Ending the COVID-19 pandemic requires an understanding of how to manage the inflammatory dysfunction that the virus causes.
Consider that whether young or old, our bodies never encountered SARS-CoV-2 before 2019. Unlike a seasonal respiratory infection—a cold or flu virus that a mature immune system has seen many times before in different strains—SARS-CoV-2 requires an entirely new immune response.
That has a profound effect on how our bodies respond to it. Without existing antibodies that target the virus, the immune system launches an extremely aggressive inflammatory reaction.
In fact, thanks to COVID-19, we’re dealing with a larger number of cases of severe, runaway inflammation around the world than we’ve ever seen with previous respiratory infections. As a pharmacist with a background in pharmacological research, I’ve been especially interested in this inflammatory response and the tools we have to manage it. It’s not just the fight against the virus and its transmission we need to understand, but how we can deal with the inflammatory dysfunction that it leads to.
COVID-19 as inflammatory overdrive: What that means and how our body’s innate intelligence really responds
We usually experience a strong inflammatory reaction, such as fever, chills, sore throat, and other common symptoms of being sick. It can be taxing to the body on a cellular level as well, but typically the body has guardrails that keep the immune response focused where it needs to be and constrained so that it won’t do collateral damage.
Our bodies quickly eradicate the invader, then switch off the inflammation and return to normal. Unfortunately, in COVID-19 infections, the immune response can become dysregulated.
In the most extreme scenario, immune cells produce more and more immune mediators called cytokines, which in turn attract other immune cells, which in turn produce more cytokines, in a runaway feedback loop that can become dangerous or deadly. This cycle is responsible for the lung damage that occurs in COVID-19 cases, which shows up on the characteristic X-ray images we associate with COVID-19.
Unfortunately, immune mediators can also attack the kidneys, the cardiac system, and cause significant blood coagulation problems and clotting. This inflammatory crisis, called a cytokine storm, is something that most people probably never heard of until COVID-19 came into existence.
Cytokine storms have actually been recognized in medical science for a few decades now and may be what killed so many healthy young people during the Spanish Flu epidemic in 1918. Cytokine storms are the core part of the process that drives sepsis, a dangerous whole-body reaction to an infection that dumps huge numbers of cytokines into the blood. It’s remarkable how many people are now familiar with this once-obscure term, and how relevant the idea of inflammation has become in our understanding of disease.
Because cytokine storms are hard to predict and happen in extreme situations, there just hasn’t been enough research into preventing them. When they occur, physicians turn to some extremely potent immune-suppressing steroid drugs to stop them.
When it comes to COVID-19, though, steroids are blunt tools. Given early in the infection, steroids can suppress immune activity so much that the infection is able to progress further, leading to more severe disease.
Given later on, they can save a person’s life; however, tissue damage has already occurred and it takes a bigger intervention to stop it from progressing. Steroids that suppress the immune system also increase the risk of secondary bacterial infections.
Similarly, the inherent risks of strong immune-suppressing steroids may outweigh the benefits they would offer at preventing the post-illness COVID-19 symptoms of inflammation, including inflammation in the brain and nervous system. Those symptoms include brain fog, ongoing fatigue, and loss of smell and taste—when they continue for weeks or months it is known as “long COVID,” which represents the other major challenge with this disease.
Questions for research: Antivirals or anti-inflammatories?
The omicron variant is currently surging around the world, poised to reach every corner of the population and infect even those who are vaccinated. While the news on big pharma is focused on antivirals, anti-inflammatories are the real belle of the ball.
We need to find safer, more accessible ways to reduce inflammatory symptoms for larger numbers of people with COVID-19, quickly and at low cost. We also need to find ways to target the more destructive aspects of inflammation and prevent the lasting post-infection symptoms, without preventing the immune system from doing its work to clear the virus.
About the Author
Jackie Iversen, RPh, MS, thought leader and founder, head of Clinical Development at Sen-Jam Pharmaceutical.