Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity DOI Creative Commons

Chloé Loyer,

Arnaud Lapostolle, Tomas Urbina

et al.

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: May 30, 2022

Abstract Background A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are components early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought decipher the role neutrophil phenotypes, functions, and homeostasis COVID-19 disease severity outcome. Methods By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 ICU patients with those 22 SARS-CoV-2-negative hospitalized for severe community-acquired pneumonia (CAP) 38 healthy controls. also assessed correlations between these phenotypic functional indicators markers endothelial damage well severity. Results At admission, circulating showed continuous basal hyperactivation seen CAP patients, associated higher levels soluble E- P-selectin, which reflect platelet activation. Furthermore, had expanded aged-angiogenic reverse transmigrated subsets—both involved dysfunction vascular Simultaneously, significantly lower oxidative burst bacterial formyl peptide. Moreover dying expansion subset greater impairment than survivors. Conclusions These data suggest that exhaustion may be pathogenesis identify angiogenic potentially harmful fatal Graphic

Language: Английский

The immunology and immunopathology of COVID-19 DOI Open Access
Miriam Mérad, Catherine A. Blish, Federica Sallusto

et al.

Science, Journal Year: 2022, Volume and Issue: 375(6585), P. 1122 - 1127

Published: March 10, 2022

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify drivers of and fatal COVID-19, understand what leads prolongation symptoms after disease resolution. We review results almost years COVID-19 immunology discuss definitive findings remaining questions regarding our understanding pathophysiology. emerging differences in responses seen those with without Long Covid syndrome, also known as post-acute sequelae SARS-CoV-2. hope that knowledge gained from this will be applied studies inflammatory processes involved critical chronic illnesses, which remain a major unmet need.

Language: Английский

Citations

698
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection DOI Creative Commons
Feargal J. Ryan, Christopher M. Hope, Makutiro G. Masavuli

et al.

BMC Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Jan. 14, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus which responsible for the disease 2019 (COVID-19) pandemic. It increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms many months after infection, condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), syndrome, or post condition. However, despite plethora research on relatively little known about molecular underpinnings these long-term effects.We have undertaken an integrated analysis immune responses in blood at transcriptional, cellular, and serological level 12, 16, 24 weeks post-infection (wpi) 69 patients recovering mild, moderate, severe, critical comparison healthy uninfected controls. Twenty-one were long COVID clinic > 50% reported ongoing more than 6 post-infection.Anti-Spike anti-RBD IgG largely stable up wpi correlated with severity. Deep immunophenotyping revealed significant differences multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) adaptive populations (T helper, T follicular regulatory cells) convalescent individuals compared controls, most strongly evident 12 16 wpi. RNA sequencing perturbations gene expression convalescents until least post-infection. We also uncovered transcriptome not.Variation rate recovery infection cellular transcriptional may explain persistence associated some individuals.

Language: Английский

Citations

234
Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19 DOI Creative Commons
Sarthak Sinha, Nicole L. Rosin, Rohit Arora

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 28(1), P. 201 - 211

Published: Nov. 15, 2021

Abstract Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects dexamethasone severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, bacterial was associated with expansion distinct neutrophil states characterized by interferon (IFN) prostaglandin signaling. Dexamethasone affected circulating neutrophils, altered IFN active downregulated interferon-stimulated genes activated IL-1R2 + neutrophils. expanded immunosuppressive immature neutrophils remodeled cellular interactions changing information receivers into providers. Male patients had higher proportions preferential steroid-induced expansion, potentially affecting outcomes. Our atlas (see ‘Data availability’ section) defines COVID-19-enriched molecular action develop targeted immunotherapies COVID-19.

Language: Английский

Citations

198
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19 DOI Creative Commons
Avraham Unterman, Tomokazu S. Sumida, Nima Nouri

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 21, 2022

Abstract Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, signatures associated with immunopathology poorly understood. Here we use multi-omics single-cell analysis to probe dynamic hospitalized patients stable or progressive course of COVID-19, explore V(D)J repertoires, and assess cellular effects tocilizumab. Coordinated profiling gene expression cell lineage protein markers shows that S100A hi /HLA-DR lo classical monocytes activated LAG-3 T cells hallmarks disease highlights abnormal MHC-II/LAG-3 interaction on myeloid cells, respectively. We also find skewed receptor repertories expanded effector CD8 + clones, unmutated IGHG B mutated clones somatic hypermutation frequency over time. In conclusion, our in-depth reveals dyssynchrony innate adaptive

Language: Английский

Citations

157
Functional inference of gene regulation using single-cell multi-omics DOI
Vinay K. Kartha, Fabiana M. Duarte, Yan Hu

et al.

Cell Genomics, Journal Year: 2022, Volume and Issue: 2(9), P. 100166 - 100166

Published: Aug. 4, 2022

Language: Английский

Citations

149
SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages DOI Creative Commons
Giovanny J. Martínez-Colón, Kalani Ratnasiri, Richard Chen

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(674)

Published: Sept. 22, 2022

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet underlying mechanism unknown. To explore whether severe acute respiratory syndrome 2 (SARS-CoV-2) infection tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled response SARS-CoV-2 in vitro. In cases, identified RNA adipocytes an inflammatory infiltrate. We two distinct cellular targets infection: a subset tissue-resident macrophages. Mature were permissive infection; although macrophages abortively infected, initiated responses within both infected bystander preadipocytes. These data suggest that could contribute severity through replication virus induction local systemic driven

Language: Английский

Citations

87
Comparative analysis of cell–cell communication at single-cell resolution DOI Open Access
Aaron J. Wilk, Alex K. Shalek, Susan Holmes

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(3), P. 470 - 483

Published: May 11, 2023

Language: Английский

Citations

62
Made to order: emergency myelopoiesis and demand-adapted innate immune cell production DOI
James W. Swann, Oakley C. Olson, Emmanuelle Passegué

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(8), P. 596 - 613

Published: March 11, 2024

Language: Английский

Citations

19
Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung DOI Creative Commons
Ting-Hsuan Wu, Kyle J. Travaglini, Arjun Rustagi

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(6)

Published: April 10, 2024

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects SARS-CoV-2 virus by productively infecting healthy human lung tissue using scRNA-seq reconstruct the transcriptional program “infection pseudotime” for individual cell types. predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands viral RNA molecules, taking over 60% transcriptome forming dense bodies while inducing host profibrotic (TGFB1, SPP1) inflammatory (early interferon response, CCL2/7/8/13, CXCL10, IL6/10) programs destroying architecture. Infected alveolar (AMs) showed none these extreme responses. Spike-dependent entry into AMs used ACE2 Sialoadhesin/CD169, whereas IM DC-SIGN/CD209. These results identify IMs as a prominent site takeover, focus inflammation fibrosis, suggest targeting CD209 prevent early pathology pneumonia. This approach be generalized any infection evaluate therapeutics.

Language: Английский

Citations

18
Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection DOI
Leslie Chan,

Kassandra Pinedo,

Mikayla A. Stabile

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(783)

Published: Jan. 29, 2025

At this stage in the COVID-19 pandemic, most infections are "breakthrough" that occur individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity breakthrough infections. We performed single-cell transcriptomic, proteomic, functional profiling of primary to compare immune responses from unvaccinated vaccinated during SARS-CoV-2 Delta wave. Breakthrough were characterized by a less activated transcriptomic profile monocytes natural killer cells, induction pathways limiting monocyte migratory potential cell proliferation. Furthermore, observed female-specific increase proteomic activation multiple subsets These insights suggest vaccination prevents overactivation discernible sex-specific patterns underscore harnessing vaccines mitigating pathologic resulting overactivation.

Language: Английский

Citations

3