Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19 DOI Creative Commons
Xue Li, Ziqi Zhang, Zhenling Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 13, 2022

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has dramatically influenced various aspects the world. It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies prevent treat this threatening disease. universally acknowledged that cell death autophagy are essential crucial maintaining host homeostasis participating in pathogenesis. At present, more than twenty different types have been discovered, some parts which fully understood, whereas need investigation. Increasing studies indicated might play an important role virus pathogenicity. However, knowledge interactions related SARS-CoV-2 between lacks systematic elucidation. Therefore, review, we comprehensively delineate how manipulates diverse (including apoptosis, necroptosis, pyroptosis, ferroptosis, NETosis) itself benefits, simultaneously involved occurrence progression COVID-19, aiming provide a reasonable basis existing interventions further development novel therapies.

Language: Английский

Single-cell multi-omics analysis of the immune response in COVID-19 DOI Creative Commons
Emily Stephenson, Gary Reynolds, Rachel A. Botting

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(5), P. 904 - 916

Published: April 20, 2021

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T B lymphocyte antigen receptor analyses over 780,000 peripheral mononuclear from a cross-sectional cohort 130 patients with varying severities COVID-19. identified expansion nonclassical monocytes expressing complement transcripts (CD16

Language: Английский

Citations

621
Natural killer cells in antiviral immunity DOI Open Access
Niklas K. Björkström, Benedikt Strunz, Hans‐Gustaf Ljunggren

et al.

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(2), P. 112 - 123

Published: June 11, 2021

Language: Английский

Citations

356
Human genetic and immunological determinants of critical COVID-19 pneumonia DOI Open Access
Qian Zhang, Paul Bastard, Adem Karbuz

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 587 - 598

Published: Jan. 28, 2022

Language: Английский

Citations

323
Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19 DOI Creative Commons
Carly G.K. Ziegler, Vincent N. Miao, Anna H. Owings

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(18), P. 4713 - 4733.e22

Published: July 23, 2021

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper symptoms, suggesting potential to constrain viral pathology the nasopharynx. Which cells primarily targets and how influences epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy COVID-19 participants. During COVID-19, we observe expansion of secretory, loss ciliated, epithelial cell repopulation via deuterosomal expansion. In mild moderate express anti-viral/interferon-responsive genes, while in have muted anti-viral responses despite equivalent loads. RNA

Language: Английский

Citations

283
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19 DOI Creative Commons
Monique G.P. van der Wijst, Sara E. Vazquez, George C. Hartoularos

et al.

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(612)

Published: Aug. 24, 2021

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the caused by severe acute respiratory syndrome 2 (SARS-CoV-2). However, prevalence of these antibodies, their longitudinal dynamics across severity scale, and functional effects on circulating leukocytes remain unknown. Here, 284 COVID-19, we IFN–specific peripheral blood samples from 19% 6% disease. We no IFN individuals moderate Longitudinal profiling over 600,000 mononuclear cells using multiplexed single-cell epitope transcriptome sequencing 54 COVID-19 26 non–COVID-19 controls revealed a lack IFN–stimulated gene (ISG-I) responses myeloid This was especially evident dendritic cell populations isolated producing autoantibodies. Moreover, elevated expression inhibitory receptor leukocyte-associated immunoglobulin-like 1 (LAIR1) surface monocytes early course. LAIR1 is inversely correlated ISG-I response but not expressed healthy controls. The deficient observed without supports unifying model for pathogenesis involving suppression through convergent mechanisms.

Language: Английский

Citations

202
Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells DOI Creative Commons
Mario Witkowski, Caroline Tizian, Marta Ferreira‐Gomes

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7888), P. 295 - 301

Published: Oct. 25, 2021

Language: Английский

Citations

202
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19 DOI Open Access
Keith Sacco, Riccardo Castagnoli, Svetlana Vakkilainen

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(5), P. 1050 - 1062

Published: Feb. 17, 2022

Language: Английский

Citations

199
Activation or exhaustion of CD8+ T cells in patients with COVID-19 DOI Creative Commons
Min‐Seok Rha, Eui‐Cheol Shin

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(10), P. 2325 - 2333

Published: Aug. 19, 2021

Abstract In addition to CD4 + T cells and neutralizing antibodies, CD8 contribute protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. COVID-19, exhibiting activated phenotypes are commonly observed, although the absolute number of is decreased. addition, several studies have reported upregulation inhibitory checkpoint receptors, such as PD-1, expression exhaustion-associated gene signatures from COVID-19. However, whether truly exhausted during COVID-19 has been a controversial issue. present review, we summarize current understanding T-cell exhaustion describe available knowledge on functions context activation exhaustion. We also recent reports regarding phenotypical functional analyses SARS-CoV-2-specific discuss long-term memory.

Language: Английский

Citations

167
Innate immunological pathways in COVID-19 pathogenesis DOI
Søren R. Paludan, Trine H. Mogensen

Science Immunology, Journal Year: 2022, Volume and Issue: 7(67)

Published: Jan. 7, 2022

Coronavirus disease 2019 (COVID-19) is a characterized by profound dysregulation of the innate immune system. This knowledge has emerged from large body single-cell omics studies patients with COVID-19, which have provided one most detailed cellular atlases human ever. However, we are only beginning to understand immunological pathways that govern host defense and immunopathology in COVID-19. In this review, discuss emerging understanding how SARS-CoV-2 host-derived molecules activate specific pattern recognition receptors elicit protective interferon responses pathological cytokine responses, particular focus on acute infection lung pathophysiology critical addition, these modulated virus-host interactions stress-sensing pathways. In-depth mechanisms will likely uncover molecular targets for treatment COVID-19 other viral infections. it reveal fine balance between beneficial versus causing responses.

Language: Английский

Citations

164
SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care DOI Creative Commons
Clemens Gutmann, Kaloyan Takov, Sean A. Burnap

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 7, 2021

Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 123), non-COVID-19 ICU sepsis 25) and healthy controls 30). Severe acute respiratory syndrome 2 (SARS-CoV-2) RNA was detected plasma or serum (RNAemia) of when neutralizing antibody response low. RNAemia is associated higher 28-day mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for age sex). comparable performance to the best protein predictors. Mannose binding lectin pentraxin-3 (PTX3), two activators complement pathway innate immune system, are positively mortality. Machine learning identified 'Age, RNAemia' PTX3' as binary signatures In longitudinal comparisons, have a distinct proteomic trajectory mortality, recovery many liver-derived proteins indicating survival. Finally, system galectin-3-binding (LGALS3BP) interaction partners SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake spike-induced cell-cell fusion vitro.

Language: Английский

Citations

149