Copyright © 2016 - 2020, The Troy Press
Copyright © 2016 - 2020, The Troy Press
IMAGE: This diagram illustrates the where, what, and some statistics of how often SARS-CoV-2 attacs the body creating the Covid-19 disease. Image source is from the Wikimedia Commons and is used with permission.
As a follow up to my earlier article about SARS-CoV-2, also known as 2019-nCoV (the virus that causes Covid-19) I have a lot to share, including some great news and some sobering facts. Most of you will know that I have a strong scientific background, and, urged by events and people around me, I've applied myself to this to do what little bit I can to help. And sharing this email is a big part of what I can do since the better informed we are, the better outcome we'll all have. Here, I'm sharing some of the more important facts of what humanity knows scientifically about this virus at this point in time that everyone should know, and I've included links to my sources and other information. This is a long article but I don't apologize for that; many have asked me to share, and the ones I have shared with so far have expressed appreciation.
- Part I - Vaccines
- Part II - Treatments & Possible Cures
- Part III - Important Facts About SARS-CoV-2 & Covid-19
- Part IV - Scientific Modeling
But before I get into the meat of the materials, I want to say that a lot of people I've been interacting with about the virus have had either one or the other of two harmful reactions. Some are in a panic, and that may be causing more pain at this point than the virus itself, with tanking the stock market robbing a third to half of people's savings and being economically threatened through lost work. And, there shouldn't be a run on toilet paper! However a large number of people are on the polar opposite of that; denial that there's anything wrong at all, thinking it's a hoax or that they'll survive so it's not an issue. I urge people to take neither extreme position. What we need is good information, solid thinking and rational action, and to remember that whoever WE may spread the virus to could cost a life, either theirs or someone they give it to. … And we need a competent government, which seem to be in questionable supply.
I was spurred into doing this work by reading some pretty crappy work in the media. So, I created a scientific model of this virus - MUCH more on that below. Discussion of that is long and may be perceived as uncheerful. The reality is, in short, there's plenty of reason to be concerned. So, I cover that last.
I've also taken the time to look into what humanity is doing about this from a scientific perspective. There are two bodies of work to consider here: Vaccines and Treatments or Cures. I cover both of these topics with links. And, there's some great news on both fronts, including that clinical trials in humans began earlier this week for a vaccine. The bad news about vaccines is that even if successful, no vaccine will arrive in useful quantities until late summer at the very earliest - at least as things stand now. But for those who get infected, there may be something we can do other than conventional treatments for symptoms, and there's even talk about there already being a cure, though I've found no proof of this yet. … Both of these topics are covered below. Beyond this, I have more to share about this virus that I've learned along the way, and links to share. So, I'm dividing this up into four groupings . You can just scan for the section titles (e.g. Part I) to get to the area(s) that interest you.
Just as this virus was getting underway, January, 2020, Netflix released "Pandemic: How to Prevent an Outbreak", a 6 part series of hour-long programs discussing various issues around pandemics. It introduced us to some key people. More about the Netflix Video here.
Among the material they chronicle is the story of Jake Glanville and Sarah Ives, who are researching a universal flu vaccine, in a company that's been completely self-funded. The story was filmed last year and in the last episode we learn that their trials in pigs was successful and from that success, they got funding from the Bill & Melinda Gates Foundation to move to human trials in 2020. They hint that the trials should be done by early to mid-summer 2020. If successful, this could be a pandemic-ending vaccine at least for a great many viruses that attack the human respiratory system. …Jake and Sarah have a head-start over most other vaccines for the virus that causes Covid-19. Read up on Jake Glanville's work here.
In addition, presently there are at least 5 approaches being taken using different technologies to develop a vaccine against SARS-CoV-2, but presently there are none approved for use. Potential vaccines can be classified into six types: viral vector-based, DNA based, "subunit vaccines", nanoparticle-based, inactivated-whole virus and live-attenuated vaccines. The efforts on-going now that are specific to the SARS-CoV-2 and for which I could find good data include:
- Whole-virus vaccines these present the body with an actual virus to elicit an immune response.
- Adenovirus-vectored vaccine using AdVac® and PER.C6® technology by Johnson & Johnsons Janssen https://www.jnj.com/coronavirus
- A live-attenuated vaccine by Codagenix/Serum Institute of India
- University of Hong Kong has a vaccine that expresses SARS-CoV-2
- A codon deoptimization technique to attenuate the virus is being pursued by Codagenix.
- Subunit vaccines these elicit an immune response against the S-spike protein the virus uses to dock with the ACE2 receptor in the respiratory tract, a key trait of this virus and others in the same virus family.
- Protein-based vaccine using Molecular Clamp platform by University of Queensland/CEPI.
- A Recombinant nanoparticle vaccine by Novavax.
- An S-trimer recombinant protein using Trimer-Tag technology vaccine by Clover Bipharmacenticals
- An oral recombinant protein vaccine using the VAAST platform by Vaxart.
- Nucleic acid vaccines nucleic acids are the constituent parts of both DNA and RNA (genetic material)
- On March 12, INOVIO Pharmaceuticals, Inc. announced a new grant from the Bill & Melinda Gates Foundation to accelerate the testing and scale-up of CELLECTRA 3PSP, its proprietary smart device for the intradermal delivery of INO-4800, a DNA vaccine. This is a very novel approach and why they think they need to use a smart device is unclear to me. In any event, its a DNA vaccine based on previous INO-4800 and INO-4700 MERS vaccine.
- On March 16, Moderna, Inc, announced first dosing of a human test subject in a Phase 1 trial for their vaccine known as mRNA-1273. This is being conducted by the NIH itself, and the sub-type is mRNA.
- It was also reported that within an hour of the SARS-CoV-2s genetic code being provided, U.S. researchers developed a design for a vaccine. [CITATION MISSING!]
All these vaccines will have to transit through a process to ensure safety and efficacy. These begin with a phase 1 clinical trials for safety and immunogenicity, and later, phase 2 and phase 3 trials to ensure both safety and efficacy.
The SARS-CoV-2 virus - also known as 20190nCoV - is a member of the Betacoronavirus family which also contains SARS-CoV, Middle East respiratory syndrome CoV (MERS-CoV) and several others. Several drugs, such as ribavirin, interferon, lopinavir-ritonavir, corticosteroids, have been used in patients with SARS or MERS, although the efficacy of some drugs remains controversial. And, there are other antiviral drugs that are known and have been used in the past which also could help with this virus. Additionally remdesivir and Hydroxychloroquine are also known to be effective against members of the Betacoronavirus family.
On February 6, 2020, a new study and clinical trial began for a treatment and possible cure for this virus using Hydroxychloroquine. In the initial reporting, there were claims that some small groups are saying they've cured patients with this technique, but the effort has not been confirmed. However, there's a long body of knowledge and experience with Hydroxychloroquine in anti-viral applications. The bad news here is that the trial is scheduled to be completed by the end of August, with the study that encompasses the trial to be completed by the close of the year. On the other hand, that timeline will likely not hold; as others hear of this work, and as the pandemic grows, there will be strong pressure to perform other studies faster as that sure seems to me - as I'm sure it will seem to others - as far too long of a study. https://clinicaltrials.gov/ct2/show/NCT04261517
In the study described here: https://www.nature.com/articles/s41422-020-0282-0 a number of FDA approved drugs were tested with some promising results.
We know that the virus can be transmitted through the placenta to a fetus, and there are documented cases of babies born with the infection.
We know that the number of known cases of infection below ten years of age "approach zero, " with no known deaths.
We know that from age 10 to age 40, most people experience infection as a mild case of the common cold or flu and dismiss it out of hand, losing only a day or so to it. (Read the case of a 33 year old German cited below.)
We know that people in their 40s typically get hit hard enough to know they have something substantial but it is extremely rare that it's fatal - we think it's well less than 1%.
We know that from 50 years of age onward the severity of the infection begins a steep increase and that by age 70, about 17.8% - or thereabouts - of patients die of the disease. For people in their 50s, the CFR - Case Fatality Rate - is about 5%. Above 70, there's too little information to know if it gets even steeper with greater age.
We know that most severe cases of this Covid-19 is experienced as pneumonia - liquid collecting in the lungs. The virus' activity is visible in imaging of the lower lungs, and mortality is about the same for all other causes of pneumonia, which is from 5 to 10% of hospitalized cases, and up to 30% in the worst cases. However, some people acquire SARS - Severe Acute Respiratory Syndrome - in which the virus makes the breathing tubes susceptible to ordinary bacteria that then infect the patient. The mortality rate of these cases is about 50%, and, reportedly, most all of those who survive this have permanently diminished lung capacity.
Perhaps the worst known fact about this virus is that it can be transmitted before the patient has visible symptoms. Here's an article about how we know that, based on a 33 year old German man - "Patient 1". Ultimately, this means we have to be a LOT more careful than we otherwise would be! Now maybe you can understand why all the social distancing makes sense and why we're concerned about our older people! Isolate your older family members, do what you can to keep them as far away from infection as you can. If it's YOU, maybe go live in a cabin in the wilderness for a few months!
As some of you know, I have a long scientific history going back decades, and I have even stronger computer science skills, so when I repeatedly found panic-inducing bad-math in the media along with some half-assed but good-willed attempts at back-of-the-envelope improvements to it, I was inspired to make a model of this virus myself to help better assess what we can expect. I have now done so, validated the model using the experience of Italy, updated it repeatedly with what we're learning from new developments, and now we can run it and get something of an idea what could happen in the USA.
The architecture of this model is necessarily simplistic since there was no funding, and no time to do better, but it's still useful for exploring and understanding possibilities. Most importantly, it assumes an unprepared, unprotected population and that nothing effective is done during the period under study to mitigate the virus' spread. Secondly, it does not have any provisions for handling demographics that are known to be important for this disease, like age and smoking habits. And thirdly, it does not factor in any differences in quality / effectiveness of health-care that may be provided to the sick.
There are five key inputs, and several of these are not known well enough to have discrete values and instead are only known, scientifically, as being within a range of possible values. (More on this below.) These inputs are:
When the model was first run, it instantly became obvious that the best-case values were too friendly because the every-day flu is worse. Likewise, it was instantly clear the worst case couldn't be true either else we'd all have been infected already. So, I updated the model to find median values and while the results were better, I didn't have a lot of confidence in them. So, I began searching for reputable sources that had different values to try, like the CDC, NIH, Johns Hopkins, NEJM, and so forth. Along the way, the BRN range was tightened to 1.5 and 3.5, and the New England Journal of Medicine (NEJM) decided to hang its hat on a BRN of 2.2 and an incubation period of 5.2 days. I tried these values and found them interesting.
Then I showed my work to an immunologist friend of mine, Fred Cowan, who's a few decades my senior, and asked his opinion. He really liked the work and encouraged me to see if I could improve the model values based on some good solid numbers he'd found for what has been happening in Italy, which is about two months further into the pandemic than the USA is. I did so and found that if the NEJM value for incubation period was used, and the BRN adjusted to 2.9 the curves for number of cases would match very closely, and if, then, the CFR were adjusted to 8%, the deaths would also match. This validated the model AND gave good values for comparison to a known location / demographic. And that's very useful. From this work, I'm pretty sure the average incubation period of 5.2 days from NEJM is accurate.
Before giving model output numbers, it's worth reminding that the model presumes we'll do nothing about the spread of the virus spread, and yet we are doing things, like ending large public gatherings, and some places are under lock-down (here where I am called "sheltering in place"). That said, the model tells us that if we did nothing - or if what we do is ineffective - from Now, March 20 to the last day of April (43 days), we can expect infections to jump from where they are today (16,638) to about 20 million! WOW, that's bad!
Notably, the USA doesn't have as old a population as Italy, we don't have anything like their population density, and the prevalence and severity of smoking is much lower in the USA, too. So our BRN should be markedly lower and our CFR shouldn't be around 8% but closer to the values discussed above. Here's the full model output for today, asking for the extra output for comparison with Italy's experience:
Pandemic Statistics Calculator
+ Basic Reproduction Number, BRN: new cases, per infected.
+ Case Fatality Rate (min - max - median): 2.3% - 3.4% - 2.85%
+ Location Specific Values for Italy: BRN: 2.9 CFR: 8.0%
Calculating with 16638 initial infections for 43 days and 5.2 day incubation:
At BRN 1.5, Infections: 639,604 deaths: 14,710 to 21,746 Median: 18,228
At BRN 2.2, Infections: 20M deaths: 572,451 to 682,924 Median: 572,451
At BRN 3.5, Infections: 1.31B deaths: 30.16M to 44.58MMedian: 37.37M
Using location Italy's CFR (8.0%) deaths: 0
At BRN 1.5, Infections: 639,604 deaths: 51,168
At BRN 2.2, Infections: 20M deaths: 1.6MM
At BRN 3.5, Infections: 1.31B deaths: 104.9M
Using location Italy's BRN (2.9) Infections:58.24M
CFR Minimum (2.3%) Deaths: 1.33M
CFR Maximum (3.4%) Deaths: 1.98M
CFR Median (2.85%) Deaths: 1.66M
CFR from Italy (8.0%) Deaths: 4.65M
If everyone on in the USA were Infected (328M), deaths:
Minimum 7.54M Median 9.34M With Italy's CFR: 26.24M Maximum 11.15M
If everyone on Earth were Infected (7.8B), deaths:
Minimum 179.4M Median 222.3M With Italy's CFR: 624M Maximum 265.2M
In short, if we don't do anything about it, or if whatever we do is ineffectual, we can expect about 20 million infected by May 1, and a little over half a million dead. Most of whoever dies will be our older people, some of our most valuable resources since experience is precious. While this is a bad projection, this is what is motivating the actions we're now seeing from government, to help ensure this doesn't happen, and this is why we all need to be respecting the need to take personal action to help prevent spread. Above all, don't panic, use your head, and do what you can to help older people avoid infection.
I had intended to provide a lot more links for my model values, but I'm tired and want to get this out now; I'll gladly provide them upon request.
OK, that's it. ... Corrections, new materials, ANY input gratefully appreciated - just send me an email!