SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1716 - 1716

Published: Feb. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Language: Английский

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Morphological, cellular, and molecular basis of brain infection in COVID-19 patients

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(35)

Published: Aug. 11, 2022

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum cerebral impact acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranging from alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to damage confirmed brain tissue samples extracted orbitofrontal region (via endonasal transethmoidal access) who died COVID-19. In an independent cohort 26 COVID-19, we used histopathological signs a guide for possible SARS-CoV-2 infection found that among 5 exhibited those signs, all them had genetic material virus brain. Brain these five patients also foci replication, particularly astrocytes. Supporting hypothesis astrocyte neural stem cell-derived human astrocytes vitro are susceptible through noncanonical mechanism involves spike-NRP1 interaction. SARS-CoV-2-infected manifested changes energy metabolism key proteins metabolites fuel neurons, well biogenesis neurotransmitters. Moreover, elicits secretory phenotype reduces neuronal viability. Our data support model which reaches brain, infects astrocytes, consequently, leads death or dysfunction. These deregulated processes could contribute structural functional seen brains patients.

Language: Английский

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Epidemiology and organ specific sequelae of post-acute COVID19: A narrative review

Journal of Infection, Journal Year: 2021, Volume and Issue: 83(1), P. 1 - 16

Published: May 14, 2021

"Long COVID", a term coined by COVID-19 survivors, describes persistent or new symptoms in subset of patients who have recovered from acute illness. Globally, the population people infected with SARS-CoV-2 continues to expand rapidly, necessitating need for more thorough understanding array potential sequelae COVID-19. The multisystemic aspects been subject intense investigation, but long-term complications remain poorly understood. Emerging data lay press, social media, commentaries, and emerging scientific reports suggest that some survivors experience organ impairment and/or debilitating chronic symptoms, at times protean nature, which impact their quality life.

Language: Английский

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COVID-19 and cognitive impairment: neuroinvasive and blood‒brain barrier dysfunction

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Sept. 7, 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. Although COVID-19 was initially described as disease, there is growing evidence that SARS-CoV-2 able invade the brains of patients and cause cognitive impairment. It been reported may have invasive effects on variety cranial nerves, including olfactory, trigeminal, optic, vagus spread other brain regions via infected nerve endings, retrograde transport, transsynaptic transmission. In addition, blood-brain barrier (BBB), composed neurovascular units (NVUs) lining microvasculature, acts physical between cells circulating immune system regulate transfer substances blood parenchyma. Therefore, BBB be an important structure for direct indirect interaction with circulation. this review, we assessed potential involvement neuroinvasion under infection, impact disorder infection

Language: Английский

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SARS-CoV-2 productively infects human brain microvascular endothelial cells

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: June 15, 2022

The emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and high mortality rate in patients. However, there very limited information on effect infection integrity blood-brain barrier (BBB).RNA-sequencing profiling was performed to analyze transcriptomic changes human brain microvascular endothelial cells (hBMECs) after infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, Western blotting analysis explore biological phenotypes.A total 927 differentially expressed genes identified, 610 which significantly upregulated while remaining 317 downregulated. We verified significant induction cytokines, chemokines, adhesion molecules hBMECs by SARS-CoV-2, suggesting an activation vascular endothelium brain. Moreover, we demonstrated that could increase BBB permeability, downregulating as well remodeling intercellular tight junction proteins.Our findings can cause dysfunction, providing novel insights into understanding neuropathogenesis. this finding shall constitute new approach future prevention treatment SARS-CoV-2-induced CNS

Language: Английский

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Association of COVID-19 with Comorbidities: An Update

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(3), P. 334 - 354

Published: Feb. 27, 2023

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which was identified in Wuhan, China December 2019 and jeopardized human lives. It spreads at an unprecedented rate worldwide, with serious still-unfolding health conditions economic ramifications. Based on the clinical investigations, severity of COVID-19 appears to be highly variable, ranging from mild infections including death infected individual. To add this, patients comorbid such as age or concomitant illnesses are significant predictors disease's progression. SARS-CoV-2 enters inside host cells through ACE2 (angiotensin converting enzyme2) receptor expression; therefore, comorbidities associated higher expression may enhance virus entry infection. has already been recognized that age-related Parkinson's disease, cancer, diabetes, cardiovascular diseases lead life-threatening COVID-19-infected patients. infection results excessive release cytokines, called "cytokine storm", causes worsening conditions. Different mechanisms leading intensive care unit (ICU) admissions deaths have hypothesized. This review provides insights into relationship between various We further discuss potential pathophysiological correlation medical interventions for Toward end, different therapeutic options discussed

Language: Английский

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iPSC‐derived human cortical organoids display profound alterations of cellular homeostasis following SARS‐CoV‐2 infection and Spike protein exposure

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(4)

Published: Feb. 14, 2025

Abstract COVID‐19 commonly leads to respiratory issues, yet numerous patients also exhibit a diverse range of neurological conditions, suggesting detrimental impact SARS‐CoV‐2 or the viral Spike protein on central nervous system. Nonetheless, molecular pathway behind pathology and presumed neurotropism remains largely unexplored. We generated human cortical organoids (HCOs) derived from induced pluripotent stem cells (hiPSC) assess: (1) expression main entry factors; (2) their vulnerability infection; (3) infection exposure transcriptome. Results proved that HCOs express receptors co‐receptors; may be productively infected by SARS‐CoV‐2; particles released SARS‐CoV‐2‐infected are able re‐infect another cellular line; (4) resulted in activation apoptotic stress pathways, along with inflammatory processes. Notably, these effects were recapitulated when exposed alone. The data obtained demonstrate likely infects probably through binding ACE2, CD147, NRP1 factors. Furthermore, alone sufficient disrupt homeostasis induce neurotoxic effects, potentially contributing onset long‐COVID symptoms.

Language: Английский

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SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19

Brain Pathology, Journal Year: 2021, Volume and Issue: 31(6)

Published: Aug. 13, 2021

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new responsible for pandemic disease in last year, is able to affect central nervous system (CNS). Compared with its well-known pulmonary tropism and complications, little has been studied about neurotropism pathogenesis of neurological manifestations, but also postmortem histopathological findings CNS patients who died from COVID-19 (coronavirus 2019). We present a systematic review, carried out according Preferred Reporting Items Systematic Review standards, neuropathological features COVID-19. found 21 scientific papers, majority which refer examinations; total amount cases 197. Hypoxic changes are most frequently reported alteration brain tissue, followed by ischemic hemorrhagic lesions reactive astrogliosis microgliosis. These do not seem be specific infection, they more likely because systemic inflammation coagulopathy caused More studies needed confirm this hypothesis detect other possible alterations neural tissue. Brain examination dead should included protocol standardized criteria perform autopsies on these subjects.

Language: Английский

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Prevalence of Headache in Patients With Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of 14,275 Patients

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 27, 2020

Background: Coronavirus disease 2019 (COVID-19) started to spread globally since December from Wuhan, China. Headache has been observed as one of the clinical manifestations in COVID-19 patients. We aimed conduct a comprehensive systematic review and meta-analysis estimate overall pooled prevalence headache Methods: PubMed, Scopus, ScienceDirect, Google Scholar databases were searched identify studies published between March 2020. Adult (≥18 years) patients considered eligible. used random-effects model with 95% confidence intervals (CIs). Quality assessment was done using Joanna Briggs Institute critical appraisal tools. This study is registered PROSPERO (CRD42020182529). Results: identified 2,055 studies, which 86 ( n = 14,275, 49.4% female) included meta-analysis. Overall, 10.1% [95% CI: 8.76–11.49]. There no significant difference severe or vs. non-severe (RR: 1.05, p 0.78), survived (recovered discharged) non-survived 1.36, 0.23), ICU non-ICU 1.06, 0.87) detected 64.0, 34.9, 1.1% high, moderate, low quality, respectively. Conclusions: From first 4-month data outbreak, adult

Language: Английский

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Cognitive decline following acute viral infections: literature review and projections for post-COVID-19

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2021, Volume and Issue: 272(1), P. 139 - 154

Published: June 25, 2021

Recently, much attention has been drawn to the importance of impact infectious disease on human cognition. Several theories have proposed, explain cognitive decline following an infection as well understand better pathogenesis dementia, especially Alzheimer's disease. This article aims review state art regarding knowledge about acute viral infections cognition, laying a foundation explore possible followed coronavirus 2019 (COVID-19). To reach this goal, we conducted narrative systematizing six current COVID-19 and its Recent findings suggest probable short- long-term impacts in even asymptomatic individuals, which could be accounted for by direct indirect pathways brain dysfunction. Understanding scenario might help clinicians health leaders deal with wave neuropsychiatric issues that may arise pandemic other infections, alleviate sequelae these around world.

Language: Английский

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