COVID‐19 and plasma cells: Is there long‐lived protection?*

Immunological Reviews, Journal Year: 2022, Volume and Issue: 309(1), P. 40 - 63

Published: July 8, 2022

Infection with SARS-CoV-2, the etiology of ongoing COVID-19 pandemic, has resulted in over 450 million cases more than 6 deaths worldwide, causing global disruptions since early 2020. Memory B cells and durable antibody protection from long-lived plasma (LLPC) are mainstay most effective vaccines. However, ending pandemic been hampered by lack immunity after infection or vaccination. Although immunizations offer severe disease hospitalization, breakthrough infections still occur, likely due to new mutant viruses overall decline neutralizing antibodies months. Here, we review current knowledge cells, extrafollicular memory populations, a focus on distinct cell subsets, such as early-minted blood antibody-secreting bone marrow LLPC, how these humoral compartments contribute SARS-CoV-2 immunization.

Language: Английский

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Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(7)

Published: June 16, 2022

SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 demonstrated circulating 19 out 20 non-survivor contain SARS-CoV-2 robust correlation outcome. Platelets containing might originate bone marrow lung megakaryocytes (MKs), platelet precursors, which were found infected by autopsies. Accordingly, MKs undergoing shortened differentiation expressing anti-viral IFITM1 IFITM3 RNA as sign viral sensing enriched circulation deadly Infected reach concomitant specific MK-related cytokine storm rich VEGF, PDGF inflammatory molecules, anticipating Lung macrophages capture SARS-CoV-2-containing vivo. The virus contained is carrying propagates infection to vitro, process blocked an anti-GPIIbIIIa drug. Altogether, alter pathogenesis provide powerful fatality marker. Clinical targeting prevent spread, thrombus formation exacerbated inflammation at once increase survival

Language: Английский

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The S1 Subunit of the SARS-CoV-2 Spike Protein Activates Human Monocytes to Produce Cytokines Linked to COVID-19: Relevance to Galectin-3

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 22, 2022

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly evolved into a pandemic –the likes of which has not been experienced in 100 years. While novel vaccines show great efficacy, and therapeutics continue to be developed, persistence disease, with concomitant threat emergent variants, continues impose massive health socioeconomic issues worldwide. Studies that susceptible individuals, SARS-CoV-2 infection can progress toward lung injury distress (ARDS), evidence for an underlying dysregulated innate immune response or cytokine release (CRS). The mechanisms responsible this CRS remain poorly understood, yet hyper-inflammatory features were also evident predecessor viruses within β-coronaviridae family, namely SARS-CoV-1 Middle East Respiratory Syndrome (MERS)-CoV. It is further known spike protein (S) (as first reported other β-coronaviruses) possesses so-called galectin-fold N-terminal domain S1 subunit (S1-NTD). This fold (or pocket) shows structural homology nearly identical human galectin-3 (Gal-3). In respect, we have recently shown Gal-3, when associated epithelial cells anchored solid phase matrix, facilitates activation cells, including basophils, DC, monocytes. A synthesis these findings prompted us test whether segments might activate manner similar observed our Gal-3 studies. Indeed, immobilizing S components onto microtiter wells, only (with NTD) activates monocytes produce near pattern cytokines as those COVID-19-related CRS. contrast, both S1-CTD/RBD, binds ACE2, S2 (stalk), failed mediate same effect. Overall, provide central COVID-19, thus providing insight potential therapeutic interventions.

Language: Английский

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Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 10, 2023

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting competent host immune system response. is composed of primary/secondary lymphoid structures initially eight types cell types, many subtypes, traversing membranes utilizing signaling cascades that contribute towards clearance pathogenic proteins. Other proteins discussed cluster differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), chemokines (CXC). historical concepts immunity are the innate adaptive systems. represented T cells, B antibodies. macrophages, neutrophils, dendritic complement system. viruses can affect regulate cycle progression for example, in cancers papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis C (HB/HC: hepatocellular carcinoma) Leukemia Virus-1 (T leukemia). Bacterial infections also increase risk developing cancer (e.g.,

Language: Английский

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Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release

Science Signaling, Journal Year: 2023, Volume and Issue: 16(782)

Published: April 25, 2023

Macrophages are key cellular contributors to the pathogenesis of COVID-19, disease caused by virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset macrophages at sites infection in humans. Here, we investigated whether can enter macrophages, replicate, and release new viral progeny; need sense replicating drive cytokine release; and, if so, involved these mechanisms. We found that could enter, but did not replicate within, ACE2-deficient human primary induce proinflammatory expression. By contrast, overexpression THP-1–derived permitted entry, processing replication, virion release. ACE2-overexpressing THP-1 sensed active replication triggered proinflammatory, antiviral programs mediated kinase TBK-1 limited prolonged These findings help elucidate role its absence macrophage responses infection.

Language: Английский

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Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals

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

Published: April 3, 2023

Background Monocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of post-acute sequelae infection (PASC) are not fully elucidated. Methods A cross-sectional study was conducted comparing plasma cytokine monocyte levels among three groups: participants with pulmonary PASC (PPASC) reduced predicted diffusing capacity for carbon monoxide [DLCOc, <80%; (PG)]; recovered from no residual symptoms (recovered group, RG); negative (negative NG). The expressions cytokines were measured cohort by Luminex assay. percentages numbers subsets (classical, intermediate, non-classical monocytes) activation (defined CD169 expression) analyzed using flow cytometry analysis peripheral blood mononuclear cells. Results Plasma IL-1Ra elevated but FGF PG compared NG. Circulating monocytes significantly higher RG exhibited + counts expression detected intermediate than that found Further correlation revealed negatively correlated DLCOc%, positively IL-1α, IL-1β, MIP-1α, Eotaxin, IFN-γ. Conclusion This present evidence COVID convalescents exhibit alteration beyond COVID-19 period even symptoms. Further, results suggest increased activated may impact function convalescents. observation will aid understanding immunopathologic feature development, resolution, subsequent therapeutic interventions.

Language: Английский

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Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 12, 2025

The emergence of the COVID-19 pandemic made it critical to understand immune and inflammatory responses SARS-CoV-2 virus. It became increasingly recognized that response was a key mediator illness severity its mechanisms needed be better understood. Early infection both tissue cells, such as macrophages, leading pyroptosis-mediated inflammasome production in an organ system for systemic oxygenation likely plays central role morbidity wrought by SARS-CoV-2. Delayed transcription Type I III interferons may lead early disinhibition viral replication. Cytokines interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor α (TNFα), some which produced through involving nuclear kappa B (NF-κB), contribute hyperinflammatory state patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) CD8+ T-cells, B-cells, can disease reflect direct cytopathic effects or end-organ sequestration. Direct activation endothelial cells mechanism systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation microthrombi development seen lungs other organs throughout body, heart, gut, brain. kidney most impacted extrapulmonary owing high concentration ACE2 exposure kidney, acute tubular injury, myofibroblast activation, collapsing glomerulopathy select populations account COVID-19-related AKI CKD development. COVID-19-associated nephropathy (COVAN), particular, mediated IL-6 signal transducer activator 3 (STAT3) signaling, suggesting connection between chronic disease. Chronic manifestations also include conditions like Multisystem Inflammatory Syndrome Children (MIS-C) Adults (MIS-A) post-acute sequelae (PASC), spectrum clinical presentations persistent dysregulation. lessons learned those undergoing continued study have broad implications understanding infections’ immunologic consequences beyond coronaviruses.

Language: Английский

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Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

Biomedicines, Journal Year: 2021, Volume and Issue: 9(9), P. 1253 - 1253

Published: Sept. 17, 2021

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute patients at emergency room arrival, showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status limited anti-SARS-CoV-2-specific T cell response. Most these alterations had normalized post-COVID-19 6 months after discharge. Acute transcriptome upregulation anti-inflammatory tissue repair genes such as BCL6, AREG IL-10 increased accessibility chromatin. Some transcriptomic epigenetic features still remained monocytes. Importantly, a poorer expression molecules IRF1 gene transcription admission defined patient group impaired SARS-CoV-2-specific response risk requiring intensive care or dying. useful stratification designing innate immunity-focused therapies.

Language: Английский

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Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes disease 19 (COVID-19) has numerous risk factors leading to severe with high mortality rate. Oxidative stress excessive production of reactive oxygen species (ROS) lower glutathione (GSH) levels seems be a common pathway associated the COVID-19 mortality. GSH is unique small but powerful molecule paramount for life. It sustains adequate redox cell signaling since physiologic level oxidative fundamental controlling life processes via signaling, oxidation and tissue damage. The water-soluble tripeptide (γ-L-glutamyl-L-cysteinyl-glycine) present in cytoplasm all cells. at 1–10 mM concentrations mammalian tissues (highest concentration liver) as most abundant non-protein thiol protects against stress. also activates Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related (Nrf2)-antioxidant response element (ARE) regulator pathway, releasing Nrf2 regulate expression genes control antioxidant, inflammatory immune system responses, facilitating activity. exists thiol-reduced disulfide-oxidized (GSSG) forms. Reduced prevailing form accounting >98% total GSH. GSSG their molar ratio are indicators functionality its alteration related various human pathological including COVID-19. plays prominent role SARS-CoV-2 infection following recognition viral S-protein by angiotensin converting enzyme-2 receptor pattern receptors like toll-like 4, activation transcription nuclear kappa B, subsequently activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) succeeded ROS production. depletion may have pathophysiology, host severity Therapies enhancing could become cornerstone reduce fatal outcomes increasing prevent subdue disease. value makes research field biology medicine key

Language: Английский

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Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 24, 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes coronavirus-19 (COVID-19), has caused significant morbidity and mortality globally. In addition to the respiratory manifestations seen in severe cases, multi-organ pathologies also occur, making management a much-debated issue. addition, emergence of new variants can potentially render vaccines with relatively limited utility. Many investigators have attempted elucidate precise pathophysiological mechanisms causing COVID-19 systemic disease. Spillover lung-derived cytokines cytokine storm is considered cause However, recent studies provided contradictory evidence, whereby extent insufficient illness. These issues are highly relevant, as approaches considering classic form acute distress syndrome could translate unfounded clinical decisions, detrimental patient trajectory. Additionally, immune cell signatures that characterize disease varying severity remain contentious. We provide an up-to-date review on dysregulation by highlight pertinent discussions scientific community. The response from community been unprecedented regarding development effective cutting-edge research novel therapies. hope this furthers conversations held scientists informs aims future projects, will further our understanding its pathogenesis.

Language: Английский

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