Advances and Challenges in Sepsis Management: Modern Tools and Future Directions DOI Creative Commons
Elena Santacroce,

Miriam D’Angerio,

Alin Liviu Ciobanu

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 439 - 439

Published: March 2, 2024

Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, metabolic changes. The complexity of sepsis stems not only from its pathophysiology also the heterogeneity patient responses, posing significant challenges developing universally effective therapies. review emphasizes importance phenotyping enhance patient-specific diagnostic therapeutic strategies. Phenotyping cells, which categorizes patients based on clinical immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as crucial tool this endeavor, offering rapid, low cost detailed analysis cell populations their functional states. Indeed, technology facilitates understanding dysfunctions contributes identification novel biomarkers. Our underscores potential integrating flow with omics data, machine learning observations refine management, highlighting shift towards personalized medicine care. approach could lead more precise interventions, improving outcomes heterogeneously affected population.

Language: Английский

Diverse functional autoantibodies in patients with COVID-19 DOI Creative Commons
Eric Y. Wang, Tianyang Mao, Jon Klein

et al.

Nature, Journal Year: 2021, Volume and Issue: 595(7866), P. 283 - 288

Published: May 19, 2021

Language: Английский

Citations

835
SARS-CoV-2 pathogenesis DOI Open Access
Mart M. Lamers, Bart L. Haagmans

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(5), P. 270 - 284

Published: March 30, 2022

Language: Английский

Citations

712
Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19 DOI Creative Commons
Yapeng Su, Daniel Chen, Dan Yuan

et al.

Cell, Journal Year: 2020, Volume and Issue: 183(6), P. 1479 - 1495.e20

Published: Oct. 28, 2020

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics 139 COVID-19 patients representing all levels disease severity, from serial blood draws collected during first week infection following diagnosis. identify a major shift between mild moderate disease, at which point elevated inflammatory signaling is accompanied by loss specific classes metabolites metabolic processes. Within this stressed environment multiple unusual cell phenotypes emerge amplify with increasing severity. condensed over 120,000 features into single axis to capture how different coordinate in response SARS-CoV-2. This immune-response independently aligns composition changes, metrics clotting, sharp transition disease. study suggests that may provide most effective setting for therapeutic intervention.

Language: Английский

Citations

558
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity DOI Creative Commons
Marcin F. Osuchowski, Martin Sebastian Winkler, Tomasz Skirecki

et al.

The Lancet Respiratory Medicine, Journal Year: 2021, Volume and Issue: 9(6), P. 622 - 642

Published: May 7, 2021

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into epidemiology of COVID-19, important questions remain about clinical complexities and underlying mechanisms disease phenotypes. Severe most commonly involves respiratory manifestations, although other systems are also affected, acute is often followed by protracted complications. Such complex manifestations suggest dysregulates host response, triggering wide-ranging immuno-inflammatory, thrombotic, parenchymal derangements. We review intricacies pathophysiology, its various phenotypes, anti-SARS-CoV-2 response at humoral cellular levels. Some similarities exist between failure origins, but evidence for many distinctive mechanistic features indicates constitutes a new entity, emerging data suggesting involvement an endotheliopathy-centred pathophysiology. Further research, combining basic studies, needed advance understanding pathophysiological characterise immuno-inflammatory derangements across range phenotypes enable optimum care patients COVID-19.

Language: Английский

Citations

479
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

360
COVID-19 vaccines: The status and perspectives in delivery points of view DOI Open Access

Jee Young Chung,

Melissa N. Thone, Young Jik Kwon

et al.

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 170, P. 1 - 25

Published: Dec. 24, 2020

Language: Английский

Citations

355
K18-hACE2 mice develop respiratory disease resembling severe COVID-19 DOI Creative Commons
Claude Kwe Yinda, Julia R. Port, Trenton Bushmaker

et al.

PLoS Pathogens, Journal Year: 2021, Volume and Issue: 17(1), P. e1009195 - e1009195

Published: Jan. 19, 2021

SARS-CoV-2 emerged in late 2019 and resulted the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small study pathogenesis of severe fast-tracked medical countermeasure development. Here, we show transgenic mice expressing human receptor (angiotensin-converting enzyme 2 [hACE2]) under cytokeratin 18 promoter (K18) are susceptible infection dose-dependent lethal course. After inoculation with either 104 TCID50 or 105 TCID50, rapid weight loss both groups uniform lethality group. High levels viral RNA shedding were observed from upper lower respiratory tract intermittent was intestinal tract. Inoculation high infectious virus titers nasal turbinates, trachea lungs. The interstitial pneumonia pulmonary pathology, replication evident pneumocytes, similar reported cases COVID-19. macrophage lymphocyte infiltration lungs upregulation Th1 proinflammatory cytokines/chemokines. Extrapulmonary cerebral cortex hippocampus several animals at 7 DPI but not 3 DPI. inflammatory response pathology bears resemblance Additionally, demonstrate mild course can be simulated by low dose 102 SARS-CoV-2, resulting minimal clinical manifestation near survival. Taken together, these data support future application this model studies

Language: Английский

Citations

299
Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19 DOI Creative Commons
Shea A. Lowery, Alan Sariol, Stanley Perlman

et al.

Cell Host & Microbe, Journal Year: 2021, Volume and Issue: 29(7), P. 1052 - 1062

Published: May 17, 2021

Language: Английский

Citations

263
Unique immunological profile in patients with COVID-19 DOI Creative Commons
Stefania Varchetta, Dalila Mele, Barbara Oliviero

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(3), P. 604 - 612

Published: Oct. 15, 2020

The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with COVID-19, some whom succumbed. A control population healthy subjects was included. Patients COVID-19 had altered distribution peripheral blood lymphocytes, increased proportion mature natural killer (NK) cells low T-cell numbers. NK CD8+ T overexpressed immunoglobulin mucin domain-3 (TIM-3) CD69. cell exhaustion attested by frequencies programmed death protein 1 (PD-1) positive reduced group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing cells, associated a ability to secrete interferon (IFN)γ. poor outcome showed contraction immature CD56bright expansion CD57+ FcεRIγneg adaptive compared survivors. Increased serum levels IL-6 were also more frequently identified deceased Of note, monocytes secreted abundant quantities IL-6, IL-8, IL-1β which persisted at lower several weeks after recovery concomitant normalization CD69, PD-1 TIM-3 expression restoration hyperactivated/exhausted response dominate SARS-CoV-2 infection, probably driven uncontrolled secretion inflammatory cytokines monocytes. These findings unveil unique immunological profile that will help design effective stage-specific treatments for this potentially deadly disease.

Language: Английский

Citations

243
Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data DOI Creative Commons
Tiphanie P. Vogel, Karina A. Top, Christos Karatzios

et al.

Vaccine, Journal Year: 2021, Volume and Issue: 39(22), P. 3037 - 3049

Published: Feb. 25, 2021

This is a Brighton Collaboration Case Definition of the term "Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)" to be utilized evaluation adverse events following immunization. The case definition was developed by topic experts convened Coalition for Epidemic Preparedness Innovations (CEPI) context active development vaccines SARS-CoV-2. format followed, including an exhaustive review literature, develop consensus defined levels certainty. document underwent peer Network selected expert external reviewers prior submission. comments were taken into consideration edits incorporated this final manuscript.

Language: Английский

Citations

220