The impact of hypoxia on B cells in COVID-19.

BACKGROUND: Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19. METHODS: Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice. FINDINGS: We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions. INTERPRETATION: Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes. FUNDING: Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.

Beastly Boasts and Apocalyptic Affects: Reading Revelation in a Time of Trump and a Time of Plague

Waxing “biblical,” Donald Trump has described the COVID-19 pandemic as a “plague.” In a different but related register, millions of Christians worldwide have interpreted the pandemic as one of the eschatological plagues prophesied in the Book of Revelation. This article appropriates the reading tactics of Gilles Deleuze and Félix Guattari, together with the resources of affect theory, to connect the Book of Revelation with both the Trump phenomenon and the COVID-19 pandemic. Specifically, the article attempts to relate Revelation’s Beast to Trump (to unleash the Beast against Trump) non-eschatologically, in a non-representationalist reading strategy, and to analyze how Trump has manipulated the pandemic for his post-ideological ends.