Plasma Cells and Endothelitis in COVID-19 Lung Pathology

Veerdonk, Frank L. van de; Looijen-Salamon, Monika; Heuvel, Michel van den; Mast, Quirijn van der; Meer, C. van der; Vos, Shoko; Belle, Sarah van; Vermorgen, Sanne; Hoeven, Johannes G. van der; Netea, Mihai G.; Grünberg, Katrien

doi:10.2139/ssrn.3596608

Cited by 3 publications

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“…Based on these results and previously published autopsy reports, we aimed to confirm that hyperactivated neutrophils not only play an important role in systemic COVID-19 disease manifestations, but also contribute to severe COVID-19 pneumonia 35,36 . We therefore performed scRNA-seq on fresh BAL fluid from 6 COVID-19 and 5 non-COVID pneumonia cases, sequencing the transcriptomes of 26,605 cells in total (Fig.…”

Section: Resultsmentioning

confidence: 80%

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

et al. 2021

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Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

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Section: Resultsmentioning

confidence: 80%

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

et al. 2021

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“…Overall, these data show that besides an increase in neutrophil counts, there is increased neutrophil activation and NET release in COVID-19 linked to disease severity. Importantly, these evaluations were performed in plasma, clearly indicating that circulating NETs contribute to systemic inflammatory responses and this is not resulting from mechanical ventilation-induced pulmonary stress.Based on these results and previously published autopsy reports, we aimed to confirm hyperactivated neutrophils not only play an important role in systemic COVID-19 disease manifestations, but also contribute to severe COVID-19 pneumonitis15,34 . Therefore, we performed scRNA-seq on BAL fluid from 6 COVID-19 and 5 non-COVID pneumonia cases, sequencing the transcriptomes of 26,605 cells in total (fig.…”

mentioning

confidence: 86%

Monocyte-Driven Atypical Cytokine Storm and Aberrant Neutrophil Activation as Key Mediators of COVID19 Disease Severity

et al. 2020

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Epidemiological and clinical reports have indicated that the host immune response to SARS-CoV-2, more so than viral factors, determines COVID-19 disease severity. To elucidate the immunopathology underlying COVID-19 severity, cytokine and multiplex immune profiling was performed in mild-moderate and critically-ill COVID-19 patients. Hypercytokinemia in COVID-19 differed from the IFN-γ-driven cytokine storm in macrophage activation syndrome, and was more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels followed by deep-immune profiling showed that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Expression of antigen presenting machinery was reduced in critical disease, while also neutrophils contributed to disease severity and local tissue damage by amplifying hypercytokinemia and neutrophil extracellular trap formation. We suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

show abstract

“…Patients with severe COVID-19 show dysfunction in myeloid cells, with a particularly large population of immature and dysfunctional neutrophils and monocytes with an inflammation-promoting phenotype (lack of HLA-DR) (Schulte-Schrepping et al, 2020). Hyperactivated neutrophils not only play an important role in systemic COVID-19 disease manifestations but also contribute to severe COVID-19-associated pneumonia and tissue damage (van de Veerdonk et al, 2020;Barnes et al, 2020). Consistent with the existing literature, we observed that COVID-19 patients display a high level of immature neutrophils and inflammatory monocytes.…”

Section: Some Preclinical Studies Have Indicated Beneficial Effects O...mentioning

confidence: 99%

Poly(I:C) enhances mesenchymal stem cell control of myeloid cells from COVID-19 patients

et al. 2022

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Plasma Cells and Endothelitis in COVID-19 Lung Pathology

Cited by 3 publications

References 0 publications

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity

Monocyte-Driven Atypical Cytokine Storm and Aberrant Neutrophil Activation as Key Mediators of COVID19 Disease Severity

Poly(I:C) enhances mesenchymal stem cell control of myeloid cells from COVID-19 patients

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