The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19 DOI
Ralph Rogers, Deborah Wentworth, Andrew Phillips

et al.

Annals of Internal Medicine, Journal Year: 2022, Volume and Issue: 175(10), P. 1401 - 1410

Published: Aug. 29, 2022

Background: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding the pathogenesis COVID-19. Objective: To evaluate whether levels can predict short-term clinical outcomes identify viral factors associated hospitalized SARS-CoV-2. Design: Cross-sectional study baseline level from 2540 participants enrolled TICO (Therapeutics for Inpatients With COVID-19) platform trial August 2020 to November 2021, additional data on day 5 outcome time discharge. Setting: 114 centers 10 countries. Participants: Adults acute infection 12 days or less symptoms. Measurements: Baseline N was measured at a central laboratory. Delta variant status determined nasal swabs using reverse transcriptase polymerase chain reaction. Associations between patient characteristics were assessed both unadjusted multivariable modeling. Association elevated 1000 ng/L greater outcomes, including worsening ordinal pulmonary scale hospital discharge, evaluated logistic regression Fine–Gray models, respectively. Results: Plasma below quantification 5% enrollment, 57%. severity illness strongly level, mean 3.10-fold higher among those requiring noninvasive ventilation high-flow cannula compared room air (95% CI, 2.22 4.34). who lacked antispike antibodies (6.42 fold; 5.37 7.66) (1.73 1.41 2.13). Additional included male sex, shorter since admission, decreased remdesivir, renal impairment. In contrast, race, ethnicity, body mass index, immunocompromising conditions not levels. markedly odds worsened (odds ratio, 5.06 [CI, 3.41 7.50]) longer discharge (median, 7 vs. 4 days; subhazard 0.51 0.45 0.57]), ratios similar across all severity. Limitations: samples drawn presentation. No point-of-care test measure is currently available. Conclusion: Elevated highly clinically outcomes. Multiple are These support potential role ongoing replication patients. Primary Funding Source: U.S. government Operation Warp Speed National Institute Allergy Infectious Diseases.

Language: Английский

ADAR1 and ZBP1 in innate immunity, cell death, and disease DOI Creative Commons
Rajendra Karki, Thirumala‐Devi Kanneganti

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(3), P. 201 - 216

Published: Jan. 27, 2023

Language: Английский

Citations

53
SARS-CoV-2 and innate immunity: the good, the bad, and the “goldilocks” DOI Creative Commons
Benjamín L. Sievers, Mark T. K. Cheng,

Kata Csiba

et al.

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 171 - 183

Published: Nov. 20, 2023

Abstract An ancient conflict between hosts and pathogens has driven the innate adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that be leveraged therapeutically. The humoral response to SARS-CoV-2 infection been focus intense research, role immune system received significantly less attention. Here, we review current knowledge various means employs evade defense systems. We consider immunity in vaccines phenomenon long COVID.

Language: Английский

Citations

51
The roles of critical pro‐inflammatory cytokines in the drive of cytokine storm during SARS‐CoV‐2 infection DOI Creative Commons
Muhammad Suhaib Qudus, Mingfu Tian,

Summan Sirajuddin

et al.

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(4)

Published: April 1, 2023

Abstract In patients with severe COVID‐19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive uncontrolled release of pro‐inflammatory cytokines. High levels numerous crucial cytokines, such as interleukin‐1 (IL‐1), IL‐2, IL‐6, tumor necrosis factor‐α, interferon (IFN)‐γ, IFN‐induced protein 10 kDa, granulocyte‐macrophage colony‐stimulating factor, monocyte chemoattractant protein‐1, IL‐10 so on, have been found in COVID‐19. They participate cascade amplification pathways responses through complex inflammatory networks. Here, we review involvements these critical cytokines SARS‐CoV‐2 infection discuss their potential roles triggering or regulating help to understand pathogenesis So far, there rarely effective therapeutic strategy for storm besides using glucocorticoids, proved fatal side effects. Clarifying key involved network will develop an ideal intervention, neutralizing antibody certain inhibitor some signal pathways.

Language: Английский

Citations

50
PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis DOI Creative Commons
Rajendra Karki, Thirumala‐Devi Kanneganti

Current Opinion in Immunology, Journal Year: 2023, Volume and Issue: 83, P. 102348 - 102348

Published: May 31, 2023

The innate immune response provides the first line of defense against infection and disease. Regulated cell death (RCD) is a key component activation, RCD must be tightly controlled to clear pathogens while preventing excess inflammation. Recent studies have highlighted central role for sensor Z-DNA-binding protein 1 (ZBP1) as an activator form inflammatory called PANoptosis, which regulated by multifaceted complex PANoptosome. In influenza A virus infection, ZBP1 activates nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, then acts integral ZBP1-PANoptosome drive death, PANoptosis. this context, NLRP3 inflammasome critical caspase-1 activation proinflammatory cytokine interleukin (IL)-1β IL-18 maturation, but dispensable due functional redundancies between PANoptosome molecules. Similarly, also absent in melanoma 2 (AIM2)-PANoptosome; forms Francisella novicida herpes simplex incorporates AIM2 component. review, we will discuss roles mediating responses through inflammasomes, PANoptosomes, PANoptosis during infection. An improved understanding molecular mechanisms immunity essential development targeted modalities that can improve patient outcomes mitigating severe

Language: Английский

Citations

46
Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management DOI Open Access
Zarina Mohd Zawawi,

Jeevanathan Kalyanasundram,

Rozainanee Mohd Zain

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6142 - 6142

Published: March 24, 2023

The coronavirus disease 2019 (COVID-19) became a worldwide concern at the beginning of 2020 and has affected millions. Several previous studies revealed impact imbalanced innate immune response on progression COVID-19 its outcomes. High levels proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) interleukins are produced readily by cells to fight Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Nonetheless, cytokine-mediated inflammatory events also linked detrimental lung injury respiratory failure, which can result in deaths among patients. TNF-α is amongst early mediate responses enhance cell infiltration SARS-CoV-2 In COVID-19, TNF-α-mediated inflammation cause tissue damage gradually promotes fibrosis, later results pneumonia, pulmonary edema, acute distress syndrome. This review, therefore, aims deliberate immunomodulatory roles promoting relation with morbidity mortality. addition, this review proposes potential biomarker for prognosis severe related complications molecular target anti-TNF-α therapy.

Language: Английский

Citations

45
Mitochondria-Targeting Type-I Photodrug: Harnessing Caspase-3 Activity for Pyroptotic Oncotherapy DOI
Zhigao Yi,

Xujuan Qin,

Li Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9413 - 9421

Published: March 20, 2024

Precise control of cellular signaling events during programmed cell death is crucial yet challenging for cancer therapy. The modulation signal transduction in cells holds promise but limited by the lack efficient, biocompatible, and spatiotemporally controllable approaches. Here we report a photodynamic strategy that modulates both apoptotic pyroptotic altering caspase-3 protein activity associated crosstalk. This employs mitochondria-targeting, near-infrared activatable probe (termed M-TOP) functions via type-I photochemical mechanism. M-TOP less dependent on oxygen more effective treating drug-resistant cells, even under hypoxic conditions. Our study shows higher doses induce caspase-3/gasdermin-E pathway, whereas lower lead to apoptosis. method across diverse gasdermin-E-expressing cells. Moreover, mediated shift from can evoke controlled inflammatory response, leading robust balanced immune reaction. effectively inhibits distal tumor growth postsurgical recurrence. work demonstrates feasibility modulating intracellular through rational design anticancer drugs.

Language: Английский

Citations

31
Toll‐like receptors in health and disease DOI Creative Commons
Kunyu Wang, Hanyao Huang, Zhan Qi

et al.

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

Published: April 29, 2024

Toll-like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition (PRRs) that central the regulation host protective adaptive immune responses. Activation TLRs in innate myeloid cells directs lymphocytes produce most appropriate effector responses eliminate infection maintain homeostasis body's internal environment. Inappropriate TLR stimulation can lead development general autoimmune diseases as well chronic acute inflammation, even cancer. Therefore, expected be targets for therapeutic treatment inflammation-related diseases, microbial infections, human cancers. This review summarizes recent discoveries molecular structural biology TLRs. The role different signaling pathways such diabetes, cardiovascular respiratory digestive cancers (oral, gastric, breast, colorectal) is highlighted new drugs related clinical treatments trials, providing an overview potential prospects TLR-related diseases.

Language: Английский

Citations

23
ACE2-dependent and -independent SARS-CoV-2 entries dictate viral replication and inflammatory response during infection DOI
Tianhao Duan, Changsheng Xing, Junjun Chu

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(4), P. 628 - 644

Published: March 21, 2024

Language: Английский

Citations

21
Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating DOI Creative Commons
Nikhila S. Tanneti,

Anant K. Patel,

Li Tan

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(4)

Published: March 13, 2024

ABSTRACT The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features each VOC linked variations replication rate. Patient-derived primary nasal cultures grown at air-liquid interface used model upper respiratory infection compared cell lines derived from lung epithelia. All VOCs replicated higher titers than ancestral virus, suggesting a for efficiency. In cultures, Omicron highest early time points, followed by Delta, paralleling comparative studies population sampling. viruses entered primarily via transmembrane serine protease 2 (TMPRSS2)-dependent pathway, more likely use an endosomal route entry. activated overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, protein kinase R activation. Among VOCs, induced expression most IFN IFN-stimulated genes. Infections resulted damage, compromise barrier integrity loss cilia ciliary beating function, especially during Delta infection. Overall, optimized tract least favorable lower line, cytopathic both cells. Our findings highlight differences among level imply distinct mechanisms pathogenesis infected individuals. IMPORTANCE Comparative analysis infections virus concern, Alpha, Beta, Omicron, indicated that selected efficiency replication. patient-derived infection, reached finding confirmed parallel sampling studies. While all dsRNA-mediated host strongest interferon-stimulated gene response. damaging cells syncytia formation, integrity, function.

Language: Английский

Citations

20
Mitophagy and cGAS–STING crosstalk in neuroinflammation DOI Creative Commons
Xiaogang Zhou, Jing Wang, Lu Yu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3327 - 3361

Published: May 13, 2024

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, crucial innate immunity. This pathway responds DNA and associated with cellular stress. Our review explores molecular details regulatory mechanisms of mitophagy pathway. We critically evaluated literature demonstrating how dysfunctional leads neuroinflammatory conditions, primarily through accumulation mitochondria, activating activation prompts production proinflammatory cytokines, exacerbating neuroinflammation. emphasizes interaction between Effective might suppress offering protection against Conversely, impaired may activate potentially leading chronic Additionally, we explored this influences neurodegenerative disorders, suggesting a common mechanism in such diseases. In conclusion, there need additional targeted research unravel complexities mitophagy–cGAS–STING interactions their role neurodegeneration. highlights potential therapies targeting these pathways, which could lead new treatments conditions. synthesis enhances our understanding foundations neuroinflammation opens therapeutic avenues disease research.

Language: Английский

Citations

16