Neuropathobiology of COVID-19: The Role for Glia
Open accessAbstract
SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has a brain neurotropism through binding to the receptor angiotensin-converting enzyme 2 expressed by neurones and glial cells, including astrocytes and microglia. Systemic infection which accompanies severe cases of COVID-19 also triggers substantial increase in circulating levels of chemokines and interleukins that compromise the blood-brain barrier, enter the brain parenchyma and affect its defensive systems, astrocytes and microglia. Brain areas devoid of a blood-brain barrier such as the circumventricular organs are particularly vulnerable to circulating inflammatory mediators. The performance of astrocytes and microglia, as well as of immune cells required for brain health, is considered critical in defining the neurological damage and neurological outcome of COVID-19. In this review, we discuss the neurotropism of SARS-CoV-2, the implication of neuroinflammation, adaptive and innate immunity, autoimmunity, as well as astrocytic and microglial immune and homeostatic functions in the neurological and psychiatric aspects of COVID-19. The consequences of SARS-CoV-2 infection during ageing, in the presence of systemic comorbidities, and for the exposed pregnant mother and foetus are also covered.
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Once the virus enters the CNS, it affects neurons, microglia, oligodendrocytes, and especially astrocytes, undermining neuron viability.
“Once the virus enters the CNS, it affects neurons, microglia, oligodendrocytes, and especially astrocytes, undermining neurons viability [17, 179, 180].”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [179]
In SARS-CoV-2, trans-nasal and trans-synaptic mechanisms might allow the virus to invade the olfactory bulb and brainstem, with both being possible initial sites for CNS invasion.
“In SARS-CoV-2, trans-nasal and trans-synaptic mechanisms might allow the virus to invade the olfactory bulb and brainstem, with both being the possible initial site for CNS invasion [179].”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [179]
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BackgroundCharacteristics of ischaemic stroke associated with COVID-19
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“Activation of astrogliotic programme instigates changes in gene expression, in astrocytic biochemistry, morphology and physiology with an ultimate goal of protecting the CNS against pathological lesion (Sofroniew, 2014, 2015; Pekny et al., 2016; Verkhratsky et al., 2017).”
BackgroundMicroglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission
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“Glial cells are thus orchestrating together the brain health and its response to systemic and local pathology (Pascual et al., 2012; Rothhammer et al., 2018; Jay et al., 2019; Vainchtein and Molofsky, 2020).”
BackgroundThe Brain’s Glymphatic System: Current Controversies
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BackgroundCoronavirus in pregnancy and delivery: rapid review
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BackgroundGuillain Barre syndrome associated with COVID-19 infection: A case report
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Self-citationThe 1918 Influenza Pandemic: Insights for the 21st Century
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BackgroundMicroglial subtypes: diversity within the microglial community
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BackgroundSelf-citationSublime Microglia: Expanding Roles for the Guardians of the CNS
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Astrocytes in physiological aging and Alzheimer’s disease
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Self-citationOligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair
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The impact of systemic infection on the progression of neurodegenerative disease
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“There is a well-defined link between systemic inflammation or major systemic diseases and cognitive deficits: systemic pathologies promote neurodegenerative process and accelerate cognitive decline (Perry et al., 2003).”
BackgroundDark microglia: A new phenotype predominantly associated with pathological states
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Self-citationMicroglial senescence: does the brain's immune system have an expiration date?
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“With ageing, microglia could further become dystrophic or senescent (Streit, 2006; Streit et al., 2009; Spittau, 2017), unable then to perform efficiently their critical surveillance, immune and physiological roles.”
BackgroundZhou, Z., Kang, H., Li, S., & Zhao, X. (2020) · Journal of Neurology · doi:10.1007/s00415-020-09929-7 · Cited by 397 · see citing works
Possible Central Nervous System Infection by SARS Coronavirus
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“The SARS-CoV-2 belongs to the group 2B of β-coronavirus family, several members of which demonstrate neurotropism (Lau et al., 2004; Xu et al., 2005; Steardo et al., 2020a; Zhou et al., 2020).”
BackgroundSystemic Immune Activation Leads to Neuroinflammation and Sickness Behavior in Mice
Biesmans, S., Meert, T. F., Bouwknecht, J. A., Acton, P. D., Davoodi, N., Haes, P. D., Kuijlaars, J., Langlois, X., Matthews, L. J. R., Donck, L. V., et al. (2013) · Mediators of Inflammation · doi:10.1155/2013/271359 · Cited by 382 · see citing works
Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19
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“For example, plasma concentration of the astrogliosis marker GFAP in patients with moderate to severe COVID-19 is significantly increased (Kanberg et al., 2020).”
BackgroundNeuroinfection may contribute to pathophysiology and clinical manifestations of COVID‐19
Steardo, L., Steardo, L., Zorec, R., & Verkhratsky, A. (2020) · Acta Physiologica · doi:10.1111/apha.13473 · Cited by 367 · see citing works
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Self-citationMicroglia phagocytose myelin sheaths to modify developmental myelination
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“More recently, microglia were also found to contribute to developmental myelination and remyelination (for instance in multiple sclerosis) through the release of trophic factors regulating oligodendrocyte progenitor’s formation and maturation, as well as removal of myelin debris required for remyelination (Domingues e…”
BackgroundVerkhratsky, A., Parpura, V., Vardjan, N., & Zorec, R. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-9913-8_3 · Cited by 315 · see citing works
Self-citationSARS-CoV-2: virus dynamics and host response
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Microglia, Lifestyle Stress, and Neurodegeneration
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“Various challenges from the external environment to which microglia respond, psychological or physiological, are associated with epigenetic, metabolic, proteomic, transcriptomic, densitometric, morphological/ultrastructural changes of these cells that can result in compromised molecular and cellular functions, normall…”
BackgroundSelf-citationBlood-brain barrier permeability and physical exercise
Małkiewicz, M. A., Szarmach, A., Sabisz, A., Cubała, W. J., Szurowska, E., & Winklewski, P. J. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1403-x · Cited by 276 · cited 1× · see citing works
“The disruption of the BBB, which is exacerbated by stress, sleep deprivation, metabolic syndrome, vascular comorbidities, as well as ageing, for instance (Małkiewicz et al., 2019), allows CNS entrance of pathological agents, including viral particles among other”
BackgroundThe influence of pain, agitation, and their management on the immature brain
McPherson, C. C., Miller, S. P., El‐Dib, M., Massaro, A. N., & Inder, T. E. (2020) · Pediatric Research · doi:10.1038/s41390-019-0744-6 · Cited by 267 · cited 1× · see citing works
“With the increase of preterm births and admissions to the neonatal intensive care unit, COVID-19 may add to the perinatal stress that is known to be deleterious on brain development (Schepanski et al., 2018; McPherson et al., 2020).”
BackgroundBrain changes in a maternal immune activation model of neurodevelopmental brain disorders
Bergdolt, L., & Dunaevsky, A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.002 · Cited by 266 · see citing works
Single-nucleus RNA-seq identifies Huntington disease astrocyte states
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“Astrogliotic programme is flexible and is disease-specific; numerous investigations demonstrating remarkable diversity of reactive astrocytic phenotypes, incompatible with the much popularised A1/A2 dichotomy (Grubman et al., 2019; Henrik Heiland et al., 2019; Al-Dalahmah et al., 2020; Wheeler et al., 2020).”
BackgroundThe circumventricular organs: An atlas of comparative anatomy and vascularization
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BackgroundAging Microglia—Phenotypes, Functions and Implications for Age-Related Neurodegenerative Diseases
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“With ageing, microglia could further become dystrophic or senescent (Streit, 2006; Streit et al., 2009; Spittau, 2017), unable then to perform efficiently their critical surveillance, immune and physiological roles.”
BackgroundEarly postmortem brain MRI findings in COVID-19 non-survivors
Coolen, T., Lolli, V. E., Sadeghi, N., Rovaï, A., Trotta, N., Taccone, F. S., Créteur, J., Henrard, S., Goffard, J., Dewitte, O., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000010116 · Cited by 256 · see citing works
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Self-citation1918 INFLUENZA, ENCEPHALITIS LETHARGICA, PARKINSONISM
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Neurological Disease as a Failure of Brain-Immune Crosstalk: The Multiple Faces of Neuroinflammation
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Inflammation and the neurovascular unit in the setting of focal cerebral ischemia
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Stratification of astrocytes in healthy and diseased brain
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“Moreover, the detrimental consequences of early-life stress exposure on microglial maturation are multiple and thus would alter profoundly microglial physiological activities during development (Paolicelli and Ferretti, 2017).”
BackgroundMorphology of Microglia Across Contexts of Health and Disease
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“Indeed, many epidemiological studies suggest that early-life adversity can be associated with an increased occurrence of neurodevelopmental, neurological or neuropsychiatric disorders later in life (Halligan et al., 2007; Lupien et al., 2009; Knuesel et al., 2014).”
BackgroundExosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis
Fleshner, M., & Crane, C. R. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.08.002 · Cited by 212 · cited 1× · see citing works
“Similarly, microglia respond to BBB disruption and DAMPs presence by increasing their phagocytic capacity and release of proinflammatory mediators, together associated with their reactivity (Fleshner and Crane, 2017).”
BackgroundMicroglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
Tay, T. L., Béchade, C., D’Andrea, I., St‐Pierre, M., Henry, M. S., Roumier, A., & Tremblay, M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00421 · Cited by 211 · see citing works
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“Similarly, the clinical presentation of COVID-19 frequently includes neurological symptoms and neuropathologies such as acute ischemic stroke, meningitis/encephalitis, acute necrotising haemorrhagic encephalopathy, acute Guillain–Barré syndrome (Beyrouti et al., 2020; Dixon et al., 2020; Oxley et al., 2020; Paterson e…”
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Self-citationGuillain-Barré syndrome following COVID-19: new infection, old complication?
Padroni, M., Mastrangelo, V., Asioli, G. M., Pavolucci, L., Abu‐Rumeileh, S., Piscaglia, M. G., Querzani, P., Callegarini, C., & Foschi, M. (2020) · Journal of Neurology · doi:10.1007/s00415-020-09849-6 · Cited by 199 · cited 2× · see citing works
“While the consequences of SARS-CoV-2 on cells of the oligodendrocytic lineage responsible for myelination remain unclear, COVID-19 resulted in several cases of demyelinating Guillain-Barré syndrome (Arnaud et al., 2020; Padroni et al., 2020; Sedaghat and Karimi, 2020; Tiet and AlShaikh, 2020; Zhao et al., 2020) and Mi…”
BackgroundMETHYLDOPA AND HqMOLYTIC ANqMIA
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Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions
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“More recently, microglia were also found to contribute to developmental myelination and remyelination (for instance in multiple sclerosis) through the release of trophic factors regulating oligodendrocyte progenitor’s formation and maturation, as well as removal of myelin debris required for remyelination (Domingues e…”
BackgroundWhen encephalitogenic T cells collaborate with microglia in multiple sclerosis
Dong, Y., & Yong, V. W. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0253-6 · Cited by 160 · cited 1× · see citing works
“As key components in compartmentalised immune responses of the CNS, both astrocytes and microglia contribute to CNS autoimmunity by regulating autoantigen-presentation, BBB or blood-cerebrospinal fluid (CSF) barrier breakdown and autoantibody leakage, as well as adaptive T- or B- cell activation for autoantibody produ…”
BackgroundLi, Y., Fu, L., Gonzales, D. M., & Lavi, E. (2004) · Journal of Virology · doi:10.1128/jvi.78.7.3398-3406.2004 · Cited by 158 · cited 1× · see citing works
“In experimental mouse models of infection with coronavirus, MHV-59A resulted in encephalitis with prominent astrogliosis and induction of astroglial synthesis of cytokines; moreover, neurovirulence correlated with the cytokine response (Li et al., 2004).”
BackgroundCovid-19: death rate is 0.66% and increases with age, study estimates
Mahase, E. (2020) · BMJ · doi:10.1136/bmj.m1327 · Cited by 152 · cited 1× · see citing works
“Ageing increases the vulnerability to SARS-CoV-2 and severity of COVID-19; the death rate in old population attained ∼10% compare to overall death rate of 0.66% (Mahase, 2020).”
BackgroundInfluentialEpigenetics Control Microglia Plasticity
Cheray, M., & Joseph, B. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00243 · Cited by 151 · see citing works
Angiotensin-Converting Enzyme 2: Central Regulator for Cardiovascular Function
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Neuroimmunological Implications of AQP4 in Astrocytes
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A Developmental Analysis of Juxtavascular Microglia Dynamics and Interactions with the Vasculature
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Astroglia dynamics in ageing and Alzheimer's disease
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“However, several questions remain unaddressed regarding the impact of MIA on neuroinflammation and microglia especially during brain development in the offspring (Madore et al., 2016).”
BackgroundSelf-citationAstroglial atrophy in Alzheimer’s disease
Verkhratsky, A., Rodriguez, J. J., Pivoriūnas, A., Zorec, R., & Semyanov, A. V. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02310-2 · Cited by 140 · cited 1× · see citing works
“Brain as an organ sustains ageing remarkably well; cognitive excellence sustains into ages when physical abilities are remarkably affected (Verkhratsky, 2019).”
BackgroundSelf-citationVanzulli, I., Papanikolaou, M., De-La-Rocha, I. C., Pieropan, F., Rivera, A. D., Gomez-Nicola, D., Verkhratsky, A., Rodríguez, J. J., & Butt, A. M. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.05.016 · Cited by 130 · see citing works
Self-citationSchepanski, S. N., Buß, C., Hanganu‐Opatz, I. L., & Arck, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02186 · Cited by 129 · see citing works
Purves-Tyson, T. D., Weber‐Stadlbauer, U., Richetto, J., Rothmond, D. A., Labouesse, M. A., Polesel, M., Robinson, K., Weickert, C. S., & Meyer, U. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0434-0 · Cited by 125 · see citing works
Burman, W. J., Cohn, D. L., Reves, R. R., & Wilson, M. L. (1995) · Clinical Infectious Diseases · doi:10.1093/clinids/20.3.564 · Cited by 122 · see citing works
Matar, R., Alrahmani, L., Monzer, N., Debiane, L. G., Berbari, E. F., Fares, J., Fitzpatrick, F., & Murad, M. H. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa828 · Cited by 117 · cited 3× · see citing works
“Most of the in utero exposed to COVID-19 were delivered by neonates caesarean section (Di Mascio et al., 2020; Matar et al., 2020), while it has been shown that caesarean section vs.”
BackgroundGlial Asthenia and Functional Paralysis
Verkhratsky, A., Marutle, A., Rodríguez-Arellano, J. J., & Nordberg, A. K. (2014) · The Neuroscientist · doi:10.1177/1073858414547132 · Cited by 112 · see citing works
Self-citationThe glial perspective of autism spectrum disorders
Zeidán‐Chuliá, F., Salmina, A. B., Malinovskaya, N. A., Noda, M., Verkhratsky, A., & Moreira, J. C. F. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.008 · Cited by 111 · see citing works
Self-citationMicroglial interactions with the neurovascular system in physiology and pathology
Zhao, X., Eyo, U. B., Murugan, M., & Wu, L. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22576 · Cited by 109 · cited 1× · see citing works
“While microglia are associated with the regulation of vascular remodelling, blood flow and BBB maintenance, the molecular mechanisms underlying these emerging functions are largely undetermined (Zhao et al., 2018; Halder and Milner, 2019; Haruwaka et al., 2019).”
BackgroundMolecular mimicry between SARS-CoV-2 and respiratory pacemaker neurons
Lucchese, G., & Flöel, A. (2020) · Autoimmunity Reviews · doi:10.1016/j.autrev.2020.102556 · Cited by 109 · see citing works
Verkhratsky, A., Augusto‐Oliveira, M., Pivoriūnas, A., Popov, A., Brazhe, A., & Semyanov, A. V. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02465-3 · Cited by 108 · see citing works
Self-citationSystemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects
Cardoso, F. L., Herz, J., Fernandes, A., Rocha, J., Sepodes, B., Brito, M. A., McGavern, D. B., & Brites, D. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0299-3 · Cited by 103 · see citing works
Astroglial Calcium Signaling in Aging and Alzheimer's Disease
Verkhratsky, A. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035188 · Cited by 99 · cited 1× · see citing works
“Brain as an organ sustains ageing remarkably well; cognitive excellence sustains into ages when physical abilities are remarkably affected (Verkhratsky, 2019).”
BackgroundSelf-citationSerum S100B protein as a marker of severity in Covid-19 patients
Aceti, A., Margarucci, L. M., Scaramucci, E., Orsini, M., Salerno, G., Sante, G. D., Gianfranceschi, G., Liddo, R. D., Valeriani, F., Ria, F., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-75618-0 · Cited by 98 · cited 1× · see citing works
“Serum levels of the astrocytic calcium binding protein S100b, associated with an increased BBB permeability, significantly correlate with COVID-19 disease severity, inflammationmarkers (ferritin, C-Reactive Protein, procalcitonin), and organ damage markers (alanine aminotransferase, creatinine) (Aceti et al., 2020).”
BackgroundEffects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons
Tekin, H., Simmons, S., Cummings, B. B., Gao, L. A., Adiconis, X., Hession, C. C., Ghoshal, A., Dionne, D. A., Choudhury, S., Yesilyurt, V., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0219-9 · Cited by 97 · cited 1× · see citing works
“, 2015) but also by both neurons and neuroglial cells (Xia and Lazartigues, 2010; Gowrisankar and Clark, 2016; Tekin et al., 2018; Nemoto et al., 2020).”
BackgroundTREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment
Jay, T. R., von Saucken, V. E., Muñoz, B., Codocedo, J. F., Atwood, B. K., Lamb, B. T., & Landreth, G. E. (2019) · Glia · doi:10.1002/glia.23664 · Cited by 97 · cited 1× · see citing works
“Glial cells are thus orchestrating together the brain health and its response to systemic and local pathology (Pascual et al., 2012; Rothhammer et al., 2018; Jay et al., 2019; Vainchtein and Molofsky, 2020).”
BackgroundA critical role for microglia in maintaining vascular integrity in the hypoxic spinal cord
Halder, S. K., & Milner, R. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1912178116 · Cited by 97 · cited 1× · see citing works
“While microglia are associated with the regulation of vascular remodelling, blood flow and BBB maintenance, the molecular mechanisms underlying these emerging functions are largely undetermined (Zhao et al., 2018; Halder and Milner, 2019; Haruwaka et al., 2019).”
BackgroundCranial neuropathies and COVID-19
Costello, F., & Dalakas, M. C. (2020) · Neurology · doi:10.1212/wnl.0000000000009921 · Cited by 95 · see citing works
Gowrisankar, Y. V., & Clark, M. A. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13641 · Cited by 92 · cited 2× · see citing works
“In particular, ACE2 populates the circumventricular organs (CVOs), the subfornical organ, paraventricular nucleus (PVN), nucleus of the tractus solitarius (NTS), and rostral ventrolateral medulla (Xia and Lazartigues, 2010; Gowrisankar and Clark, 2016).”
BackgroundCrisp, S. J., Kullmann, D. M., & Vincent, A. C. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2015.27 · Cited by 92 · see citing works
COVID-19 Infection and Neurological Complications: Present Findings and Future Predictions
Beghi, E., Feigin, V. L., Caso, V., Santalucia, P., & Logroscino, G. (2020) · Neuroepidemiology · doi:10.1159/000508991 · Cited by 85 · see citing works
Post SARS-CoV-2 Guillain-Barré syndrome
Arnaud, S., Budowski, C., Tin, S. N. W., & Degos, B. (2020) · Clinical Neurophysiology · doi:10.1016/j.clinph.2020.05.003 · Cited by 84 · cited 2× · see citing works
“While the consequences of SARS-CoV-2 on cells of the oligodendrocytic lineage responsible for myelination remain unclear, COVID-19 resulted in several cases of demyelinating Guillain-Barré syndrome (Arnaud et al., 2020; Padroni et al., 2020; Sedaghat and Karimi, 2020; Tiet and AlShaikh, 2020; Zhao et al., 2020) and Mi…”
BackgroundInfection Hospitalization Increases Risk of Dementia in the Elderly*
Tate, J. A., Snitz, B. E., Alvarez, K., Nahin, R. L., Weissfeld, L. A., López, O. L., Angus, D. C., Shah, F. A., Ives, D. G., Fitzpatrick, A. L., et al. (2013) · Critical Care Medicine · doi:10.1097/ccm.0000000000000123 · Cited by 80 · cited 1× · see citing works
“, with flu and pneumonia) can render individuals more prone to developing depression, psychosis, delirium, Parkinson’s disease and other forms of dementia, among other conditions, and even more so with a chronic stress life history (Tate et al., 2014; Bisht et al., 2018).”
BackgroundStenzel, W., Soltek, S., Schlüter, D., & Deckert, M. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.6.631 · Cited by 74 · cited 1× · see citing works
“For example, suppression of astrogliosis in glial fibrillary acidic protein (GFAP) knockout mice substantially facilitates the penetration of Staphylococcus aureus or Toxoplasma gondii into the brain, which results in vasculitis, purulent ventriculitis and severe brain oedema (Stenzel et al., 2004).”
BackgroundMicroglia are continuously activated in the circumventricular organs of mouse brain
Takagi, S., Furube, E., Nakano, Y., Morita, M., & Miyata, S. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.10.008 · Cited by 69 · cited 1× · see citing works
“, 2005) and express markers that suggest they are ready to cope with invading agents using phagocytosis and the release of various mediators such as pro-inflammatory cytokines (Takagi et al., 2019).”
BackgroundAstrocytes to the rescue! Glia limitans astrocytic endfeet control CNS inflammation
Quintana, F. J. (2017) · Journal of Clinical Investigation · doi:10.1172/jci95769 · Cited by 66 · cited 1× · see citing works
“This parenchymal wall is represented by the glia limitans externa (bordering the pia matter) and glia limitans perivascularis (plastering the intra-parenchymal blood vessels), which are formed by astroglial endfeet (Mathiisen et al., 2010; Quintana, 2017).”
BackgroundJoost, E., Jordão, M. J. C., Mages, B., Prinz, M., Bechmann, I., & Krueger, M. (2019) · Brain Structure and Function · doi:10.1007/s00429-019-01834-8 · Cited by 65 · see citing works
Role of Glia in the Regulation of Sleep in Health and Disease
Garofalo, S., Picard, K., Limatola, C., Nadjar, A., Pascual, O., & Tremblay, M. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190022 · Cited by 63 · see citing works
Self-citationShedding Light on the Dark Side of the Microglia
St‐Pierre, M., Šimončičová, E., Bögi, E., & Tremblay, M. (2020) · ASN NEURO · doi:10.1177/1759091420925335 · Cited by 63 · cited 1× · see citing works
“While dark microglia’s consequences on the BBB are still elusive, they make extensive phagocytic interactions with synapses, suggesting their implication in pathological remodelling of neuronal circuits (Bisht et al., 2016; St.-Pierre et al., 2020).”
BackgroundSelf-citationThion, M. S., Mosser, C., Férézou, I., Grisel, P., Baptista, S., Low, D., Ginhoux, F., Garel, S., & Audinat, É. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.086 · Cited by 62 · see citing works
Tay, T. L., Carrier, M., & Tremblay, M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-9913-8_6 · Cited by 61 · cited 1× · see citing works
“Microglial surveillance of the parenchyma, but also contribution to the regulation of neuronal activity, myelination, as well as synaptic plasticity, and cognition, among others essential physiological roles (Salter and Beggs, 2014; Tay et al., 2019), could be reduced or compromised as a result of their resource-consu…”
BackgroundSelf-citationDoes SARS-CoV-2 Trigger Stress-Induced Autoimmunity by Molecular Mimicry? A Hypothesis
Cappello, F., Marino, A., Dieli, F., de Macario, E. C., & Macario, A. J. L. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072038 · Cited by 60 · cited 1× · see citing works
“Autoimmune responses can be induced by viral pathogens, possibly through “molecular mimicry” (Cappello et al., 2020; Lucchese and Floel, 2020) and breakdown of Frontiers in Cellular Neuroscience | www.frontiersin.org 7 November 2020 | Volume 14 | Article 592214 physiological barriers (Alam et al.,…”
BackgroundAlam, S. B., Willows, S. D., Kulka, M., & Sandhu, J. K. (2020) · European Journal of Neurology · doi:10.1111/ene.14442 · Cited by 60 · cited 1× · see citing works
“…2020) and breakdown of Frontiers in Cellular Neuroscience | www.frontiersin.org 7 November 2020 | Volume 14 | Article 592214 physiological barriers (Alam et al., 2020; Buzhdygan et al., 2020), in which unleashed autoimmune cells cross-react to exposed autoantigens, hence causing autoimmune…”
BackgroundDelirium as a presenting feature in COVID-19: Neuroinvasive infection or autoimmune encephalopathy?
Hosseini, A. A., Shetty, A. K., Sprigg, N., Auer, D. P., & Constantinescu, C. S. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.012 · Cited by 59 · cited 2× · see citing works
“Currently, although the involvement of neurotropism and autoimmunity was suggested for SARS-CoV-2 and COVID19 neuropathies (Costello and Dalakas, 2020; Hosseini et al., 2020), there has been no solid clinical or preclinical evidence of autoantibodies positively detected in the CSF or blood of COVID-19 sufferers to sup…”
BackgroundThe immunopathogenesis of multiple sclerosis and Guillain-Barré syndrome
Giovannoni, G., & Hartung, H. (1996) · Current Opinion in Neurology · doi:10.1097/00019052-199606000-00004 · Cited by 57 · cited 1× · see citing works
“As an immune privileged site, nervous tissue is most vulnerable for autoimmune attack, which instigates various neurological and psychiatric diseases, such as the demyelinating multiple sclerosis and Guillain-Barré syndrome (Giovannoni and Hartung, 1996), as well as the recently depicted autoimmune encephalitis (Dalma…”
BackgroundNemoto, W., Yamagata, R., Nakagawasai, O., Nakagawa, K., Hung, W.-Y., Fujita, M., Tadano, T., & Tan–No, K. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.172950 · Cited by 51 · cited 1× · see citing works
“, 2015) but also by both neurons and neuroglial cells (Xia and Lazartigues, 2010; Gowrisankar and Clark, 2016; Tekin et al., 2018; Nemoto et al., 2020).”
BackgroundDevita, M., Bordignon, A., Sergi, G., & Coin, A. (2021) · Aging Clinical and Experimental Research · doi:10.1007/s40520-020-01637-6 · Cited by 48 · cited 1× · see citing works
“Similarly, neurological and cognitive deficits seem to be on increase in elderly with COVID-19 history (Devita et al., 2020; Varatharaj et al., 2020).”
BackgroundGuillain-Barré syndrome associated with COVID-19 infection: a case from the UK
Tiet, M. Y., & AlShaikh, N. (2020) · BMJ Case Reports · doi:10.1136/bcr-2020-236536 · Cited by 48 · cited 2× · see citing works
“While the consequences of SARS-CoV-2 on cells of the oligodendrocytic lineage responsible for myelination remain unclear, COVID-19 resulted in several cases of demyelinating Guillain-Barré syndrome (Arnaud et al., 2020; Padroni et al., 2020; Sedaghat and Karimi, 2020; Tiet and AlShaikh, 2020; Zhao et al., 2020) and Mi…”
BackgroundMicroglia: The Brain's First Responders.
Bilbo, S. D., & Stevens, B. (2017) · Europe PMC (PubMed Central) · Cited by 47 · see citing works
Thoughts on COVID-19 and autoimmune diseases
Askanase, A., Khalili, L., & Buyon, J. P. (2020) · Lupus Science & Medicine · doi:10.1136/lupus-2020-000396 · Cited by 47 · cited 1× · see citing works
“Patients already affected by autoimmune diseases are, arguably, more susceptible for developing cytokine storm that can initiate or exacerbate autoimmune neurology (Askanase et al., 2020).”
BackgroundPan, R., Zhang, Q., Anthony, S. M., Zhou, Y., Zou, X., Cassell, M. D., & Perlman, S. M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003432117 · Cited by 47 · cited 2× · see citing works
“Studies using other coronaviruses, such as herpes virus, revealed that cells of the oligodendrocytic lineage can be infected, yet they survived and contributed to sustaining neuroinflammation (Pan et al., 2020).”
BackgroundMethodMinami, T., Okazaki, J., Kawabata, A., KAWAKI, H., Okazaki, Y., & Tohno, Y. (1998) · Environmental Toxicology and Pharmacology · doi:10.1016/s1382-6689(97)10004-7 · Cited by 45 · see citing works
Cesarean Delivery Impacts Infant Brain Development
Deoni, S., Adams, S. H., Li, X., Badger, T. M., Pivik, R. T., Glasier, C. M., Ramakrishnaiah, R. H., Rowell, A. C., & Ou, X. (2018) · American Journal of Neuroradiology · doi:10.3174/ajnr.a5887 · Cited by 43 · cited 1× · see citing works
“vaginal deliveries may seriously impact infant immune maturation with consequences on the brain development (Curran et al., 2015a,b; Deoni et al., 2019).”
BackgroundGrotta, J. C., Jacobs, T. P., Koroshetz, W. J., & Moskowitz, M. A. (2008) · Stroke · doi:10.1161/strokeaha.107.510776 · Cited by 39 · cited 1× · see citing works
“All these structures are highly vascularised and they lack the blood-brain-barrier (BBB) (Duvernoy and Risold, 2007), which is formed by the endothelial cells lining brain vessels, together with pericytes, astrocytes, microglia, and extracellular components such as the basement membrane that together form the neurovas…”
BackgroundKriaučiūnaitė, K., Kaušylė, A., Pajarskienė, J., Tunaitis, V., Lim, D., Verkhratsky, A., & Pivoriūnas, A. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00871-w · Cited by 39 · cited 1× · see citing works
“Furthermore, astrocytes regulate the permeability of BBB through influencing expression of tight junctions in endothelial cells layer (Kriauciunaite et al., 2020).”
BackgroundSelf-citationWu, H., Brown, E. V., Acharya, N. K., Appelt, D. M., Marks, A., Nagele, R. G., & Venkataraman, V. (2016) · Brain Research · doi:10.1016/j.brainres.2016.02.026 · Cited by 35 · see citing works
Endocytic uptake of SARS-CoV-2: the critical roles of pH, Ca2+, and NAADP
Petersen, O. H., Gerasimenko, O. V., & Gerasimenko, J. V. (2020) · Function · doi:10.1093/function/zqaa003 · Cited by 34 · cited 1× · see citing works
“The actual invasion occurs through endocytosis controlled by endosomal proton pump, and by NAADP-sensitive intracellular two-pore channel 2 (TPC2) (Petersen et al., 2020) (Figure 1).”
BackgroundMaternal viral infection causes global alterations in porcine fetal microglia
Antonson, A. M., Lawson, M. A., Caputo, M. P., Matt, S. M., Leyshon, B. J., & Johnson, R. W. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1817014116 · Cited by 32 · cited 1× · see citing works
“As previously characterised in other maternal infection models, MIA-exposed microglia increase their expression of MHC class II that is coupled with an altered microglial transcriptome and with a reduced phagocytic and chemotactic activity (Mattei et al., 2017; Antonson et al., 2019; Purves-Tyson et al., 2019; Thion e…”
BackgroundAutoantibodies against N-methyl-d-aspartate receptor 1 in health and disease
Ehrenreich, H. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000546 · Cited by 30 · cited 1× · see citing works
“On the other hand, autoantibodies are not all pathogenic, can even circulate in healthy subjects (Ehrenreich, 2018), and therefore increased autoimmunity may not be specific for COVID-19.”
BackgroundTachibana, M., Mohri, I., Hirata, I., Kuwada, A., Kimura-Ohba, S., Kagitani-Shimono, K., Fushimi, H., Inoue, T., Shiomi, M., Kakuta, Y., et al. (2019) · Brain and Development · doi:10.1016/j.braindev.2018.07.008 · Cited by 28 · cited 1× · see citing works
“At the same time, viral infections may damage astrocytes: for example, a severe astrodegeneration in the form of clasmatodendrosis, an astrocytic morphological change characterised by fragmentation of the distal processes and swollen cell bodies, has been identified in the brains of influenza-associated encephalopathy…”
BackgroundDomingues, H. S., Portugal, C. C., Socodato, R., & Relvas, J. B. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00079 · Cited by 25 · cited 1× · see citing works
“…and remyelination (for instance in multiple sclerosis) through the release of trophic factors regulating oligodendrocyte progenitor’s formation and maturation, as well as removal of myelin debris required for remyelination (Domingues et al., 2016; Hughes and Appel, 2020; Traiffort et al., 2020).”
BackgroundCOVID-19: A Perspective from Clinical Neurology and Neuroscience
Pero, A., Ng, S., & Cai, D. (2020) · The Neuroscientist · doi:10.1177/1073858420946749 · Cited by 13 · cited 1× · see citing works
“Similarly, the clinical presentation of COVID-19 frequently includes neurological symptoms and neuropathologies such as acute ischemic stroke, meningitis/encephalitis, acute necrotising haemorrhagic encephalopathy, acute Guillain–Barré syndrome (Beyrouti et al., 2020; Dixon et al., 2020; Oxley et al., 2020; Paterson e…”
BackgroundEPIDEMIC ENCEPHALO-MYELITIS AND INFLUENZA.
Crookshank, F. G. (1919) · The Lancet · doi:10.1016/s0140-6736(01)25193-9 · Cited by 12 · cited 1× · see citing works
“The clinical presentation of Spanish flu included neurological and neuropsychiatric symptoms, both acute and delayed; the H1N1 virus was arguably linked to the still mysterious encephalitis lethargica, which alone claimed 500,000 death in 1920s (Crookshank, 1919; Ravenholt and Foege, 1982).”
BackgroundDevelopment of residential care services facilitated for persons with dementia in Norway
Kirkevold, Ø., Eek, A., & Engedal, K. (2012) · Aging Clinical and Experimental Research · doi:10.1007/bf03325351 · Cited by 11 · see citing works
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Microglia states and nomenclature: A field at its crossroads
Paolicelli, R. C., Sierra, A., Stevens, B., Tremblay, M.-E., Aguzzi, A., Ajami, B., Amit, I., Audinat, E., Bechmann, I., Bennett, M., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.020 · Cited by 1,973 · see citing works
Self-citationAstrocytes in human central nervous system diseases: a frontier for new therapies
Verkhratsky, A., Butt, A., Li, B., Illes, P., Zorec, R., Semyanov, A., Tang, Y., & Sofroniew, M. V. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01628-9 · Cited by 428 · see citing works
Self-citationPost-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment
Mazza, M. G., Palladini, M., Poletti, S., & Benedetti, F. (2022) · CNS Drugs · doi:10.1007/s40263-022-00931-3 · Cited by 233 · see citing works
“Accordingly, increased microglial activation in association with high levels of IL-6 and TNF-α have been observed in MDD episodes [82], whereas microglia activation has been implicated in both acute and chronic neurological complications of COVID-19 [83], and increased microglial activation has been demonstrated in po…”
BackgroundS1-Leitlinie Post-COVID/Long-COVID
Koczulla, A. R., Ankermann, T., Behrends, U., Berlit, P., Böing, S., Brinkmann, F., Franke, C., Glöckl, R., Gogoll, C., Hummel, T. R., et al. (2021) · Pneumologie · doi:10.1055/a-1551-9734 · Cited by 161 · see citing works
“[150] Tremblay ME, Madore C, Bordeleau M et al.”
BackgroundCould SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?
Theoharides, T. C. (2022) · Molecular Neurobiology · doi:10.1007/s12035-021-02696-0 · Cited by 154 · see citing works
“Increasing evidence indicates the involvement of neuroinflammation [71, 88, 89] that may damage brain blood vessels [90, 91], as well as brain cells [88, 92, 93], possibly via activation of microglia [94, 95] and mast cells [96].”
BackgroundNeurological complications and infection mechanism of SARS-CoV-2
Wan, D., Du, T., Hong, W., Chen, L., Que, H., Lu, S., & Peng, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00818-7 · Cited by 132 · 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
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
Koczulla, A. R., Ankermann, T., Behrends, U., Berlit, P., Berner, R., Böing, S., Brinkmann, F., Frank, U., Franke, C., Glöckl, R., et al. (2022) · Pneumologie · doi:10.1055/a-1946-3230 · Cited by 111 · see citing works
“[281] Tremblay ME, Madore C, Bordeleau M et al.”
BackgroundLong COVID and neuropsychiatric manifestations (Review)
Efstathiou, V., Stefanou, M., Demetriou, M., Siafakas, N., Makris, M. P., Tsivgoulis, G. K., Zoumpourlis, V., Kympouropoulos, S. P., Tsoporis, J. N., Spandidos, D. A., et al. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11290 · Cited by 113 · see citing works
“Patients affected by ‘long COVID’ include also those who initially had mild or asymptomatic disease, pointing to residual effects that involve multiple organ systems, including the peripheral and central nervous system (CNS) (23,31,32).”
InfluentialDamiano, R. F., Guedes, B. F., de Rocca, C. C., de Pádua Serafim, A., Castro, L. H. M., Munhoz, C. D., Nitrini, R., Filho, G. B., Miguel, E. C., Lucchetti, G., et al. (2022) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-021-01286-4 · Cited by 98 · see citing works
“Once the virus enters the CNS, it affects neurons, microglia, oligodendrocytes, and especially astrocytes, undermining neurons viability [17, 179, 180].”
BackgroundBoroujeni, M. E., Simani, L., Bluyssen, H. A. R., Samadikhah, H. R., Benisi, S. Z., Hassani, S., Dilmaghani, N. A., Fathi, M., Vakili, K. G., Mahmoudiasl, G., et al. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00111 · Cited by 79 · see citing works
Petersen, M., Nägele, F. L., Mayer, C., Schell, M., Petersen, E., Kühn, S., Gallinat, J., Fiehler, J., Pasternak, O., Matschke, J., et al. (2023) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2217232120 · Cited by 28 · see citing works
“Evidence of neuroinflammation was reported in histopathological and clinical studies of COVID-19 patients: virus invasion (24, 25), activation of glial cells (9, 26, 27), and a cytokine response in the cerebrospinal fluid accompanying neurological and psychiatric COVID-19 symptoms (10).”
Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?
Verkhratsky, A., Li, Q., Melino, S., Melino, G., & Shi, Y. (2020) · Biology Direct · doi:10.1186/s13062-020-00282-3 · Cited by 78 · see citing works
Self-citationTheoharides, T. C., & Kempuraj, D. (2023) · Cells · doi:10.3390/cells12050688 · Cited by 81 · see citing works
“We advance the premise that brain perivascular inflammation is a critical pathogenetic factor in long COVID mostly due to SARS-CoV-2 activating brain mast cells and microglia resulting in the release of inflammatory, neurotoxic, and vasoactive mediators [60,61].”
BackgroundElucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection
Pacheco‐Herrero, M., Soto-Rojas, L. O., Harrington, C. R., Flores-Martinez, Y. M., Villegas-Rojas, M. M., León-Aguilar, A. M., Martínez-Gómez, P. A., Campa-Córdoba, B. B., Apátiga-Pérez, R., Corniel-Taveras, C. N., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.660087 · Cited by 69 · see citing works
Neurotropic Viruses, Astrocytes, and COVID-19
Verdev, P. T., Potokar, M., Kolenc, M., Korva, M., Avšič‐Županc, T., Zorec, R., & Jorgačevski, J. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.662578 · Cited by 65 · see citing works
“This phenomenon is typical for severe COVID-19 pathogenesis, which eventually leads to BBB alterations and neuroinflammation (Najjar et al., 2020; Tremblay et al., 2020).”
BackgroundAwogbindin, I. O., Ben‐Azu, B., Olusola, B. A., Akinluyi, E. T., Adeniyi, P. A., Paolo, T. D., & Tremblay, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.670298 · Cited by 60 · see citing works
“Despite their CNS homeostasis and neuronal cell functions, microglia and astrocytes are mainly involved in the protective immune responses during neuroinflammation (Facci et al., 2018; Jha et al., 2019; Tremblay et al., 2020).”
BackgroundSelf-citationDid the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy?
Azar, G., Bonnin, S., Vasseur, V., Faure, C., Salviat, F., Vignal‐Clermont, C., Titah, C., Farès, S., Boulanger-Scemama, É., Derrien, S., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10215038 · Cited by 59 · see citing works
Proust, A. M., Queval, C. J., Harvey, R., Adams, L., Bennett, M., & Wilkinson, R. J. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02861-3 · Cited by 57 · see citing works
SARS-CoV-2 involvement in central nervous system tissue damage
Sabra, M., Kobeissy, F. H., Bizri, M., Haidar, M. A., Shakkour, Z., Reslan, M. A., Al-Haj, N., Chamoun, P., Habashy, K. J., Kaafarani, H., et al. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.327323 · Cited by 57 · see citing works
COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route
Mingoti, M. E. D., Bertollo, A. G., Simões, J. L. B., Francisco, G. R., Bagatini, M. D., & Ignácio, Z. M. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02004-y · Cited by 56 · see citing works
“Given the presence of ACE2 receptors in microglia and astrocytes, it may be possible to relate SARS-CoV-2 with glial activation (Tremblay et al. 2020).”
BackgroundBrain microstructural changes and fatigue after COVID-19
Bispo, D. D. D. C., Brandão, P. R. D. P., Pereira, D., Maluf, F., Dias, B. A., Paranhos, H. R., von Glehn, F., de Oliveira, A. C. D., Regattieri, N., Silva, L., et al. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.1029302 · Cited by 48 · see citing works
“Neurons, oligodendrocytes, and other glial cells may have impaired physiological functions during SARS-CoV-2 inflammatory insult, leading to a disturbance of brain homeostasis (62).”
BackgroundNeurological complications associated with Covid‐19; molecular mechanisms and therapeutic approaches
Mehrabani, M. M., Karvandi, M. S., Maafi, P., & Doroudian, M. (2022) · Reviews in Medical Virology · doi:10.1002/rmv.2334 · Cited by 52 · see citing works
Abdi, A., AlOtaiby, S., Badarin, F. A., Khraibi, A., Hamdan, H., & Nader, M. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112518 · Cited by 47 · see citing works
Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19
Dąbrowska, E., Galińska-Skok, B., & Waszkiewicz, N. (2021) · Life · doi:10.3390/life11101056 · Cited by 47 · see citing works
Stoian, A., Stoian, M., Bajkó, Z., Maier, S., Andone, S. R., Cioflinc, R. A., Moțățăianu, A., Bărcuţean, L., & Bălașa, R. (2022) · Biomedicines · doi:10.3390/biomedicines10040774 · Cited by 42 · see citing works
“The brain’s defensive system and systemic inflammation can influence the CNS through both innate and adaptive immune systems through their cellular elements [64,97].”
BackgroundInfluentialCOVID-19 in People With Schizophrenia: Potential Mechanisms Linking Schizophrenia to Poor Prognosis
Mohan, M., Perry, B. I., Saravanan, P., & Singh, S. P. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.666067 · Cited by 40 · see citing works
de Andrade, E. G., Šimončičová, E., Carrier, M., Vecchiarelli, H. A., Robert, M.-È., & Tremblay, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.647378 · Cited by 37 · see citing works
“Besides, reactive microglia generally adopt different morphologies, for example, shifting to amoeboid shapes with bigger somas and less ramified processes, as opposed to the steady-state, highly branched “surveilling” phenotype (Figure 1; Savage et al., 2019; Tremblay et al., 2020).”
BackgroundSelf-citationVarghese, S. M., Patel, S., Nandan, A., Jose, A., Ghosh, S., Sah, R. K., Menon, B., Athira, K. V., & Chakravarty, S. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04205-5 · Cited by 37 · see citing works
Naidu, S. A. G., Wallace, T. C., Davies, K. J. A., & Naidu, A. S. (2021) · Journal of Dietary Supplements · doi:10.1080/19390211.2021.1922567 · Cited by 36 · see citing works
“Furthermore, microglia modulate the CNS micro-milieu, thereby reduce the severity of demyelination, and influence neuronal repair in cerebral cortex (Lavi and Cong 2020; Tremblay et al. 2020).”
BackgroundNeurological sequela and disruption of neuron-glia homeostasis in SARS-CoV-2 infection
Savelieff, M. G., Feldman, E. L., & Stino, A. M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105715 · Cited by 36 · see citing works
“The virus also triggers a pro-inflammatory response, which can render the BBB susceptible to damage, leading to immune cell infiltration into the brain along with viral penetration (Tremblay et al., 2020; Solomon, 2021).”
Szabo, M. P., Iba, M., Nath, A., Masliah, E., & Kim, C. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00755-7 · Cited by 35 · see citing works
Chiappalupi, S., Salvadori, L., Donato, R., Riuzzi, F., & Sorci, G. (2021) · Biomolecules · doi:10.3390/biom11060876 · Cited by 34 · see citing works
“The increase in circulating levels of chemokines and interleukins subsequent to SARS-COV-2 pulmonary infection compromises the blood–brain barrier (BBB), favoring the entry of the virus into the brain parenchyma and leading to inflammation, with the subsequent risk of neurological damage [107].”
BackgroundTREM2, microglial and ischemic stroke
Wang, H., Li, X., Wang, Q., Ma, J., Gao, X., & Wang, M. (2023) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2023.578108 · Cited by 32 · see citing works
Defining Microglial States and Nomenclature: A Roadmap to 2030Preprint
Paolicelli, R. C., Sierra, A., Stevens, B., Tremblay, M., Aguzzi, A., Ajami, B., Amit, I., Audinat, É., Bechmann, I., Bennett, M. L., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4065080 · Cited by 33 · see citing works
Self-citationWhat can neuroimmunology teach us about the symptoms of long-COVID?
Mondelli, V., & Pariante, C. M. (2021) · Oxford Open Immunology · doi:10.1093/oxfimm/iqab004 · Cited by 32 · see citing works
Müller, K., Poppele, I., Ottiger, M., Zwingmann, K., Berger, I., Thomas, A., Wastlhuber, A., Ortwein, F., Schultz, A.-L., Weghofer, A., et al. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20021468 · Cited by 30 · see citing works
Role of Demyelination in the Persistence of Neurological and Mental Impairments after COVID-19
Khodanovich, M. Y., Kamaeva, D. A., & Naumova, A. V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911291 · Cited by 31 · see citing works
Astrocytes and the Psychiatric Sequelae of COVID-19: What We Learned from the Pandemic
Steardo, L., Steardo, L., & Scuderi, C. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03709-7 · Cited by 32 · see citing works
COVID-19: a new emerging respiratory disease from the neurological perspective
El-Sayed, A., Aleya, L., & Kamel, M. S. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-12969-9 · Cited by 29 · see citing works
“All these routes were proposed based on current evidences (Satarker and Nampoothiri 2020; Tremblay et al. 2020; Lima et al. 2020; Jakhmola et al. 2020).”
BackgroundTheoharides, T. C. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11090860 · Cited by 29 · see citing works
Disrupted Sleep During a Pandemic
Kumar, N., & Gupta, R. M. (2022) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2021.10.006 · Cited by 30 · see citing works
“Once inside the brain, SARS-CoV2 invades tissues with ACE-2 receptors including the frontotemporal cortex, circumventricular organs, thalamus, and brainstem involving the rostral ventrolateral medulla among others.(28,29) ACE-2 expression has also been reported in the hypothalamus and pituitary gland.”
BackgroundZhang, Y., Archie, S. R., Ghanwatkar, Y., Sharma, S., Nozohouri, S., Burks, E., Mdzinarishvili, A., Liu, Z., & Abbruscato, T. J. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00339-7 · Cited by 29 · see citing works
“Given that the large number of functions performed by glial cells in the neuroinflammatory response, it could be expected that activation of astrocytes has a major impact on the CNS during SARSCoV-2 infection [23, 24].”
BackgroundVestibular disorders in patients after COVID-19 infection
Pazdro-Zastawny, K., Dorobisz, K., Misiak, P., Kruk-Krzemień, A., & Zatoński, T. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.956515 · Cited by 28 · see citing works
Plasmalogens and platelet‐activating factor roles in chronic inflammatory diseases
Tremblay, M., Almsherqi, Z. A., & Deng, Y. (2022) · BioFactors · doi:10.1002/biof.1916 · Cited by 28 · see citing works
“Genetic variants and environmental risk factors altering these microglial functions are further associated with most if not all CNS disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative.(99,100) These findings highlight the importance of evaluating the outcomes of decreased, but also restore…”
BackgroundSelf-citationTsilioni, I., & Theoharides, T. C. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03493-7 · Cited by 28 · see citing works
“Increasing evidence indicates the involvement of neuro-inflammation [64–66] that may damage brain blood vessels [67, 68] and brain cells [64, 69, 70] possibly via activation of microglia [71, 72].”
BackgroundCOVID ‐19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain
Roczkowsky, A., Limonta, D., Fernandes, J. P., Branton, W. G., Clarke, M., Hlavay, B. A., Noyce, R. S., Joseph, J. T., Ogando, N. S., Das, S., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26679 · Cited by 27 · see citing works
Principles of Astrogliopathology
Verkhratsky, A., Li, B., Scuderi, C., & Parpura, V. (2021) · Advances in Neurobiology · doi:10.1007/978-3-030-77375-5_3 · Cited by 21 · see citing works
“These conditions include neurotrauma (Burda et al. 2016; Faulkner et al. 2004), systemic inflammation and sepsis (Shulyatnikova and Verkhratsky 2019; Tremblay et al. 2020), microbial or viral neuroinfection (Soung and Klein 2018; Zorec et al. 2019), toxic encephalopathies (Li et al. 2021;…”
BackgroundSelf-citationFu, Y., Guo, Z., Wang, Y., Zhang, H., Zhang, F., Xu, Z., Shen, X., Roppongi, R. T., Mo, S., Gu, W., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.967356 · Cited by 22 · see citing works
Sideratou, C.-M., & Papaneophytou, C. P. (2023) · Infectious Disease Reports · doi:10.3390/idr15060072 · Cited by 22 · see citing works
“This cascade of events can dysregulate neurogenesis and disrupt the normal functioning of neurons, oligodendrocytes, and neuroglial cells [100].”
BackgroundGiorgio, A. D., Mirijello, A., Gennaro, C. D., Fontana, A., Alboini, P. E., Florio, L., Inchingolo, V., Zarrelli, M. M., Miscio, G., Raggi, P., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12020544 · Cited by 19 · see citing works
Acute and long-term effects of COVID-19 on brain and mental health: A narrative review
Bremner, J. D., Russo, S. J., Gallagher, R., & Simon, N. M. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.11.007 · Cited by 19 · see citing works
Yan, L., Jayaram, M., Chithanathan, K., Zharkovsky, A., & Tian, L. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.750373 · Cited by 18 · see citing works
“Glia-induced neuroinflammation is a common pathological observation in neurological cases of COVID-19 (Tremblay et al., 2020; Vargas et al., 2020), as microglia and astrocytes are key pathogen-combating players in the brain during SARS-CoV-2 infection (McMahon et al.”
BackgroundSelf-citationCăliman-Sturdza, O. A., Gheorghita, R. E., & Lobiuc, A. (2025) · Life · doi:10.3390/life15030439 · Cited by 26 · see citing works
Newhouse, A. L., Kritzer, M. D., Eryilmaz, H., Praschan, N. C., Camprodon, J. A., Fricchione, G. L., & Chemali, Z. N. (2022) · Journal of the Academy of Consultation-Liaison Psychiatry · doi:10.1016/j.jaclp.2022.08.007 · Cited by 17 · see citing works
“24 In addition, studies of single-nucleus transcriptomes of frontal cortex and the choroid plexus in 30 SARS-CoV-2 patients reveal cellular changes in COVID-19-associated microglia and astrocytes that share features with pathological cell states in neurodegenerative disorders, such as Alzheimer…”
Fetal brain vulnerability to SARS-CoV-2 infection
McMahon, C. L., Castro, J., Silvas, J. A., Perez, A. M., Estrada, M., Carrion, R., & Hsieh, J. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.06.015 · Cited by 17 · see citing works
Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions
Qiu, Y., Mo, C., Chen, L., Ye, W., Chen, G., & Zhu, T. (2024) · MedComm · doi:10.1002/mco2.513 · Cited by 16 · see citing works
“119 Glial activation and neuroinflammation may play an important role in cognitive impairment caused by COVID-19.”
BackgroundHayden, M. R. (2021) · Neuroglia · doi:10.3390/neuroglia2010004 · Cited by 18 · see citing works
“Furthermore, the major histocompatibility complex (MHC)positive antigen presenting cells will present these viral antigens to the acquired immune system’s auto-reactive T-cells that will form the antibody which will then develop the antigen–antibody complex [94,99].”
BackgroundImmunological Interfaces: The COVID-19 Pandemic and Depression
Perlmutter, A. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.657004 · Cited by 17 · see citing works
Genetics of COVID‐19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review
Tziastoudi, M., Cholevas, C., Stefanidis, I., & Theoharides, T. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51631 · Cited by 16 · see citing works
“Microglia have been implicated in COVID-19(228) and were also associated with neuroinflammation.(229) Microglia have important functions both in health and disease of the central nervous system (CNS), especially with respect to neuroinflammation 232 and neurodegenerative diseases.”
BackgroundAstrocytes in the pathophysiology of neuroinfection
Zorec, R., & Verkhratsky, A. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220082 · Cited by 15 · see citing works
Self-citationSARS-CoV-2 Infection: Paving Way for Sleep Disorders in Long Term!
Gupta, R. M., & Pandi-Perumal, S. R. (2021) · Sleep and Vigilance · doi:10.1007/s41782-021-00145-5 · Cited by 14 · see citing works
“, brainstem, circumventricular organ, subfornical area, paraventricular nucleus, and rostroventrolateral medulla [10].”
BackgroundPost‐COVID‐19 neuropsychiatric syndrome: Is maladaptive glial recovery to blame?
Steardo, L., Steardo, L., Verkhratsky, A., & Scuderi, C. (2021) · Acta Physiologica · doi:10.1111/apha.13717 · Cited by 14 · see citing works
Self-citationVolk, P., Manesh, M. R., Warren, M. E., Besko, K., de Andrade, E. G., Wicki‐Stordeur, L. E., & Swayne, L. A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16016 · Cited by 13 · see citing works
Microglia as potential key regulators in viral-induced neuroinflammation
Ismail, F. S., Faustmann, T. J., Faustmann, P. M., & Corvace, F. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1426079 · Cited by 13 · see citing works
Nelson, B. K., Farah, L. N., Grier, A., Su, W., Chen, J., Sossi, V., Sekhon, M. S., Stoessl, A. J., Wellington, C. L., Honer, W. G., et al. (2024) · NeuroImage · doi:10.1016/j.neuroimage.2024.120859 · Cited by 14 · see citing works
“We found lower MD in the long COVID group, but no differences in other DTI metrics or cognitive performance.”
Backgroundda Cunha, L. N. O. L., Tizziani, T., Souza, G. B., Moreira, M. A., Neto, J. S. S., Santos, C. V. D. D., de Carvalho, M. G., Dalmarco, E. M., Turqueti, L. B., Scotti, L., et al. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210726094955 · Cited by 12 · see citing works
Neuroinvasion and neurotropism by SARS-CoV-2 variants in the K18-hACE2 mousePreprint
Seehusen, F., Clark, J. J., Sharma, P., Bentley, E. G., Kirby, A., Subramaniam, K. S., Wunderlin, S., Hughes, G. L., Patterson, E. I., Michael, B. D., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.16.440173 · Cited by 12 · see citing works
DiNicolantonio, J., McCarty, M., Barroso-Aranda, J., Assanga, S., Luján, L. M. L., O, & Keefe, J. H. (2021) · Open Heart · doi:10.1136/openhrt-2021-001663 · Cited by 11 · see citing works
Valenza, M., Steardo, L., Steardo, L., Verkhratsky, A., & Scuderi, C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.748136 · Cited by 12 · see citing works
Self-citationGonçalves, C., Sesterheim, P., Wartchow, K. M., Bobermin, L. D., Leipnitz, G., & Quincozes‐Santos, A. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.905218 · Cited by 11 · see citing works
“Another very important aspect of COVID-19 is the greater vulnerability of elderly patients; possibly the aging of astrocytes makes these individuals more susceptible to Sars-CoV-2-induced dysfunction (Tremblay et al., 2020).”
BackgroundKhullar, S., & Wang, D. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad009 · Cited by 11 · see citing works
Autopsy findings of pediatric COVID-19: a systematic review
Octavius, G. S., Wijaya, J. H., Tan, A. O., Muljono, M. P., Chandra, S., & Juliansen, A. (2022) · Egyptian Journal of Forensic Sciences · doi:10.1186/s41935-022-00288-0 · Cited by 11 · see citing works
SARS-CoV-2 infection is associated with increased odds of insomnia, RLS and dream enactment behavior
Kumar, N., Goyal, A., Hussain, A., Saini, L. K., Chawla, O., Arora, P. K., Daga, R., Tikka, S. K., Goyal, S., Kanchan, S., et al. (2022) · Indian Journal of Psychiatry · doi:10.4103/indianjpsychiatry.indianjpsychiatry_586_21 · Cited by 10 · see citing works
“[17] Thus, the present study was planned to study the effect of SARS-CoV-2 infection to the occurrence of insomnia, RLS and DEB.”
Peripheral nervous system involvement associated with COVID-19. A systematic review of literature
Hanganu, A. R., Constantin, A. M., Moise, E.-S., Niculae, C., Olaru, I. D., Băicuş, C., & Hristea, A. (2023) · PLoS ONE · doi:10.1371/journal.pone.0283827 · Cited by 10 · see citing works
SARS-CoV-2 hampers dopamine production in iPSC-derived dopaminergic neurons
Cappelletti, G., Carsana, E. V., Lunghi, G., Breviario, S., Vanetti, C., Fonzo, A. D., Frattini, E., Magni, M., Zecchini, S., Clerici, M., et al. (2023) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2023.104874 · Cited by 10 · see citing works
Dialogue between Neuroinflammation and Neurodegenerative Diseases in COVID-19
Chowdhury, B., Sharma, A., Satarker, S., Mudgal, J., & Nampoothiri, M. (2021) · Journal of Environmental Pathology Toxicology and Oncology · doi:10.1615/jenvironpatholtoxicoloncol.2021038365 · Cited by 10 · see citing works
SARS-CoV-2-Induced Amyloidgenesis: Not One, but Three Hypotheses for Cerebral COVID-19 Outcomes
Gonçalves, C., Bobermin, L. D., Sesterheim, P., & Netto, C. A. (2022) · Metabolites · doi:10.3390/metabo12111099 · Cited by 10 · see citing works
“Note that the brain endothelium is closely surrounded by the feet of astrocytes, forming the BBB [19].”
BackgroundInfluentialEvidence of Microglial Immune Response Following Coronavirus PHEV Infection of CNS
Zhang, J., Li, Z., Lu, H., Shi, J., Gao, R., Ma, Y., Lan, Y., Guan, J., Zhao, K., Gao, F., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.804625 · Cited by 10 · see citing works
COVID‐19 and cognitive impairment: From evidence to SARS‐CoV‐2 mechanism
Pan, H., Niu, J., Feng, L., Yin, Y. L., Dang, C., Lu, Y., Li, L., Ji, J., Yang, K., Wang, L., et al. (2024) · Brain‐X · doi:10.1002/brx2.58 · Cited by 8 · see citing works
Crosstalk between SARS-CoV-2 Infection and Neurological Disorders: A Review
Azhar, A., Wali, M. A., Rashid, Q., Khan, W. H., Alhosaini, K. A., Owais, M., & Kamal, M. A. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220418114009 · Cited by 8 · see citing works
Post-Acute Sequelae of SARS-CoV-2 Infection: A Descriptive Clinical Study.
Gutiérrez-Martínez, L., Karten, J., Kritzer, M., Josephy-Hernandez, S., Kim, D., Newhouse, A., Pasinski, M., Praschan, N., Razafsha, M., Rubin, D., et al. (2022) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.21070193 · Cited by 6 · see citing works
Human Brain In Vitro Model for Pathogen Infection-Related Neurodegeneration Study
Yan, Y., & Cho, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126522 · Cited by 7 · see citing works
“During severe COVID-19, the increase in circulating chemokines and interleukins can compromise the BBB, allowing these inflammatory mediators to affect glial cells [174].”
BackgroundRole Of Retroelements In The Development Of COVID-19 Neurological Consequences
Mustafin, R. N., Kazantseva, A. V., Kovas, Y. V., & Хуснутдинова, Э. К. (2022) · Russian Open Medical Journal · doi:10.15275/rusomj.2022.0313 · Cited by 7 · see citing works
“The key factor in CNS inflammation caused by SARS-CoV-2 is the activation of astrocytes and microglia [95], which are the main sources of cytokines in the inflamed CNS, including interferon and interleukins involved in the development of a cytokine storm in the brain [96].”
BackgroundChoi, S. S. A., Chan, H. H., Chan, C. M., Wang, X., Webb, S., Leung, K. W., Tsim, K. W. K., & Miller, A. L. (2022) · Journal of Virology · doi:10.1128/jvi.01418-22 · Cited by 7 · see citing works
“It has been proposed that such entry pathways might contribute to the long-term effects of COVID-19 (long-COVID) infection (75, 115, 116, 150), which at present are not well understood and might have the potential to be targeted by antiviral agents (53, 114, 151).”
BackgroundDeveloping brain under renewed attack: viral infection during pregnancy
Recaioglu, H., & Kolk, S. M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1119943 · Cited by 6 · see citing works
“Exceptionally, yolk sac-derived microglial cells appearing and migrating to the developing brain (GW4-24; Menassa and Gomez-Nicola, 2018) not only participate in brain development in critical stages but also are the resident macrophages of the brain acting as first-line defenders against pathogens (Tremblay et al., 20…”
BackgroundOneyear longitudinal study on biomarkers of blood–brain barrier permeability in COVID-19 patients
Wallensten, J. C., Havervall, S., Power, Y., Åsberg, M., Borg, K., Nager, A., Thålin, C., & Mobarrez, F. (2024) · Scientific Reports · doi:10.1038/s41598-024-73321-y · Cited by 7 · see citing works
“One hypothesis is that SARS-CoV-2 activates microglia and astrocytes, inducing an inflammatory response and increasing cytokine production, which results in a feedback loop that affects glia cells in the brain 9 and subsequently the BBB integrity 3 .”
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Neurotropic SARS-CoV-2: Causalities and Realities
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Impact of COVID-19 on Anxiety and Depression - Biopsychosocial Factors
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SARS-CoV-2 Attacks in the Brain: Focus on the Sialome
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“The potential disruption of the BBB, a protective barrier against foreign molecules, facilitates the virus’s ability to infect the brain [22,69].”
BackgroundInfluentialCappelletti, G., Brambilla, L., Strizzi, S., Limanaqi, F., Melzi, V., Rizzuti, M., Nizzardo, M., Saulle, I., Trabattoni, D., Corti, S. P., et al. (2025) · The FASEB Journal · doi:10.1096/fj.202401604rrr · Cited by 5 · see citing works
“59,116,117 The initiation of an inflammatory reaction in SARS- CoV- 2-infected HCOs was further substantiated by the increased expression of genes associated with the inflammasome pathway, particularly NLRP3 and IL-18.”
Lipid metabolism, microglia, and stroke
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“Microglia are extremely dynamic and constantly responding to episodes of health or disease by adapting diverse states and fulfilling different functions (Vay et al., 2018; Tremblay et al., 2020).”
SARS-CoV-2 and Brain Health: New Challenges in the Era of the Pandemic
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“As a result, the cell composition in the CNS collapses and neuronal cells can also be seriously damaged [11,13,14].”
BackgroundMild chronic hypoxia and the brain: an ambiguous relationship
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“Hypoxia serves as both a direct trigger of CNS inflammation through HIF-1α-mediated immune cell activation and an indirect facilitator through BBB compromise and peripheral immune cell infiltration [112, 133].”
Microglia and putative macrophages of the subfornical organ: structural and functional features
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- Authors
- Tremblay, M.-E., Madore, C., Bordeleau, M., Tian, L., & Verkhratsky, A.
- Affiliations
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Université Laval (CA)
- Peking University (CN)
- Ikerbasque (ES)
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2020-11-11
- Volume
- 14
- Pages
- 592214-592214
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC7693550
- OpenAlex
- W3101561456
- Cited by
- 159
- References
- 188
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 20 · 2023: 25 · 2022: 60 · 2021: 36 · 2020: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion)
- cIRcle (University of British Columbia) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship@McGill (McGill) (submittedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Open Collections
- Funders
- European Commission
- Eesti Teadusagentuur (MOBTT77)
- Fondation pour la Recherche Médicale
- Canadian Institutes of Health Research (Tier 2)
- Topics
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- COVID-19 pandemic, SARS-CoV-2, glial cells, astrocytes, microglia, neurotropism, ACE2 receptor, blood-brain barrier, neuroinflammation, chemokines, interleukins, circumventricular organs, autoimmunity, innate immunity, adaptive immunity, neurological complications, psychiatric aspects, aging, comorbidities, pregnancy, fetus
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