Determination of the Hemoadsorption Impact as Adjunctive Treatment Upon the Support Therapy of COVID-19

Coronavirus disease-19 (COVID-19) has emerged as a serious pandemic recently, with high
mortality especially in those patients who went on to develop acute respiratory failure
(around 50%), and especially in those who also developed acute kidney injury (AKI) (80%).
Extracorporeal cytokine removal has been recommended by international expert. Two technical
approaches have been studied one from Jafron® HA380 (Jafron Biomedical, Zhuhai, Chine) and
Cytosorb® (Cytosorbents Corporation, NJ, USA). Basically, it is a single -use sorbent
technology that can be used together with an hemofiltration circuit in CVVHD mode only. The
cartridge is made of adsorptive porous polymeric beats that represent all together an active
surface of 60,000 square meters.The cut-off of these cartridge is about 60,000 daltons and
all the cytokines smaller can easily removed by the cartridge especially in the blood stream.
The elimination percentage goes from 4 to 30 % with the CytoSorb® and remain steady for the
first 6 to 12 hours. The full elimination from the blood stream vary amongst cytokines. It is
about 28 % for IL-6- (p = 0.006) and somewhat less for TNF-alpha (8,5%, p = 0.13). Currently,
there is no available randomized controlled trial that assess morbidity and mortality in ARDS
secondary to COVID infections. There is one pilot study looking at 20 patients with early
(<24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrine>10
μg/min, procalcitonin (PCT) > 3 ng/mL without the need for renal replacement therapy were
randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24
h. This was the first trial to investigate the effects of early extracorporeal cytokine
adsorption treatment in septic shock applied without renal replacement therapy. It was found
to be safe with significant effects on norepinephrine requirements, PCT and Big-endothelin-1
concentrations compared to controls.

Actually, other studies are only case report series upon other pulmonary infections than
COVID 19.The sorbent chose is the CytoSorb ® it is easier to install, has a CEE approval and
his temporally approval by the FDA for the time of the pandemic.

The features of acute hypoxemic respiratory failure in COVID-19 show two fundamentally
different phenotypes. One is the L-type: Low elastance; Low ventilation-to-perfusion ratio;
Low lung weight; Low lung recruitability. The H-type is characterized by the opposite
features. The latter is more similar to the classical ARDS and being investigated by several
studies. However, little is known about pathogenesis of the L-type, which can cause hypoxemia
to the same degree as the H-type. Even the pathophysiology is yet to be discovered, however,
vasoplegia is considered one of the major factors leading to severe right-to-left shunt.

It is postulated that cytokines , chemokines play a crucial role in the pathogenesis, but it
has not been investigated yet. Therefore we have chosen the clearance of these substances as
our primary endpoint. Usually, CytoSorb is attached to a CRRT circuit which has to run in a
CVVHD mode only. In some circumstances CytoSorb might be attached to the ECMO device. In
addition to cytokines complements may also play a major role in the pathophysiology of the
COVID 19. Therefore, we decided to investigate whether early treatment with blood
purification could exert any effects on the cytokine and complement profile and oxygenation
in these patients. Testing the Cytokinetic model by measuring cytokines in the blood stream
and in the BAL to see if you can create a reverse gradient allowing a massive passage of
leucocyte from the blood toward the infected lungs.