Randomised Study of Plasma Exchange in Severe COVID-19

COVID19 is a viral pandemic associated with primarily respiratory pathology, in the form of
microvascular and macrovascular thrombosis. In patients requiring hospital admission, there
is severe disease, requiring respiratory support, from high dose oxygen therapy or
ventilatory assistance, which may be invasive or non invasive. The pathology of COVID19 is
poorly understood, but it is accepted there is an inflammatory-thrombotic basis. Despite
current therapeutic platforms, there is no consensus on a specific therapy within a trial
setting that has proven benefit in severe COVID 19.

Thrombotic microangiopathies, such as TTP, are a different disease, but have a comparable
prothrombotic phenotype, and similar or higher inflammatory parameters, including D Dimers,
ferritin, LDH and IL-6 at acute presentation and resolve with plasma exchange (PEX). The
rationale in severe COVID19 infection is to undertake PEX to aid reduction of the
hyperinflammation and reduce the morbidity and mortality to the lungs, but also systemically,
such as the heart, kidneys and brain. A feasibility study of PEX therapy has been undertaken
and confirmed a reduction in the inflammatory markers, no VTE/arterial events and
normalisation of the renal function and cardiac function throughout the period of therapy. As
plasma exchange is an intensive treatment modality, blocks of 5 daily PEX will be undertaken.
Further blocks of PEX treatment can be initiated as dictated by the clinical and laboratory
parameters. Unlike many therapeutic schedules, there is no immunosuppression associated with
PEX; indeed, the resulting decrease in inflammatory markers were shown to be associated with
an increase and sustained lymphocytes count. Therefore, as patients with COVID-19 have
elevated procoagulant factors including VWF and factor VIII secondary to direct endothelial
activation. This is associated with an exaggerated pro-inflammatory immune response and
microvascular thrombosis; resulting in multi-organ dysfunction and eventually death. PEX will
improve coagulopathy, as measured by VWF:ADAMTS 13 ratio and D Dimers, with an associated
reduction in inflammation, organ-related microthrombosis, and ventilatory support.