The Immunopathogenesis of a Cytokine Storm: The Key Mechanisms Underlying Severe COVID-19

Cytokine & Growth Factor Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A cytokine storm is marked by excessive pro-inflammatory release, and has emerged as a key factor in severe COVID-19 cases - making it critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients' immune systems then fail to shift from innate adaptive immunity, suppressing interferon responses leading pyroptosis neutrophil activation. This amplifies tissue damage inflammation, creating loop. The result the disruption of Th1/Th2 Th17/Treg balances, lymphocyte exhaustion, extensive blood clotting. Cytokine treatments include glucocorticoids suppress system, monoclonal antibodies neutralize specific cytokines, JAK inhibitors block receptor signalling. most treatment options for mitigating infection remain vaccines preventive measure antiviral drugs early stages infection. article synthesizes insights into dysregulation COVID-19, offering framework better understand storms improve monitoring, biomarker discovery, strategies other conditions involving storms.

Language: Английский

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Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Pathogens, Journal Year: 2024, Volume and Issue: 13(3), P. 240 - 240

Published: March 8, 2024

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed currently affected. Many causation hypotheses AD exist, yet intriguing link between viral infection its possible contribution known etiology has become an attractive focal point research for field challenging study task. In this review, we will explore historical perspective milestones that led investigate connection AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along others mentioned, include various presently considered within field. We delve into strong evidence implicating these in development lytic replication axonal transport HSV-1, mechanisms ZIKV neurotropism through human protein Musashi-1 (MSI1), spread SARS-CoV-2 transfer BBB endothelial cells glial then neurons via transsynaptic transfer. also beyond mere associations by carefully analyzing potential which may contribute pathology. This includes but not limited direct neuronal infections, dysregulation immune responses, impact on processing (Aβ42 hyperphosphorylated tau). Controversies challenges virus–AD relationship emerge tease out mechanisms. Looking forward, emphasize future directions, distinct questions proposed experimentations explore, should take tackle remaining unanswered glaring gaps persist. Overall, review aims provide comprehensive survey past, present, infections their association while encouraging further discussion.

Language: Английский

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Matrix metalloproteinase/Fas ligand (MMP/FasL) interaction dynamics in COVID-19: An in silico study and neuroimmune perspective

Heliyon, Journal Year: 2024, Volume and Issue: 10(10), P. e30898 - e30898

Published: May 1, 2024

The initiator of cytokine storm in Coronavirus disease (COVID-19) is still unknown. We recently suggested a complex interaction matrix metalloproteinases (MMPs), Fas ligand (FasL), and viral entry factors could be responsible for the outrage In COVID-19. explored molecular dynamics FasL/MMP7-9 COVID-19 conditions

Language: Английский

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Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2715 - 2715

Published: Feb. 1, 2023

The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications minor or non-neurological symptoms are needed understand their potential as indicators CNS injury vulnerability. Plasma fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays 45 samples from infection [moderate (n = 35), severe 10)] symptoms; 26 fully recovered after ~2 months clinical follow-up 23), 3)]; 14 non-infected controls. SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), also Western blot. Patients without substantial had significantly higher concentrations GFAP, a marker astrocytic activation/injury, NfL T-tau, markers axonal damage degeneration, compared All these correlated at phase. T-tau all normalized recovery. Recovery was observed return normal values quotient between ACE2 fragment circulating full-length species, following change noticed infection. None displayed differences recovery when subjects sub-grouped according occurrence re-evaluation 3 episode (so called post-COVID “long COVID”), such asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache memory loss. Our study demonstrated altered manifestation disease, providing suitable indication vulnerability; but fail predict delayed

Language: Английский

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Role of Inflammation in the Development of COVID-19 to Parkinson’s Disease

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 3259 - 3282

Published: May 1, 2024

The coronavirus disease 2019 (COVID-19) can lead to neurological symptoms such as headaches, confusion, seizures, hearing loss, and loss of smell. link between COVID-19 Parkinson's (PD) is being investigated, but more research needed for a definitive connection.

Language: Английский

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The Orexin System and Its Impact on the Autonomic Nervous and Cardiometabolic System in Post-Acute Sequelae of COVID-19

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 545 - 545

Published: Feb. 21, 2025

Orexins (OXs) are critical for regulating circadian rhythms, arousal, appetite, energy metabolism, and electrolyte balance, affecting both the autonomic nervous system (ANS) cardiovascular (CVS). Disruption of OX can result in symptoms similar to those observed post-acute sequelae COVID-19 (PASC). This review emphasizes adverse effects dysregulation on cardiometabolic functions patients with PASC. Additionally, we highlight potential anti-OX therapies provide neuroprotective, anti-inflammatory, immunoregulatory benefits, offering hope alleviating some debilitating associated

Language: Английский

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Alterations in cerebral artery flow velocity acceleration pattern correlate with cognitive impairment in diabetes mellitus

Applied Neuropsychology Adult, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: Feb. 24, 2025

Flow velocity acceleration pattern is related to shear stress, pressure changes, cardiovascular risk factors, diabetes mellitus, hypertension, endothelial dysfunction and arterial stiffness. Considering the hemodynamic alterations in cognitive impairment, perturbations cerebral artery flow may correlate with which could enhance our understanding of how factors drive decline from a mechanistic point view. The first derivative middle waveforms obtained via transcranial Doppler were computed visualize acceleration/deceleration waves (a,b,c,d,e) ensemble-averaged signals. Vascular Aging Index was calculated per its definition (VAI:(b-c-d-e)/a). Relationship between multiple domains VAI evaluated standard statistical tests. significantly correlated HVLT total recall (Hopkins Verbal Learning Test-revised) (r: -0.310 p: 0.046, n: 42), delayed -0.396 0.009), % Retention -0.305 0.050) components RCFT(Rey-Osterrieth Complex Figure Test), namely raw copy score -0.524 p < 0.001), immediate -0.323 0.037). Controlling for age, body mass index, gray matter volume duration yielded stronger correlations but lower group numbers due missing data. Correlation coefficients -0.439 (p: 0.012) -0.444(p: 0.011 36) respectively. Likewise adjusted RCFT improved (Raw Copy r: -0.557 0.001, Immediate Recall -0.440 0.012, Delayed -0.358 0.044). In patients diabetes, correlates performance visuo-constructional verbal domains. Computational fluid dynamics aid developing better hemodynamics-cortical function coupling.

Language: Английский

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Emerging Viral Infections (ZIKV, SARS‐CoV‐2, and MPXV) and Depression: Ketamine and (S, R)‐Ketamine as Promising Antidepressants

Reviews in Medical Virology, Journal Year: 2025, Volume and Issue: 35(3)

Published: April 9, 2025

ABSTRACT Emerging viral pathogens, newly reported or rapidly evolving viruses, are a significant public health concern worldwide. Beyond their characteristic clinical presentations, emerging such as monkeypox virus (MPXV) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been increasingly implicated in the development of various neuropsychiatric complications including depression, mainly due to ability induce neuroinflammation, immune dysfunction, neurotransmitter imbalances. Depression is common mental condition characterised by continuous low mood sadness, pessimism, anxiety, even tendency suicide main symptoms. Post depression commonly shows challenges, traditional antidepressant agents exhibit suboptimal efficacy prolonged onset action. Regarding this, ketamine its enantiomers, S‐ketamine R‐ketamine, recently received increasing attention potential options light potent effective properties. The present review describes underlying pathophysiological mechanisms associated with highlighting role neuroinflammation disturbances inneurotransmitter systems. It also discusses current evidence demonstrating effectiveness safety, especially case treatment‐resistant growing relevance for linked infections, depression. Although preliminary reports propose effectiveness, additional studies needed optimal treatment strategies, long‐term incorporation into practice. Addressing these challenges will be critical optimising ketamine‐ (S, R)‐ketamine‐containing therapeutic protocols treating infections.

Language: Английский

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Assessing Biomarkers in Viral Infection

Advances in experimental medicine and biology, Journal Year: 2023, Volume and Issue: unknown, P. 159 - 173

Published: Jan. 1, 2023

Language: Английский

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Viral Infections, a Trigger and Risk Factor of Alzheimer’s Disease?

Published: Feb. 8, 2024

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed currently affected. Many causation hypotheses AD exist, yet intriguing link between viral infection its possible contribution known etiology has become an attractive focal point research for field challenging study task. In this review, we will explore historical perspective milestones that led investigate connection AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along others mentioned, include various presently considered within field. We delve into strong evidence implicating these in development also extend beyond mere associations by carefully analyzing potential mechanisms which may contribute pathology. This includes but not limited direct neuronal infections, dysregulation immune responses, impact on protein processing. Controversies challenges viral-AD relationship emerge tease out considered. Looking forward, emphasize future directions should take tackle remaining unanswered questions glaring gaps persist. Overall, review aims provide comprehensive survey past, present, infections their association development.

Language: Английский

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