The impact of hypoxia on B cells in COVID-19

Kotagiri, Prasanti; Mescia, Federica; Hanson, Aimee L.; Turner, Lorinda; Bergamaschi, Laura; Peñalver, Ana; Richoz, Nathan; Moore, Stephen D.; Ortmann, Brian; Dunmore, Benjamin J.; Ruffieux, Hélène; Morgan, Michael D.; Tuong, Zewen Kelvin; Rogers, Rachael Bashford; Hosmillo, Myra; Baker, Stephen; Elmer, Anne; Goodfellow, Ian; Gupta, Ravindra; Kingston, Nathalie; Lehner, Paul J.; Matheson, Nicholas J; Richardson, Sylvia; Saunders, Caroline; Weekes, Michael P.; Göttgens, Berthold; Toshner, Mark; Hess, Christoph; Maxwell, Patrick H.; Clatworthy, Menna R.; Nathan, James A.; Bradley, John R.; Lyons, Paul; Burrows, Natalie; Smith, Kenneth

doi:10.1101/2021.07.12.21260360

Cited by 2 publications

(3 citation statements)

References 45 publications

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“…In addition, we observed that the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor (TF), which might affect B cell function and induce B cell abnormalities in COVID-19 patients 34,35 , showed a signi cantly higher activity at both progression and convalescence in naïve B cells of COVID-19 CVID patients (Figure 2c), despite the previously described impaired HIF-1α upregulation in CVID patients upon BCR in vitro stimulation 36 . Moreover, in ammation-related genes, such as IL1B, IL6, LTA and TNF, showed an impaired upregulation in naïve B cells of CVID individuals during SARS-CoV-2 infection compared with COVID-19 controls (Supp.…”

Section: Dysfunctional B Cell Receptor and Nf-κb Signaling Pathways I...mentioning

confidence: 86%

“…The fact that these patients showed an impaired NF-κB pathway activation in the naïve B cell compartment, suggests that additional pathways might be involved. Hypoxia has been previously reported to affect B cell function and induce B cell abnormalities in COVID-19 patients 34,35 , so this molecular feature might have an additional negative impact on setting up a proper B cell response in these immunode cient patients.…”

Section: Discussionmentioning

confidence: 99%

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COVID-19 progression and convalescence in common variable immunodeficiency patients shows incomplete adaptive responses and persistent inflammasome activation

Rodríguez-Ubreva

Handfield

Keller

et al. 2022

Preprint

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Patients with common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, are characterized by hypogammaglobulinemia, poorly protective vaccine titers and increased susceptibility to infections. New pathogens such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), might constitute a particular threat to these immunocompromised patients since many of them experience a slower recovery and do not achieve full response to SARS-CoV-2 vaccines. To define the molecular basis of the altered immune responses caused by SARS-CoV-2 infection in CVID patients, we generated longitudinal single-cell datasets of peripheral blood immune cells along viral infection and recovery. We sampled the same individuals before, during and after SARS-CoV-2 infection to model their specific immune response dynamics while removing donor variability. We observed that COVID-19 CVID patients show defective canonical NF-κB pathway activation and dysregulated expression of BCR-related genes in naïve B cells, as well as enhanced cytotoxic activity but incomplete cytokine response in NK and T cells. Moreover, monocytes from COVID-19 CVID patients show persistent activation of several inflammasome-related genes, including the pyrin and NLRC4 inflammasomes. Our results shed light on the molecular basis of the prolonged clinical manifestations observed in these immunodeficient patients upon SARS-CoV-2 infection, which might illuminate the development of tailored treatments for COVID-19 CVID patients.

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Section: Dysfunctional B Cell Receptor and Nf-κb Signaling Pathways I...mentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

COVID-19 progression and convalescence in common variable immunodeficiency patients shows incomplete adaptive responses and persistent inflammasome activation

Rodríguez-Ubreva

Handfield

Keller

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In the humoral immune response, B cells are essential for presenting antigens to other immune cells, producing pathogen-specific antibodies, and secreting proinflammatory cytokines. Low B cell counts of some subsets such as memory B cells and expression of B cells related genes such as heavy chain and light V chain genes are observed in severe COVID-19 patients (3; 4; 5).…”

Section: Introductionmentioning

confidence: 99%

Different B cell activation patterns in asymptomatic and symptomatic COVID-19 patients

Pham

Talih

Ehrhart³

et al. 2022

Preprint

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Early and persistent defects in B cell subsets such as memory B cells were shown to be correlated with poor outcomes in COVID-19 patients. This research aimed to develop a molecular pathway model to understand the B cell development in COVID-19. A B cell transcriptomics dataset, obtained from COVID-19 patients, was analyzed on the resulting pathway model to study B cell activation. The pathway showed two distinct gene expression profiles between asymptomatic and symptomatic patients. In asymptomatic patients, there is an increase in transcript levels of antiviral interferon-stimulated genes such as ISG15, IFITM1, and NEAT1 and a driving gene for the extrafollicular pathway CXCR4 indicating a formation of plasmablast. In symptomatic patients, the results suggest an inhibition occurring at the germinal center hinting at a reduction in memory B cell production. Transcripts of driver gene CXCR5 involved in germinal center development is one of the most downregulated genes. This could contribute to the shortage in the formation of memory B cells in COVID-19. Concluding, in SARS-CoV-2 infection, B cells follow different activation routes in asymptomatic and symptomatic patients. In this study, we constructed a pathway that allowed us to analyze and interpret activation patterns of B cells in COVID-19 patients and their link to disease severity. Importantly, the pathway and approach can be reused for further research in COVID-19 or other diseases.

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The impact of hypoxia on B cells in COVID-19

Cited by 2 publications

References 45 publications

COVID-19 progression and convalescence in common variable immunodeficiency patients shows incomplete adaptive responses and persistent inflammasome activation

COVID-19 progression and convalescence in common variable immunodeficiency patients shows incomplete adaptive responses and persistent inflammasome activation

Different B cell activation patterns in asymptomatic and symptomatic COVID-19 patients

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