Series on COVID Therapy Studies – Cytokine Storm
With the onslaught by COVID and its coinciding onslaught of self-proclaimed experts with every opinion under the sun, I choose to respond with a series of research study reports so you can choose for yourself. Each edition will bring a few studies describing possible therapies for COVID under investigation or reported in past research. As my recent Facebook Live video noted, we do not know enough about this virus to be definite at this time. I am not claiming any of these are the preventive or curative answer for you or your family’s safety. I just want you to be aware of these studies and have knowledge so that you can grow in wisdom rather than stumble about in panic.
(See appendix paragraph for further thoughts on finding effective COVID therapies)
Daily we have reports of various studies regarding COVID, its genomes, mechanisms, mortality, morbidity, therapies and more. This may be the most rapid proliferation of scientific understanding the world has ever witnessed. With that tidal wave, we need to pause from our progress through therapies to consider a mechanism of illness called cytokine storm. By better understanding this mechanism (whether you are a front-line researcher, clinician, or at-risk citizen), each can better recognize promising therapies.
Beginning in 1993 the term “cytokine storm” arrived in the setting of graft-host disease but over the following years was applied across multiple infectious agents. As it sounds, the cytokines of the immune system whip into a frenzy, crossing over to the dark side. These chemical messengers of the immune which normally direct the proper defense of our bodies build to the tipping point and begin to cause uncontrolled inflammation. Organs no longer function correctly. Lungs fill with fluid. Cardiovascular systems go into shock. Brains turn delirious. The review in Microbiology and Molecular Biology Reviews by Tisoncik et al provides a full explanation linked in references (1).
Tisoncik et al lists various infections where this may occur: cytomegalovirus, EBV, group A Strep, and the last SARS (also a coronavirus from 2003). A correspondence by Mehta Puja et al in the online Lancet suggests that our current COVID 19 may cause its most severe forms by this mechanism of cytokine storm (2). Mehta, Puja bases this on correlations with other cytokine storm conditions and a letter published in Intensive Care Medicine March 3, 2020. This letter reported data from a series of 150 patients in Wuhan. In this series, markers of increased inflammation were found in those who died of COVID 19 versus those were hospitalized and survived. This elevated C reactive protein, ferritin, and Interleukin 6 does not prove the mechanism was cytokine storm, but does suggest the possibility (3).
A review by Channappanavar and Perlman in Seminars in Immunopathology from 2017 also postulates the possibility that pathogenic coronaviruses like severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) may cause their worst outcomes through a dysregulated hyperinflammatory process (4). There exists good evidence that these viruses (cousins of our COVID 19) work through several mechanisms to create an over-exuberant inflammation causing lung failure. These include an extremely high rate of viral replication creating a larger burden of infected cells simultaneously, a disabling of the first line innate arm of our immune system, and a greater proportion of non-lymphocyte immune cells contributing to the inflammatory process.
Research on COVID 19 indicates that similar mechanisms may be at work with our current pandemic. Chen et al again describe the acute respiratory distress syndrome and organ failure form COVID 19 and link these severe manifestations to cytokine storm (5). They note the current research into an interleukin-6 antibody blocker, stem cell therapy, and plasma infusions from people who survive the illness. These are being investigated to counter the cytokine storm. (note: article in Chinese, this paragraph is based on abstract alone).
An extremely interesting side note: Be careful reading article bibliographies. It can lead to a huge rabbit trail. In this case, I will refrain from chasing it any farther than mentioning the punch line here. Some scientists are researching curcumin in viral diseases with cytokine storms as a potential therapy to lower the cytokines (6). Curcumin lowers the cytokines Interleukin-1, interkeukin-6 and tumor necrosis factor alpha.
Without embarking on a Ph.D. in virology or immunology, this provides an overview of the immune event called cytokine storm. If this process does play a role in the worst cases of COVID, therapies targeting the over reaction of the immune system deserve attention in research. Besides attacking the virus directly in terms of replication or person to person spread, we need therapies which could modulate the inflammatory response and prevent the lung failure and death.
I believe we will learn that the potential therapy hydroxychloroquine will turn out to be an immune modulator as much as an anti-viral. If other natural therapies ultimately are found to benefit COVID patients, they will likely include ones that modulate this excessive inflammation response. Likewise, therapies which overly activate the immune system may worsen COVID patients. This question will arise when we examine some natural therapies like elderberry. Hydroxychloroquine and elderberry will be addressed in future posts.
(1) Tisoncik, J. R., et al. (2012). “Into the eye of the cytokine storm.” Microbiology and molecular biology reviews : MMBR 76(1): 16-32.
(2) Mehta, P., et al. (2020). “COVID-19: consider cytokine storm syndromes and immunosuppression.” Lancet.
(3) Ruan, Q., et al. (2020). “Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.” Intensive Care Medicine.
(4) Channappanavar, R. and S. Perlman (2017). “Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology.” Semin Immunopathol 39(5): 529-539.
(5) Chen, C., et al. (2020). “[Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies].” Zhonghua Shao Shang Za Zhi 36(0): E005.
(6) Sordillo, P. P. and L. Helson (2015). “Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.” In Vivo 29(1): 1-4.
One huge challenge in identifying effective therapies for COVID lies in the novelty of it all. Research requires time, something of which we have little in an emerging pandemic. We don’t have the luxury of studying 100 years of research or 10,000 past experiments. This battle requires a great deal of extrapolation. Extrapolation means that we take the little information we do have and attempt to use it in predicting what we don’t know. This process takes place every time an experiment proceeds in science, but the urgency in this case makes it more frustrating than usual. As we walk through a different possible therapy each post, keep this paragraph in mind.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.