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Tuesday, July 28, 2020

I didn’t make it to the theater last weekend because of a hurricane. As Hurricane Douglas headed toward Oahu yesterday, the Hawaii Shakespeare Festival had to cancel Sunday night’s Zoom performance of “As You Like It.” People were taking shelter, taking in anything that might blow away, and preparing for a possible power outage. Luckily the storm just brushed by the islands. But it reminded me that maybe this is a good time to take a look at the “cytokine storm” we hear so much about.

The term is relatively new, but it didn’t begin with COVID-19. The term cytokine storm was first used by James L. M. Ferrara in 1993 to describe graft-versus-host disease (GVHD) in bone marrow transplant patients, in which the implanted bone marrow cells mount an immune attack against the host’s own cells: “Perturbation of the cytokine network may function as a final common pathway of target organ damage, and the rapid onset of severe, acute GVHD can be considered a ‘cytokine storm.’ ” (1).

By 2003 the term had entered into the media, referring to a rapid, life-threatening condition that was sometimes seen in influenza and other viral respiratory infections such as H5N1 (avian influenza). (2) One colorful definition reads, “A cytokine storm response has been used to describe a fierce systemic release of more than 150 proinflammatory cytokines . . .” (3, p. 356).

Let’s take a closer look at this statement:

  1. Cytokine: A protein released by cells to summon the action of other cells in the immune system. Cytokines trigger cell proliferation and inflammation.
  2. Storm: A metaphor for things getting out of control.
  3. Inflammation: The observable signs of an immune response to infection characterized by swelling, redness, pain, and heat.
  4. Systemic: Affecting the whole body, as opposed to localized.
  5. Proinflammatory: Some cytokines are pro-inflammatory and some are anti-inflammatory. Ideally they work in balance to keep the reaction under control.

Although we often think of COVID as a respiratory disease, the systemic effect of proinflammatory cytokines goes beyond the lungs, manifesting itself in high fever, rapid heartbeat, falling blood pressure, inflammation, pain, and nausea. It can lead to clot formation and shut down the lungs, kidneys, and liver, leading to multiple organ failure and death.

For this reason and others, COVID is now often described as a systemic disease rather than a respiratory disease. The virus binds to ACE2 receptors which are found on cells lining the nose, intestines, kidneys, and blood vessels allowing it to spread throughout the body. The earlier coronavirus pandemic disease SARS had the same affinity. But here we are entering complicated territory and as the NIH headline wisely states, “COVID-19 is an emerging, rapidly evolving situation.” If you want to know more about the systemic effects of COVID, I’ve listed some articles on that topic below.

As for the cytokine storm, there is good news. Most COVID cases are mild and don’t get to the storm stage. Moreover, the storm is better understood now, having been observed in two other coronavirus diseases, SARS and MERS, as well as in influenza and pancreatitis. By now hospitals are aware of the signs and monitor patients for symptoms. There are known treatments and new ones specific for COVID coming along soon. For example, one treatment is to filter excess cytokines by circulating the blood through a filter, similar to dialysis.(5)

Today Hurricane Douglas is gone, my families in Hawaii are safe and sound and the nice folks at the Hawaiian Shakespeare Festival offered to exchange my virtual tickets. We’ll be seeing “Love’s Labour’s Lost” on Sunday, August 9. Care to join us? Go to http://hawaiishakes.org/

Related Articles:

“The COVID-19 Cytokine Storm; What We Know So Far,” Front Immunol. 2020; 11: 1446, June 16, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308649/

“Watch: It’s not just the lungs: The Covid-19 virus attacks like no other ‘respiratory’ infection,” Stat, Sharon Begley, June 26, 2020. https://www.statnews.com/2020/06/26/from-nose-to-toe-covid19-virus-attacks-like-no-other-respiratory-infection/

“Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020,” Early Release, CDC Morbidity and Mortality Weekly Report (MMWR). https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm

https://youtu.be/KzKvIYwqQkE
“What doctors are learning from autopsy findings of new coronavirus patients,” Mike Hansen, M.D. May 6, 2020.

References:

  1. “Cytokine dysregulation as a mechanism of graft versus host disease,” J.L. Ferrara, Curr Opin Immunol, 1993 Oct;5(5):794-9. https://www.sciencedirect.com/science/article/abs/pii/095279159390139J

2. “Into the Eye of the Cytokine Storm,” Microbiology and Molecular Biology Reviews, Mar 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426/

3. “Virus File 12-2: The Perfect Storm of Cytokines That Can Kill You.” Understanding Viruses, Teri Shors, Jones & Bartlett Learning, 2017 . p. 356. https://www.google.com/books/edition/Understanding_Viruses_Second_Edition/pr3Aq2ZMgUMC?hl=en&gbpv=1&dq=cytokine+storm&pg=PA356&printsec=frontcover

4. “Coronavirus Disease 2019 (COVID-19) as a Multi-Systemic Disease and its Impact in Low- and Middle-Income Countries (LMICs),” SN Compr Clin Med. 2020 Jul 20 : 1–11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371790/

5. “Coronavirus Can Set Off a ‘Cytokine Storm.’ These Drugs May Calm It.” The New York Times, June 11, 2020. https://www.nytimes.com/2020/06/11/health/coronavirus-cytokine-storm.html

Why am I doing this?

The coronavirus pandemic will be indelibly written on our memories just as the Great Depression or the Battle of Britain left their mark on past generations. It is my intention to journal the events of these days from three perspectives: as a retired medical technologist, a historian (Ph.D., 2014), and an ordinary person living through an extraordinary crisis.

You are on History’s Edge.

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