How does COVID affect your lungs

So, let's say you inhale the SARS-CoV-2 virus. This is the virus responsible for causing a disease now referred to as COVID-19. What happens to your lungs? Here's what to know. 

The virus travels down your airway. And it attaches to an airway cell. It enters the cell and starts to make changes inside the cell. Within several days, it turns the cell into a virus-making factory. Soon, there are so many viruses inside the cell that that cell bursts. This sends thousands of viruses into the surrounding airway cells. And, of course, those viruses enter those cells to turn them into virus-making factories. 

Your immune system plays a role here too. Airway cells that viruses attach to release chemicals. And these chemicals tell immune cells that there is an invader. So, immune cells release more chemicals that travel to the infected tissue. These chemicals are pro-inflammatory chemicals. They cause inflammation of your respiratory tract, including your nose and airways. And this is what causes your COVID symptoms.

Sometimes, viruses make it down into your alveoli. According to studies, about 14% of people who develop COVID develop severe COVID. And this happens when the virus causes inflammation of both your airways and your alveoli. Inside the alveoli, this inflammation causes the puss to fill the alveoli. And this is diagnosed as COVID pneumonia. When this happens, your oxygen levels may drop. this is because, while oxygen gets to your alveoli, it is unable to travel through them to your blood. (1)

According to another study, 40% of COVID patients develop ARDS. And about 20% of ARDS cases become severe. And these patients are most likely to require hospitalization and supplemental oxygen. And these patients are at the greatest risk for developing pulmonary fibrosis. Studies show that about one-third of those with severe COVID will develop pulmonary fibrosis. (2-3)

The exact mechanisms of how pulmonary fibrosis develops from COVID remains unknown. What is known is that the SARS-CoV-2 virus uses an angiotensin-2-converting enzyme (ACE2). This ultimately leads to "interstitial lung damage followed by parenchymal lesions." (3)

The most common cause is idiopathic. This means the method of development or cause of fibrosis is unknown. However, one common theory is the "cytokine storm" theory. (2) This theory postulates that 

the same inflammatory chemicals that cause inflammation damage cells. How does this happen? 

Usually, inflammatory cells are released when cells are damaged. This causes inflammation. This inflammation causes goblet cells to release extra mucus. And a combination of inflammation and mucus traps and kills viruses. This is how we get better. Of course, this inflammation also causes your symptoms, as noted above. 

Usually, the infection goes away, and the inflammation subsides. And the inflammatory chemicals subside. But, a prolonged infection, or one that seemingly lasts a long time, causes those inflammatory markers to stay elevated. This causes an abnormally elevated level of inflammatory chemicals, such as cytokines. And this is referred to as a cytokine storm. (2)

So, when inflammatory markers are high in number, they may be cytotoxic (harmful) to cells. They start to cause changes or damage to cells. And this damage causes scar tissue or fibrotic tissue that makes airways stiff. This is what may lead to pulmonary fibrosis secondary to a COVID-19 infection. (3)

This fibrosis develops in alveoli. Alveoli are mostly lined by type I pneumocytes. These are cells that are ideal for gas exchange. Scattered between these are type II pneumocytes. These are cells that secrete surfactant, the soap-like substance that reduces surface tension that makes your lungs expand more easily.  (4-6)

Type II pneumocytes are also involved in the repair of alveoli following certain disease conditions like pneumonia (i.e. COVID pneumonia). They are involved in alveolar tissue repair and regeneration. And, during disease states like pneumonia, type II alveolar hyperplasia may occur. And hyperplasia is when a cell is reproduced over and over.  When this happens with type II alveolar cells, It can cause an abnormal amount of type II alveolar cells. And this causes a thickening of alveolar walls. (5, 7

So, COVID pneumonia, or ARDS from COVID pneumonia, causes "diffuse alveolar damage and resultant type II pneumocyte hyperplasia." This hyperplasia is the result of an acute lung injury, such as what occurs with COVID pneumonia. And this causes alveolar walls to be abnormally thick and stiff. This is a change that may be described as scarred or fibrotic alveolar walls. This can reduce gas exchange and make it difficult to oxygenate, thereby reducing oxygen levels. (5, 7-9)

There are many cytokines involved in the cytokine storm responsible for severe COVID. Some cytokines involved are interleukins IL-1, IL-2, IL- 4, IL-7, IL-10, IL-12, IL-13, IL-17. Although, those most likely to require critical care admissions are those with elevated levels of IL-6, IL-2, IL-7, IL-10, GCSF, IP10, CCL2, MIP1A, and TNFα. (10)

Of these cytokines, two are noted to be most likely responsible for pulmonary fibrosis  They are called Interliekine 6 (IL6) and TNFα. Another substance that may play a role in the development of pulmonary fibrosis is a protein called VEGF. These are thought to be the leading agents in the cytokine storm in patients with severe COVID that lead to pulmonary fibrosis. (2, 10) 

I will delve into these further in a future post. So I will not describe them further here. That said, to help prevent or reduce the incidence of pulmonary fibrosis in patients with COVID-19, researchers are looking into medicines that will block the effects of these cytokines. (10)

Those who develop ARDS and severe COVID are the most likely to have a prolonged COVID illness.

And this may increase their risk of developing pulmonary fibrosis.  And the cytokines responsible for the "escalation of disease" and severe illness may be IL6 and TNFα. These cytokines may partly explain why 10 percent of those with severe COVID die. Further research may confirm or shoot this theory down. (10). 

In those who survive, this pulmonary fibrosis would then continue even as the patient recovers from COVID. This pulmonary fibrosis has no treatment. Therefore, it would be something these patients would have to deal with for the rest of their lives.  And this is an area where researchers are continuing to research. And the goal of this research is to find ways of presenting pulmonary fibrosis, or ways of treating it in those who do develop it. 

References. 

1. "What does COVID-19 do to your lungs," Web MD, https://www.webmd.com/lung/what-does-covid-do-to-your-lungs#2, accessed 12/5/2021
2. Rai, et al., "Post COVID pulmonary fibrosis: Is it a real threat?" Indian Journal of Tuberculosis," 2021, July, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654356/, accessed 12/5/2021
3. Alhiyari, et al, "Post COVID-19 fibrosis, an emerging complication of SARS-CoV-2 infection," ID Cases -- Journals, 2020, December 31, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785952/, accessed 12/5/2020
4. Brandt, Joseph P., Pujyitha Mandiga, "Histology: Alveolar Cells," NCBI, 2021, April 25, https://www.ncbi.nlm.nih.gov/books/NBK557542/, accessed 12/5/2021
5. "Type II Pneumocytes," Science Direct, 2013, "https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/type-ii-pneumocyte, accessed 12/5/2021
6.  "Pulmonary surfactant in newborn infants and children," https://breathe.ersjournals.com/content/9/6/476, accessed 12/5/2021
7. "Hyperplasia, My Pathology Report, https://www.mypathologyreport.ca/definition-hyperplasia/, accessed 12/5/2021
8. "Hyperplasia," Medline Plus, https://medlineplus.gov/ency/article/003441.htm, accessed 12/5/2021
9. Stanley, M. W., et al, "Hyperplasia of type II pneumocytes in acute lung injury. Cytologic findings of sequential bronchoalveolar lavage," American Journal of Clinical Pathology, 1992, May, https://pubmed.ncbi.nlm.nih.gov/1575213/, accessed 12/5/2021
10. Kovalchuck, et al., "Fighting the storm: could novel anti-TNFα and anti-IL-6 C. sativa cultivars tame cytokine storm in COVID-19?" NCBI, 2021, January 31, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880317/, accessed 12/5/2021