Virus-induced senescence is a driver and therapeutic target in COVID-19

Nature, Год журнала: 2021, Номер 599(7884), С. 283 - 289

Опубликована: Сен. 13, 2021

Язык: Английский

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Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

Nature Medicine, Год журнала: 2021, Номер 28(1), С. 201 - 211

Опубликована: Ноя. 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.

Язык: Английский

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Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Cell, Год журнала: 2021, Номер 185(3), С. 493 - 512.e25

Опубликована: Дек. 28, 2021

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, it remains unclear whether T cells contribute disease pathology. Here, we combined single-cell transcriptomics proteomics with mechanistic studies assess pathogenic cell functions inducing signals. We identified highly activated CD16

Язык: Английский

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Advances and Utility of the Human Plasma Proteome

Journal of Proteome Research, Год журнала: 2021, Номер 20(12), С. 5241 - 5263

Опубликована: Окт. 21, 2021

The study of proteins circulating in blood offers tremendous opportunities to diagnose, stratify, or possibly prevent diseases. With recent technological advances and the urgent need understand effects COVID-19, proteomic analysis blood-derived serum plasma has become even more important for studying human biology pathophysiology. Here we provide views perspectives about developments possible clinical applications that use mass-spectrometry(MS)- affinity-based methods. We discuss examples where proteomics contributed valuable insights into SARS-CoV-2 infections, aging, hemostasis offered by combining with genetic data. As a contribution Human Proteome Organization (HUPO) Plasma Project (HPPP), present PeptideAtlas build 2021-07 comprises 4395 canonical 1482 additional nonredundant detected 240 MS-based experiments. In addition, report new Extracellular Vesicle 2021-06, which five studies 2757 extracellular vesicles blood, 74% (2047) are common PeptideAtlas. Our overview summarizes advances, impactful applications, ongoing challenges translating utility precision medicine.

Язык: Английский

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High‐resolution serum proteome trajectories in COVID‐19 reveal patient‐specific seroconversion

EMBO Molecular Medicine, Год журнала: 2021, Номер 13(8)

Опубликована: Июль 7, 2021

A deeper understanding of COVID-19 on human molecular pathophysiology is urgently needed as a foundation for the discovery new biomarkers and therapeutic targets. Here we applied mass spectrometry (MS)-based proteomics to measure serum proteomes patients symptomatic, but PCR-negative controls, in time-resolved manner. In 262 controls 458 longitudinal samples 31 patients, hospitalized COVID-19, remarkable 26% proteins changed significantly. Bioinformatics analyses revealed co-regulated groups shared biological functions. Proteins innate immune system such CRP, SAA1, CD14, LBP, LGALS3BP decreased early time course. Regulators coagulation (APOH, FN1, HRG, KNG1, PLG) lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over course disease. global correlation map provides system-wide functional association between proteins, processes, clinical chemistry parameters. Importantly, five SARS-CoV-2 immunoassays against antibodies excellent correlations with an extensive range immunoglobulin regions, which were quantified by MS-based proteomics. The high-resolution profile all regions showed individual-specific differences commonalities potential pathophysiological relevance.

Язык: Английский

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Social Media Efficacy in Crisis Management: Effectiveness of Non-pharmaceutical Interventions to Manage COVID-19 Challenges

Frontiers in Psychiatry, Год журнала: 2022, Номер 12

Опубликована: Фев. 7, 2022

The new identified virus COVID-19 has become one of the most contagious diseases in human history. ongoing coronavirus created severe threats to global mental health, which have resulted crisis management challenges and international concerns related health issues. As September 9, 2021, there were over 223.4 million patients with COVID-19, including 4.6 deaths 200 recovered reported worldwide, made outbreak deadliest pandemics aggressive public implementations endorsed various precautionary safety preventive strategies suppress minimize disease transmission. second, third, fourth waves continue pose management, as its evolution implications are still unfolding. This study posits that examining strategic ripostes pandemic experiences sheds light on combatting this emergency. recommends two model help reduce adverse effects immune systems general population. present paper NPI interventions (non-pharmaceutical intervention) combine measures, such suppression strategy (lockdown restrictions) mitigation decrease burden systems. current influenced all vital economic sectors developed problems. supply vaccines is not sufficient manage In crisis, NPIs helpful spillover impacts pandemic. It articulates prominence resilience agility resume activities resolve healthcare primarily focuses role social media tackle crises posed by economies, business activities, burdens, government support for societies businesses, provision disruptions. suggests intervention can control rapid spread hands-on system will normal conditions quickly. Global economies revitalize scientific contributions collaborations, science industries, through support.

Язык: Английский

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COVID-19 and cellular senescence

Nature reviews. Immunology, Год журнала: 2022, Номер 23(4), С. 251 - 263

Опубликована: Окт. 5, 2022

Язык: Английский

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Epigenetic scores for the circulating proteome as tools for disease prediction

eLife, Год журнала: 2022, Номер 11

Опубликована: Янв. 13, 2022

Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of circulating proteome and incident diseases. Using from four cohorts, trained tested scores (EpiScores) for 953 plasma proteins, identifying 109 that explained 1% 58% variance in protein levels after adjusting known quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent sample (Generation Scotland; n = 9537) relating them morbidities over a follow-up 14 years, uncovered 137 EpiScore-disease associations. These associations were largely immune cell proportions, common lifestyle health factors, biological aging. Notably, found our diabetes-associated highlighted previous top biomarker proteome-wide assessments diabetes. can therefore be valuable resource prediction risk stratification.

Язык: Английский

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Mass spectrometry‐based high‐throughput proteomics and its role in biomedical studies and systems biology

PROTEOMICS, Год журнала: 2022, Номер 23(7-8)

Опубликована: Ноя. 9, 2022

Abstract There are multiple reasons why the next generation of biological and medical studies require increasing numbers samples. Biological systems dynamic, effect a perturbation depends on genetic background environment. As consequence, many conditions need to be considered reach generalizable conclusions. Moreover, human population clinical only sufficient statistical power if conducted at scale with precise measurement methods. Finally, proteins remain without functional annotations, because they have not been systematically studied under broad range conditions. In this review, we discuss latest technical developments in mass spectrometry (MS)‐based proteomics that facilitate large‐scale by fast efficient chromatography, scanning spectrometers, data‐independent acquisition (DIA), new software. We further highlight recent which demonstrate how high‐throughput (HT) can applied capture diversity, annotate gene functions or generate predictive prognostic models for diseases.

Язык: Английский

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Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Авг. 11, 2021

In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate we conduct detailed longitudinal analysis systemic and pulmonary responses, corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages lungs exert earliest strongest transcriptional response to including induction pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence productive react, depending on cell subtypes, by strong early expression anti-viral, pro-inflammatory, T recruiting genes. Recruitment cytotoxic well emergence IgM antibodies precede viral clearance day 5 post infection. Investigating infected thus identifies type-specific effector functions, providing insights into pathomechanisms informing therapeutic strategies.

Язык: Английский

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