Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Human Endogenous Retrovirus K Envelope in Spinal Fluid of Amyotrophic Lateral Sclerosis Is Toxic.

OBJECTIVE: Human endogenous retroviruses have been implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Expression of human endogenous retrovirus K (HERV-K) subtype HML-2 envelope (Env) in human neuronal cultures and in transgenic mice results in neurotoxicity and neurodegeneration, and mice expressing HML-2 Env display behavioral and neuromuscular characteristics resembling ALS. This study aims to characterize the neurotoxic properties of HML-2 Env. METHODS: Env neurotoxicity was detected in ALS cerebrospinal fluid and confirmed using recombinant Env protein in a cell-based assay and a mouse model. The mechanism of neurotoxicity was assessed with immunoprecipitation followed by mass spectrometry and Western blot, and by screening a panel of inhibitors. RESULTS: We observed that recombinant HML-2 Env protein caused neurotoxicity resulting in neuronal cell death, retraction of neurites, and decreased neuronal electrical activity. Injection of the Env protein into the brains of mice also resulted in neuronal cell death. HML-2 Env protein was also found in the cerebrospinal fluid of patients with sporadic ALS. The neurotoxic properties of the Env and the cerebrospinal fluid could be rescued with the anti-Env antibody. The Env was found to bind to CD98HC complexed to ß1 integrin on the neuronal cell surface. Using a panel of compounds to screen for their ability to block Env-induced neurotoxicity, we found that several compounds were protective and are linked to the ß1 integrin pathway. INTERPRETATION: HERV-K Env is released extracellularly in ALS and causes neurotoxicity via a novel mechanism. Present results pave the way for new treatment strategies in sporadic ALS. ANN NEUROL 2022;92:545-561.

Neurovascular injury with complement activation and inflammation in COVID-19.

The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.

Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features.

OBJECTIVE: To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed Diseases Program. METHODS: Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing, and the phage-display assay, VirScan, for viral immune responses. An etiological diagnosis was established postmortem. RESULTS: Using VirScan, enrichment of dengue viral antibodies was detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months antemortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency, and sequencing of the virus demonstrated wild-type dengue virus in the central nervous system. INTERPRETATION: Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self-limiting, and chronic dengue infections have not been previously reported. Our findings suggest that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology. ANN NEUROL 2019;86:695-703.

Comparison of Laparoscopic Cornual Resection and Cornuotomy for Interstitial Pregnancy.

STUDY OBJECTIVE: To compare the clinical efficacy and safety of laparoscopic cornuotomy and cornual resection in the treatment of interstitial pregnancy. DESIGN: Retrospective chart review between 2006 and 2014 (Canadian Task Force classification II-2). SETTING: Two academic tertiary care hospitals. PATIENTS: Seventy-five patients with interstitial pregnancy treated by laparoscopy. MEASUREMENT AND MAIN RESULTS: In the 75 patients, 53 who underwent cornual resection and 22 who underwent cornuotomy, we evaluated operating time, changes in hemoglobin levels after surgery, the rate of major complications, and the incidence of persistent interstitial pregnancy. The mean operating time was significantly shorter for cornuotomy than for cornual resection (59.36 ± 19.32 minutes vs. 77.11 ± 23.97 minutes, respectively). Changes in hemoglobin level after the operation, rates of major complications, and the incidence of persistent interstitial pregnancy were not significantly different in the 2 surgery groups. CONCLUSION: Laparoscopic cornuotomy yielded clinical results comparable to those of cornual resection. Laparoscopic cornuotomy may reduce the time of operation, and had the same incidence of persistent interstitial pregnancy as cornual resection.

Anatomical configuration of the inferior alveolar neurovascular bundle: a histomorphometric analysis.

PURPOSE: The inferior alveolar neurovascular bundle (NVB) is important in implant placement and many other surgeries in dentistry because it is a major supplier of sensation and blood to the mandible via the mandibular canal. The purposes of the present study were to determine the areas and diameters of the NVB, the inferior alveolar nerve (IAN), and the inferior alveolar artery (IAA), and to verify the buccolingual location of the mandibular canal. METHODS: The anatomical configuration of the NVB was examined by histomorphometrically analyzing 20 embalmed dentulous hemimandibles. The areas and maximum horizontal and vertical diameters of the NVB, IAN, and IAA were measured according to tooth region. The distances from the internal border of the mandibular canal to the outer surface of the buccal and lingual cortical plates were also measured. RESULTS: The areas of the vertically oval-shaped NVB and IAN appeared to be constant between the molar and premolar regions, which contain the mental branch, and decreased sharply in the lateral incisor after branching off of the mental branch via the mental canal. The mandibular canal was located close to the lingual cortical plate in the posterior tooth region before passing through the mental canal, immediately after which it was situated quite close to the buccal cortical plate, and then closer to the middle toward the anterior tooth region. CONCLUSIONS: The findings of this study provide useful anatomical information that should help to minimize the risk of injury to the NVB during surgical procedures in the mandibular region.

MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell.

MicroRNA (miRNA) is a small noncoding RNA molecule, 19-25 nucleotides in length, which regulates several pathways including cell development, cell proliferation, carcinogenesis, apoptosis, etc. In this study, the over-expression of microRNA-205 (miR-205) increased the number of apoptotic cells by at least 4 times compared to the control. In addition, over-expressed miRNA in KB oral cancer cells triggered apoptosis via the caspase cascade, including the cleavage of caspase-9, caspase-7, caspase-3, and PARP. Flow cytometry showed that apoptotic cell death was increased significantly by 35.33% in KB oral cancer cells with over-expressed miR-205 compared to the control. The microarray data showed that axis inhibitor protein 2 (Axin2) was down-regulated in KB oral cancer cells transfected with miR-205. In addition, Axin2 was down-regulated by approximately 50% by over-expressed miR-205 at both the mRNA and protein levels. Interestingly, Axin2 was up-regulated in KB oral cancer compared to human normal oral keratinocytes. Furthermore, the cell cytotoxicity and apoptotic population of KB oral cancer cells were increased significantly after Axin2 siRNA transfection. These results suggest that Axin2 is might be as potential oncogene in KB oral cancer cells. The luciferase assay showed that over-expressed miR-205 in KB oral cancer cells suppressed AXIN2 expression through an interaction with its own binding site at AXIN2 3'UTR (64-92). These results suggest that miR-205 is a novel anti-oncogenic miRNA in KB oral cancer cells, and may have potential applications in oral cancer therapy.

Topographical relationship of the greater palatine artery and the palatal spine. Significance for periodontal surgery.

AIM: The aims of this study were to (1) identify the branching pattern and course of the greater palatine artery (GPA), (2) carry out a morphological analysis of the palatal bony prominence that divides the medial and lateral grooves and (3) characterize the topographical relationships between these two structures. METHODS: Thirty-six hemimaxillae were studied with the aid of a surgical microscope to elucidate the GPA. A further 25 dry skulls were examined to establish the morphology of the palatal spine. RESULTS: The most common GPA branching pattern was type I (41.7%, 15 sides), which gave off the medial and canine branches after the bony prominence. The distances from the CEJ to the lateral branch of the GPA were 9.04 ± 2.93 mm (canine), 11.12 ± 1.89 mm (first premolar), 13.51 ± 2.08 mm (second premolar), 13.76 ± 2.86 mm (first molar) and 13.91 ± 2.20 mm (second molar). The palatal spine was frequently observed as the bony prominence (66.3%, 57 sides), and was located at 6.49 ± 1.76 mm from the greater palatine foramen, with a length of 10.42 ± 2.45 mm. There was no a correlation between the bony prominence shape and the GPA branching pattern. CONCLUSIONS: These results could provide the reference data regarding the topography of the GPA for periodontal surgery.

Automatic Assessment of Upper Extremity Function and Mobile Application for Self-Administered Stroke Rehabilitation.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.

TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 protein (ASRGL1) cleaves isoaspartates, which alter protein folding and susceptibility to proteolysis. ASRGL1 gene harbors a copy of the human endogenous retrovirus HML-2, whose overexpression contributes to ALS pathogenesis. Here we show that ASRGL1 expression was diminished in ALS brain samples by RNA sequencing, immunohistochemistry, and western blotting. TDP-43 and ASRGL1 colocalized in neurons but, in the absence of ASRGL1, TDP-43 aggregated in the cytoplasm. TDP-43 was found to be prone to isoaspartate formation and a substrate for ASRGL1. ASRGL1 silencing triggered accumulation of misfolded, fragmented, phosphorylated and mislocalized TDP-43 in cultured neurons and motor cortex of female mice. Overexpression of ASRGL1 restored neuronal viability. Overexpression of HML-2 led to ASRGL1 silencing. Loss of ASRGL1 leading to TDP-43 aggregation may be a critical mechanism in ALS pathophysiology.

Impaired neurogenesis and neurite outgrowth in an HIV-gp120 transgenic model is reversed by exercise via BDNF production and Cdk5 regulation.

Human immunodeficiency virus (HIV) infection-associated neurocognitive disorders is accompanied with brain atrophy. In these patients, impairment of adult neurogenesis and neurite outgrowth in the hippocampus may contribute to cognitive dysfunction. Although running exercises can enhance neurogenesis and normalize neurite outgrowth, the underlying molecular mechanisms are not well understood. The HIV envelope protein, gp120, has been shown to impair neurogenesis. Using a gp120 transgenic mouse model, we demonstrate that exercise stimulated neural progenitor cell (NPC) proliferation in the hippocampal dentate gyrus and increased the survival rate and generation of newborn cells. However, sustained exercise activity was necessary as the effects were reversed by detraining. Exercise also normalized dendritic outgrowth of neurons. Furthermore, it increased the expression of hippocampal brain-derived neurotrophic factor (BDNF) and normalized hyperactivation of cyclin-dependent kinase 5 (Cdk5). Hyperactivated Cdk5 or gp120 treatment led to aberrant neurite outgrowth and BDNF treatment normalized the neurite outgrowth in NPC cultures. These results suggest that sustained exercise has trophic activity on the neuronal lineage which is mediated by Cdk5 modulation of the BDNF pathway.

Histomorphologic approach for the modiolus with reference to reconstructive and aesthetic surgery.

The modiolus is strongly associated with facial expression, beauty, and aging, and so it is often viewed as the main facial landmark, both functionally and aesthetically. This study examined the modiolus and the surrounding structures histomorphologically with the aim of providing useful information for reconstructive and aesthetic surgery. Nineteen embalmed cadavers (38 hemifaces; 8 males and 11 females; mean age at death, 66.9 years) were examined in this study. For macroscopic observations, the modiolus and facial artery in the perioral region of 28 hemifaces were revealed by meticulous dissection. The modiolus and its surrounding structures were then prepared from 12 hemifaces for routine histology and stained with hematoxylin-eosin and Masson trichrome. A tendinous tissue nodule in the modiolus was found in 21.4% of cases (ie, 6 hemifaces). The facial artery passed approximately 1 mm lateral to the lateral border of the modiolus. In the central region of modiolus, which was an area of convergence of muscle fibers, the tendinous structure appeared as dense irregular collagenous connective tissue. Particularly in the middle layer between the skin and the oral mucosa, it appeared as a dense, compact, and prominent shape horizontally. The finding of the existence of a tendinous structure in the central region of the modiolus, which could act as an anchor for the converging facial muscles, is expected to provide critical information in the field of facial plastic surgery.

Histomorphometric analysis of the palatal mucosa associated with periodontal plastic surgery on cadavers.

PURPOSE: The palatal mucosa is a major donor site for connective tissue in the field of periodontal plastic surgery, since it satisfies both the esthetic and functional demands of patients. The purpose of this study was to use histomorphometric analysis to measure the thicknesses of the palatal mucosa and the lamina propria including the epithelium on cadavers. METHODS: Thirty-four hemimaxillae of cadavers were examined (13 male and 4 female, mean age 57.2 years). Each maxilla was processed for histological sectioning and subsequently for histomorphometric analysis. The thicknesses of the palatal mucosa and the lamina propria including the epithelium were measured at three points starting from the alveolar crest, at intervals of 4 mm, with the aid of Adobe Photoshop. RESULTS: The thickness of the palatal mucosa at the alveolar crest and at 4 and 8 mm below the alveolar crest were 2.51 ± 0.83 (mean ± SD), 2.92 ± 0.80, and 3.62 ± 0.99 mm, respectively, and thus increasing from the alveolar crest toward the midpalatal suture. Conversely, the thicknesses of the lamina propria including the epithelium at these same positions were 2.06 ± 0.70, 1.54 ± 0.48, and 1.28 ± 0.46 mm, respectively, thus decreasing toward the midpalatal suture. CONCLUSIONS: The present results indicate that clinicians need to be particularly careful when harvesting palatal mucosa that is destined to be used as autogenous donor material for connective tissue in periodontal plastic surgery.

Detection of SARS-CoV-2 Nucleocapsid and Microvascular Disease in the Brain: A Case Report.

BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide range of neurologic complications; however, its neuropenetrance during the acute phase of the illness is unknown. METHODS: Extracellular vesicles were isolated from brain biopsy tissue from a patient undergoing epilepsy surgery using ultracentrifugation and analyzed by Western blot and qPCR for the presence of virus protein and RNA, respectively. Biopsy tissue was assessed by immunohistochemistry for the presence of microvascular damage and compared with 3 other non-COVID surgical epilepsy brain tissues. RESULTS: We demonstrate the presence of viral nucleocapsid protein in extracellular vesicles and microvascular disease in the brain of a patient undergoing epilepsy surgery shortly after SARS-CoV-2 infection. Endothelial cell activation was indicated by increased levels of platelet endothelial cell adhesion molecule-1 and was associated with fibrinogen leakage and immune cell infiltration in the biopsy tissue as compared with control non-COVID surgical epilepsy brain tissues. DISCUSSION: Despite the lack of evidence of viral replication within the brain, the presence of the nucleocapsid protein was associated with disease-specific endothelial cell activation, fibrinogen leakage, and immune cell infiltration.

Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.

Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2-specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.

Fluconazole Is Neuroprotective via Interactions with the IGF-1 Receptor.

There is a continuing unmet medical need to develop neuroprotective strategies to treat neurodegenerative disorders. To address this need, we screened over 2000 compounds for potential neuroprotective activity in a model of oxidative stress and found that numerous antifungal agents were neuroprotective. Of the identified compounds, fluconazole was further characterized. Fluconazole was able to prevent neurite retraction and cell death in in vitro and in vivo models of toxicity. Fluconazole protected neurons in a concentration-dependent manner and exhibited efficacy against several toxic agents, including 3-nitropropionic acid, N-methyl D-aspartate, 6-hydroxydopamine, and the HIV proteins Tat and gp120. In vivo studies indicated that systemically administered fluconazole was neuroprotective in animals treated with 3-nitropropionic acid and prevented gp120-mediated neuronal loss. In addition to neuroprotection, fluconazole also induced proliferation of neural progenitor cells in vitro and in vivo. Fluconazole mediates these effects through upregulation and signaling via the insulin growth factor-1 receptor which results in decreased cAMP production and increased phosphorylation of Akt. Blockade of the insulin growth factor-1 receptor signaling with the selective inhibitor AG1024 abrogated the effects of fluconazole. Our studies suggest that fluconazole may be an attractive candidate for treatment of neurodegenerative diseases due to its protective properties against several categories of neuronal insults and its ability to spur neural progenitor cell proliferation.

Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain.

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection - without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.