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Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [PASC]

ABSTRACT: Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [PASC]

PROVIDER: PRJNA973049 | ENA |

REPOSITORIES: ENA

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Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [PASC]

Project description:As many as 10–30% of the nearly 750 million survivors of COVID-19 develop persistent symptoms that define the post-acute sequelae of COVID-19 (PASC) syndrome. To understand the molecular basis of this syndrome, we combined a machine learning based analysis of lung computed tomography (CT) with flow cytometry and single cell RNA-sequencing analysis of bronchoalveolar lavage fluid and nasal curettage samples in a cohort of thirty-five patients with respiratory symptoms and radiographic abnormalities more than 90 days after infection with COVID-19. CT images from patients with PASC revealed primarily fibrotic abnormalities involving 73 +/- 28% of the lung, most of which improved on subsequent imaging. The presence of profibrotic monocyte-derived alveolar macrophages in BAL fluid was significantly associated with increased levels of alveolar cytokines and fibrotic abnormalities on CT. Persistent infection with SARS-CoV-2 was identified in 6 patients and secondary bacterial or viral infections in two others. These findings suggest persistent alveolar inflammation characterized by the ongoing recruitment of monocyte derived alveolar macrophages is associated with fibrotic CT changes in some COVID-19 survivors with implications for diagnosis and therapy.

2024-05-12 | GSE232627 | GEO

Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [NEP]

2024-05-12 | GSE232623 | GEO

Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [BAL]

2024-05-12 | GSE232616 | GEO

Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

Project description:Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

| PRJNA973047 | ENA

Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [NEP]

Project description:Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [NEP]

| PRJNA973041 | ENA

Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [BAL]

Project description:Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19 [BAL]

| PRJNA973026 | ENA

Cardiovascular symptoms of PASC are associated with trace-level circulatory cytokines that affect the function of primary human cardiomyocytes

Project description:Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be determined. Here, we show that compared to individuals with a resolved SARS-CoV-2 infection (and no persistent symptoms), individuals with prolonged PASC-CVS had elevated levels of pro-inflammatory cytokines. However, these cytokines were found to be present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of primary human cardiomyocytes in vitro. Proteomics analyses demonstrated further differences in PASC-CVS and recovered plasma including increased abundance of complement and coagulation associated proteins.

2024-11-01 | PXD050202 | Pride

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein

Project description:Many people experiencing long COVID symptoms, or post-acute sequelae of SARS-CoV-2 infection (PASC), suffer from debilitating neurologic symptoms (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether virus-specific adaptive immunity is affected in these individuals. We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4+ T cell responses toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. In contrast, Neuro-PASC patients also have diminished activation of CD8+ memory T cells and increased IL-6 production to Nucleocapsid. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction. These data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.

2023-05-24 | GSE225942 | GEO

Expansion of profibrotic monocyte-derived alveolar macrophages in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-05-12 | GSE232628 | GEO

Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations

Project description:PASC (Post-Acute Sequelae of COVID-19) involves many organs, including most prominently the central nervous system. Most studies of PASC in laboratory animals were performed in the context of mild disease, but higher PASC prevalence is observed in patients with severe disease. Here, to investigate the basis of chronic neurological disease, we infected mice with mouse-adapted SARS-CoV-2 that causes severe respiratory disease but does not infect the brain. We assessed long-term effects on olfactory and substantia nigra (SN) function. While anosmia resolved within a few days, we observed long term loss of tyrosine hydroxylase (TH) expression in the olfactory bulb glomeruli, indicating chronically altered function of olfactory sensory neurons. These changes were accompanied by increased inflammation suggesting the involvement of the host immune response in anosmia-related changes. We also observed decreased neurotransmitter expression in the substantia nigra (SN) accompanied by increased levels of proinflammatory cytokines and neurobehavioral changes. Microglia have been implicated in long term changes in SARS-CoV-2 infected mice and in human neurodegenerative disease. RNAseq analysis of mouse brain microglia isolated several months after infection demonstrated key roles for these cells in ongoing pathogenesis. Finally, we showed that early treatment with antivirals (nirmatrelvir and molnupiravir) reduced virus titer and inflammation in the lung but did not prevent neurological abnormalities. Together these results show that these mice will be useful for probing the role of SARS-CoV-2 in the development of neurodegenerative disease, an aspect of disease not amenable to study in patients and that neurological PASC is not ameliorated by anti-viral therapy.

2024-02-23 | GSE254984 | GEO

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