Just saw a report on this. Current kits only have a sensitivity of 30-60%. Nowhere near good enough. A paper out of China actually suggests chest CT as the most accurate screening test. Now if we could only come up with a few thousand more CT machines! Although if the $3500 price tag on the aforementioned test kits is accurate, chest CTs might be cheaper!
Another interesting tidbit I stumbled across: If, like me, you are taking losartin for high blood pressure, you are probably relatively protected from COVID-19 as it blocks the ACE-2 receptor I was talking bout earlier.
Those are true-true unrelated facts. The pending shortage of generic antihypertensives (and antibiotics) is due to most (90% by report) requiring raw materials from China during manufacture. I don’t think the ARB-as-prophylaxis tidbit is common enough knowledge that supplies are threatened yet due to demand. Give it a couple days though!
ACE and ACE2 are different proteins. The ACE protein, the drug target for ACE inhibitors, converts Angiotensin I to Angiotensin II, which then is bound to the AT1R receptor (blocked by the ARB drugs) causing, indirectly, vasoconstriction and elevation of blood pressure.
ACE2 is a counter-regulatory protein to ACE. It binds Angiotensin II and converts it to Ang(1-7). Ang(1-7) eventually binds to the mas receptor and causes vasodilation and lowering of BP. There has been a fair amount of speculation about the potential that mas could be a drug target, but I’ve not heard of anything close to the clinic yet.
ACE2 is not affected by classical ACE inhibitors.
The binding site of 2019-nCoV is distinct from the active site of the enzyme. Binding results in endocytosis of the virus particle. The ACE2 protein is not known otherwise to function as a receptor; that is, there’s no known endobiotic substance that internalizes upon binding to ACE2, but both the SARS and 2019-nCoV viruses express a xenobiotic protein that has the effect.
Binding of 2019-nCoV to the ACE2 site may account for the increased death rate among hypertensive COVID-19 patients, if it interferes with the AngII->Ang(1,7) pathway. That would make ARB’s or ACE inhibitors protective against some of the disease’s effects by blocking the effects of the unconverted AngII, without interfering with the virus’s infectious pathway.
It is a logical conclusion that blocking the ACE-2 receptor, as ARBs are wont to do, should offer some protection against the virus by inhibiting it’s site of attachment. Now, logical conclusions that should be true are deadly errors in medicine. I would absolutely not recommend starting an ARB for this purpose, nor depending on your BP meds for protection if you are already on one. That said, should this pan out in actual studies, it would be an intriguing target for further manipulation. Add chloroquine as a potential treatment and we have some possible weapons already in hand. If only they will work in practice.
ARB’s block the AT1R receptor; ACE inhibitors block the ACE membrane-bound enzyme (technically not a receptor since it doesn’t endocytose anything, nor is it G-protein or kinase coupled). ACE2 is a distinct protein from both of these.
Right. And the proposed mechanism of action is to restore the delicate balance between ACE and ACE2 in a situation where the ACE2 is virus-bound or otherwise exogenously down-regulated.
I’d imagine that if pulmonary hypertension is part of the disease process, that sildenafil or tadalafil might also be protective, but ‘stands to reason’ doesn’t count for much in biology.
If you need a CT or a £3500 test, that means that all numbers on infected from developing countries are junk. They can never afford to find out if people are infected. It’ll just be like Iran where people started dying with no previous warning.
Exactly true. The test that the WHO uses is (i think) along the lines of $50, but the US has to Be Best ®. Unfortunately, the WHO test also lacks adequate sensitivity to be used for screening. Which is why so many people from Diamond Princess tested negative on-site only to test positive upon returning home.
I do think that is a given. The cases we have found so far have been seriously ill. There ought to be 5-6 mildly ill patients and maybe a couple asymptomatic (especially kids) for each of those. And it appears to have been circulating far longer than initially appreciated. There’s a big honking berg underneath what is currently visible.
