Individual Immune Responses Determine COVID Severity

A collaboration of researchers evaluated 780,000 immune cells from 130 patients and found different immune responses in those with severe COVID19 disease.  The question then becomes one of the chicken or the egg, or in other words, are we seeing a cause or an effect here?  With the age old debate of terrain theory of disease against germ theory still in play, we don’t have a quick answer in this case but the evidence is compelling.  In this case, terrain theory outshines germ theory and makes the most sense of why some patients have very mild COVID19 and why some become critically ill.

For those unfamiliar with terrain theory versus germ theory, I offer a quick introduction.  The terrain theory explains a patients infection as a dysfunction of the immune system which allows a given microbial invader to gain the upper hand and cause symptoms we call the disease.  The terrain represents the body and its defenses where the defenses fight the incoming germ.  In contrast, most of modern medicine operates with the germ theory which recognizes the strength of the germ, the microbe, as the ultimate determinant of the disease occurring.

For those in functional medicine we acknowledge both theories, but lean towards the terrain theory.  Yes, we have superbugs out there which are drug resistant and make great headlines.  Yes, we have some viruses and bacteria which cause more problems than others.  But, we are confident from experience and common sense that the terrain theory explains much of the disease prevalence in our current society.  Our world has spiraled into an epidemic of undernutrition combined with overnutrition.  We see more vitamin deficiencies from over dependence on processed foods and overnutrition from excessive intake of these inflammatory high calorie foods.

With this British based study, the large team divided and conquered the massive amount of data collection and processing for 780,000 immune cells.  They  found patterns of immune upregulation and downregulation which had been noted in prior smaller studies.

Those with milder COVID 19 disease demonstrated higher levels of B cells and certain T cells .  The B cells produce antibodies and were found in the nasal mucosa where coronaviruses would enter.  The T cell subtype called T helper cells were found in higher numbers and assist other immune cells in fighting infections, coordinating the response to provide adequate immunity without excessive inflammation that might cause more harm than good.

The more severe COVID 19 patients demonstrated lower B cells, higher T killer cells, and higher platelet activation.  The lower B cells likely means fewer antibodies to attack the virus when it enters.  The T killer cells destroy viral infected cells which is a good function, but in high numbers are likely behind the hyperinflammatory state in severe COVID disease.  The increased platelet activation means that patients clot easier, another clinical contributor to severe COVID patients which leads to the strokes and organ clotting and even death.

From this initial research they hope that understanding the underlying mechanisms will lead to better predictive tests to predict which person with COVID will progress to severe disease and deserves more intensive early therapy.  They also hope that more effective therapies can target the steps which differentiate one class of COVID patients from another.

In 2021 and beyond, we need more research like this where a large team collaborates to do what none of them could do alone in processing some large amounts of study data.  We need more foundational understanding of our immune system and its terrain simultaneously with understanding how viruses like SARS CoV2 interact with our terrain.  Functional medicine would add that we need an understanding of how to modulate these newly discovered pathways and processes with both natural and synthetic therapies without overly disrupting the immune terrain.  We also need to strengthen the terrain with the basics of nutrition and natural therapies while limiting inflammation and toxins.  With this combined effort of research and functional medicine we can see hope for withstanding COVID and other infectious threats.

Original Article:

Emily Stephenson, Gary Reynolds, Rachel A. Botting, Fernando J. Calero-Nieto, Michael D. Morgan, Zewen Kelvin Tuong, Karsten Bach, Waradon Sungnak, Kaylee B. Worlock, Masahiro Yoshida, Natsuhiko Kumasaka, Katarzyna Kania, Justin Engelbert, Bayanne Olabi, Jarmila Stremenova Spegarova, Nicola K. Wilson, Nicole Mende, Laura Jardine, Louis C. S. Gardner, Issac Goh, Dave Horsfall, Jim McGrath, Simone Webb, Michael W. Mather, Rik G. H. Lindeboom, Emma Dann, Ni Huang, Krzysztof Polanski, Elena Prigmore, Florian Gothe, Jonathan Scott, Rebecca P. Payne, Kenneth F. Baker, Aidan T. Hanrath, Ina C. D. Schim van der Loeff, Andrew S. Barr, Amada Sanchez-Gonzalez, Laura Bergamaschi, Federica Mescia, Josephine L. Barnes, Eliz Kilich, Angus de Wilton, Anita Saigal, Aarash Saleh, Sam M. Janes, Claire M. Smith, Nusayhah Gopee, Caroline Wilson, Paul Coupland, Jonathan M. Coxhead, Vladimir Yu Kiselev, Stijn van Dongen, Jaume Bacardit, Hamish W. King, Anthony J. Rostron, A. John Simpson, Sophie Hambleton, Elisa Laurenti, Paul A. Lyons, Kerstin B. Meyer, Marko Z. Nikolić, Christopher J. A. Duncan, Kenneth G. C. Smith, Sarah A. Teichmann, Menna R. Clatworthy, John C. Marioni, Berthold Göttgens, Muzlifah Haniffa. Single-cell multi-omics analysis of the immune response in COVID-19. Nature Medicine, 2021; DOI: 10.1038/s41591-021-01329-2

Thanks to Science Daily:

Wellcome Trust Sanger Institute. “Differing immune responses discovered in asymptomatic cases vs those with severe COVID-19.” ScienceDaily. ScienceDaily, 20 April 2021. <www.sciencedaily.com/releases/2021/04/210420121500.htm>.

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Cell Atlas Work Helps Us Better Understand Our Immune System

The methods and applications of cell atlas studies not only benefits COVID 19 research but is helping scientists understand how our immune system develops and functions in various organs and disease conditions.  The results described in my last blog were built upon work in these studies below if you want to read more about how researchers “map” out the cells in our immune system.

Original Articles:

Jong-Eun Park, et al. A cell atlas of human thymic development defines T cell repertoire formation. Science, 2020; 367 (6480): eaay3224 DOI: 10.1126/science.aay3224

Benjamin J. Stewart, et al. Spatiotemporal immune zonation of the human kidney. Science, 2019; 365 (6460): 1461 DOI: 10.1126/science.aat5031

Roser Vento-Tormo, et al.  Single-cell reconstruction of the early maternal–fetal interface in humans. Nature, 2018; 563 (7731): 347 DOI: 10.1038/s41586-018-0698-6

Science Daily Links
Wellcome Trust Sanger Institute. “Origins of immune system mapped, opening doors for new cancer immunotherapies: Cell atlas of human thymus could help engineer improved therapeutic T cells.” ScienceDaily. ScienceDaily, 20 February 2020. <www.sciencedaily.com/releases/2020/02/200220141708.htm>.

Wellcome Trust Sanger Institute. “Human kidney map charts our growing immune defense: New cell atlas reveals immune cells present in zones of human kidney.” ScienceDaily. ScienceDaily, 26 September 2019. <www.sciencedaily.com/releases/2019/09/190926141708.htm>.

Wellcome Trust Sanger Institute. “Human cell atlas study reveals maternal immune system modifications in early pregnancy: Cell map of healthy pregnancy could also help understand miscarriages or pre-eclampsia.” ScienceDaily. ScienceDaily, 14 November 2018. <www.sciencedaily.com/releases/2018/11/181114132037.htm>.