Covid-19 Infection and Cytokine Storm
by Dr. David Borenstein M.D. 4/2020
Coronavirus 19 infection is a novel disease that has spread across the world. Since it is a new infection, all of the world’s population is at risk. Although the characteristics of this infection continue to be discovered, some factors have become clear. Individuals who are 50 years old or greater have increased susceptibility. In addition, individuals with co-morbidities have an increased mortality.
Coronavirus 19 infection is a disorder that affects the respiratory system. Covid-19 gains access to the pulmonary system and starts replicating in lung tissue. The immune system recognizes this foreign invader and releases a response to remove the virus.
The respiratory system is beautifully designed for oxygen transfer. Oxygen is brought to specialized structures called alveoli. Alveoli consist of a very thin membrane a few cells thick with air on one side and capillaries, very small blood vessels, on the other side. The thinness of the membrane allows oxygen to transfer to the blood vessels while carbon dioxide is eliminated. This mechanism works well when there is no swelling of the membranes or excess fluid in the lung. If excess fluid appears, oxygen exchange is decreased and an individual will experience shortness of breath.
Individuals with more severe Covid-19 infection experience shortness of breath and cough. If the immune system is excessive in its response, a cytokine storm may occur. A cytokine storm occurs when immune factors that initiate and maintain an immune response are not inhibited. This excessive response will cause extensive lung tissue damage. Membranes will become swollen and impair oxygen exchange. With that change in lung function, individuals need to be placed on ventilators to produce positive back pressure to allow the membranes of the lung to work.
Interleukin (IL) – 6 is a cytokine identified to be a major factor in the immune process. IL-6 activates T cells, B, cell, macrophages, osteoclasts, and the production of liver factors that result in fever. IL-6 is thought to be one of the prime mediators of cytokine storm. IL-6 causes vascular leakage, activation of the complement and coagulation cascades, disseminated intravascular coagulopathy, and weakening of heart muscle. Inhibition of Il-6 in Covid-19 patients with respiratory distress has the potential to quiet the storm and allow the lung to heal.
Il-6 is a cytokine that also mediates the inflammatory response in rheumatoid arthritis. Therapy of rheumatoid arthritis includes Anti-IL6 biologic drugs. These agents are currently available for the treatment of RA but may also be of use in the treatment of Covid-19 infection.
Tocilizumab (Actemra) is a humanized anti-human IL-6 receptor antibody of the IgG1 class. The biologic is made by attaching a mouse anti-human IL6 variable portion to a constant human FC portion of an IgG antibody. The antibody can be administered intravenously or subcutaneously. In severe cases of Covid-19 pulmonary involvement, intravenous tocilizumab has been utilized with some success. A clinical trial is underway to determine if Tocilizumab if effective in Covid-19 pneumonia.
Sarilumab is a fully humanized IgG1class antibody directed at IL-6 receptors attached on cell surfaces and in blood. This biologic agent is administered as a subcutaneous injection. Clinical trials are underway to determine the efficacy of this biologic for treatment of severe lung Covid-19 infection.
The vast majority of individuals with Covid-19 infection will be asymptomatic or will be mildly ill. About 20% will have a noticeable infection and may require medical care. A lower number will be hospitalized. In these individuals with more severe disease, the use of anti-IL6 antibodies has the potential to prevent lung damage and result in decreased mortality from this illness.