Modulation of Hyperinflammation in COVID-19

The coronavirus disease 2019 (COVID-19) is a novel virus that was first reported in December
2019 from Wuhan, China. So far, over 8,000,000 cases have been reported around the globe with
>400,000 reported deaths overwhelming hospitals and constraining resources. Death is mainly
due to severe acute respiratory syndrome (SARS), requiring mechanical ventilation; however,
many hospitals do not have sufficient equipment (i.e. ventilators) to meet the requirements.
It had been suggested that severe SARS-related injury may have be related to an excessive
reaction of the host's immune system, and a dysregulation of pro-inflammatory cytokines
called cytokine storm syndrome. This is characterized by a hyper-inflammatory state leading
to fulminant multi-organ failure and elevated cytokine levels. There is a critical and
imminent need to identify effective treatments to reduce mortality.

The study team proposes to use slow low-efficiency daily dialysis (SLEDD) to provide an
extracorporeal circuit to target this cytokine storm using immunomodulation of neutrophils
with a novel leukocyte modulatory device (L-MOD) to generate an anti-inflammatory phenotype,
without depletion of circulating factors.

This is a single center, prospective, randomized controlled pilot study in the Critical Care
Trauma Centre at Victoria Hospital and Critical Care at University Hospital, London, Ontario.
Critical Care at University Hospital is comprised of two units, the Medical-Surgical ICU and
the Cardiac Surgical Recovery Unit. The study team will randomize patients requiring ICU
admission of COVID-19 into one of two groups; either to standard of care for severe COVID-19
infection or in the active treatment group (standard supportive care + treatment with
leukocyte modulation (using L-MOD)), on 1:1, basis. They will know what treatment group they
are randomized to.

The study team will use block randomization to randomize the patients into one of these two
groups. A computer algorithm is used to generate the randomization sequence in blocks of four
(two for standard of care and two for active treatment). This is used to make sure that equal
numbers of people get allocated to each arm of the study and that the allocation is equal
throughout the lifespan of the trial.

Slow low-efficiency daily dialysis will be performed twice, for approximately 12 hours, 2
days in a row. Due to the nature of the intervention, it is not possible to blind neither the
patient nor study team members to the treatment group the patient gets randomized to, with
the exception of study team members analyzing the data who will be blinded to the patients'
treatment group. Additionally, the study uses robust objective measurements that will be
unaffected by the patients' awareness of the group they have been randomized to.

Blood work will be collected before each dialysis treatment initiation, at the end of each
session, and then on after day 4 and no later than day 7 in the ICU for the patients
receiving intervention. Patients receiving standard of care will have blood work done on day
1, day 2, and after day 4 and no later than day 7 of admission. We will also collect a urine
sample from all participants before the first dialysis session only and then again at after
day 4 and no later than day 7 in the ICU. End of study will be defined as the last patient
discharged from the hospital.