The immunology of long COVID

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 618 - 634

Published: July 11, 2023

Language: Английский

---

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis

Science Immunology, Journal Year: 2023, Volume and Issue: 8(83)

Published: May 5, 2023

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, C-reactive protein levels as well imaging abnormalities shortly vaccination. Contrary to early hypotheses, did not demonstrate features hypersensitivity myocarditis, nor they have exaggerated SARS-CoV-2-specific or neutralizing antibody responses consistent hyperimmune humoral mechanism. We additionally found no evidence cardiac-targeted autoantibodies. Instead, unbiased systematic serum profiling revealed elevations in circulating interleukins (IL-1β, IL-1RA, IL-15), chemokines (CCL4, CXCL1, CXCL10), matrix metalloproteases (MMP1, MMP8, MMP9, TIMP1). Subsequent deep using single-cell RNA repertoire sequencing peripheral blood mononuclear cells during acute disease expansion activated CXCR3

Language: Английский

---

Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2

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

Published: Feb. 10, 2023

Long COVID (LC), a type of post-acute sequelae SARS-CoV-2 infection (PASC), occurs after at least 10% infections, yet its etiology remains poorly understood. Here, we used multiple "omics" assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global SARS-CoV-2-specific immunity from blood individuals with clear LC non-LC clinical trajectories, 8 months following prior receipt any vaccine. Our analysis focused on deep phenotyping T cells, which play important roles in against may also contribute COVID-19 pathogenesis. findings demonstrate that exhibit systemic inflammation immune dysregulation. This is evidenced by differences cell subset distribution ways imply ongoing responses, as well sex-specific perturbations cytolytic subsets. Individuals harbored increased frequencies CD4+ cells poised migrate inflamed tissues, exhausted CD8+ cells. They significantly higher levels antibodies, contrast individuals, exhibited mis-coordination between their B responses. RNAseq/scRNAseq Olink analyses similarly revealed dysregulatory mechanisms, along non-immune associated perturbations, LC. Collectively, our data suggest proper crosstalk the humoral cellular arms adaptive has broken down LC, this, perhaps context persistent virus, leads dysregulation, inflammation, symptoms this debilitating condition.

Language: Английский

---

Facile synthesis of N-doped carbon nanorods for antibiotics degradation via PMS activation: Mechanism insight and biotoxicity assessment

Separation and Purification Technology, Journal Year: 2024, Volume and Issue: 340, P. 126849 - 126849

Published: Feb. 20, 2024

Language: Английский

---

Mucosal immune response in biology, disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Language: Английский

---

Systems analysis of innate and adaptive immunity in Long COVID

Seminars in Immunology, Journal Year: 2024, Volume and Issue: 72, P. 101873 - 101873

Published: March 1, 2024

Language: Английский

---

SARS-CoV-2 infection induces a long-lived pro-inflammatory transcriptional profile

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: Sept. 12, 2023

Abstract Background The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19 patients has been extensively investigated. However, much less is known about the long-term effects of and how it could affect system its capacity respond future perturbations. Methods Using a targeted single-cell multiomics approach, we have recently identified prolonged anti-inflammatory gene expression signature T NK cells type 1 diabetes treated with low-dose IL-2. Here, investigated dynamics this three independent cohorts patients: (i) Oxford Multi-omics Blood Atlas (COMBAT) dataset, cross-sectional cohort including 77 ten healthy donors; (ii) INCOV consisting 525 samples taken from 209 during after infection; (iii) longitudinal dataset 269 whole-blood 139 followed for period up 7 months onset symptoms using bulk transcriptomic approach. Results We discovered that SARS-CoV-2 leads alteration profile circulating T, B monocytes. Some genes affected were same as those present IL-2-induced but regulated opposite direction, implying pro-inflammatory status. altered transcriptional was detected at least disease not observed influenza or sepsis. Gene network analysis suggested central role factor NF-κB regulation alterations. Conclusions causes increase status predispose post-acute development health consequences, autoimmune disease, reactivation other viruses disruption host system-microbiome ecosystem.

Language: Английский

---

Are repeat COVID infections dangerous? What the science says

Nature, Journal Year: 2023, Volume and Issue: 616(7958), P. 650 - 652

Published: April 26, 2023

Language: Английский

---

Divergent adaptive immune responses define two types of long COVID

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 20, 2023

Background The role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or excessive associated inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell patients prior SARS-CoV-2 vaccination. Methods Long who were seropositive (LC+, n=28) seronegative (LC-, n=23) by spike ELISA assay recruited based on (i) initial infection documented PCR the conjunction three major signs COVID-19 (ii) persistence resurgence at least 3 symptoms for over months. They compared resolved (RE, n=29) uninfected control individuals (HD, n=29). Results spectrum persistent proved similar both groups, a trend higher number group (median=6 vs 4.5; P=0.01). use highly sensitive S-flow enabled detection low levels spike-specific IgG 22.7% ELISA-seronegative (LC-) patients. In contrast, uniformly high LC+ RE groups. Multiplexed antibody analyses 30 different viral antigens showed that LC- had defective all proteins tested but most cases preserved other viruses. A primary line revealed detectable SARS-CoV-2-specific CD4 39.1% patients, while frequencies Correlation overall strong associations between cellular responses, exceptions group. Conclusions These findings provide evidence two types COVID. Seropositive coordinated as those recovered specific cells and/or antibodies close half (52.2%). divergent sharing comparable raise possibility multiple etiologies

Language: Английский

---

Increased fibrinaloid microclot counts in platelet-poor plasma are associated with Long COVID

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract Outcomes following SARS-CoV-2 infection are variable; whilst the majority of patients recover without serious complications, a subset develop prolonged illness termed Long COVID or post-acute sequelae (PASC). The pathophysiology underlying remains unclear but appears to involve multiple mechanisms including persistent inflammation, coagulopathy, autoimmunity, and organ damage. Studies suggest that microclots, also known as fibrinaloids, play role in COVID. In this context, we developed method quantify microclots investigated relationship between microclot counts We show cohort, platelet-poor plasma from samples had higher count compared control groups retained wide distribution counts. Recent COVID-19 infections were seen be associated with than equivalent subsequent time-dependent reduction Our findings could potential biomarker disease and/or treatment target some patients.

Language: Английский

---