Archive

Posts Tagged ‘2019-nCov’

Assorted Observations about the COVID-19 aka SARS-2 Pandemic: 2

April 9, 2020 25 comments

In the previous post of this series, I briefly touched on some things we still don’t fully understand about the disease caused by SARS-2 virus. Also, I am going to start calling it as the SARS-2 virus instead of COVID-19 since it displays high genetic similarity (sequence homology) to the original SARS virus. Most notably, the similarity extends to the main host protein used by both viruses to enter cells, main organs affected as well as pathological changes and diseases process caused by them. Therefore, SARS-2 is best understood as a significantly less lethal but more easily spread version of the original SARS virus. This is not to say that SARS-2 evolved from SARS- far more likely, both evolved from a common ancestor. With that out of the way, let us start by talking about ventilators or why they are of limited utility- at best.

1] During the past 2-3 weeks every politician and public figure has been incessantly talking about how we need tens of thousands more ventilators. To be fair, western countries which adopted the “neoliberal consensus” over past two-three decades ended up starving their healthcare systems to vary degrees. Hence a chronic shortage of ventilators have been a fact of life for many years especially during bad influenza seasons. While we could cerainly use more ventilators, ICU beds, more hospital beds and other medical resources in general- a large increase in those resources is unlikely to have a beneficial effect on the course of the SARS-2 pandemic. Here is why..

Based on a examination of multiple studies from countries such as Italy, Spain, UK and China- it appears that ventilators (at least as they are used right now) don’t help much with the survival of the most vulnerable group of patients. Let me put it this way, about 70-80% of people of people over 80 who end up on a ventilator due to this disease die. For those between 70-80, the number is closer to 50%, while the majority of those below 60 survive their stint on the ventilator. But why do these numbers matter. Well.. because the vast majority of those ill enough to require ventilators are over 60. To be clear, I am not claiming that nobody below 60 requires a ventilator. It is just that they are a small percentage of that age group of patients.

In other words, ventilators have poor efficacy in the age group who needs them the most. Unless significantly better protocols for medical intervention in very old and ill patients are developed, we should reconsider the wisdom of putting people above 80 with serious multiple comorbidities on ventilators- especially if there aren’t enough of them. People above 80. but without significant comorbidities. and in otherwise OK health have a better than 50% chance of survival as are those between 70-80. Any body below 70 who is not in poor health has a pretty good (better than 60%) chance of coming out alive. We should make resource allocations accordingly. I am not suggesting we go all soylent-green, but a realistic assessment of the chance of survival for each patient in the ICU with SARS-2 is necessary.

2] Talking about pre-existing conditions, it seems that the previously reported strong link of poor survival to hypertension is mostly an artifact. See.. most people above 75 have a slightly higher blood pressure than what is defined as “normal”. More relevantly, there is no evidence that blood pressures upto 150/95 are associated are bad for those over 75. Indeed, supposedly healthy systolic blood pressures below 130 have a link to slightly increased in those over 75. Having said that, there is now good evidence that the link between increased mortality from SARS-2 and cardiovascular disease and Type II diabetes is real. Infact, given that ACE2 receptors (which allow the virus to infect cells) are found on the endothelial lining of most blood vessels, it appears that the quality of baseline endothelial function is a significant factor in how ill a patient will end up.

Disturbed microvascular perfusion and tiny clots in lungs which disturb normal oxygenation of blood might also explain why so many patients in ICU due this virus have normal lung tissue compliance but really low oxygen saturation in their blood. All the cytokines released due to this infection in some patients (Il-1 and Il-6) don’t help microvascular function either. To make a long story short, very impaired microvascular perfusion and oxygen exchange in the lungs due to damaged and dead endothelial (and related) cells + severe inflammation and small clots is likely what puts most people in ICU. Clearly, we need a different and better treatment protocol for this disease than treating it as if was not different from the most common presentations of ARDS.

3] With those things out of the way, for now, let us talk about therapeutic options for SARS-2. As luck would have it, the vast majority (over 80%) who are symptomatic do not require anything more than bed-rest and anti-pyretics. This is especially the case for those below 60 years, who account for the majority of population- even in old and demographically stagnant western countries. Furthermore there is emerging evidence that the number of people who develop and recover from an asymptomatic form of this disease might be far higher than previously believed. But what about all those patients (15-20 %) who have symptoms which require some degree of medical intervention? Well.. this is where things start getting controversial.

But before we go there, let me say something else about potential treatments. It is my opinion that drugs that have to be injected or biological in nature (antibodies, recombinant proteins) are unsuitable for mass treatment of this disease because quickly scaling up facilities which make injectables or antibodies/ proteins etc is not easy. This does not mean that such drugs have no role in treating this disease. It is just that they would be most useful for people who are ill enough to be in an ICU. But as I mentioned in the earlier parts of this post, most older patients who end up in ICU end up dying- at least with current treatment protocols. The key, then, is to keep as many patients from deteriorating enough to need the ICU. In other words, we require effective orally available drugs to have a significant effect on the mortality rates due to SARS-2.

So what are the options? Well.. the most hyped drug, Remdesivir, does have activity in animal models of many viral diseases including Coronaviruses. However, it cannot be administered orally and hence will be used only in very ill patients- and that is a bad thing. See.. viral infections unlike their bacterial counterparts have to be treated early since peak viral levels are reached (and most of damage has been done) around the time people are sick enough to be require hospitalization. You can see why a drug which cannot be administered orally (and therefore used only in hospitalized patients) might provide very little therapeutic benefit in later stages of the disease. Now let us talk about Chloroquine (CQ) and Hydroxychloroquine (HCQ).

While Trump haters in media and bureaucracies are trying their best to discredit CQ and HCQ, the reality is that we have known that both drugs have decent activity against coronaviruses at concentrations achievable with normal anti-malaria or lupus dosages since 2003 (link 1, link 2, link 3, link 4). It doesn’t hurt that both drugs also have an immunomodulatory/anti-inflammatory effect. Multiple reports from China (mostly preprints) strongly suggest that normally used doses of both drugs are effective at treating SARS-2 in human beings. To be more specific, they are most effective at reducing the number of people who go on to develop severe disease if given within first 4-5 days of symptoms. No serious person is suggesting that they are miracle cures for patients ill enough to need intubation and ventilators. However, it also quite obvious that they speed up recovery from disease, reduce peak viral loads and significantly reduce the risk of complications when given early. It also helps that they can be given orally and synthesized very easily and on a large scale (by the metric ton).

Since we are already past a thousand words, I Will write about other potential drugs and therapeutic options such and convalescent plasma, monoclonal antibodies and vaccines in next post of this series.

What do you think? Comments?

Assorted Observations about the COVID-19 aka SARS-2 Pandemic: 1

April 3, 2020 27 comments

Since I have been following this viral pandemic pretty closely, and actually possess professional expertise in the topic, I thought it might be an good idea to create yet another series for posting about assorted bits of news and my musings on them. With that in mind, let us start now..

1] We still do not understand why children under 10 years of age or even teens and youth under 20 seldom get seriously ill, given that cells in their bodies also express the ACE2 protein which is used by this virus to enter cells. Sure.. man in his 80s with serious cardiovascular issues might express more of that protein on their cells, but not that much more and in any case the difference is not enough to explain the very different course of infection in the below-20 vs the above-80. Variations in amount of ACE2 expression is totally inadequate to explain why many in the younger age-groups don’t even have symptoms versus why many above 80 quickly go into respiratory failure and then cardiogenic shock so quickly.

2] Many of you might also have noticed that rich and middle-class people between 20 and 80 are noticeably less likely to develop the more serious forms of the disease than the poor or working class people. Why? Why does the course of this disease vary so much with socio-economic status? What part of being from a higher social-economic status translates into the more benign form of this illness and which aspects of being poor or working-class result in a substantially higher percentage becoming seriously ill? This is especially relevant since we do not, yet, have good and specific treatments for this infection. Also, why is mortality among blacks in USA noticeably higher than whites or latinos. Yes, this observation is based on fairly preliminary data from certain states such as Michigan and New York– but it is just too obvious to ignore.

3] We also still do not know what percentage of those infected experienced an asymptomatic or mildly-symptomatic version of the disease. This is important since the vast majority of testing in western countries is still limited to those showing some symptoms, usually serious enough to seek medical attention. But we already know that a significant minority of the infected don’t even develop symptoms and then go on to develop immunity to it without experiencing the disease. What is the percentage of those who never develop even a fever or cough serious enough to seek medical attention and why is the course of the disease so mild or nonexistent in them? What makes some people resistant to the disease even if they have no prior immunity to it?

4] How many older people who died of Acute Respiratory Distress Syndrome (ARDS) due to an unidentified reason (not bacterial pneumonia, influenza etc) in the past two months in USA, and countries such as Italy or Spain, actually died from COVID-19. I suspect that the number of such deaths might be far higher than most “serious people” are willing to accept right now. There is evidence that doctors in Italy were seeing isolated cases of serious viral pneumonia that could not be attributed to influenza or other common virus, as early as November and December 2019. In USA, this is especially obvious in certain urban areas such as Cook County and New Orleans. We require far more extensive testing of the population- both for the virus and resultant antibodies.

5] If you look at the “official” symptoms of COVID-19 or SARS-2, you will see stuff such as fever, dry cough and difficult breathing. However even a cursory glance at published data and accounts of medical professionals attending them paint a different picture. For example, symptoms such as sudden loss of smell (anosmia), some GI symptoms in elderly patients, anomalously low blood pressure, puffy allergy-like eyes carry far more diagnostic significance to this disease than typical symptoms supposedly associated with it. For example, patients who display hypotension are far more likely to progress to more serious forms of the disease than those who don’t. What is the mechanism behind these unusual symptoms and their correlation with disease severity?

In the next part, I will write about potential drug therapies to treat this infection as well as possible routes for rapid vaccine development.

What do you think? Comments?

An Unusual Observation about Ongoing Coronavirus Outbreak in China

February 8, 2020 18 comments

As mentioned in the previous post on this topic, it is my opinion that the coronavirus outbreak in China is far more hype than reality. To be clear, I am not denying that a bit over 700 people are dead from this particular outbreak at the time of writing this post. Then again, a few thousand people die from influenza and its many complications in USA every single year- in a ‘good’ year. My point is that we should look at the actual evidence to make decisions and prognostications rather than let racism and stupidity make them. With that in mind, here is an odd feature of this current outbreak which sorta validates my initial assessment. It began with an observation about the prognosis of 2019-nCov infections outside China.

As some of you might have heard there are over a couple of hundred confirmed infections of this specific virus outside China, but only one death- thus far. So what is going on? Why is the death rate of patients outside China less than 1%? After posing this question on twitter, I got an interesting reply in the form of an attached table- based on available data from two days ago. Have a look at highlighted row- specifically the low death rate of patients in China (0.21 %) outside Wuhan and the province of Hubei. Note that this rate is rather close to that of cases outside China (0.39%). So, what is going on? Why does the fatality rate for this outbreak drop depending on your distance from Wuhan (4.11%), even in the province of Hubei (0.81%)?

Now let us consider and go through a few hypothesis which might provide an explanation for this unusual pattern. But before we do that, let me say something that is obvious but has to be stated for the benefit of delusional white racists. The numbers provided by Chinese government seem to be as accurate as those which would be provided by the american government under similar circumstances. This is bolstered by the fact that this outbreak seems to noticeably less deadly (on a percentage basis) than SARS. Let me remind you that SARS killed 43 people or almost 20% of the people who got infected in Canada and almost all nations with more than 10 cases ended up with mortality rates over 10%. On to the hypotheses..

1] Are people of Chinese ancestry more susceptible to infection by 2019-nCov and die from it? While the overwhelming majority of those infected and dead, so far, are of Chinese ancestry, the significantly lower death rates outside city of Wuhan (but still in Hubei) suggest that ethnicity and race are unlikely to be an important factor. Also, the majority of 2019-nCov cases outside China (to date) have occurred in travelers of Chinese ancestry from China. In other words, there is no real evidence that people of Chinese ancestry are somehow more susceptible to infection by 2019-nCov or die from it. They were just at the wrong place at a bad time.

2] The virus strain inside Wuhan is different, and more lethal, than the one outside that city? While its certainly possible that more than one strain of 2019-nCov is in circulation, the evidence we have so far suggests that all known isolates are extremely similar and have jumped into human hosts very recently. Having said that, it is common for RNA-based viruses such as Coronaviruses to mutate from more lethal strains into less lethal ones which spread more easily. Need I remind you that some species of coronaviruses are among the many which cause the common cold. In other words, it is possible – but there is a much more likely explanation.

3] In my opinion, the most likely explanation is as follows: there are far more milder infections in Wuhan than have been acknowledged. Imagine that only 1 in 10 or 20 patients have symptoms bad enough to seek medical attention. Now this will result in a 10-20 fold concentration of the worst cases in hospitals. If the infection has a death rate of 0.5%. and only the most ill 10% seek medical attention, the recorded mortality rate at hospitals will immediately jump from 0.5% to 5%. It is therefore likely that, over the next few weeks, we will find out that majority of infections caused by 2019-nCov are mild or asymptomatic and only a small percentage get ill enough to seek medical attention. Not sure if this soothes existing worries, creates new ones or both.

What do you think? Comments?

Some Initial Thoughts about the Recent Coronavirus Outbreak in China

January 31, 2020 12 comments

More than one commentator on my previous post wanted me to write something about the recent Coronavirus outbreak in China, especially regarding how bad it really is or might become in the near future. Since useful and concrete information about this outbreak has been overshadowed by a lot of racist mental projections in the declining west, I thought it was a good idea to write down my initial thoughts about the situation. FYI, one of my degrees is in microbiology. So let us talk about about this outbreak, starting with what we know for sure about the virus in question.

1] The Coronavirus (2019-nCoV) behind this outbreak is fairly close in its sequence to one which caused the SARS outbreak in 2003. And yes, it is closer to some known bat coronaviruses, but not others. Also, both SARS and 2019-nCoV almost certainly jumped from bats to human hosts. The odd thing, though, is that most bat species in Wuhan are currently hibernating and the initial outbreak occurred at a seafood market, suggesting that another mammalian species acted as an intermediate host between bats and humans.. perhaps a sick cat, dog etc.

2] Initial sequence analysis of virus samples from multiple patients and comparing them to each other strongly suggests that the jump from bats to humans occurred very recently, mostly likely within the past 2-3 months. Interestingly it seems to bind to the same human protein (for entry into cells) as the coronavirus which caused SARS. Given the fairly high similarity in sequence, same protein used for entry into cells and similar clinical disease produced by 2019-nCov and SARS we can make an educated guess that many other characteristic (infectivity etc) are also similar. Think of 2019-nCOV as a sibling or cousin of SARS.

3] It therefore follows that 2019-nCov is likely to be similar in its infectivity to the one which caused SARS in 2003. While some preliminary analysis by western scientists pretend that the former is more infectious than the later, everything we know about viruses tells us that they are very similar viruses which use the same protein to gain entry into human cells. I do not expect 2019-nCov to be significantly harder to control than SARS. The key word is ‘harder’ as 2019-nCov might end up infecting more people than SARS- but ease of control will be similar.

4] So far, the percentages of 2019-nCov infections ending in death is around 10%, and is similar to what we saw over the entirety of SARS outbreak. It is well known that viral strains which cause severe infections and high rates of mortality evolve into ones that cause mild infections and low rates of mortality because the former burn themselves out due to lack of new hosts. We can therefore expect the mortality and morbidity rates due to this virus to drop over the course of time due to better quarantine (corrals more aggressive strains) and treatment (lower mortality). Some of you might have noticed that the increase in number of deaths is now far slower than the number of confirmed infections- which is a good sign.

5] It is highly unlikely that 2019-nCov was developed by China as a biological weapon for the simple reason that biological weapons are, for the lack of better words, stupid and dangerous. See.. unlike nuclear weapons (which China posses), biological weapons cannot be controlled once unleashed and are likely to kill as many on your side as the other side. This is especially so, if there is no readily available vaccine or decent drugs to treat that infection. Furthermore, modern scientific techniques allow us to track back their creation to a degree that was unimaginable in even as late as the 1980s. Being greedy is not the same as being stupid.

6] Most hype about 2019-nCov has a lot to do with the increasingly rapid decline of the dying west. To make matters worse, it is now obvious that the western system of corporation-controlled capitalism is vastly inferior to the Chinese system of state-controlled and directed “capitalism”. In case you think otherwise, tell me how people similar to Trump (fraudulent right-wing populists) are increasingly getting elected in western countries. Every white idiot (and non-white idiot from subservient countries) expressing public alarm about 2019-nCov outbreak is subconsciously or consciously driven to do so because of a combination of racism and the unspoken recognition that their own system is in terminal decline with no realistic hope of recovery.

7] To be clear, I am not minimizing the potential problems this outbreak could cause. Having said that, the Chinese system is probably the most capable of actually stopping such an outbreak. As mentioned above, having a state-controlled system of governance not beholden to corporations and other short-sighted moneyed interests allows you to get things done and devote resources in ways that are impossible for corporation-controlled “democracies” such as USA, not to mention semi-functional anarchies such as India. You can be certain that Chinese government will things done, regardless of the financial cost and suppression of worthless “human rights”.

What do you think? Comments?