Interesting article in Science about how SARS-CoV-2 attacks the body:
https://www.sciencemag.org/news/2020/04/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes#
Again, the speed of the current research is astounding. I believe it was InKellyWeTrust who first cited the NY intesivist's claim that this was a blood-disease more than a pure respiratory one. It looks like everyone could be right.
What are your thoughts, doc?
I read this article a couple days ago. It is well written and makes great observations.
One of the most interesting aspects of COVID 19 is the myriad of presentations of the virus. There are now reports and case series outlining nearly every organ system with some percentage of involvement, even to the extent of being the chief complaint when visiting an office or ED. Pneumonia, cardiomyopathy, arrhythmias, headaches, seizures, conjunctivitis, rashes, GI symptoms, kidney failure, hepatitis, etc. Literally every major organ system is listed with potential involvement when you look at the literature.
There are a few key things to consider with the above in mind:
1) It is well known the ACE2 receptor is found on cells throughout the epithelial lining of the respiratory tract. This is the main receptor the virus attaches to and enter through to infect human cells. This receptor also happens to be ubiquitous on vasculature throughout the body. This is a pretty terrifying feature of this virus. It means it can literally attach and infect cells lining the blood vessels in any organ of the body.
2) Interestingly, elevated D-dimer (a marker of blood clotting) has been shown to have the single highest odds ratio of death among COVID patients presenting to the ED. Higher than hypoxia. Higher than any blood count, etc.
3) So you have ubiquitous receptors all throughout the body in blood vessels and known significant mortality in patients with elevated markers of increased blood clotting. There is obviously something more to this virus than a respiratory infection, even one as significant as ARDs.
4) Add to this the idea of a "cytokine storm" in critically ill patients. The basic understanding here is the body's immune system goes into hyperdrive, pumping out pro-inflammatory mediators throughout the body without much regulatory counter measures. Some believe this is causing more damage than the virus itself. Interestingly, there is literature that confirms higher IL-6 levels and lower lymphocyte levels at baseline in elderly adults. IL-6 is one of the main pro-inflammatory cytokines. Lymphocytes are critical in both humoral and innate immune responses to viruses. Lymphocytopenia has been shown to have a high odds ratio of death in initial studies as well (just not as high as elevated d-dimer). These factors certainly have some role in the relative morbidity and mortality of the elderly with this virus. Especially given the early positive data on monoclonal antibodies to IL6 such as tocilizumab.
5) So you have this virus which can attach to the lining of any blood vessel, which also likely triggers an aggressive local and systemic immune response. This environment is likely very pro-thrombotic. Diffuse intravascular coagulation (DIC) has similar features - its something found in patients with overwhelming sepsis. But it appears patients with COVID are not bleeding, just clotting. DIC patients have both. I can't say why this is, but the diffuse clotting appears to be a very legitimate feature of severe COVID and likely the driving force (along with cytokine storm) behind the multiorgan failure you get at end stage COVID
6) Confounding all this is previous literature on similar viruses such as MERs and SARs1. They didn't appear to behave similarly. But naturally a coronavirus with similar features, at least at surface level, has been treated similarly by physicians because we don't know any better...yet. We are now being flooded with literature, data, and studies daily. It is difficult to analyze and synthesize all this information in real time. But I will say there seems to be a shift in the treatment paradigm for this disease over the last couple weeks.
