Could ARDS in Covid-19 patients result from inferior waste clearance by a compromised lung microvasculature causing local build up of excess cytokines?
I am VERY unimpressed with the magnitude of elevation of cytokine levels via blood tests. If I correctly recall some analyses I conducted on patterns of cytokine elevations during cytokine storms, you would see many multiple units of magnitude deviation from normal values. Covid-19 patient values are far from this, and it seems like labeling these blood levels as storms is a stretch. Thoughts? Am I mistaken?
Further, death attributable to organ damage associated with uncontrolled cytokine storms kill the young with robust immune systems. These storms are generally considered an over-reaction of a healthy immune system. Covid-19 is remarkably sparing of the young. Covid-19 is burning through the old and elderly, particularly men. These guys can barely get a good piss going, no less any kind of big storm.
Interestingly, I DO believe that a sizable contribution to patients developing ARDS is due to extensive damage to lung tissue attributable to a cytokine response. I believe there is a localized cytokine storm in lungs attributable to lack of normal, timely clearance. Creation of tissue damage due to slow clearance, this new lung tissue damage provokes a second cytokine response.....
Reviewing list of comorbidities significantly associated with Covid-19 patient death, with the exception of heart disease, I believe they all share a major common, physiological impact. Diabetes, high blood pressure, ......regularly lead to narrowing of capillaries as well as loss of their flexibility to expand is well documented as present lung tissue, among many places. This may impact effective clearance of over-sized WBCs as body is actively battling an infection, further degrading waste clearance ability by slowing or blocking blood flow.
As for obesity, it is highly coincident with high blood pressure and diabetes, so I suspect it’s association with increased mortality is predominantly mediated through the effects of the other significant comorbidities.
Heart disease is the exception that proves the rule. Great stress is placed on the heart under the unrelenting pressure to increase throughput in response to oxygen starved systems, even while it is also oxygen starved. This is not a sustainable situation in any event, and has an even shorter time horizon with an unhealthy heart.
Ive read that many believe the deficiency in ACE2 by Coronavirus interferes with normal vasculature regulation and that has prompted trials of ACE inhibitors to further drive regulation through a sole mechanism prompting a increased blood flow. Could work if vasculature can be responsive, can’t work if microvasculature is to compromised by effects of comorbid conditions.
Thoughts?
Has this already been discussed by others elsewhere?
I have many doubts and I explain why. What do we really know about the pathological actions of this virus in humans? For now, very little. We know quite well where and how SARS-CoV-2 enters human cells. Everything else we know mainly refers to patients with serious and hospitalized symptoms. We have discussed much and thought about these patients by analogy to what is already known for similar diseases. We have made many comparisons. We have seen, for example, that there were high levels of IL6 and reactive protein C. This led to think of the already known cytokine storm. But there is an underlying problem. If the storm exists, and it is certain that in some patients it exists (but in others it does not), what is its origin? Is it an exacerbated response by the body in an attempt to defend itself or is it triggered and totally controlled by the virus? We don't know it. Almost no one studies the evolution of the disease in patients who have remained at home with few symptoms or in the early stages, so we only have data for events in the late stages of the disease progression. It makes a big difference to know that the virus with a handful of proteins (nine and unnecessary for its reproduction), takes control of the host's metabolism and defenses or that instead the human response is determined by an exacerbated and complex defensive response, through a series of metabolic pathways that continually inter-convert, creating functional and pathological anomalies. For a targeted treatment with a drug it is much better if we are dealing with a few viral proteins rather than a metabolic "tangle" where we do not know where and how to hit. If we knew how to manage the "tangle", we would have already defeated all the diseases that generate the storm, for example, rheumatoid arthritis. But it is not so. That the virus easily adapts with strategies aimed at so very different human pathological phenotypes to achieve its unique strategic goal (reproduction), would suggest a viral control, not a human one. Moreover, cytokines are pleiotropic proteins that work in very large groups. Never alone. IL6 is sometimes pro-inflammatory, other times, always in humans, it is anti-inflammatory. We can test it only by making multiplexing analyses of the group of cytokines with which IL6 is currently operating, but it is necessary to test at least 40 or 50 different cytokines. The techniques are already there in many hospital settings. Someone did these checks, about patients at home or in hospital? I think nobody. So we continue to think by analogy, learning more and more how to solve the many serious complications, but not really curing the disease. This lack of knowledge prevents us from making reliable hypotheses through which mechanisms the complications are strengthened during the progression of the virosis. At the moment, we are only thinking about how to block them.
greetings
Dear researchers I searching for data, support, and explanations for the dramatic worst mortality data of Lombardia (N. Italy) in the first pandemic phase. Thanks for possible aid.
https://www.researchgate.net/post/The_novel_Coronavirus_in_N_Italy_Lombardia_COVID19_2019nCoV_SARSCoV2_shows_a_fatality_rate_compatible_with_SARS-MERS_Why
Linked pre-print papers: https://www.researchgate.net/publication/341325862
Stay safe --sv--