The world receives a daily serving of medical education as it waits expectantly for a silver bullet therapy against COVID. As the public watches the unfolding of the COVID 19 pandemic, each morning comes with an eagerness for reports that might tell us of a wonder drug against this invisible foe. One area which receives much attention as a potential field from which such a therapy might arise are the monoclonal antibody drugs used in cancer or autoimmune diseases. One such drug, tocilizumab, showed potential initially, but this study deflates our collective hopes in that no benefit to the mortality rate was found with its use. It did not seem to save lives.
Monoclonal antibodies, hence the ending of the drug name with “-mab”, act as silver bullets in their respective diseases. Our immune systems make antibodies from cells called B Cells. These protein molecules possess two ends. One end can attach to other immune cells to activate them. Our B cells make the other ends with countless nuanced shapes so they can bind other molecules, especially ones on microbes like viruses that attack us. This variable end will stick to the invader and use the other end of the antibody to trigger our immune system to react. Even the binding of the antibody to a virus or bacteria may prevent the microbial invader from hurting us any longer.
Scientists create monoclonal antibodies as clones of one type. Rather than a multitude of varieties made by our immune system, scientists isolate one antibody that will either block or activate one metabolic process. For tocilizumab, they created an antibody which will block an immune messenger called IL-6 or Interleukin 6. This immune messenger, or cytokine, normally acts to rev up our immune systems. In autoimmune diseases, elevated IL-6 contributes to inflammation and tissue damage. Turning IL-6 down in autoimmune arthritis provides great benefit to the patient.
For COVID-19, excessively elevated IL-6 appears to contribute to severe cases of COVID-19 called cytokine storm. Scientists hoped that tocilizumab would turn out as a helpful means of preventing this cytokine storm of runaway levels of IL-6. In this study, 452 patients across 62 hospitals were divided into 294 patients who received the monoclonal antibody and 144 who received the fake placebo for comparison. After 28 days, they found that the treatment offered no obvious mortality benefit. In other words, the death rate appeared unchanged in those receiving the therapy.
This obviously disappointed the researchers and disappoints the waiting public, hoping for a silver bullet against COVID. At best, the drug seemed to shorten intensive care unit stays and that led the researchers to express hope for its use in some fashion. For those of us in functional medicine, we are not shocked that a single step therapy targeting one single cytokine immune messenger would fall short in treat an inflammatory process involving multiples cytokines and steps. Our bodies are not simple, and COVID-19 is not a simple disease.
This complexity of our bodies and the diseases which attack them lead us in functional medicine to approach both from a more comprehensive perspective. We are looking to research that evaluates natural therapies targeting multiple steps in the process. COVID-19 involves steps of viral replication, viral cloaking through glycosylation, viral activation through furan cleavage, and multiple opportunities for immune modulation, each of which can be addressed with naturally available and safe options. Thankfully, God has provided many of these to choose from if we can just identify them in nature and determine how to best use them for our patients. This work is developing as we seek to help our patients’ liver healthier more abundant lives despite the threat of COVID 19.
Ivan O. Rosas, Norbert Bräu, Michael Waters, Ronaldo C. Go, Bradley D. Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S. Aziz, Nichola Cooper, Ivor S. Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J. De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. New England Journal of Medicine, 2021; DOI: 10.1056/NEJMoa2028700
Thanks to Science Daily:
University of California – San Diego. “Repurposed arthritis drug did not significantly improve severe COVID-19 pneumonia: But researchers say tocilizumab, a monoclonal antibody treatment, may reduce ventilator use and shorten hospital stays.” ScienceDaily. ScienceDaily, 1 March 2021. <www.sciencedaily.com/releases/2021/03/210301171018.htm>.
Another report on ineffectiveness:
Viviane C Veiga, João A G G Prats, Danielle L C Farias, Regis G Rosa, Leticia K Dourado, Fernando G Zampieri, Flávia R Machado, Renato D Lopes, Otavio Berwanger, Luciano C P Azevedo, Álvaro Avezum, Thiago C Lisboa, Salomón S O Rojas, Juliana C Coelho, Rodrigo T Leite, Júlio C Carvalho, Luis E C Andrade, Alex F Sandes, Maria C T Pintão, Claudio G Castro, Sueli V Santos, Thiago M L de Almeida, André N Costa, Otávio C E Gebara, Flávio G Rezende de Freitas, Eduardo S Pacheco, David J B Machado, Josiane Martin, Fábio G Conceição, Suellen R R Siqueira, Lucas P Damiani, Luciana M Ishihara, Daniel Schneider, Denise de Souza, Alexandre B Cavalcanti, Phillip Scheinberg. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ, 2021; n84 DOI: 10.1136/bmj.n84
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.