Endothelial Extracellular Vesicles Enriched in microRNA-34a Predict New-Onset Diabetes in Coronavirus Disease 2019 (COVID-19) Patients: Novel Insights for Long COVID Metabolic Sequelae

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 389(1), P. 34 - 39

Published: Feb. 9, 2024

Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it known presence of other metabolic alterations poses a considerably high risk to develop severe COVID-19; 2) patients who survived acute respiratory syndrome 2 (SARS-CoV-2) infection have an increased developing new-onset diabetes. However, mechanisms underlying this association are mostly unknown, there no reliable biomarkers predict development In present study, we demonstrate specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts COVID-19. This was independent age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, D-dimer. SIGNIFICANCE STATEMENT: We for first time able after having contracted (COVID-19). Our findings also relevant when considering emerging importance post-acute sequelae COVID-19, with systemic manifestations observed even months viral negativization (long COVID).

Language: Английский

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Single‐cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Although our understanding of the immunopathology and subsequent risk severity COVID-19 disease is evolving, a detailed account immune responses that contribute to long-term consequences pulmonary complications in infection remains unclear. Few studies have cytokine profiles associated with post-acute sequelae SARS-CoV-2 (PASC) persistent symptoms. The dysregulation system drives survivors PASC sufferers largely unknown.

Language: Английский

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Inflammation and Epstein–Barr Virus at the Crossroads of Multiple Sclerosis and Post-Acute Sequelae of COVID-19 Infection

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 949 - 949

Published: April 12, 2023

Recent studies have strengthened the evidence for Epstein-Barr Virus (EBV) as an important contributing factor in development of multiple sclerosis (MS). Chronic inflammation is a key feature MS. EBV

Language: Английский

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Low avidity circulating SARS-CoV-2 reactive CD8+ T cells with proinflammatory TEMRA phenotype are associated with post-acute sequelae of COVID-19

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

Published: June 2, 2023

The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae COVID-19 (PASC) is not well explored, although a growing population convalescent patients with manifestation PASC observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry 40 non-specific 15 healthy donors. Although frequencies SARS-CoV-2-reactive CD4+ T cells were similar between studied cohorts, stronger reactive CD8+ cell characterized by IFNγ production predominant TEMRA phenotype but low functional TCR avidity was detected compared to controls. Of interest, high comparable groups demonstrating sufficient cellular antiviral response PASC. In line immunity, capacity inferior conclusion, our data suggest that may be driven an inflammatory triggered expanded pro-inflammatory cells. These are known activated or even without stimulation lead tissue damage. Further studies including animal models required for better understanding underlying immunopathogensis. Summary: A persistent responsible observed patients.

Language: Английский

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Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier?

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(2), P. 367 - 377

Published: Jan. 5, 2023

The pandemics of coronavirus disease 2019 (COVID-19) and non-alcoholic fatty liver (NAFLD) coexist. Elevated function tests are frequent in COVID-19 may influence damage NAFLD, while preexisting from NAFLD the course COVID-19. However, prognostic relevance this interaction, though, is unclear. Obesity a risk factor for presence as well severe Cohort studies reveal conflicting results regarding on illness severity. Striking molecular similarities cytokine pathways both diseases, including postacute sequelae COVID-19, suggest common chronic low-activity inflammation. This review will summarize existing data interaction diseases discuss possible mechanisms one other.

Language: Английский

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SARS-CoV-2 infection and immune responses

AIMS Microbiology, Journal Year: 2023, Volume and Issue: 9(2), P. 245 - 276

Published: Jan. 1, 2023

<abstract> <p>The recent pandemic caused by the SARS-CoV-2 virus continues to be an enormous global challenge faced healthcare sector. Availability of new vaccines and drugs targeting sequelae COVID-19 has given world hope in ending pandemic. However, emergence mutations viral genome every couple months different parts is a persistent danger public health. Currently there no single treatment eradicate risk COVID-19. The widespread transmission due Omicron variant necessitates continued work on development implementation effective vaccines. Moreover, evidence that receptor domain spike glycoprotein led decrease current vaccine efficacy escaping antibody recognition. Therefore, it essential actively identify mechanisms which evades host immune system, study long-lasting effects develop therapeutics infections humans preclinical models. In this review, we describe pathogenic infection as well innate adaptive responses infection. We address ongoing need provide protection against variants SARS-CoV-2, validated endpoint assays evaluate immunogenicity pipeline, medications, anti-viral drug therapies health measures, will required successfully end pandemic.</p> </abstract>

Language: Английский

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SARS-CoV-2 infection dysregulates NAD metabolism

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

Published: June 29, 2023

Introduction Severe COVID-19 results initially in pulmonary infection and inflammation. Symptoms can persist beyond the period of acute infection, patients with Post-Acute Sequelae COVID (PASC) often exhibit a variety symptoms weeks or months following phase resolution including continued dysfunction, fatigue, neurocognitive abnormalities. We hypothesized that dysregulated NAD metabolism contributes to these Methods RNAsequencing lungs from transgenic mice expressing human ACE2 (K18-hACE2) challenged SARS-CoV-2 revealed upregulation biosynthetic enzymes, NAPRT1, NMNAT1, NAMPT, IDO1 6 days post-infection. Results Our data also demonstrate increased gene expression consuming enzymes: PARP 9,10,14 CD38. At same time, SIRT1, protein deacetylase (requiring as cofactor involved control inflammation) is downregulated. confirmed our findings by mining sequencing died infection. validated demonstrating turnover suggested modulating pathways may alter disease progression offer therapeutic benefits. Specifically, we treating K18-hACE2 nicotinamide riboside (NR), potent precursor, mitigate lethality improve recovery tested potential an anti- monomeric NAMPT antibody using model. Treatment high dose anti-NAMPT resulted significantly decreased body weight compared control, which was mitigated combining HD NR. observed significant increase lipid metabolites, eicosadienoic acid, oleic palmitoyl carnitine low + NR group. related metabolites treated animals. Discussion suggest perturbs pathways, identify novel mechanisms explain some pathophysiology CoVID-19 strategies for both treatment prevention.

Language: Английский

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Epstein–Barr virus-acquired immunodeficiency in myalgic encephalomyelitis—Is it present in long COVID?

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 17, 2023

Abstract Both myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID (LC) are characterized by similar immunological alterations, persistence of viral infection, autoimmunity, inflammatory state, reactivation, hypocortisolism, microclot formation. They also present with symptoms such as asthenia, exercise intolerance, sleep disorders, cognitive dysfunction, neurological gastrointestinal complaints. In addition, both pathologies Epstein–Barr virus (EBV) indicating the possibility this being link between pathologies. Therefore, we propose that latency recurrent EBV reactivation could generate an acquired immunodeficiency in three steps: first, develops individuals “weak” HLA-II haplotypes, which prevents control I cells. Second, ectopic lymphoid structures form different tissues (including CNS), promoting responses further impairment cell-mediated immunity. Finally, immune exhaustion occurs due to exposure antigens, consolidation disease. case LC, prior first step, there is previous SARS-CoV-2 infection haplotypes against and/or EBV.

Language: Английский

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SARS‐CoV‐2 cellular tropism and direct multiorgan failure in COVID‐19 patients: Bioinformatic predictions, experimental observations, and open questions

Cell Biology International, Journal Year: 2022, Volume and Issue: 47(2), P. 308 - 326

Published: Oct. 13, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes disease 2019 (COVID-19), has led to an unprecedented public health emergency worldwide. While common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure severe patients. Organ damage patients partially associated with indirect effects of SARS-CoV-2 infection (e.g., systemic inflammation, hypoxic-ischemic damage, coagulopathy), but early processes trigger a chain connected direct cells virus. To understand transmission routes and reasons for wide-spectrum complications outcomes COVID-19, it important identify targeted SARS-CoV-2. This review summarizes major steps investigation most recent findings regarding cellular tropism possible connection between stages COVID-19. The pandemic first epidemic which data extracted from single-cell RNA-seq (scRNA-seq) gene expression sets have been widely used predict tropism. analysis presented here indicates predictions accurate enough estimating potential susceptibility different infection; however, appears not all susceptible may be infected

Language: Английский

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Long COVID: An approach to clinical assessment and management in primary care

South African Family Practice, Journal Year: 2023, Volume and Issue: 65(1)

Published: June 23, 2023

Long COVID is an emerging public health threat, following swiftly behind the surges of acute infection over course COVID-19 pandemic. It estimated that there are already approximately 100 million people suffering from globally, 0.5 whom South African, and for our incomplete understanding condition has forestalled appropriate diagnosis clinical care. There several leading postulates complex, multi-mechanistic pathogenesis COVID. Patients with may present a diversity phenotypes, often significant overlap, which exhibit temporal heterogeneity evolution. Post-acute care follow-up, targeted screening, diagnosis, broad initial assessment more directed subsequent assessments necessary at primary level. Symptomatic treatment, self-management rehabilitation mainstays However, evidence-based pharmacological interventions prevention treatment beginning to emerge. This article presents rational approach assessing managing patients in setting.

Language: Английский

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