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COVID-19 For Non-Premed Majors
Let’s talk SARS CoV2. It is a very simple RNA virus, that is a capsid of proteins that contains a single strand of RNA. Your body uses RNA to direct cells to build proteins. It’s like a hard-coded program, directions, that organize cell function for growth and repair. SARS CoV2 attaches to certain cells in the body that play a part in a feedback loop that monitors and controls blood pressure. Unfortunately, this includes lung, heart, kidney, fat and even nervous system tissues.
When you are exposed to the virus, it travels into your eyes, nose, lungs or mouth and literally, by happenstance, may come in contact with its favorite cell (ACE 2) receptor. The more viruses you inhale (initial exposure) the higher the probability that a virus will bind with a receptor. The virus capsid itself is a spiky little sphere. When one of about ninety spikes touches a receptor, it binds. Within ten minutes, instead of receiving chemical signals from your body, the receptor opens and becomes an entry way for the viral RNA. The viral RNA enters the cell, reprograms the cell’s normal RNA directed functions and turns the cell into a SARS CoV2 factory. Within 7-8 hours, some 7000 newly created SARS CoV2 viruses begin exiting the infected cell. The infected cell does not “burst” at the end of its reproductive cycle spilling a massive dose of viruses and toxic byproducts as is characteristic with a cold or the flu. Hence, a COVID 19 infection lacks the characteristic fever/chill reproductive cycle that accompanies other common viral infections.
The infection is exponential, within days creating multiple billions of cloned viruses. The sheer number of viruses created increases the likelihood that a mutation in the viral RNA will occur, potentially creating a new form of the virus. However, study of the SARS CoV2 genome has led scientist to believe that SARS CoV2 contains genetic material that protects against random deleterious mutation. The virus is already a very efficient one. And it is not like influenza viruses, which are multi-RNA strand (8) viruses and prone to genetic material swapping in a host infected by more than one flu strain. Flu reproduction can much more easily result in a viable “new” viral infection.
We know that SARS CoV2 infections (COVID 19) are disproportionately more dangerous and lethal in those over 65. Of course, those with significant health concerns are more susceptible to any infection, not just COVID 19. But more specifically, there are two issues that have been suggested that may be the primary contributors to age-related risk. Many older people suffer from hypertension and have been prescribed medications that inhibit ACE 2 reception, which results in the creation of more ACE 2 receptors, especially in the lungs. This availability of receptors would in turn provide the virus easier entry, hence a larger initial dose of virus at the time of initial infection. In addition, researchers also speculate that prior coronavirus infections (not SARS CoV2 but common “cold” type coronaviruses which make up about 20% of all colds) are more likely present in older patients. The related antibodies for these “lesser” coronaviruses may contribute to an over-reaction to COVID 19, especially in the lungs, causing a destructive, sometimes fatal, auto-immune response.
The suggested ACE 2 inhibition mechanism would also at least partially explain the susceptibility of certain populations. Hypertension disproportionately affects people of African and Native American descent and type 2 diabetes and hypertension nearly always flock together and are also disproportionately reflected among those same groups.
A destructive autoimmune response to a new viral infection attributed to the existence of anti-bodies from other similar earlier infections has been noted with other viruses, like the flu. That would explain why the elderly would be more susceptible to that aspect of COVID 19. They are far more likely to have been exposed to other nominal coronaviruses. Younger people, on the other hand, would not suffer this immune over-reaction as their immune-historical exposure to coronaviruses would be far more limited.
Obesity, some medical researchers suggest, is likely itself a contributing factor to SARS CoV2 infection irrespective of hypertension and type 2 diabetes. Fat cells also have ACE 2 receptors and obesity seems to increase the number of ACE 2 receptors in the body, so the obese may provide the virus with a more receptive host. Also, obesity in general comes with other health issues that could exacerbate an auto-immune over-reaction to the virus.
New studies are, in addition to looking at existing anti-virals and other possible treatments, looking at vitamin D deficiency as a potential risk factor that could be easily remedied. We know that the virus can persist on some surfaces for a very long time, that it is susceptible to ultra-violet light, that thrives in certain environments where relative humidity is low and temperatures are moderate and that it is most likely shed with exhalation. The virus itself is quite small, however, N95 masks can do a decent job filtering out the virus and any mask will significantly slow the velocity of any virus expelled by an infected individual. Of course, the handling of potentially contaminated masks posits another potential problem.
Researchers also believe that initial exposure, that is how much virus an individual was exposed to, either at one time or over a number of days before the immune system could initiate a significant response, strongly correlates with the severity of COVID 19 and its lethality, especially for people under the age of 65. This would explain why certain otherwise young and healthy people, especially health care workers, have succumbed to the disease. So while wearing a mask, washing hands and social distancing might not provide great protection from infection, these steps will likely lessen potential initial exposure and lead to a lesser, even asymptomatic result should one be infected.
Unfortunately, since so many cells in the body play a part in the internal blood pressure monitoring loop, all receptor tissues are susceptible to COVID 19. While COVID related pneumonia may be the most difficult and common problem associated with the disease, we now know that kidney, heart, and even nervous tissue damage (encephalitis) can occur. COVID 19 has even been associated with clotting disorders leading to strokes. These complications are not common or unique to COVID 19, but they are worth noting.
There are several notable immunization efforts underway and some have shown early promise. However, it should be noted that previous attempts to produce any sort of coronavirus vaccine have all failed.
The initial US response to the SARS CoV2 was mixed. States that took steps to protect the elderly and most vulnerable fared the best. Those who mixed COVID 19 patients with at-risk patients in the same facilities fared the worst.
Initial responses may have been effective in keeping the health delivery system from being overwhelmed by infection, however, this strategy may have only delayed the achievement of exposure-related herd immunity, prolonging the crisis. The response did overestimate the severity of infection in most people and the virus’s negligible effect on those under 20. The delay did, however, allow the medical profession some time to learn about the infection and develop tests, protocols and treatments for dealing with it. These treatments have significantly decreased the severity and lethality of the disease and hospital stays for those with more severe infections have declined.
For all the effort put into attempts to control the spread of COVID 19, we have seen an increase in deaths from all other factors throughout the country. Suicides, overdoses, alcohol-related deaths, murders as well as deaths related to heart disease, cancer, strokes, and other chronic conditions have all reportedly increased. People at risk with chronic issues have obviously not sought care for fear of contracting COVID 19 or for lack of insurance brought on by job loss. As for the other categories, financial uncertainty and job losses caused by the COVID 19 response have likely contributed significantly to reported increases in death in those categories.
Published in General
This epidemiologist says that there a cheap and fast test is easily possible, but at the price of being less-sensitive than the present tests. He argues that the lowered sensitivity really doesn’t much matter because the virus is reproducing so fast during the critical period that the sensitivity difference represents only a matter of hours, and the faster results and more-frequent use of the alternative test will more than make up for the sensitivity difference.
More here.
Any thoughts?
I heard about a cheek swab test that could produce results in 2 hours.
I prefer cheek swab.
As it is, I’d rather just self quarantine than go to the doctor for the test that’s on offer if I suspect infection.
Thanks for the science, Doug.
I am not buying the part about older people having more reactive immune systems than middle aged folks. Nope. I think the falloff in T-cell immunity with age is a better explanation. Also, cool dry air (like a meat-packing plant) is best for virus stability in air. Warm and humid sort of melts the shell.
The article I read speculated that SARS CoV2 may be able to detect the existence of antibodies resulting from previous corona virus infections expressed on immune and epitheal cells. SARS CoV2 may bind to their Fc receptors, infecting those cells. Breakdown of the epithelial layer in the lungs results in an excessive auto-immune response, the cytokine storm effect.
Amen! Today we are overwhelmed by BS from every side, and every scrap of actual scientific knowledge is like a bottle of champagne in Nazi-occupied France.
My information is out of date. Early on it was specuilated that relatively high humidity (Seattle, cruise ships, Wuhan province) shared a profile of relatively high humidity, leading researchers to conclude a “high humidity” profile for SARS CoV2. More recent research follows the old viral pattern – that dry climes may contribute to easier spread as huamns are more susceptible to viral infections in dry environs. Not sure about the “melting capsid” theory, but the final conclusion seems intuitive. I changed the essay. Thanks.
Outstanding overview, Doug.
I’m sure docs have improved their protocols, despite being largely denied the hydroxychloroquine cocktail, and some seem to have developed outstanding treatments, but I’m wondering whether another reason for the decline in deaths isn’t the one offered last spring by nobel scientist Luc Montagnier, namely, that in his judgment, the virus, engineered, he says, in a lab, would begin losing strength (actually, losing bits of HIV) and eventually disappear, though not before causing a lot of destruction. Montagnier is the co-discoverer of HIV.
Thank you for this comprehensive and easy to understand summary.
Also Known As: perfectly predictable side effects of the Fauci experimental treatment for America. Mind you, not a one of the nation’s leading experts in a single one of these other medical specialties was invited to prevent competing scary charts at any point, especially when the die was cast at the 15 days to slow the spread briefing. Disgraceful medical malpractice. Murderous.
I don’t know what to make of Montagnier’s work. It is certainly interesting. We’ll see.
I get all of my information from Ricochet (I do hope some of you start taking your responsibility more seriously – I mean, come on, I’m an idiot so there’s a lot of fertile ground for improvement here! Do I need to start a GoSmartMe?) and I haven’t been listening to the various health department press conferences from the local level all the way up to the big orange guy in DC. But nothing I’ve read has been this clear or informative. And concise to boot. Bravo!
It seems that people taking blood pressure medication–ACE 2 inhibitors–would fare well in confrontation with this virus.
I would think then that a preventive strategy would be to put vulnerable people on ACE 2 inhibitors as a matter of routine, at least for now. Right?
So what you are describing seems to be a very serious disease, especially if the actual remedies for the disease are withheld from the public at large.
From Turkey to Japan, from the Philippines to Israel, the citizens of many nations whose total population numbers at 225 million – those citizens face a fatality rate of 0.004%, or 4 out of every one hundred thousand cases. Why? Because HCQ + AZ pac + zinc, or else alternatively the asthma med favipiravir, those items actually work in taking down COVID.
But we had 33,000 deaths from COVID in NYC, with its population base at 8,000,000.
This is a four percent fatality rate…
Why no remedies for American citizens, unless they know the right doctors?
On the bright side, finally Trump has posted Dr Atlas to the corona virus task force. This happened today. Perhaps the tyrannical bid for power via the vaccine that the Global Medical Mafia wants so badly will finally have been ended, and we can live as freely as the people in Sweden are doing.
The common blood pressure meds are ACE-1 inhibitors, and despite early concern don’t seem to have much effect on ACE-2 or COVID-19 outcome. The ones that do increase ACE-2 receptors are the ARBs (angiotensin II receptor blockers) which is a different family of drugs.
Okay. I thought–mistakenly, I gather–that Prinivil was an ACE 2 inhibitor. Thank you.
IIUC, ACE-2 modulates the activity of ACE-1 and can lower blood pressure. Interestingly, an ACE inhibitor cough sometimes responds to zinc supplementation.
I’ve been following Dr. Mina via some of the MedCram videos. The crucial thing about the lowered sensitivity is that it isn’t a random sensitivity, resulting in random errors. (Which was not known when these tests got some bad press early on.) Rather, they don’t detect below a higher threshold, and below that threshold doesn’t matter much for infectiousness. In other words, these tests aren’t so great in telling you whether you’ve ever had Covid, but they are pretty good at telling whether you are infectious. The latter is the important thing in determining whether it’s safe to go to school or to work, etc.
There is a problem, though, with FDA regulations. Their job is to evaluate it as a diagnostic test, so that’s what they insist on. It seems to be no federal agency’s job to approve it as a public health measure that can determine infectiousness. So there are some regulatory hurdles to overcome in getting it approved so that any companies that are capable of ramping up to manufacture these tests on a large scale will do so.
President Trump could give it publicity and push for this test as a public health measure, but the haters (aka news media, Democrats) will then denounce the test, go out of their way to misrepresent what it is supposed to do, etc., because of any association with Trump. So we’ll have to apply our own rubber hoses to get the FDA to do something useful.
I am a biochemist and part-time biosafety professional, and I endorse this message.
Damn fine work, @dougkimball
Exactly the opposite. ACE 2 inhibitors retard the chemical communications between certain cells and hormones controlling blood pressure, heart rate, etc. Since ACE 2 enzymes once detected by ACE 2 cellular receptors cause certain tissues to constrict (like the tissues lining the inside of your lungs or the the tissues lining your blood vessels, among many) retarding this enzyme makes this constriction (narrowing blood vessels and raising blood pressure) less effective. This lowers blood pressure. However, over time, our systems compensate for this inhibition by increasing the number of ACE 2 receptors on those cells. If there are more ACE 2 receptors present on the surface of a cell, SARS CoV2 has more opportunities to bind. So folks who have been on ACE 2 inhibitors for prolonged periods would be more susceptible to COVID 19.
I don’t think that there are any ACE-2 inhibitors on the market. Lisinopril (the Privinase which @marcin mentioned) acts on ACE-1. In animals, ARBs can increase the number of ACE-2 receptors, but there’s no clearcut clinical benefit or detriment seen so far.
Me too. The “mainstream media” has been awful, and so many other “scientific” sources read like they are driven more by a political agenda than “science.”
OK. I’ve exposed my lack of STEM training. I did some more research and realize that there is no simple way to describe this whole ACE inhibitor/Receptor blocking issue. Now that I’ve looked at it more closely, I take back what I wrote earlier and can say definitively that I don’t have a clue. But I did learn this. The tissues infected with COVID 19 via the ACE2 channel are really important (lining of the lung, cells involved with O2-CO2 exchange, heart, blood vessels, kidneys, etc.) and especially, for lung function. SARS does stand for Severe Acute Respiratory Syndrome. ACE2 also acts as the breaks on the ACE1 receptor loop, that is the signals to constrict and increase blood pressure. Even I can see that if the virus attacks vital respiratory function while allowing blood pressure to rise unchecked, you have, well, SARS. The connection to the elderly might be as simple as exacerbating a pre-existing hypertension problem. So you are likely correct in assuming that ACE inhibitors and Reception Blockers would help. I also saw evidence that treatment with ACE2 might confuse the virus.
Science is so confusing. Forget what I wrote above. @MarciN
Double Like. I’ve learned something about the process of learning through self-study. In school, all the steps are forward because the teacher already knows the answers. We read them back and got an “A” and felt we’d learned. In teaching ourselves, we keep stepping forward then backward, and feel that we’ve not learned as much as we did in school, and feel guilty about leading others down our erratic path. But we are truly learning and truly teaching. The conventional way is always to some extent illusory learning and teaching.
You’ve taught me a good bit about this subject. If our knowledge is now shown to be imperfect, I know what questions to seek answers for. Not knowing the questions was why I was ignorant before reading your article and the discussion.
If a test is fast enough and cheap enough, multiple iterations are possible, and that mitigates against false negatives or positives. As long as the distribution of errors is relatively random, two out of three is perfectly fine. I don’t understand why NFL teams don’t have mid-res PCR machines on the sidelines and test every player every day. The cost for the whole team is less than one person’s veteran minimum salary.
It’s not clear. First the hypothesis was that ACE inhibitors would help, then hurt, then ???
ARBs also. All of which means if there’s an effect, it’s probably not a huge effect.
Multiple iterations are the idea. But the distribution of errors is decidedly non-random, which is actually good for the purpose.
One other problem with the FDA is they sort of gave their blessing to this sort of thing, IF it was accompanied by a reporting mechanism by which every test and its results were reported to the authorities. That means any drug company that develops this is going to have to become a software company, too, for interacting with millions of Americans, and it kills the idea of a $1-$2 test that most people can afford to take even as often as every day.
What about gelsolin as a treatment for covid?
https://apnews.com/17c69d5d82f5090402a6aed73f07344a
Here is a screenshot from MedCram update #98. The X axis is time, and the Y axis is the ct value, a measure of the amount of viral load in a person. (It’s a log scale. Low values indicate a huge viral load.) During early stages of infection it shoots up fast, then comes down more gradually.
The PCR tests (like the ones I had a couple weeks ago) detect everyone who is above the green horizontal line. I.e. they are highly sensitive.These tests test for rna, which towards the end of the course of a person’s disease tend to be mere fragments that cannot be replicated into a whole virus. However, for diagnostic purposes those rna fragments are useful in indicating that a person had covid-19.
The brown horizontal line, drawn at about a ct value of 32 in this chart, represent the threshold above which the cheap paper tests are said to detect the virus. These tests do not detect rna; rather, they detect antigens. Maybe half the people who test positive on the PCR test will test positive on the paper tests. However, it’s not a random half. It’s the people who are at the infectious stage of their disease. For purposes of knowing whether a person should go to school or to work, that’s what would be good to know.
However, the FDA is having a hard time groking that purpose. They think in terms of diagnosing for the disease, which of course is what the PCR test is good for, and the paper tests are not so good at. Maybe the enabling legislation for the FDA gives them that mission and no other. Maybe it’s the rules the FDA made for themselves. I don’t know.
I highly recommend the video. Some MedCram videos get deeper into biochemistry than I can follow very well; however, this is not one of those.