Working hypothesis: how cartilage damage is connected to respiratory tract symptom progression, particularly within the context of COVID-19.

The body senses the presence of virus-infected cells, so the immune system starts to produce messenger molecules (cytokines) as part of its attack on those cells. Some of the cytokines--IL-1beta, IL-6, and TNFa--induce degradation of hyaline cartilage in the nose, larynx, trachea, bronchi, and other locations throughout the body. The degraded cartilage releases atypical or virus-bound forms of chondroitin sulfate or other glycosaminoglycans (GAGs) that the immune system perceives as a threat. The body then begins to have a delayed hypersensitivity reaction to those atypical or virus-bound GAG molecules. The hypersensitivity reaction increases the very cytokines that cause degradation of cartilage, thus creating a positive feedback loop, so symptoms--which include fever, pain, and increased secretions of protective and cartilage matrix reparative substances--continue to worsen. Underlying conditions that predispose to higher levels of those cytokines contribute to strengthening that feedback loop. The increased secretions of protective and reparative cartilage matrix substances contribute to "clogging" the lungs, some of which reparative substances have adhesive properties; their presence in the alveoli counteracts the surfactant that usually keeps the alveoli clear, and if they are not cleared, hyaline membranes--a characterizing feature of diffuse alveolar damage--form in the lung lobes. 

[I'll be returning to this post frequently over the next few days to post supporting evidence and explanations below. And likely to edit the paragraph above, for it is a work in progress. I apologize for any sloppiness of language. My formal educational/employment background is in law, computer programming, and math, so while I'm good at logic and analysis, my use of biology terms is sometimes imprecise.]

* A delayed hypersensitivity reaction to an atypical GAG is plausible and has been proven to happen. A 2012 case study reports how a middle-aged man inadvertently gave himself fever, dry cough, and lung congestion (the described symptoms are strikingly similar to the main ones seen with serious COVID-19 cases) merely by taking sodium chondroitin sulfate as a supplement:

"A case of drug-induced pneumonia caused by sodium chondroitin sulfate"
T. Itoh, Y. Hamanaka,
Japanese Journal of Chest Diseases 71(6):593-598, June 2012

Abstract: A 49-year-old man was admitted to the hospital with complaints of fever and dry cough. Chest X-ray film revealed ground-glass attenuation in both lung fields, so he was transferred to our hospital for further examination. Chest CT film showed ground-glass attenuation in both lung fields. A transbronchial lung biopsy revealed infiltration of lymphocytes and neutrophils, thickening of alveolar walls and proliferation of type II pneumocytes. By careful history taking, he admitted he had taken sodium chondroitin sulfate for one month before admission. The lymphocyte-stimulation test was positive for sodium chondroitin sulfate. Based on the above findings, we diagnosed this case as drug-induced pneumonia caused by sodium chondroitin sulfate. He recovered after discontinuation of the drug without corticosteroid therapy.

https://www.researchgate.net/publication/287575000_A_case_of_drug-induced_pneumonia_caused_by_sodium_chondroitin_sulfate

* The envelope protein of the Zika virus (a flavivirus) was found to bind tightly to chondroitin sulfate and heparin sulfate. See https://pubmed.ncbi.nlm.nih.gov/28151637/. Like other coronaviruses, Covid-19 has a viral envelope. See https://cen.acs.org/biological-chemistry/infectious-disease/know-novel-coronaviruss-29-proteins/98/web/2020/04

* This hypothesis indicates two ways to interfere with symptom progression:

1) Protect the hyaline cartilage from damage, and
2) Reduce secretions of cartilage glycosaminoglycans that can contribute to covering the alveolar surfaces and, if atypical or virus-bound, increase the immune system's attacks.

COVID-19 researchers are already successfully investigating how to reduce cytokines that help cause degradation of cartilage, but I don't know if they are looking at which proteins are involved in secreting adesive molecules that could promote accumulations within the lung lobes; I recommend looking at reducing activity of SOX9, for it is increased by EGCG (found in tea) and pomegranate juice, which could partially explain the rapid increase in serious cases seen in Hubei (where panicked people contributed to damaging cartilage by spraying everyone down with bleach) and then Iran. Another possibility is temporary suppression of the body's own production of chondroitin sulfate, perhaps via an inhibitor of glycosyltransferases.