Contrary to what doctors have thought, the excessive reaction of the immune system known as the cytokine storm is not responsible for most of the severe forms of COVID-19. On the contrary, in most cases, death was caused because the virus damaged the immune system. A conclusion that will force us to review the treatments administered to patients.
Coronavirus
For many doctors and scientists, the sudden deterioration in COVID-19 patients is in many cases associated with an excessive reaction of the immune system caused by the release of an excessive amount of cytokines, the molecules secreted by cells such as lymphocytes and macrophages to fight viruses. “There is growing evidence that a proportion of patients with a severe form of COVID-19 are susceptible to Cytokine storm syndrome,” wrote researchers at University College London Hospital (UK) in The Lancet.
What is a cytokine storm?
Cytokines are inflammatory molecules secreted by immune cells such as lymphocytes and macrophages. They are released by the body when attacked by a pathogen and usually act locally. In some cases, however, the immune system gets “carried away” and produces too many cytokines, which are released throughout the body and cause tissue damage. This inadequate immune response can lead to septic shock and be fatal.
The overproduction of cytokines is particularly known in severe forms of respiratory diseases. This has been highlighted to explain the dangers of SARS and MERS. It is also thought to have happened in flu pandemics, such as the Spanish flu that killed about 50 million people in 1918-1919.
Less than 5 percent of severe COVID-19 cases
However, the cytokine storm explanation for the high mortality rates may not explain all the deaths, according to two new studies. “Less than 5% of Covid-19 patients, including the sickest, had a hyperinflammatory and potentially fatal immune response known as Cytokine Storm Syndrome,” according to the authors of the first study, published in Science Advances, in which 168 Covid-19 patients participated. These patients, who suffered from severe forms, actually had less inflammation than the average person with the flu, adds the study, which examined 168 adults with COVID-19 and 25 adults with the flu.
It is believed that the severity of the disease is related to a deeply suppressed immune response, especially in older people. “The SARS-CoV-2 virus is a kind of a double-blow for the elderly,” said Sean Leng, Professor of Medicine and Immunology at Johns Hopkins University. Older people initially have a weaker immune system, so it is easier for the virus to enter and develop. And when the virus starts killing the remaining immune cells, their situation becomes even worse.
Not very high cytokine levels
A second study published in JAMA confirms these results. The authors compared the blood concentrations of three essential cytokines in patients admitted to intensive care units (ICU) with several different diseases (COVID-19, severe acute respiratory infection, bacterial septic shock, cardiac arrest, or severe trauma). In these five patient groups, cytokine levels in patients with Covid-19 were significantly lower than in patients with septic shock or severe acute respiratory infection, and similar to patients with trauma or cardiac arrest, “conditions not known as cytokine storms”, the authors observed.
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Anti-inflammatory treatments
These conclusions call into question the anti-cytokine treatments administered to patients with severe forms of COVID-19, such as tocilizumab or sarilumab, which have nevertheless attracted considerable interest. Most patients with Covid-19 would also not be candidates for treatment with corticosteroids such as dexamethasone, the researchers say. Dexamethasone is effective in treating critically ill patients, reducing the risk of mortality by 34%. “Limiting immunosuppressive therapies only to the small subset of COVID-19 patients with an overactive immune response is the only way to know if these approaches are ultimately useful,” said Philip Mudd, an emergency physician at Barnes-Jewish Hospital in St. Louis and co-author of the Science Advances study.
References
Mudd, P. A., Crawford, J. C., Turner, J. S., Souquette, A., Reynolds, D., Bender, D., Bosanquet, J. P., Anand, N. J., Striker, D. A., & Ellebedy, A. H. (2020). Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm. Science Advances, 6(50), eabe3024. https://doi.org/10.1126/sciadv.abe3024
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., Manson, J. J., & HLH Across Speciality Collaboration, UK. (2020). COVID-19: Consider cytokine storm syndromes and immunosuppression. The Lancet, 395(10229), 1033–1034. https://doi.org/10.1016/S0140-6736(20)30628-0
