Teachable moment in classrooms:

  1. tissues chapter – elastin and collagen fibers in connective tissues
  2. respiratory system chapter – microscopic structure of alveoli
  3. respiratory system chapter – changes in lung volume during ventilation
  4. cellular basis of life chapter – general action of receptors on cell surface

The news item:  Recently the following article appeared online:

Overactive genes contribute to long COVID lung fibrosis

A handful of overactive genes that regulate the immune response cause debilitating lung fibrosis, researchers find.

The article describes research that identified interleukin 6, CD47 and pJUN genes that make COVID-19 survivors’ lungs resemble the lungs with pulmonary fibrosis. The article also states that those three genes are active in scar formation, and that in mice the fibrosis was stopped by blocking interleukin 6 and CD47 action.

So, Why Do I Care??  Currently, approximately 23 million people in the US have long-COVID (defined by having disease symptoms longer than 3 months after the initial infection). Many of these people have respiratory symptoms such as debilitating shortness of breath and difficulty breathing. Research into the causes into the molecular details of the chronic fibrosis might lead to remedies that greatly improve the quality of life of long-COVID patients.

Plain English, Please!!!  Let’s talk about what the nature of the fibrosis is seen in the lungs of long-COVID patients. In the walls of alveoli, away from the respiratory membrane, there is a layer of connective tissue normally dominated by the stretchable elastic fibers. In lung fibrosis the elastin fibers are degraded and replaced with collagen fibers that are not stretchable. The cells that make the connective tissue are called fibroblasts. The increased volume of collagen-rich connective tissue and increased number of fibroblasts is the hallmark of fibrosis we observe in the lungs of long-COVID patients. Apparently, this process is similar to scar formation in the skin.

Second, let’s talk about how fibrosis limits lung function. The accumulation of fibrotic tissue in the lung doesn’t affect the gas exchange process in the alveoli, but, rather, it makes ventilation more difficult. During inhalation the stretchy elastin fibers of the un-diseased alveoli allow expansion while filling with air, and during exhalation the elastic fibers recoil to squeeze air out of the alveoli. On the other hand, the alveoli of the long-COVID patients expand to a lesser degree because the collagen fibers resist expansion, and there is little recoil during exhalation. Long-COVID patients can, therefore, inhale and exhale less air, which, in turn, causes the shortness of breath.

Third, let’s talk about how we can possibly reverse long-COVID by countering IL6 function. The article tells us that interleukin 6 (IL6) contributes to the build-up of fibrotic tissue. IL6 is a protein made by cells of the immune system and instructs the fibroblasts to make more collagen fiber. Picture a finger pushing a doorbell. In molecular terms, the finger is IL6, the doorbell is the receptor protein for IL6, and the house is the fibroblast. The house responds to the ringing doorbell by making more collagen fibers. Blocking the action of IL6 can be done by using an antibody (a protein molecule) that covers up the receptor. Once the doorbell is covered up, the IL6 finger cannot push the doorbell, and the fibroblast makes lesser amount of collagen fibers. This results in lower amount of fibrotic tissue, lessening the harmful effect of fibrosis.

Fourth, let’s talk about how we can possibly reverse long-COVID by countering CD47 function. The article tells us that CD47 contributes to the build-up of fibrotic tissue. During fibrosis there is a proliferation of the fibroblasts. The molecule CD47 blocks the removal of fibroblast by macrophages. Picture CD47 molecules as molecular fingers that stick out from the surface of the fibroblasts.  When a macrophage touches the fibroblast, the CD47 pushes a receptor (a doorbell) on the macrophage, and the macrophage responds to the ringing of that doorbell by not “eating”, not phagocytosing the fibroblast. Blocking the action of CD47 can be done by using an antibody (a protein molecule) that covers up the CD47 finger. Once the finger is covered up, the doorbell cannot be pushed, the fibroblast is phagocytosed, gobbled up, by the macrophage. Fewer fibroblasts make lesser amount of collagen fibers. The result is lower amount of fibrotic tissue, lessening the harmful effect of fibrosis.