Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis

Post-COVID syndrome (PCS) or Long-COVID is an increasingly recognised complication of acute SARS-CoV-2 infection, characterised by persistent fatigue, reduced exercise tolerance chest pain, shortness of breath and cognitive slowing. Acute COVID-19 is strongly linked with increased risk of thrombosis; a prothrombotic state, quantified by elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio, and is associated with severity of acute COVID-19 infection. We investigated if patients with PCS also had evidence of a pro-thrombotic state associating with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk including VWF(Ag):ADAMTS13 ratio, was investigated. An elevated VWF(Ag):ADAMTS13 ratio (≥1.5) was raised in nearly one-third of the cohort and four times more likely in patients with impaired exercise capacity as evidenced by desaturation ≥3% and/or rise in lactate level more than 1 from baseline on 1-minute sit to stand test and/or 6-minute walk test (p<0.0001). 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (p<0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight a potential role for antithrombotic therapy in the management of these patients

Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein

BACKGROUND: Patients with antibody deficiency respond poorly to COVID-19 vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesised that immunoglobulin preparations will now contain neutralising SARS-CoV-2 spike antibodies which confer protection against COVID-19 disease and may help to treat chronic infection. METHODS: We evaluated anti-SARS-CoV-2 spike antibody in a cohort of patients before and after immunoglobulin infusion. Neutralising capacity of patient samples and immunoglobulin products was assessed using in vitro pseudo-virus and live-virus neutralisation assays, the latter investigating multiple batches against current circulating omicron variants. We describe the clinical course of nine patients started on IRT during treatment of COVID-19. RESULTS: In 35 individuals with antibody deficiency established on IRT, median anti-spike antibody titre increased from 2123 to 10600 U/ml post-infusion, with corresponding increase in pseudo-virus neutralisation titres to levels comparable to healthy donors. Testing immunoglobulin products directly in the live-virus assay confirmed neutralisation, including of BQ1.1 and XBB variants, but with variation between immunoglobulin products and batches.Initiation of IRT alongside Remdesivir in patients with antibody deficiency and prolonged COVID-19 infection (median 189 days, maximum over 900 days with an ancestral viral strain) resulted in clearance of SARS-CoV-2 virus at a median of 20 days. CONCLUSIONS: Immunoglobulin preparations now contain neutralising anti-SARS-CoV-2 antibodies which are transmitted to patients and help to treat COVID-19 in individuals with failure of humoral immunity

The Wasp and the Orchid

Published in A ranked literary journal Southerly, 66.2 (2006

Entering writers' rooms: reading interviews with novelists

This paper examines the literary interview as a form, and as a source of research material for creative writing and literary studies. In the article, I discuss theoretical and methodological approaches to conversations with writers and the usefulness of the interview for creative writing scholars. Novelist Charlotte Wood published The Writer’s Room: Conversations about Writing (2016) soon after her award-winning fifth novel, The Natural Way of Things (2015), appeared; the two books were constructed at around the same time. Through an interview I conducted with Wood about The Writer’s Room and her reasons for speaking to contemporary writers, I assess the statements Wood makes in the introduction to her collection and explore the texture of literary interviews. The article examines what information interviews provide about an individual writer’s working methods and looks at the emotions or affect around authors’ writing lives as a means of gauging the utility of the interview for scholars and writers. I argue that while the apparent aim of the interview is to obtain insights into an author’s praxis, related objectives may be to build connections between authors and their readers, and to augment communities of writer

Three Monkeys

Overland 183 (2006): 48-53 (4100 words

Creatureliness and Justice in Cormac McCarthy's All the Pretty Horses

In this chapter, which focuses on the portrayal of justice in the novel, I argue that the American characters are rendered "creaturely" by this experience

Myth-busting women and literature

I would like to bust this myth in true myth-busters fashion, preferably with explosives, as Jamie and Adam kind of bust the myth that a room filled with methane gas can be blown up by placing a magazine in an electric toaster and turning it on.