development of severe COVID-19-related leukoencephalopathy;(5,14,15) the paucity of postmortem studies to date contributes to this uncertainty.(16) Our purpose, therefore, has been to characterize the clinical,…”
Background
Mental Health in Patients with Coronavirus Disease-19 and the Quarantined People
Park, H. Y. (2021) · 신경정신의학 · doi:10.4306/jknpa.2021.60.1.11 · Cited by 19
Olfactory bulb SARS‐CoV‐2 infection is not paralleled by the presence of virus in other central nervous system areas
Lopez, G., Tonello, C., Osipova, G., Carsana, L., Biasin, M., Cappelletti, G., Pellegrinelli, A., Lauri, E., Zerbi, P., Rossi, R. S., et al. (2021) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12752 · Cited by 19
SARS-CoV-2 S1 Protein Induces Endolysosome Dysfunction and Neuritic Dystrophy
Datta, G., Miller, N., Halcrow, P. W., Khan, N., Colwell, T., Geiger, J. D., & Chen, X. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.777738 · Cited by 21
K18- and CAG-hACE2 Transgenic Mouse Models and SARS-CoV-2: Implications for Neurodegeneration Research
Dedoni, S., Avdoshina, V., Camoglio, C., Siddi, C., Fratta, W., Scherma, M., & Fadda, P. (2022) · Molecules · doi:10.3390/molecules27134142 · Cited by 20
Neurological reasons for consultation and hospitalization during the COVID-19 pandemic
García‐Moncó, J. C., Muras, A. C., Fernández, A. C., Erburu‐Iriarte, M., Armenteros, P. R., Oyarzun‐Irazu, I., Cóndor, D. M., Bilbao‐González, A., Carmona‐Abellán, M., Romero, I. C., et al. (2020) · Neurological Sciences · doi:10.1007/s10072-020-04714-w · Cited by 19
“This is consistent with the lack of specific viral changes in the brain of 2 recent series of autopsies [12, 13].”
Result
The Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Development of Case Report Forms for Global Use
McNett, M., Fink, E. L., Schober, M. E., Mainali, S., Helbok, R., Robertson, C., Mejía-Mantilla, J. H., Kurtz, P., Righy, C., Roa, J. D., et al. (2020) · Neurocritical Care · doi:10.1007/s12028-020-01100-4 · Cited by 19
Neurological complications in COVID-19 patients from Latin America
Brucki, S. M. D., Corazza, L. A., de Queiroz, A. P., Barros, M. P., Tatsch, J. F. S., Riso, I. L., Batista, N. A., Manfroi, G., Sawada, L. A., BATISTA, L. L. R., et al. (2020) · Brain · doi:10.1093/brain/awaa440 · Cited by 21
Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
Wang, H., Zhang, Z., Zhou, J., Han, S., Kang, Z., Chuang, H.-Y., Fan, H., Zhao, H., Wang, L., Ning, Y., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.782731 · Cited by 20
“Sevenof theCSF samples showed a clear colorless appearance, with a normal range of white blood cells (WBCs) ([4-8] x 10(6)/L) and slightly increased proteins (0.”
Background
Neuropathological findings in fatal COVID-19 and their associated neurological clinical manifestations
Ruz‐Caracuel, I., Pian-Arias, H., Corral, Í., Carretero‐Barrio, I., Bueno-Sacristán, D., Perez‐Mies, B., García‐Cosío, M., Caniego-Casas, T., Pizarro, D., García-Narros, M. I., et al. (2022) · Pathology · doi:10.1016/j.pathol.2022.03.006 · Cited by 21
“In one of the early series published, Solomon et al.(8) found acute hypoxic ischaemic damage as a common feature in all patients.”
BackgroundInfluential
COVID-19 neuropsychiatric repercussions: Current evidence on the subject
Júnior, R. T. D. S., Apolonio, J. S., Cuzzuol, B. R., da Costa, B. T., Silva, C. S., Araújo, G. R. L., Luz, M. S., Marques, H. S., Santos, L. K. D. S., Pinheiro, S. L. R., et al. (2022) · World Journal of Methodology · doi:10.5662/wjm.v12.i5.365 · Cited by 19
Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence
Gelpí, E., Klotz, S., Beyerle, M., Wischnewski, S., Harter, V., Kirschner, H., Stolz, K., Reisinger, C., Lindeck‐Pozza, E., Zoufaly, A., et al. (2023) · Viruses · doi:10.3390/v15040908 · Cited by 19
Detection of blood–brain barrier disruption in brains of patients with COVID-19, but no evidence of brain penetration by SARS-CoV-2
Song, H., Tomasevich, A., Acheampong, K. K., Schaff, D. L., Shaffer, S. M., Dollé, J.-P., Johnson, V. E., Mikytuck, B., Lee, E. B., Nolan, A., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02624-7 · Cited by 20
“Autopsy studies on limited available cases have reported a spectrum of neuropathological changes in COVID-19 patients, in particular neuroinflammation and microvascular injury [3, 5, 11, 14].”
Background
Brain fog in central disorders of hypersomnolence: a review
Rosenberg, R. P., Thorpy, M. J., Doghramji, K., & Morse, A. M. (2024) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.11014 · Cited by 19
Comprehensive Review on Neuro-COVID-19 Pathophysiology and Clinical Consequences
Khaljiri, H. J., Jamalkhah, M., Harandi, A. A., Pakdaman, H., Moradi, M., & Mowla, A. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00389-z · Cited by 21
COVID-19 and the Pediatric Nervous System: Global Collaboration to Meet a Global Need
Schober, M. E., Robertson, C., Wainwright, M. S., Roa, J. D., & Fink, E. L. (2021) · Neurocritical Care · doi:10.1007/s12028-021-01269-2 · Cited by 22
COVID-19 and its impact on neurological manifestations and mental health: the present scenario
Sultana, S., & Ananthapur, V. (2020) · Neurological Sciences · doi:10.1007/s10072-020-04695-w · Cited by 20
“Hypoxic changes can be attributed to patient-specific comorbidities and secondary effects due to immune complexes and inflammatory mediators from viral infection [12].”
Background
The blood-brain barrier in health, neurological diseases, and COVID-19
Chen, J., Tan, R., Mo, Y., & Zhang, J. (2022) · Fundamental Research · doi:10.1016/j.fmre.2022.03.003 · Cited by 19
Citicoline and COVID-19: vis-à-vis conjectured
Al-Kuraishy, H. M., Albuhadily, A. K., Al-Gareeb, A. I., Alorabi, M., Al-Harcan, N. A. H., El-Bouseary, M. M., & Batiha, G. E. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02284-6 · Cited by 18
“Interestingly, post-mortem studies demonstrated that SARS-CoV-2 proteins and genes were identified in COVID19 victims (Solomon et al. 2020; Rovere Querini et al. 2020).”
Background
Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas
Stein, J. A., Kaes, M., Smola, S., & Schulz‐Schaeffer, W. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1229641 · Cited by 21
“(11) achieved mixed results and argued that samples might have been contaminated by blood (11).”
Background
COVID‐19 and the impact on Alzheimer's disease pathology
Furman, S., Green, K. N., & Lane, T. E. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15985 · Cited by 18
“…the brain can contribute to these changes given that some autopsy studies have failed to detect virus, or only small traces of RNA have been found within the brain, often only in those with severe disease (Matschke et al., 2020 ; Solomon et al., 2020 ; Stein et al., 2022; Thakur et al., 2021).”
COVID-19 and Alzheimer’s Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future
Amadoro, G., Latina, V., Stigliano, E., & Micera, A. (2023) · Cells · doi:10.3390/cells12222601 · Cited by 20
“…direct neuro-invasive capacity of SARS-CoV-2 to enter the brain [264,265] while others do not confirm the presence of the virus within the brain [38,266,267] or report very low levels of detectable RNA and viral protein brains [37,140], suggesting that the virus neuropathology is more likely to…”
Background
What HIV in the Brain Can Teach Us About SARS-CoV-2 Neurological Complications?
Al‐Harthi, L., Campbell, E. M., Schneider, J. A., & Bennett, D. A. (2020) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2020.0161 · Cited by 18
“The level of virus detected by quantitative reverse transcription-PCR (qRT-PCR) in one study ranged from <5 to 59 copies per cubic millimeter(64) and the virus was mostly found in medulla, frontal lobes, and olfactory nerves(64); however, immunohistochemistry verification did not detect the virus in the brain in this…”
BackgroundInfluential
Hospitalized COVID-19 Patients Were Five Times More Likely to Suffer From Total Sleep Deprivation Compared to Non-COVID-19 Patients; an Observational Comparative Study
van den Ende, E. S., van Veldhuizen, K. D. I., Toussaint, B., Merten, H., van de Ven, P. M., Kok, N. A., & Nanayakkara, P. W. B. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.680932 · Cited by 18
Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice
Kuruppuarachchi, K. A. P. P., Jang, Y., & Seo, S. H. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2711316 · Cited by 18
Case 26-2020: A 60-Year-Old Woman with Altered Mental Status and Weakness on the Left Side
Singhal, A. B., González, R. G., Chwalisz, B. K., & Mukerji, S. S. (2020) · New England Journal of Medicine · doi:10.1056/nejmcpc2004976 · Cited by 17
Imaging Diagnostics and Pathology in SARS-CoV-2-Related Diseases
Scimeca, M., Urbano, N., Bonfiglio, R., Montanaro, M., Bonanno, E., Schillaci, O., & Mauriello, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186960 · Cited by 17
Addressing the ‘hypoxia paradox’ in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues
Begemann, M., Groß, O., Wincewicz, D., Hardeland, R., Gastaldi, V. D., Vieta, E., Weißenborn, K., Miskowiak, K. W., Moerer, O., & Ehrenreich, H. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00381-5 · Cited by 18
Movement Disorders Associated with COVID-19
Salari, M., Harofteh, B. Z., Etemadifar, M., Sedaghat, N., & Nouri, H. (2021) · Parkinson s Disease · doi:10.1155/2021/3227753 · Cited by 18
“However, the aforementioned neuropathological data from autopsy studies call this hypothesis into question [8, 9].”
Background
Comparative pathology of the nasal epithelium in K18-hACE2 Tg mice, hACE2 Tg mice, and hamsters infected with SARS-CoV-2
Yü, P., Deng, W., Bao, L., Qu, Y., Xu, Y., Zhao, W., Han, Y., & Qin, C. (2022) · Veterinary Pathology · doi:10.1177/03009858211071016 · Cited by 15
A review on the biological, epidemiological, and statistical relevance of COVID-19 paired with air pollution
Yates, E. F., Zhang, K., Naus, A. E., Forbes, C., Wu, X., & Dey, T. (2022) · Environmental Advances · doi:10.1016/j.envadv.2022.100250 · Cited by 17
“(Heusinkveld et al., 2016) The presence of both viral particles and particulate matter may synergistically promote intra-cerebral inflammation.”
The nervous system during COVID ‐19: Caught in the crossfire
Natale, N. R., Lukens, J. R., & Petri, W. A. (2022) · Immunological Reviews · doi:10.1111/imr.13114 · Cited by 19
“All of these forms of cellular damage reduce the respiration capacity of the lungs which leads to a dangerous hypoxic state in a variety of organs, especially the brain 171,172 .”
Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19
Frank, M. G., Fleshner, M., & Maier, S. F. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.04.009 · Cited by 19
“COVID-19 patients (Solomon et al., 2020), and found low levels of viral RNA in 6 brain sections obtained from 5 patients; however, even with PCR, the virus could not be detected in most samples.”
Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections
Valdetaro, L., Thomasi, B. B. D. M., Ricciardi, M. C., Santos, K. D. M., Coelho‐Aguiar, J. D. M., & Gomes, A. L. T. (2023) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00229.2022 · Cited by 18
SARS-CoV-2-specific neuropathology: fact or fiction?
Pröbstel, A., & Schirmer, L. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.10.006 · Cited by 18
“The presence of SARS-CoV-2 in neuroglial cells of the olfactory tract has been demonstrated by qRT-PCR [2–4,6–8] and by cell type-specific assays such as in situ hybridization [3,8] and immunohistochemistry [3–5] for virusspecific N (nucleocapsid) [2,4,7,8] and S (spike) [2–5,8] RNA transcripts and proteins.”
Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection
Weiss, J. J., Attuquayefio, T., White, E. B., Li, F., Herz, R. S., White, T. L., Campbell, M., Geng, B., Datta, R., Wyllie, A. L., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248025 · Cited by 17
“A growing body of evidence has demonstrated the potential for SARS-CoV-2 to infect neurons [26, 27], and our results lend support to the hypothesis that smell loss may be related to central nervous system infection by SARS-CoV-2, consistent with studies reporting MRI abnormalities in the olfactory bulb in a subset of…”
Result
Neurosensory Rehabilitation and Olfactory Network Recovery in Covid-19-related Olfactory Dysfunction
Chung, T. W., Zhang, H., Wong, F. K.-C., Sridhar, S., Chan, K., Cheng, V. C., Yuen, K., Hung, I. F., & Mak, H. K. (2021) · Brain Sciences · doi:10.3390/brainsci11060686 · Cited by 17
Pathomechanism and Management of Stroke in COVID-19: Review of Immunopathogenesis, Coagulopathy, Endothelial Dysfunction, and Downregulation of ACE2
Rahmawati, P. L., Tini, K., Susilawathi, N. M., Wijayanti, I. A. S., & Samatra, D. P. G. P. (2021) · Journal of Clinical Neurology · doi:10.3988/jcn.2021.17.2.155 · Cited by 17
Subtle vascular and astrocytic changes in the brain of coronavirus disease 2019 ( COVID ‐19) patients
Roşu, G. C., Mateescu, V. O., Simionescu, A., Istrate-Ofiţeru, A.-M., Curcă, G. C., Pirici, I., Mogoantă, L., Mîndrilă, I., Kumar‐Singh, S., Hostiuc, S., et al. (2022) · European Journal of Neurology · doi:10.1111/ene.15545 · Cited by 15
Bayesian machine learning analysis with Markov Chain Monte Carlo techniques for assessing characteristics and risk factors of Covid-19 in Erbil City-Iraq 2020–2021
Khidir, H. A., Etikan, İ., Kadir, D. H., Mahmood, N. H., & Sabetvand, R. (2023) · Alexandria Engineering Journal · doi:10.1016/j.aej.2023.07.052 · Cited by 19
Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review
Chen, T., Chang, C., Yang, C., Tsai, I., Wei, C., Yang, H.-W., & Yang, C. (2023) · Nutrients · doi:10.3390/nu15173802 · Cited by 17
Clinical significance of angiotensin-converting enzyme 2 receptors for severe acute respiratory syndrome coronavirus 2 (COVID-19) on peripheral small-fiber sensory neurons is unknown today
Oaklander, A. L. (2020) · Pain · doi:10.1097/j.pain.0000000000002050 · Cited by 16
“staining in the choroid plexus of 7 patients could have reflected circulating blood-borne virus.(36) The prolonged comas and slow brain recoveries are increasingly linked to nonspecific effects of long exposures to sedatives and suboptimal oxygenation for hours, days, or weeks.”
Background
Background to new treatments for COVID‐19, including its chronicity, through altering elements of the cytokine storm
Clark, I. A. (2020) · Reviews in Medical Virology · doi:10.1002/rmv.2210 · Cited by 15
Human pluripotent stem cell-based organoids and cell platforms for modelling SARS-CoV-2 infection and drug discovery
Giani, A. M., & Chen, S. (2021) · Stem Cell Research · doi:10.1016/j.scr.2021.102207 · Cited by 16
“However, several clinical studies reported mixed findings or did not detect SARS-CoV-2 presence in brain tissues (Schaller et al., 2020; Solomon et al., 2020).”
SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids
Trevisan, M., Riccetti, S., Sinigaglia, A., & Barzon, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052356 · Cited by 16
The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study
Aksenova, A. Y., Likhachev, I. V., Grishin, S. Y., & Galzitskaya, O. V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113502 · Cited by 16
Pain paths among post‐COVID‐19 condition subjects: A prospective cross‐sectional study with in‐person evaluation
Kubota, G. T., Soares, F. H. C., da Fonseca, A. S., Rosa, T. D. S., da Silva, V. A., Gouveia, G. R., Faria, V. G., da Cunha, P. H. M., Brunoni, A. R., Teixeira, M. J., et al. (2023) · European Journal of Pain · doi:10.1002/ejp.2094 · Cited by 18
Post‐ COVID ‐19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies
van Eijk, L. E., Tang, G., Bourgonje, A. R., den Dunnen, W. F. A., Hillebrands, J., & van Goor, H. (2025) · The Journal of Pathology · doi:10.1002/path.6443 · Cited by 16
“Early autopsy studies reported hypoxia-related injury with neuronal loss in the brains of acute COVID-19 patients [53,62].”
Experimental Models to Study COVID-19 Effect in Stem Cells
Chugh, R. M., Bhanja, P., Norris, A. J., & Saha, S. (2021) · Cells · doi:10.3390/cells10010091 · Cited by 16
Immune landscape and redox imbalance during neurological disorders in COVID-19
Thakur, A., Sharma, V., Averbek, S., Liang, L., Pandya, N., Kumar, G., Cili, A., & Zhang, K. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06102-6 · Cited by 15

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: Solomon, Isaac H.
Normandin, Erica
Bhattacharyya, Shamik
Mukerji, Shibani S.
Adams, Gordon
Hornick, Jason L.
Padera, Robert F.
Sabeti, Pardis
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
DOI: 10.1056/nejmc2019373
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 › Clinical 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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