The signal pathways and treatment of cytokine storm in COVID-19

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 7, 2021

Abstract The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It affected significant proportion of the population both physically mentally, destroyed businesses societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation monocytes macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, especially, cytokine storm (CS). CS characterized by hyperproduction an array pro-inflammatory cytokines closely associated with poor prognosis. These excessively secreted initiate different inflammatory signaling pathways via their receptors on immune tissue cells, resulting in complicated medical symptoms fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress multiorgan failure, ultimately leading to death most severe cases. Therefore, it clinically important understand initiation develop effective treatment strategies COVID-19. Herein, we discuss latest developments immunopathological characteristics focus current research status involved. We also induction, function, downstream signaling, existing potential interventions targeting these related signal pathways. believe comprehensive understanding will help better effectively control this disease diseases.

Language: Английский

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Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 699 - 699

Published: March 19, 2023

The COVID-19 pandemic has caused havoc all around the world. causative agent of is novel form coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components system, decide fate disease. Recent studies reported an subset known as regulatory (Tregs), possess immunosuppressive immunoregulatory properties play a crucial role prognosis shown that patients considerably fewer Tregs than general population. Such decrement may impact on number ways, including diminishing effect inflammatory inhibition, creating inequality Treg/Th17 percentage, raising chance failure. Having enhance likelihood long COVID development addition to contributing disease's poor prognosis. Additionally, tissue-resident provide tissue repair activities, aid recovery patients. severity illness also linked abnormalities Tregs' phenotype, such reduced expression FoxP3 other cytokines, IL-10 TGF-beta. Hence, this review, we summarize mechanisms their possible roles Furthermore, perturbations associated with disease severity. are explained COVID. This review discusses potential therapeutic management COVID-19.

Language: Английский

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Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

Viruses, Journal Year: 2021, Volume and Issue: 13(10), P. 1993 - 1993

Published: Oct. 4, 2021

SARS-CoV-2 is the etiological agent responsible for ongoing COVID-19 pandemic, which continues to spread with devastating effects on global health and socioeconomics. The susceptibility of domestic wild animal species infection a critical facet ecology, since reverse zoonotic spillover events resulting in outbreaks populations could result establishment new virus reservoirs. Adaptive mutations also complicate mitigation strategies combat SARS-CoV-2. In addition, susceptible are essential as standardized preclinical models development efficacy testing vaccines therapeutics. this review, we summarize current findings regarding different experimental provide detailed descriptions clinical disease transmissibility these animals. outline documented natural infections animals that have occurred at human–animal interface. A comprehensive understanding crucial inform public health, veterinary, agricultural systems, guide environmental policies.

Language: Английский

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SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 28, 2021

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels inflammatory cytokines (IL-6, IL-8 IL-10), elevation many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase natriuretic peptide type B. The spleens hilar lymph nodes (LNs) six additional post-mortem examinations were also collected, histopathologic detection both organs manifested tissue damage apoptosis cases. In situ hybridization assays illustrated SARS-CoV-2 viral RNA accumulates tissues, transmission electronic microscopy confirmed coronavirus-like particles visible LNs. Spike Nucleocapsid protein (NP) accumulated LNs, NP antigen restricted angiotensin-converting enzyme 2 (ACE2) positive macrophages dendritic cells (DCs). Furthermore, triggered transcription Il6 , Il8 Il1b genes infected primary DCs vitro SARS-CoV-2-NP + IL-6 IL-1β, which might directly decimate human LNs subsequently lead to vivo . Collectively, demonstrated induced by promoting systemic inflammation direct neutralization spleen

Language: Английский

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Development of a coronavirus disease 2019 nonhuman primate model using airborne exposure

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(2), P. e0246366 - e0246366

Published: Feb. 2, 2021

Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne SARS-CoV-2 have not been investigated. A comparative evaluation COVID-19 in rhesus macaques, and cynomolgus macaques following was performed determine critical disease parameters associated progression, establish correlations between COVID-19. Respiratory abnormalities viral shedding were noted for all animals, indicating successful infection. Cynomolgus developed fever, thrombocytopenia measured monkeys macaques. Type II pneumocyte hyperplasia alveolar fibrosis more frequently observed lung tissue monkeys. The data indicate that, addition can successfully infected by SARS-CoV-2, providing viable macaque natural medical countermeasure evaluation.

Language: Английский

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The role of CD4⁺FoxP3⁺ regulatory T cells in the immunopathogenesis of COVID-19: implications for treatment

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(6), P. 1507 - 1520

Published: Jan. 1, 2021

The severe cases of Coronavirus Disease 2019 (COVID-19) frequently exhibit excessive inflammatory responses, acute respiratory distress syndrome (ARDS), coagulopathy, and organ damage.The most striking immunopathology advanced COVID-19 is cytokine release or "cytokine storm" that attributable to the deficiencies in immune regulatory mechanisms.CD4 + FoxP3 T cells (Tregs) are central regulators responses play an indispensable role maintenance homeostasis.Tregs likely involved attenuation antiviral defense at early stage infection ameliorating inflammation-induced injury late COVID-19.In this article, we review summarize current understanding change Tregs patients infected with coronavirus 2 (SARS-CoV-2) discuss potential COVID-19.The emerging concept Treg-targeted therapies, including both adoptive Treg transfer low dose IL-2 treatment, introduced.Furthermore, Treg-boosting effect therapeutic agents used treatment COVID-19, dexamethasone, vitamin D, tocilizumab sarilumab, chloroquine, hydroxychloroquine, azithromycin, adalimumab tetrandrine, discussed.The problems study future perspectives also addressed.

Language: Английский

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Animal models for SARS-CoV-2

Current Opinion in Virology, Journal Year: 2021, Volume and Issue: 48, P. 73 - 81

Published: April 6, 2021

Language: Английский

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Zoonotic and Reverse Zoonotic Transmissibility of SARS-CoV-2

Virus Research, Journal Year: 2021, Volume and Issue: 302, P. 198473 - 198473

Published: June 9, 2021

Language: Английский

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SARS‐CoV‐2 Productively Infects Human Hepatocytes and Induces Cell Death

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(1)

Published: Jan. 1, 2025

SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing conditions experience more severe disease. While it was known that infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication spread, highlights direct hepatocyte damage. Viral readily detectable upon primary hepatocytes hepatoma cells ancestral SARS-CoV-2, Delta, Omicron variants. Hepatocytes express receptor ACE2 host cell protease TMPRSS2, knocking down TMPRSS2 impaired infection. Progeny viruses released from infected showed typical coronavirus morphology electron microscopy proved infectious when transferred to fresh cells, indicating can contribute virus spread. Importantly, rapidly induced death in a replication-dependent fashion, variant showing faster onset but less extensive death. C57BL/6 wild-type mice mouse-adapted strain high levels RNA lung tissues. ALT peaked cleared liver. Liver histology revealed profound tissue damage immune infiltration, cytopathic effects immune-mediated killing pathology.

Language: Английский

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The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18–59 years: A phase I randomized, double-blinded, controlled trial

Vaccine, Journal Year: 2021, Volume and Issue: 39(20), P. 2746 - 2754

Published: April 9, 2021

Language: Английский

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