Cytokine adsorption devices are designed to reduce elevated concentrations of cytokines in the blood. Elevated cytokine levels have been seen in some patients with COVID‑19 and respiratory failure. Increased concentrations of cytokines may indicate an uncontrolled immune response, called cytokine release syndrome or cytokine storm. This can result in severe inflammation, shock, respiratory failure, organ failure, and in some cases, death.
The adsorption devices are cartridges containing adsorbent materials, such as porous polymer beads or resin. Blood or plasma is pumped out of the body and through the adsorption cartridge. This non-selectively captures molecules, such as cytokines, within the pores of the adsorbent material. The blood, or plasma, is then returned to the body with a reduced level of inflammatory markers and cytokines.
Each cartridge is single-use and can be used for continuous treatment cycles for between 2 and 12 hours per session. Patients with COVID‑19 are often more likely to experience blood clotting, so healthcare professionals should ensure anticoagulation treatment is effective before starting haemoperfusion therapy. Because adsorption technologies may affect the concentration of drugs in the blood, pharmacological treatment will need to be carefully monitored. The following technologies were identified as being cytokine adsorption devices:
D2000 Plasma Adsorption Cartridge and Spectra Optia Apheresis System (Marker Therapeutics AG and Terumo BCT). The D2000 plasma adsorption cartridge is used with the Spectra Optia Apheresis System as a secondary blood purification device. The adsorbent material in the cartridge is made of a blend of non-ionic resins. Plasma, separated from blood using the Spectra Optia plasma exchange protocol, is pumped through the cartridge to remove cytokines. The person's own plasma is then mixed back into the blood and returned to the body. The company advised the treatment should be given for 2 hours every day for 2 to 3 sessions.
CytoSorb adsorbent cartridge (CytoSorbents Corporation). CytoSorb can be added to most commercially available extracorporeal machines such as dialysis machines, haemofiltration machines, heart and lung machines and extracorporeal membrane oxygenation machines. The absorbent material in the cartridge is beads made of porous polymer. Blood is pumped through the cartridge, removing molecules up to 55 kDa in size such as cytokines, and returned to the body. The company advised that the treatment can be used for up to 24 hours per device and for up to 7 consecutive days. The company states the technology should not be used with plasma exchange devices.
HA330 and HA380 Haemoperfusion Cartridges (Jafron). The HA330 and HA380 cartridges have been described by Health Technology Wales in a topic exploration report. New evidence has been included in the evidence section of this briefing.
Similar devices have been designed to use adsorption devices to reduce toxins released from bacteria in the blood (endotoxin). The literature reports that a technology has been used for treating septic shock as a secondary complication of flu. There is currently no evidence for its use in patients with COVID‑19 and so it is not included in this briefing.
The technology is not new, but it is new to use cytokine adsorption devices specifically to treat COVID‑19. The devices are intended to return the cytokine concentration in the blood to normal levels. This is expected to prevent organ failure and death as a result of cytokine release syndrome in people with COVID‑19. Unlike drug therapies, adsorption cartridges are concentration dependent, so the cytokines in the blood at the highest concentrations will be removed from the blood at a faster rate.
NHS clinical guidance for the management of critical care for adults with COVID-19 during the coronavirus pandemic notes that while antiviral therapies and vaccines are in development, none are currently recommended, and clinical trials of new treatments should be supported. People with COVID‑19 and respiratory failure are treated using invasive or non-invasive ventilation to reach target oxygen saturation (SpO2). This would be 92% to 96% for most people but may be lower in some patient groups, such as people with chronic obstructive pulmonary disease. Routine high-dose corticosteroids are not recommended because these could lead to prolonged viral shedding, bacterial superinfection and worse outcomes.
The British Thoracic Society has published guidance on COVID-19: information for the respiratory community to provide respiratory support for people with COVID‑19 who are acutely unwell. People with oxygen saturation of less than 94% in room air should be given oxygen using a Venturi mask and can be moved to a non-respiratory COVID-19 ward for monitoring if oxygen saturation returns to above 94%. People whose oxygen saturation does not improve should be escalated to intensive care for intubation if appropriate.
NHS guidance for the role and use of non-invasive respiratory support in adult patients with COVID-19 gives further recommendations on the types of invasive and non-invasive ventilation that should be used.
World Health Organisation guidance on clinical management of severe acute respiratory infection when COVID-19 is suspected notes that people with COVID‑19 should be closely monitored for signs of clinical deterioration such as respiratory failure. Vital signs should be monitored and early warning scores such as NEWS2 should be used to identify people whose treatment needs to be escalated. Standard laboratory blood tests should also be used to identify any complications such as acute kidney injury, acute cardiac injury or shock. Each person's treatment should take into consideration whether they have any comorbid conditions, to consider whether other treatments should be temporarily stopped and the potential for interactions between drugs.
None of the published guidance for treating respiratory failure in people with COVID‑19 includes the use of cytokine adsorption. If cytokine release syndrome is suspected in people who do not have COVID‑19, standard care includes treatments to suppress the inflammatory response, such as tocilizumab and intravenous immunoglobin.
Cytokine adsorption devices are for people who have tested positive for COVID‑19 and have imminent or confirmed respiratory failure. The treatment is given by intensive care consultants and specialist nurses on critical care units. Imminent respiratory failure may be characterised by a faster deterioration of a person's condition including increased heart rate, shortness of breath or increased rate of breathing, sweating and diminished consciousness. Indicators for starting treatment include severe acute respiratory distress syndrome with or without suspected acute kidney injury, raised inflammatory biomarkers or hypotension. The companies advised that the technology should be used as soon as possible in people with potential respiratory failure.
The technologies may be used as a standalone therapy or with other extracorporeal therapies including renal replacement therapy and oxygenation membrane therapy. Training is needed and is provided by the companies. In trusts where healthcare professionals are familiar with using extracorporeal circuits the companies advised that remote training is offered for the use of the cartridge. If staff are not familiar with the extracorporeal machines more extensive training is needed.
Each D2000 cartridge costs £1,785 (excluding VAT).
Each CytoSorb cartridge costs £920 (excluding VAT).
Each HA330 and HA380 cartridge costs £450 (excluding VAT).
Extracorporeal machines, such as haemodialysis machines, heart–lung machines and extracorporeal membrane oxygenation (ECMO) machines cost between £10,000 to £40,000. It is expected that most hospitals will already have access to the appropriate machines. The cost of the Spectra Optia Apheresis System is £58,338.31 per unit (excluding VAT) including full set up; annual service charge is an additional £4,083. Some hospitals, such as teaching hospitals and specialist care centres, will already have access to the Spectra Optia Apheresis System.
The 2019/20 National Tariff Payment System estimates the cost of respiratory failure with multiple interventions to range between £4,500 and £8,200, depending on the length of hospital stay. The 2018/19 National Cost Collection reports the average cost of critical care ranges from £516 to £1,673 per bed per day.
While these figures give an indication of the cost of respiratory failure, no COVID‑19 cost data have been included in these estimates and so the costs do not reflect COVID‑19 cases.
The Spectra Optia Apheresis System is already being widely used for different indications in 73 locations in the UK, including teaching hospitals and specialist care centres. Similarly, haemofiltration and haemodialysis machines are available in all NHS trusts. ECMO machines are currently available in approximately 8 trusts. Heart and lung machines are available in specialist centres.
Cytokine adsorption devices would be used in addition to standard care so will cost more. However, the company claims the technology could reduce COVID‑19 mortality rate and speed up recovery.