Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19 DOI Creative Commons
Harish Narasimhan, In Su Cheon, Wei Qian

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 14, 2023

ABSTRACT The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae COVID-19 (PASC), are rapidly evolving into a major public health concern. underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation impaired tissue repair in context unclear. With insights from three independent clinical cohorts patients with lung function viral infection-mediated pulmonary fibrosis, we established clinically relevant mouse model post-viral sequelae investigate pathophysiology respiratory PASC. By employing combination spatial transcriptomics imaging, identified dysregulated proximal interactions between cells epithelial progenitors unique fibroproliferation not acute or idiopathic fibrosis (IPF). Specifically, found central role for lung-resident CD8 + T cell-macrophage maintaining Krt8 hi transitional ectopic Krt5 basal cell progenitors, thus impairing alveolar regeneration fibrotic after pneumonia. Mechanistically, derived IFN-γ TNF stimulated macrophages chronically release IL-1β, resulting accumulation dysplastic fibrosis. Notably, therapeutic neutralization TNF, IL-1β resolution infection resulted markedly improved restoration function. Together, our findings implicate immune-epithelial progenitor niche Moreover, contrast other approaches requiring early intervention, highlight strategies rescue disease aftermath infections, addressing current unmet need management disease.

Language: Английский

Aggregate Index of Systemic Inflammation (AISI), Disease Severity, and Mortality in COVID-19: A Systematic Review and Meta-Analysis DOI Open Access
Angelo Zinellu, Panagiotis Paliogiannis, Arduino A. Mangoni

et al.

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(14), P. 4584 - 4584

Published: July 10, 2023

Combined indices of different haematological cell types appear to be particularly promising for investigating the link between systemic inflammation and coronavirus disease 2019 (COVID-19). We conducted a systematic review meta-analysis assess aggregate index (AISI), an emerging derived from neutrophil, monocyte, platelet, lymphocyte counts, in hospitalized COVID-19 patients with severity survival status. searched electronic databases 1st December 10th June 2023 assessed risk bias certainty evidence. In 13 studies, severe disease/death was associated significantly higher AISI values on admission vs. non-severe disease/survival (standard mean difference (SMD) = 0.68, 95% CI 0.38 0.97, p < 0.001). The also five studies reporting odds ratios (4.39, 2.12 9.06, ˂ 0.001), but not three hazard (HR 1.000, 0.999 1.002, 0.39). pooled sensitivity, specificity, area under curve were 0.66 (95% 0.58 0.73), 0.78 0.73 0.83), 0.79 0.76 respectively. Our study has shown that can effectively discriminate outcome (PROSPERO registration number: CRD42023438025).

Language: Английский

Citations

15
Brain Leukocytes as the Potential Therapeutic Target for Post-COVID-19 Brain Fog DOI Open Access
Itsuro Kazama

Neurochemical Research, Journal Year: 2023, Volume and Issue: 48(8), P. 2345 - 2349

Published: March 23, 2023

Language: Английский

Citations

14
SARS-CoV-2: A Glance at the Innate Immune Response Elicited by Infection and Vaccination DOI Creative Commons
Nicola Manfrini, Samuele Notarbartolo, Renata Grifantini

et al.

Antibodies, Journal Year: 2024, Volume and Issue: 13(1), P. 13 - 13

Published: Feb. 8, 2024

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to almost seven million deaths worldwide. SARS-CoV-2 causes infection through respiratory transmission and can occur either without any symptoms or with clinical manifestations which be mild, severe or, in some cases, even fatal. Innate immunity provides the initial defense against virus sensing pathogen-associated molecular patterns triggering signaling pathways that activate antiviral inflammatory responses, limit viral replication help identification removal of infected cells. However, temporally dysregulated excessive activation innate immune response is deleterious for host associates COVID-19. In addition its defensive role, pivotal priming adaptive polarizing effector function. This capacity relevant context both natural vaccination. Here, we provide an overview current knowledge responses

Language: Английский

Citations

5
Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols DOI
Abdul Mannan Baig,

Sandy Rosko,

B.R. Jaeger

et al.

Inflammopharmacology, Journal Year: 2024, Volume and Issue: 32(4), P. 2075 - 2090

Published: May 21, 2024

Language: Английский

Citations

5
Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models DOI Open Access

Hong‐Yi Zheng,

Tian‐Zhang Song,

Yong‐Tang Zheng

et al.

动物学研究, Journal Year: 2024, Volume and Issue: 45(4), P. 747 - 766

Published: Jan. 1, 2024

The distribution of the immune system throughout body complicates

Language: Английский

Citations

4
Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report DOI
Sara C. Auld, Ajay Sheshadri, Jennifer Alexander‐Brett

et al.

Annals of the American Thoracic Society, Journal Year: 2024, Volume and Issue: 21(9), P. 1219 - 1237

Published: July 25, 2024

Continued improvements in the treatment of pulmonary infections have paradoxically resulted a growing challenge individuals with postinfectious complications (PIPCs). PIPCs been long recognized after tuberculosis, but recent experiences such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic underscored importance following other lower tract infections. Independent causative pathogen, most available studies focus on short-term outcomes rather than long-term morbidity among survivors. In this document, we establish conceptual scope for discussion globally significant pathogens and an examination how these can damage different components lung, resulting spectrum PIPCs. We also review potential mechanisms transition from infection to PIPC, including interplay between pathogen-mediated injury aberrant host responses, which together result Finally, identify cross-cutting research priorities field facilitate future incidence PIPCs, define common mechanisms, therapeutic strategies, ultimately reduce burden survivors

Language: Английский

Citations

4
Outcomes of Severe Covid-19 Among Patients Who Did and Did Not Receive Tocilizumab: A Two-year Prospective Cohort Study DOI
Branko Beronja, Tatjana Gazibara,

Olja Stevanović

et al.

Published: Jan. 20, 2025

Abstract Evidence about long-term effects of tocilizumab (TCZ) treatment after COVID-19 is sparse. This study explored COVID-19-related outcomes over a two-year period among people who received TCZ and those did not. Patients were recruited from two healthcare centers in Serbia, March 2021 to December 2022. Demographic, clinical, laboratory data collected hospital records. Outcomes years follow-up, such as post-COVID syndrome (PCS) mortality, retrieved records or through telephone calls. Cumulative mortality the cohort (150; 32.8% patients) was 20.6%, non-TCZ (307 patients; 67.2%) 24.7%. In recipients there lower cumulative incidence PCS (3.4% vs. 9.9%, p = 0.018). Predictors both cohorts included age, receiving intensive care unit treatment, having insulin-dependent diabetes, elevated C-reactive protein creatinin kinase on admission. addition, chest pain admission, being smoker, pre-existing respiratory diseases cancer along with high aspartate aminotranspherase admission predictive higher cohort. had rates follow-up. suggests that has potential health benefits for hospitalized COVID-19.

Language: Английский

Citations

0
Post-COVID-19 sequelae are associated with sustained SARS-CoV-2-specific CD4+ immune responses DOI
Chiara Venegoni, Davide Raineri, Camilla Barbero Mazzucca

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114103 - 114103

Published: Jan. 27, 2025

Language: Английский

Citations

0
Bronchoalveolar lavage single-cell transcriptomics reveals immune dysregulations driving COVID-19 severity DOI Creative Commons
Njinju Asaba Clinton,

Razieh Bitazar,

Patrick Labonté

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0309880 - e0309880

Published: Feb. 10, 2025

The continuous threats posed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, including emergence of potentially more infectious and deadly variants, necessitate ongoing studies to uncover novel detailed mechanisms driving disease severity. Using single-cell transcriptomics, we conducted a secondary data analysis bronchoalveolar lavage fluid (BALF) from COVID-19 patients varying severities healthy controls comprehensively examine immune responses. We observed significant cell alterations correlating with In severe cases, macrophages showed upregulation pro-inflammatory genes TNFα IL1β, contributing inflammation tissue damage. Neutrophils exhibited increased activation, marked S100A8, CXCL8, IL1β expression, extended viability reduced phagocytosis. Genes such as MCL1 HIF1α supported viability, while MSR1 MRC1 indicated Enhanced formation neutrophil extracellular traps (NETs) clearance, NET-associated markers, were linked thrombo-inflammation organ Both neutrophils in cases impaired efferocytosis, decreased expression TREM2 downregulation FCGR3B neutrophils, leading accumulation apoptotic cells exacerbating inflammation. characterized M1 high milder had M2 elevated PPARγ. Dendritic (DCs) proportions attenuated MHC class I (HLA-A, HLA-B, HLA-C) co-stimulatory molecules (CD80, CD86), alongside cytochrome c indicating antigen presentation enhanced apoptosis. NK T demonstrated altered receptor gene activation markers IFNγ ISG15, suggesting paradoxical state exhaustion. This highlights critical role dysregulated neutrophil, macrophage, dendritic cell, NK, responses identifying potential therapeutic targets providing insights into disease.

Language: Английский

Citations

0
Early combined therapy for COVID-19 in immunocompromised patients: a promising approach against viral persistence and drug resistance DOI Creative Commons
Salvatore Rotundo, Francesca Serapide,

Lavinia Berardelli

et al.

BMC Infectious Diseases, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 28, 2025

Immunocompromised (IC) patients face significant challenges in managing COVID-19 due to their heightened susceptibility severe illness, persistent infections, and the potential development of drug resistance. Studies indicate that IC patients, particularly those with hematologic malignancies (HM), hematopoietic stem cell transplants (HSCTR), or solid organ (SOTR), experience higher mortality rates worse outcomes compared general population, even post-vaccination. The persistence virus these combined its rapid mutation, further complicates treatment. Recent evidence supports use neutralizing monoclonal antibodies (mAbs) direct-acting antivirals (DAAs) as a more effective approach viral clearance, reducing mortality, preventing relapses. However, rise resistant variants, especially mAbs, concerns about safety prolonged intensive therapies pose ongoing challenges. Monotherapies often fail short address issues, highlighting need for early therapy (ECT) mAbs DAAs. ECT has shown promise individuals by targeting multiple stages lifecycle, load, clearing infections at earlier stages, which helps mitigate risks disease Continued research is essential refine treatment protocols, evolves. Although studies are needed, current findings suggest may become standard care severely offering better clinical hindering persistence.

Language: Английский

Citations

0