This is a rewritten version of yesterday's article. The original article is still available here.
f you think the hysteria and misinformation from the news media and conspiracy nuts here
and abroad about the Wuhan coronavirus are confusing, try reading the medical literature
sometime.
Many of the first clinical reports about this virus were published in Lancet, which added to the confusion by publishing little editorials in which the editors speculate about the virus based on unpublished manuscripts that happened to come across their desks (and, presumably, they rejected). But gradually a picture is starting to emerge about the factors that increase your risk.
ACE2
The biggest risk seems to be the amount of ACE2 in your lungs. ACE2 is an enzyme that breaks down angiotensin II, a peptide that powerfully raises your blood pressure. Angiotensin II is created by ACE (angiotensin-converting enzyme). When ACE2 breaks it down, the new shorter peptide binds to a specific receptor (known as Mas) and counteracts the effect of angiotensin II, thereby lowering your blood pressure. So ACE and ACE2 work in opposition to each other.
SARS-CoV-2 preferentially infects patients who are being treated for hypertension, diabetes, and coronary heart disease. 99% of the patients in Italy who died had one or more of these three conditions. The standard treatments for these diseases all have the side effect of inducing angiotensin-converting enzyme 2 (ACE2), which is the receptor for the virus.
This is strong circumstantial evidence that the epidemic of fatalities was caused by an unrecognized adverse effect of drugs that affect the renin-angiotensin system. This would explain why different countries have different fatality rates: they're using different ways of treating hypertension.
The interaction between ACE2 and SARS viruses is a classic drug hypersensitivity response and it has been known about for at least two years. If the COVID-19 deaths and the worldwide chaos are really due to a drug-induced virus hypersensitivity reaction, we may be looking at the worst international drug regulatory failure in history.
Update, Apr 14 2020 A new study seems to confirm this hypothesis. Zhang et al. found that switching from ACE inhibitors or angiotensin II receptor blockers to amlodipine strongly reduces mortality. DOI: 10.1101/2020.04.08.20047134 https://www.medrxiv.org/content/10.1101/2020.04.08.20047134v1.full.pdf
Update, May 15 2020 Several other studies have now been done on this hypothesis. Most but not all have found that there is little or no risk to ACE inhibitors. Most physicians would recommend not changing your blood pressure medication.
ACE inhibitors such as captopril are commonly prescribed as antihypertensive drugs; however, they also upregulate ACE2. This is bad because ACE2 also happens to be the receptor for the SARS and COVID-19 virus.[1] The virus recognizes and binds to ACE2 from a number of species, but not mice or rats. It binds to the human enzyme inefficiently, which is good evidence that this virus could not have been engineered.
One physician noted that SARS patients often had other diseases (hypertension, diabetes, and coronary heart disease) that are often treated with ACE inhibitors and angiotensin II type I receptor blockers.[2] These drugs all upregulate ACE2, as do thiazolidinediones (such as pioglitazone, a drug used to treat type 2 diabetes).[3]
ACE2 is higher among Asians who smoke, but according to one researcher there are no other differences among ethnicities, sexes, or age groups, whether they smoke or not. This claim, which was published in Lancet, doesn't make any sense, and more studies on this are needed.
Smoking
Patients who smoke have worse outcomes than non-smokers[4]. Most studies say males are more susceptible to the disease,[5] probably because in many countries men smoke more than women.
If this is true, then countries with the highest rates of males who smoke (Indonesia, Jordan, Russia, Georgia, Cuba, and Greece) would be at higher risk. China is also high in this list, since 47.6% of Chinese men but only 1.8% of Chinese women smoke. By contrast, in the USA 19.5% of men and 15.0% of women smoke. In the UK, the rates are 19.9 and 18.4%. Italy has intermediate rates (28.3 men and 19.7 women), while the rates in Iran are 21.5 and 0.7%.
Nicotine interacts harmfully with the renin-angiotensin system[6], which controls your blood pressure, and smoking is implicated in cardiovascular and pulmonary diseases. Nicotine actually downregulates ACE2 expression,[6] so you might think smoking would be protective. But smoking worsens cardiovascular disease. It seems that it's the treatment for cardiovascular disease, not the cardiovascular disease itself, that puts people at risk.
Don't hold your breath waiting for any medical doctor to tell you that. Anyway, holding your breath would increase your risk for COVID-19. It is better always to remember to breathe. (The news media will never tell you things like that.)
TMPRSS2 and camostat
In 2015, researchers in California found that camostat (aka NI-03), an inhibitor of a protein called TMPRSS2, prevents SARS coronaviruses from infecting cells.[7] The inhibitor is also said to work against influenza[8] and SARS-CoV-2, the virus that causes COVID-19[9].
TMPRSS2 is a cellular protease that activates the SARS spike protein. It's essential for viral spread and pathogenesis in the infected host. The original 2015 paper was badly written, which might explain why it was ignored; perhaps in recognition of that fact, their 2020 Cell paper is wildly overenthusiastic. In the Cell paper, they pretend to have just now discovered all the stuff they actually published five years earlier. They fooled the editors, but their experiments seem to have been carried out correctly.
I couldn't find any records of any clinical trials on this drug other than an old Phase 1/2 trial of its safety in treating pancreatitis. This means that there has been a potential effective treatment for this virus lying on a shelf for five years and no one has ever gotten around to testing it clinically.
If that's true, it's a major scandal. There's no excuse for ignoring a potential treatment for SARS-like infections, no matter how badly the paper was written. Read the papers and decide for yourself if Stefan Pöhlman and his colleagues are right.
Aspirin
Non-steroidal anti-inflammatory drugs like aspirin and ibuprofen were initially thought to aggravate the symptoms in an infected person, and some doctors were saying that victims should take acetaminophen (which is not an anti-inflammatory drug), if they're experiencing pain.
Vaccines
Vaccines are easy to create, but within a few weeks, you'll be exposed to this virus, if you haven't been already, and your immune system will automatically start creating antibodies against it. You do not need to be infected for this to happen. Long before any vaccine is approved by the FDA, our own immune systems will have wiped out the virus and the pandemic will be over.
A few weeks from now (or months at worst) the stock market will recover and people will go back to work. The Democrats will go back to trying to impeach President Trump, and everything will be back to normal. The biggest danger is that people will draw the wrong lesson and convince themselves it's possible to wipe out a virus by taking repressive measures.
I might get in trouble for saying this, but here's some medical advice: don't panic, and remember, breathing is your friend.
1. Wan Y, Shang J, Graham R, Baric RS, Li F. (2020). Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol. Jan 29. doi: 10.1128/JVI.00127-20.
2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet Mar 11. doi: 10.1016/S0140-6736(20)30566-3.
3. Fang L, Karakiulakis G, Roth M. (2020). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. Mar 11. doi: 10.1016/S2213-2600(20)30116-8. Link
4. Liu W, Tao ZW, Lei W, Ming-Li Y, Kui L, Ling Z, Shuang W, Yan D, Jing L, Liu HG, Ming Y, Yi H. (2020). Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med J (Engl). Feb 28. doi: 10.1097/CM9.0000000000000775. PMID: 32118640
5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15, 395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5.
6. Oakes JM, Fuchs RM, Gardner JD, Lazartigues E, Yue X. (2018). Nicotine and the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. Nov 1;315(5):R895–R906. doi: 10.1152/ajpregu.00099.2018.
7. Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW, Barnard D, Pöhlmann S, McKerrow JH, Renslo AR, Simmons G (2015). Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. Apr; 116,76–84. doi: 10.1016/j.antiviral.2015.01.011. PMCID: PMC4774534
8. Yamaya M, Shimotai Y, Hatachi Y, Lusamba Kalonji N, Tando Y, Kitajima Y, Matsuo K, Kubo H, Nagatomi R, Hongo S, Homma M, Nishimura H. (2015). The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther. Aug; 33, 66–74. doi: 10.1016/j.pupt.2015.07.001. Link PMID: 26166259
9. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, Mar 4. doi: 10.1016/j.cell.2020.02.052. PMID: 32142651
This is a rewritten version of yesterday's article, where I went off-topic and started talking about the adaptive immune system. The original article is still available here.
Last edited mar 22 2020, 7:11 am
