Elevation in sphingolipid upon SARS-CoV-2 infection: possible implications for COVID-19 pathology.
Ontology highlight
ABSTRACT:
SUBMITTER: Vitner EB
PROVIDER: S-EPMC8605327 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Abstract: SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immune-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immune-coagulopathic responses and Long COVID.
| S-SCDT-10_15252-EMMM_202317376 | biostudies-other
Project description:This review article was designed to evaluate the existing evidence related to the molecular processes of SARS-CoV-2 infection in the oral cavity. The World Health Organization stated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission is produced by respiratory droplets and aerosols from the oral cavity of infected patients. The oral cavity structures, keratinized and non-keratinized mucosa, and salivary glands' epithelia express SARS-CoV-2 entry and transmission factors, especially angiotensin converting enzyme Type 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Replication of the virus in cells leads to local and systemic infection spread, and cellular damage is associated with clinical signs and symptoms of the disease in the oral cavity. Saliva, both the cellular and acellular fractions, holds the virus particles and contributes to COVID-19 transmission. The review also presents information about the factors modifying SARS-CoV-2 infection potential and possible local pharmacotherapeutic interventions, which may confine SARS-CoV-2 virus entry and transmission in the oral cavity. The PubMed and Scopus databases were used to search for suitable keywords such as: SARS-CoV-2, COVID-19, oral virus infection, saliva, crevicular fluid, salivary gland, tongue, oral mucosa, periodontium, gingiva, dental pulp, ACE2, TMPRSS2, Furin, diagnosis, topical treatment, vaccine and related words in relevant publications up to 28 December 2021. Data extraction and quality evaluation of the articles were performed by two reviewers, and 63 articles were included in the final review.
| S-EPMC8836070 | biostudies-literature
Project description:COVID-19, caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple-organ failure, but little is known about its pathophysiology. Here, we generated single-cell atlases of 23 lung, 16 kidney, 15 liver and 18 heart COVID-19 autopsy donor tissue samples, and spatial atlases of 14 lung donors. Integrated computational analysis uncovered substantial remodeling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of myofibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in COVID-19 donor heart tissue, and mapped cell types and genes implicated with disease severity based on COVID-19 GWAS. Our foundational dataset elucidates the biological impact of severe SARS-CoV-2 infection across the body a key step towards new treatments.
2021-04-09 | GSE171668 | GEO
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory system can progress to a multisystemic disease with aberrant inflammatory response. Cellular senescence promotes chronic inflammation, named senescence-associated secretory phenotype (SASP). We investigated whether coronavirus disease 2019 (COVID-19) is associated with cellular senescence and SASP.MethodsAutopsy lung tissue samples from 11 COVID-19 patients and 43 age-matched non-COVID-19 controls with similar comorbidities were analysed by immunohistochemistry for SARS-CoV-2, markers of senescence and key SASP cytokines. Virally induced senescence was functionally recapitulated in vitro, by infecting epithelial Vero-E6 cells and a three-dimensional alveosphere system of alveolar type 2 (AT2) cells with SARS-CoV-2 strains isolated from COVID-19 patients.ResultsSARS-CoV-2 was detected by immunocytochemistry and electron microscopy predominantly in AT2 cells. Infected AT2 cells expressed angiotensin-converting enzyme 2 and exhibited increased senescence (p16INK4A and SenTraGor positivity) and interleukin (IL)-1β and IL-6 expression. In vitro, infection of Vero-E6 cells with SARS-CoV-2 induced senescence (SenTraGor), DNA damage (γ-H2AX) and increased cytokine (IL-1β, IL-6, CXCL8) and apolipoprotein B mRNA-editing (APOBEC) enzyme expression. Next-generation sequencing analysis of progenies obtained from infected/senescent Vero-E6 cells demonstrated APOBEC-mediated SARS-CoV-2 mutations. Dissemination of the SARS-CoV-2-infection and senescence was confirmed in extrapulmonary sites (kidney and liver) of a COVID-19 patient.ConclusionsWe demonstrate that in severe COVID-19, AT2 cells infected by SARS-CoV-2 exhibit senescence and a proinflammatory phenotype. In vitro, SARS-CoV-2 infection induces senescence and inflammation. Importantly, infected senescent cells may act as a source of SARS-CoV-2 mutagenesis mediated by APOBEC enzymes. Therefore, SARS-CoV-2-induced senescence may be an important molecular mechanism of severe COVID-19, disease persistence and mutagenesis.
| S-EPMC8796696 | biostudies-literature
Project description:ACE2 on epithelial cells is the SARS-CoV-2 entry receptor. Single-cell RNA-sequencing data derived from two COVID-19 cohorts revealed that MAP4K3/GLK-positive epithelial cells were increased in patients. SARS-CoV-2-induced GLK overexpression in epithelial cells correlated with COVID-19 severity and vesicle secretion. GLK overexpression induced the epithelial cell-derived exosomes containing ACE2; the GLK-induced exosomes transported ACE2 proteins to recipient cells, facilitating pseudovirus infection. Consistently, ACE2 proteins were increased in the serum exosomes from another COVID-19 cohort. Remarkably, SARS-CoV-2 spike protein stimulated GLK, and GLK stabilized ACE2 in epithelial cells. Mechanistically, GLK phosphorylated ACE2 at two serine residues (Ser776, Ser783), leading to dissociation of ACE2 from its E3 ligase UBR4. Reduction of UBR4-induced Lys48-linked ubiquitination at three lysine residues (Lys26, Lys112, Lys114) of ACE2 prevented its degradation. Furthermore, SARS-CoV-2 pseudovirus or live virus infection in humanized ACE2 mice induced GLK and ACE2 protein levels, as well as ACE2-containing exosomes. Collectively, ACE2 stabilization by SARS-CoV-2-induced MAP4K3/GLK may contribute to the pathogenesis of COVID-19.
| S-SCDT-EMM-2022-15904 | biostudies-other
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.
2017-02-14 | GSE90624 | GEO
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other
Project description: Not available
| S-EPMC8225252 | biostudies-literature
Project description:To explore the relationship between SARS-CoV-2 infection in different time before operation and postoperative main complications (mortality, main pulmonary and cardiovascular complications) 30 days after operation; To determine the best timing of surgery after SARS-CoV-2 infection.
| 12454 | ecrin-mdr-crc
Project description:ObjectiveTo assess the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in selected health clinics in the three largest urban areas in Nicaragua, where data regarding coronavirus disease 2019 (COVID-19) testing, morbidity and mortality is severely limited.MethodsIn this cross-sectional study, participants were tested for SARS-CoV-2 RNA by loop-mediated isothermal amplification (LAMP), and were tested for antibodies using immunoassays. A questionnaire recorded subjects' COVID-19-associated symptoms and risk factors. Data were collected from 22 February to 19 March 2021, 1 year after the first confirmed cases of SARS-CoV-2 in Nicaragua. Study participants were enrolled while attending routine check-ups or seeking care unrelated to COVID-19. Study participation was random and voluntary. All patients were eligible to participate. Symptom history was not part of the eligibility criteria.ResultsThe prevalence of current SARS-CoV-2 infection was high (14%, LAMP-positive/seronegative). Antibody testing showed higher overall seroprevalence (38%). Cough was the symptom most strongly associated with being LAMP-positive (odds ratio 3.57, 95% confidence interval 2.65-4.81). Loss of smell had the highest positive predictive value, and was significantly associated with being LAMP-positive.ConclusionThe prevalence of current SARS-CoV-2 infection and seropositivity were fairly high. More than half of the sample population had evidence of current or past infection. Knowledge of this previously unknown elevated level of infection is crucial for healthcare providers and policy makers.
| S-EPMC8730803 | biostudies-literature