Voltage-gated T-type calcium channel blockers reduce apoptotic body mediated SARS-CoV-2 cell-to-cell spread and subsequent cytokine storm DOI Creative Commons
Thanh Kha Phan, Dylan Sheerin, Bo Shi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 6, 2023

ABSTRACT SARS-CoV-2 typically utilises host angiotensin-converting enzyme 2 (ACE2) as a cellular surface receptor and serine protease TMPRSS2 for the proteolytic activation of viral spike protein enabling entry. Although macrophages express low levels ACE2, they are often found positive in autopsied lungs from COVID-19 patients. As viral-induced macrophage inflammation overwhelming cytokine release key immunopathological events that drives exacerbated tissue damage severe patients, insights into entry therefore critical to understand pathogenesis devise novel therapies. Mounting evidence suggest is associated with apoptosis, type programmed cell death leads numerous large extracellular vesicles (EVs) called apoptotic bodies (ApoBDs). Here, we showed ApoBDs derived SARS-CoV-2-infected cells carry antigens infectious virions. Human monocyte-derived readily efferocytosed SARS-CoV-2-induced ApoBDs, resulting pro-inflammatory responses. To target this ApoBD-mediated process, screened ApoBD formation inhibitors discovered T-type voltage-gated calcium channel (T-channel) blockers can inhibit formation. Mechanistically, T-channel impaired influxes required biogenesis. Importantly, blockade by were able limit dissemination virus-induced vitro pre-clinical mouse model COVID-19. Our discovery ApoBD-efferocytosis-mediated reveals route infection storm induction, expanding our understanding offering new therapeutic avenues diseases.

Language: Английский

Development trends of human organoid‐based COVID‐19 research based on bibliometric analysis DOI Creative Commons
Minghui Li, Yuhong Yuan, Ting Zou

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(12)

Published: May 22, 2023

Abstract Coronavirus disease 2019 (COVID‐19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has posed catastrophic threat to human health worldwide. Human stem cell‐derived organoids serve as promising platform for exploring SARS‐CoV‐2 infection. Several review articles have summarized application of in COVID‐19, but research status and development trend this field seldom been systematically comprehensively studied. In review, we use bibliometric analysis method identify characteristics organoid‐based COVID‐19 research. First, an annual publications citations, most contributing countries or regions organizations, co‐citation references sources hotspots are determined. Next, systematical summaries organoid applications investigating pathology infection, vaccine drug discovery, provided. Lastly, current challenges future considerations discussed. The present study will provide objective angle give novel insights directing

Language: Английский

Citations

7
Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS‐CoV‐2 Omicron infection DOI Creative Commons
Winnie W. Y. Tso, Mike Yat Wah Kwan,

Janette Kwok

et al.

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(7)

Published: July 1, 2023

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely children may develop Omicron-related complications such as those affecting the central nervous system. To characterize spectrum clinical manifestations neuro-COVID and to identify potential biomarkers associated with outcomes, we recruited 15 hospitalized for neurological three hospitals Hong Kong (9 boys 6 girls aged 1-13 years). All were unvaccinated or vaccinated. Fourteen (93.3%) admitted convulsion, including benign febrile seizure (n = 7), complex 2), fever 3), recurrent breakthrough remaining nonconvulsive patient developed encephalopathic state impaired consciousness. None seven six eight other had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable cerebrospinal fluid (CSF) specimens patients who underwent lumbar puncture. Spike-and-wave/sharp waves frontal lobes detected four (57.1%) electroencephalogram. Children significantly higher blood levels IL-6 (p < 0.001) CHI3L1 0.022) healthy controls, CSF 0.002) non-COVID-19-related illnesses. Higher CSF-to-blood ratios IL-8 longer length stay, whereas tau level. The role CSF:blood ratio IL-6, IL-8, prognostic markers should be further evaluated.

Language: Английский

Citations

7
Current clinical findings of acute neurological syndromes after SARS‐CoV‐2 infection DOI Creative Commons
Minjin Wang, Jierui Wang, Yan Ren

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract Neuro‐COVID, a condition marked by persistent symptoms post‐COVID‐19 infection, notably affects various organs, with particular focus on the central nervous system (CNS). Despite scant evidence of SARS‐CoV‐2 invasion in CNS, increasing incidence Neuro‐COVID cases indicates onset acute neurological early infection. The Omicron variant, distinguished heightened neurotropism, penetrates CNS via olfactory bulb. This direct induces inflammation and neuronal damage, emphasizing need for vigilance regarding potential complications. Our multicenter study represents groundbreaking revelation, documenting definite presence cerebrospinal fluid (CSF) significant proportion patients. Furthermore, notable differences emerged between RNA‐CSF‐positive negative patients, encompassing aspects such as blood–brain barrier integrity, extent activation status inflammation. inherent limitations, this research provides pivotal insights into intricate interplay underscoring necessity ongoing to fully comprehend virus's enduring effects CNS. findings underscore urgency continuous investigation unravel complexities relationship, addressing long‐term consequences COVID‐19 health.

Language: Английский

Citations

2
Type I interferon signaling, cognition and neurodegeneration following COVID-19: update on a mechanistic pathogenetic model with implications for Alzheimer’s disease DOI Creative Commons
George D. Vavougios, Vasilis‐Spyridon Tseriotis, Andreas Liampas

et al.

Frontiers in Human Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 18, 2024

COVID-19’s effects on the human brain reveal a multifactorial impact cognition and potential to inflict lasting neuronal damage. Type I interferon signaling, pathway that represents our defense against pathogens, is primarily affected by COVID-19. however, known mediate cognitive dysfunction upon its dysregulation following synaptopathy, microgliosis In previous studies, we proposed model of outside-in tonic IFN-I signaling in This disruption would be mediated crosstalk between central peripheral immunity, could potentially establish feed-forward leading neuroinflammation potentially, neurodegeneration. We for CNS, second-order mediators intrinsic disease-associated molecular patterns (DAMPs) such as proteopathic seeds, without requirement neuroinvasion sustain inflammation. Selective vulnerability neurogenesis sites then lead clinical manifestations anosmia impairment. Since inception at beginning pandemic, growing body studies has provided further evidence SARS-CoV-2 infection CNS cognition. Several preclinical have displayed tauopathy gene expression neuropathological data new cases, correspondingly. Furthermore, neurodegeneration identified with predilection extended olfactory network furthermore supports neuroanatomical concept model, independence from fulminant encephalitis cause this perspective, summarize plausible mechanism impairment setting, contribution Alzheimer’s disease interplay

Language: Английский

Citations

2
SARS-CoV-2-Induced Type I Interferon Signaling Dysregulation in Olfactory Networks Implications for Alzheimer’s Disease DOI Creative Commons
George D. Vavougios, Theodorοs Mavridis,

Triantafyllos Doskas

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4565 - 4579

Published: May 10, 2024

Type I interferon signaling (IFN-I) perturbations are major drivers of COVID-19. Dysregulated IFN-I in the brain, however, has been linked to both reduced cognitive resilience and neurodegenerative diseases such as Alzheimer’s. Previous works from our group have proposed a model where peripheral induction may be relayed CNS, even absence fulminant infection. The aim study was identify significantly enriched signatures genes along transolfactory route, utilizing published datasets nasal mucosa olfactory bulb amygdala transcriptomes COVID-19 patients. We furthermore sought these signature gene networks associated with Alzheimer’s disease pathology risk. Gene expression data involving epithelium, bulb, patients transcriptomic were scrutinized for pathways. set enrichment analyses gene–Venn approaches used determine signatures. Agora web resource risk based on its aggregated multi-omic data. For all analyses, false discovery rates (FDR) <0.05 considered statistically significant. Pathways type found samples tested. Each by IFITM OAS family genes. A 14-gene CNS response pathology, whereas nine increased Agora. Our provides further support dysregulation extended network reconstructed herein, ranging epithelium extending amygdala. 14 implicated this dysregulated pathway among which HLA-C, HLA-B, HLA-A, PSMB8, IFITM3, HLA-E, IFITM1, OAS2, MX1 conferring latter. Further research into druggability IFNb therapeutics warranted.

Language: Английский

Citations

2
Cardiovascular and kidney diseases are positively associated with neuroinflammation and reduced Brain-Derived Neurotrophic Factor in patients with severe COVID-19. DOI Creative Commons
Rafael Rinaldi Ferreira, Ronaldo B. Martins,

Isabela Pires

et al.

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 41, P. 100855 - 100855

Published: Sept. 20, 2024

Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms described in many patients. However, connection between neuroimmune profile lung's inflammatory condition during COVID-19 its association reported by patients still needs further exploration. The present study characterizes infectivity

Language: Английский

Citations

2
A prospects tool in virus research: Analyzing the applications of organoids in virus studies DOI
Qi Shen, Yuhan Zhou, Yanqiu Zhou

et al.

Acta Tropica, Journal Year: 2024, Volume and Issue: 254, P. 107182 - 107182

Published: March 11, 2024

Language: Английский

Citations

1
COVID-19: Unveiling the Neuropsychiatric Maze—From Acute to Long-Term Manifestations DOI Creative Commons
Daniela Ariza,

Lily Castellar-Visbal,

María A. Marquina

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1147 - 1147

Published: May 22, 2024

The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. disease caused by this been associated with a diverse range of symptoms, including common neurological manifestations such as dysgeusia, anosmia, and myalgias. Additionally, numerous cases severe complications have reported, encephalitis, stroke, seizures, Guillain–Barré syndrome, among others. Given the high prevalence in disease, objective review is analyze mechanisms which can affect nervous system, from direct invasion aberrant activation immune system other involved neuropsychiatric manifestations, gain better understanding thus facilitate search for effective therapeutic strategies.

Language: Английский

Citations

1
Increased neurovirulence of omicron BA.5 over BA.1 in human brain organoids and K18-hACE2 mice DOI Creative Commons
Romal Stewart, Sevannah A. Ellis, Kexin Yan

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 31, 2023

Abstract The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 remains controversial. We show that a isolate was significantly more pathogenic in K18-hACE2 mice than isolate, with infections showing increased neuroinvasiveness, resulting brain infection and mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains neurons were main target infection, neuronal progenitor cells immature infected. Evidence damage certain COVID-19 patients becoming compelling, results herein illustrating increasing intrinsic neuropathogenic potential evolving variants.

Language: Английский

Citations

3
Viral Entry Inhibitors Protect against SARS-CoV-2-Induced Neurite Shortening in Differentiated SH-SY5Y Cells DOI Creative Commons
Margaux Mignolet, Jacques Gilloteaux,

Nicolas Halloin

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(10), P. 2020 - 2020

Published: Sept. 28, 2023

The utility of human neuroblastoma cell lines as in vitro model to study neuro-invasiveness and neuro-virulence SARS-CoV-2 has been demonstrated by our laboratory others. aim this report is further characterize the associated cellular responses caused a pre-alpha strain on differentiated SH-SY5Y prevent its cytopathic effect using set entry inhibitors. susceptibility was confirmed at high multiplicity-of-infection, without viral replication or release. Infection reduction length neuritic processes, occurrence plasma membrane blebs, clustering, changes lipid droplets electron density. No expression cytoskeletal proteins, such tubulins tau, could explain neurite shortening. To counteract toxic neurites, inhibitors targeting TMPRSS2, ACE2, NRP1 receptors, Spike RBD were co-incubated with inoculum. shortening be prevented highest concentration camostat mesylate, anti-RBD antibody, inhibitor, but not soluble ACE2. According degree inhibition, average amount intracellular RNA negatively correlated length. This that specific host receptors reverse neurocytopathic SH-SY5Y.

Language: Английский

Citations

3