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The Collaboration to Assess Risk and Identify LoNG-term outcomes for Children with COVID (CARING for Children with COVID): MUSIC “Long-TerM OUtcomes after the Multisystem Inflammatory Syndrome In Children”

ABSTRACT: The Collaboration to Assess Risk and Identify LoNG-term outcomes for Children with COVID (CARING for Children with COVID): MUSIC “Long-TerM OUtcomes after the Multisystem Inflammatory Syndrome In Children”

PROVIDER: PRJNA798494 | ENA |

REPOSITORIES: ENA

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The Collaboration to Assess Risk and Identify LoNG-term outcomes for Children with COVID (CARING for Children with COVID): MUSIC “Long-TerM OUtcomes after the Multisystem Inflammatory Syndrome In Children”

Project description:The Collaboration to Assess Risk and Identify LoNG-term outcomes for Children with COVID (CARING for Children with COVID): MUSIC “Long-TerM OUtcomes after the Multisystem Inflammatory Syndrome In Children”

| PRJNA798495 | ENA

Pathophysiological pathway differences in children who present with COVID-19 ARDS compared to COVID -19 induced MIS-C

Project description:Background: COVID-19 has infected more than 100-million worldwide. Children appear less susceptible to COVID-19 and present with milder symptoms. Cases of children with COVID-19 developing clinical features of Kawasaki-disease have been described. Methods: We utilised SWATH-MS proteomics to determine the plasma proteins expressed in healthy children, children with multisystem inflammatory syndrome (MIS-C) and children with COVID-19 induced ARDS. Pathway analyses were performed to determine the affected pathways. Results: 76 proteins were differentially expressed across the groups, with 85 and 52 proteins specific to MIS-C and COVID-19 ARDS. Complement and coagulation activation were implicated in these clinical phenotypes, however there was contribution of FcGR and BCR activation in MIS-C and scavenging of heme and retinoid metabolism in COVID-19 ARDS. Conclusions: We show proteome differences in MIS-C and COVID-ARDS, although both show complement and coagulation dysregulation. The results may be helpful in developing therapeutic targets that could improve the outcomes for these children.

2022-04-06 | PXD025125 | Pride

NIH RECOVER-Pediatric: Understanding the long-term impact of COVID on children and families

Project description:NIH RECOVER-Pediatric: Understanding the long-term impact of COVID on children and families

| PRJNA1033713 | ENA

Natural Mucosal Barriers and COVID-19 in Children

Project description:BACKGROUND. Coronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease. METHODS. Clinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti–SARS-CoV-2 IgG and IgA were quantified in nasal fluid. We used a subset of 21 samples for RNAseq analysis. RESULTS. SARS-CoV-2 copies, angiotensin-converting enzyme 2 (ACE2), and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti–SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died. CONCLUSION. These findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.

2021-05-11 | GSE172274 | GEO

Using Quantitative Proteomic Assessments and their Association with Long Term Healing Outcomes

Project description:Healing after Achilles tendon rupture (ATR) is protracted with high individual variation and unsatisfactory outcome. Biomarkers prognostic of healing are unknown while physical and mechanical factors are used for predicting long-term healing outcomes in clinics today. The present study was designed to investigate the proteomic profile of healing, identify potential biomarkers, and asess the association with the patient's long term outcomes after ATR. Using quantitative Mass Spectrometry (MS) analysis, 1423 proteins in healing and contralateral healthy Achilles tendon from 28 ATR patients were quantified. Comparing healing and healthy protein profiles, we identified 821 overlapping proteins. Further analysis revealed 390 up-regulated and 17 down-regulated proteins in healing compared to the healthy contralateral side,mainly related to extracellular matrix organization, inflammation, and reduced exocytosis and metabolic pathways. Our analysis based on clinical parameters, identified complement factor D (CFD) as the most reliable predictive biomarker of successful tendon healing.Our findings identidied identified prognostic biomarkers and potential therapeutic target for improving tendon or ligament injuries.

2022-05-25 | PXD029202 | Pride

Human serum LC-MS/MS for long-term persistent COVID-19 patients

Project description:The emergence of a new type of COVID-19 patients, who were retested positive after hospital discharge with long-term persistent SARS-CoV-2 infection but without COVID-19 clinical symptoms (hereinafter, LTPPs), poses novel challenges to COVID-19 treatment and prevention. Why was there such a contradictory phenomenon in LTPPs? To explore the mechanism underlying this phenomenon, we performed quantitative proteomic analyses using the sera of 12 LTPPs (Wuhan Pulmonary Hospital), with the longest carrying history of 132 days, and mainly focused on seven LTPPs without hypertension (LTPPs-NH).

2022-10-22 | PXD036609 | Pride

Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children

Project description:Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by SARS-CoV-2 antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that the hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.

2022-11-05 | GSE217370 | GEO

Understanding COVID-19 in children and adults

Project description:Understanding COVID-19 in children and adults

| PRJNA699562 | ENA

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome

Project description:Several studies have reported diverse and prolonged symptoms after COVID-19; however, how long-term pulmonary dysfunction (L-TPD) post-COVID-19 is manifested, which variables support it, and which are the concomitant consequences remain unknown. In this study patients with L-TPD were identified according to their computer-tomography and diffusing capacity-for-carbon-monoxide evaluations at 4-month post-infection. Regarding the acute phase, L-TPD was favored in elderly patients with comorbidities, supported by pathways such as cardiac dysfunction and chemotaxis of phagocytes. At 4-months post-infection, L-TPD patients exhibited a restrictive lung condition favored by CXCL9, platelets and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced CD16 expression in their monocytes, suggesting that phagocytosis of virus-antibody immune complexes was compromised in this group. Finally, one-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Overall, our data suggest that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

2023-11-22 | PXD040175 | Pride

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Project description:Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

2023-01-11 | GSE196456 | GEO

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