Category Archives: Communication

PCR and the Ct Value

In the past few weeks in San Diego, I’ve heard several stories that discuss Ct values in regards to COVID testing. Since this is my field, I thought I’d talk about what a Ct value is and it’s relation to your results. This post is going to be pretty in the weeds, so if your not interested in the detail, you can skip this one.

PCR: The Polymerase Chain Reaction (PCR) was invented in 1983, and by the 90s, it has become a commonly used technique foundational to several molecular biology techniques, including DNA sequencing, DNA manipulation, sequence detection, and many more. Basically, the technique is used to make many many copies of a small amount a DNA. The DNA molecule is double stranded, the 2 strands are reverse copies of each other, binding to each other with weak interactions.

Heat is used to separate the 2 strands, and small pieces of DNA called “primers” bind to the DNA copies at a lower temperature.

The primers are designed to perfectly match sequences in the template strands. This is why PCR reactions can be very specific to a particular target, like SARS-2.

Next, the template strands are copied by a protein called “DNA Polymerase”.

After this, the reaction is heated up again, and the process is repeated. For a PCR reaction used for detection, this is repeated 40 – 45 times. With every repetition of this process, the numbers of molecules doubles, so from every 1 molecule of starting DNA, you could theoretically end up with almost a trillion copies!

Real-time PCR: Lots of copies of DNA aren’t enough to detect it. You also need something else. Medical detection uses a process called “real-time PCR”. In this process, a third piece of DNA called a “probe” is also added. The probe has a fluorescent molecule called a “reporter” on the front end, and a molecule called a “quencher” on the back. The reporter gives off light during the reaction. The quencher is a molecule that absorbs light and coverts it to heat, effectively dimming the light coming from the reporter.

As the real-time PCR reaction progresses, the DNA Polymerase chops up the probe as well. When this happens, the quencher is separated from the reporter, and the reporter appears to give off more light! The medical instrument detects this extra light which leads to the result.

Ct values: You may have heard the term “Ct value” thrown around. As I mentioned before, with every cycle of PCR, the number of DNA copies doubles. At the same time, the reporter molecules start to give off more light. Even with all the reporter molecules around, the instrument can’t detect it until at least cycle 15. When it does, a graph of fluorescence coming from the reaction will start to show an increase.

Real-time PCR Results. This is from an ABI 7500 running version 2.3 software. The results for 5 patient samples. 3 would be reported as being positive, 1 negative. The sample giving the green line is over 40 Ct and may be repeated, or a new sample may be collected from the patient.

The more starting DNA you have in the reaction, the sooner the instrument will detect a rise in light. Scientists designing the test set a Cycle Threshold (the yellow line in “Real-time PCR Results”). This line is somewhat arbitrary at first, but when the test is validated, it is “set in stone” before being submitted to the FDA for approval. After the threshold line is set, the cycle at which the line of fluorescence for sample crosses the threshold line is called the “Ct value”. As you can see in the graph, the more starting DNA you have, the lower the Ct value is. The lower the starting DNA you have, the later the line will cross the Threshold, and the higher the Ct value.

A patient with a lot of SARS-2 in their sample will give a very low Ct value, almost never lower than 15-19. In the example above, the orange line represents a patient with a lot of virus. The higher the Ct value, the less virus a patient has in their sample. A sample that gives Ct value in the high 30s has very little virus, and is most likely not symptomatic. In fact, some scientists have even said that a Ct value of higher than 35 means the test is really just detecting viral debris after the virus has been cleared and the infection is basically over. A good test can detect as few as 50 virus molecules in a sample.

Most labs don’t even bother to report any result with Ct over 40. I’ve never heard of a lab reporting a result with a Ct over 45. Results like this are generally considered un-reliable, since PCR can give false positive results at very high cycle numbers. Most labs eliminate this possibility by just not reporting Cts over 40. A few weeks ago, a person at a San Diego County meeting claimed that many labs are reporting Cts over 45, and thus giving false positive results. I happen to know this man personally. We disagree on the proper approach to COVID, but he’s a good guy, and I like him personally. He is not a scientist. Anyway, I contacted him to ask him for evidence that labs are reporting Cts over 45, and I have not heard back. As I said before, I’ve never heard of a lab reporting a positive result for a real-time PCR test with a Ct over 45. So I’d be surprised if this was happening. If you have evidence of this, please let me know!

A local radio commentator in San Diego suggested on air that labs should report the Ct number. I’m all for this, but I know first hand that labs usually do not report the Ct number. In fact, many patients, and yes, even many physicians, don’t know what this number means and don’t actually want to see it in a report! Yes, that’s right, on one complicated test I built in which I included the Ct value in the report, doctors called to ask us to remove it! They said it was confusing the issue for them. This may have been because it was confusing their patients, but suffice it to say, many downstream users don’t want the Ct value and that’s why it’s not included. Generally, labs just report “COVID Positive” or “COVID Negative”. In some cases, “Detected” or “Not Detected” are used instead, to avoid confusion.

This is to avoid the issue of a patient saying “My result is positive! That’s great!” No, sir, it’s not that kind of positive.

I actually think the Ct number is very useful, and would love to see it included, but it probably won’t be.

Anyway, hope that was helpful. Your questions below will help me make this all clearer.

Don’t fear, but be smart!
Erik

Case Update, June 22, 2021; the Delta Variant, Spike Protein Toxicity

This is a COVID update. I also have a short note on the Delta Variant and sobering new information on vaccines.

New case numbers continue to trickle down in the US, California, and San Diego County. New cases in San Diego County have been less than 100 a day for most of last week. Unfortunately, new cases aren’t really plummeting, just trickling down, but we are still making progress.

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Endcoronavirus County Level Map, June 18, 2021
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Graph is presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Graph is presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it. The County is often making adjustments to various numbers and sometimes they do not update numbers for several days. As a result, this graph is becoming less reliable. This is likely impacted by the low number of cases, so that anomalies have a greater impact on overall trends. I may not post this graph for much longer.
Graph is by me, from data collected from Johns Hopkins University COVID site.

I did some traveling this week, and in several places, including airports, about half of the people there did not have masks on. I was OK with this, since I know most people are now vaccinated, but this is reflective of our ongoing transition back into normality.

The Delta Variant: Way back in October of 2020, a new variant arose in India. First called the India Variant, the naming of variants has changed again in the last few weeks, and it’s now being called the Delta Variant (B.1.617.2). As with other variants, it’s much more infectious than the original Wuhan strain, but it doesn’t appear to cause more severe disease. The current vaccines appear to be effective against the Delta variant, so if you’re vaccinated, you are likely protected against this variant.

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Updated from June 29th, 2021 post:
As I’ve stated before, the Delta Variant is significantly more infectious than the original Wuhan strain, as well as more infectious than the UK Variant. I said last week that it is not more pathogenic. I have to adjust that assessment. While it hasn’t so far produced more deaths than other versions, it does seem to produce more hospitalizations, so it does appear to be more pathogenic at least by that measure.

I’m going to way out on a limb and suggest that the Delta Variant will not cause large numbers of new cases in the US because of our natural immunity and our large number of vaccinations. That being said, there have been reports of fully vaccinated individuals contracting the Delta Variant. None of their symptoms were severe. I may of course end up being wrong about this and I will keep you posted on new confirmed case numbers.

Some municipalities are considering new lockdown measures. I have not supported “lockdowns” since last Spring, but as an unvaccinated person, I still wear a mask in indoor spaces in public.
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Vaccines and Spike protein toxicity: Now for a topic that is even more likely to get me cancelled than last time. I ran into a video with Bret Weinstein, Dr. Robert Malone, and Steve Kirsch. Robert Malone is the scientist that was instrumental in the development of the mRNA vaccines, like the Pfizer and Moderna vaccines. He speaks very authoritatively on the vaccine issue.

Dr. Malone is very pro-vaccine in general, and certainly believes that the mRNA vaccine is effective in principle. However, he also has come to believe that while mRNA vaccines in general are safe, the SARS-2 vaccine in particular does have a big liability. This is that the Spike protein made by the SARS-2 vaccine has a toxic effect on multiple cell types. This explains the higher than normal rate of complications related to the SARS-2 vaccines.

Part of the reason SARS-2 is such a difficult virus is that the Spike protein attaches to a cellular receptor called ACE2. The ACE2 receptor is present on many cells types in the body. This is why the SARS-2 virus can infect so many different cell types, including immune cells.

In response to the vaccine, cells make Spike protein so that the immune system can develop a response to the virus. This is true of all vaccines. However, since the Spike protein can attach to so many different cell types, there is a wide range of symptoms a person may experience in response to the vaccine. Of course, most experience no symptoms at all.

So what if you got the vaccine? Should you be concerned? It’s too early to tell how prolonged an impact Spike protein in the vaccine will have on an individual person. My guess is the impact will subside after a few days, when the Spike protein in cells is degraded. However, since the Spike protein interacts will cells and impacts their functioning, some reactions may take longer to resolve. If you had no reaction to the vaccine, you probably won’t ever have one.

If you haven’t had the vaccine, should you still get it? There is no denying that the vaccine has had a positive impact on the re-opening process and has likely saved many lives. On the other hand, it obviously carries risk. If you are in a high risk group or work with the public, you are still very likely to benefit. As you know, I haven’t gotten the vaccine because of the ADE issue and also because I’m reasonably certain I can avoid getting the virus, especially now since cases are so low. I will be less likely to get the vaccine now.

Social media censorship: The full length version of the video linked above has been removed by Y0u†ub∑. Another channel has it available for now.

If you want to watch it, you should do it soon!

I believe that the censorship of ideas present in our current culture has had a profound and negative impact on the progress of the pandemic, and on our culture in general. As I’ve said repeatedly, politics and science are a terrible mix. We’ve seen many examples this year. I deeply hope we can find our way out of this mess as soon as possible.

Don’t fear, but be smart,
Erik

What is Science?

This is a long post about the philosophy of science. I probably should have written this one a long time ago, but here it is. 

During the pandemic, we’ve often heard scientists and commentators say “I’m just following the science.”  Confusingly, we’ve heard people on all sides of the issues say this, pro-maskers, anti-maskers, vaccine fans, vaccine detractors, people who love Hydroxychloroquine, and those who think it kills people.  Very often, when people have used the word “science” in the last year, they’ve used it in a way that you DIDN’T learn in high school biology class (thanks, Mr. Walker!).  So what do people mean when they say this, and how can you evaluate what they are saying?

When you hear the word “science” on the news or in discussions on the pandemic, other definitions are often smuggled in. I’ll give you a few different ways people use the word “science”, and then I’ll talk about how you can evaluate science related discussions.

1) In actuality, science is a method for measuring things in the natural world, and using reasoning and the scientific method to make, falsify, and confirm hypotheses about natural things.  Science has been phenomenally successful at describing aspects of the natural world, as well as producing useful applications for communication, travel, health, manufacturing, the arts, and nearly every conceivable human endeavor.  The incredible success of science has given it enormous cultural power as well, and many ascribe to it powers that it does not have. By definition, science measures and describes the natural world, but cannot describe many common aspects of reality, questions like “what is justice?” or “what is the meaning of life?”. 

While many contributed to the Scientific Method, the steps were formalized by Francis Bacon.  The steps include 1) the formulation of a question, 2) the development of a hypothesis, or a guess about what actually happening, 3) a prediction about what impact the hypothesis may have on a system, 4) doing experiments to test the hypothesis, and last 5) analyzing results, to include falsifying or confirming the hypothesis and forming a new question.

The scientific process is not a slow gradual accumulation of truth.  It’s often ugly, with long searches down the wrong path before finding the right one. Fields can experience sudden, jerky changes in direction.

2) The collection of facts currently believed by the majority of scientists.  When many in our current culture use the word “science”, this is what they mean. The phrase “settled science” often refers to this.  But scientific truth is not decided by a vote.  Yes, if a “fact” is believed by most scientists, it’s more likely to be true, but science history is full of people who had “weird” ideas that later turned out to be right.  By definition, topics under current study are not well understood, and there can be widely varying opinions about what’s going on. 

It’s always OK for a scientist to question current thought.  Trust me when I say that having a PhD does not mean that other scientists have to believe you.  I’ve heard shouting matches at conferences over what to believe about seemingly simple things.  

Real “Truth” transcends opinion.  Things are true whether you believe them or not. Science is the search for the truth about the natural world, not the search for ways to force your view on others.

Which leads to…

3) The collection of facts currently believed by scientists who agree with me.  When things are murky and not well understood, which is quite often in active fields, there can be 2 or more models of how a system is working. Sometimes the evidence that is out in the world can appear to be contradictory. This may be because some of the evidence is wrong, or because conclusions based on the evidence is wrong, or because a crucial piece of evidence is still missing, or because the system is just more complicated than anyone is aware of. At this point, a good scientist will try and rethink the available evidence or perhaps design a new experiment to try and get at something still unknown.  Instead, some people, even good scientists in a moment of weakness, will simply declare that their view is correct prematurely.  Scientists must always seek to be more persuasive, and not just shout louder.

4) The collection of facts currently believed by me, right now.  This definition is common for those who believe an outlier view.  It’s not bad to have a view that is outside the current orthodoxy, this is how scientific breakthroughs happen, but a person in this position must seek even more to persuade with evidence, not just be dogmatic.  Do more internet work, read more literature, or design another experiment.

5) An atheistic worldview, as in “I believe science”. Science is great at discovering information about the natural world, but it can’t answer the big questions. What some call “science” in this way is really “naturalism”, the belief that only matter and energy exists. It rejects any worldview that includes a transcendent or supernatural component. Science alone does not support this worldview, because by definition, science can’t “prove” the non-existence of things outside the known universe. Other philosophical structures are necessary to support this view.

So how do you figure out what’s really true about a scientific opinion being presented.  This can be difficult, but it can be a little easier to figure out if someone is abusing “science.” Here are some clues that science might be being misused.  You’ll have to dig deeper to be sure:

  1. A real scientific argument includes a conclusion supported by evidence.  Does the person talking give any evidence for their position? Often, people just make an assertion, a claim without evidence.  This is OK if they can back it up, but very often they can’t.  Ask “can you clarify that?” or “how did you come to that conclusion?”
  2. When questioned, a person should have evidence for their claim. If instead they call you anti-science, or *phobic or *ist, then they are abusing science.
  3. If a story or comment starts with “X person is brilliant and has been in the business for years”, this is often a red flag for me.  While a person’s qualifications are important, they must still present evidence.  A title or degree is not enough for them to be automatically believed.  The more glowing the terms used to describe a source, the more I’m suspicious that they are about to spout nonsense.
    Yes, these even applies to me.  If you tell someone “This Facebook friend of mine is a real scientist and he says <something really smart>”, you should rightfully expect your friend to ask what evidence I had for my claim. If you don’t know, then re-read my post, or just message me!  I’m happy to work through it with you, and I’ll tell you outright if I’m just speculating.
  4. News articles are OK, but they are only a starting place.  If a person references a news article, they still have homework. What news outlet? What evidence did the author use? Journalists often misunderstand or misrepresent information from scientific sources.
  5. Real evidence can be a scientific paper, a study learned about on the radio (who presented it?), or a comment by an authoritative source (who is the source?).  Each of these can in principle still be wrong, but they have more weight than other sources.
  6. Often, we gain knowledge about the world from someone we trust, an authority on the matter.  This is a fine way to learn things. Your parents were the first authority that you used for learning much of what you needed to know.  But authorities, even good ones, are not always right.  You learned this about your parents when you were a teenager. It’s OK to pick someone you trust as an authority on scientific matters, but still don’t believe everything you hear.  The CDC, the WHO, Dr. Fauci, the President (either one), yes even me, have been right about some things and wrong about some things during COVID. During an evolving situation, expect opinions and “facts” to change as more information is gathered.  Your favorite authority doesn’t know everything.

Of course, the debate on several COVID related topics have become politicized, which can make it difficult for scientists to do good work, and often VERY difficult for lay people to know the truth. I feel for you. It can be really difficult for folks to figure out what’s true about something that’s not in their field.  I feel the same way about climate change, an important topic of frequent debate that’s not in my field.  Don’t feel dumb if you have trouble figuring out what’s going on.  Lots of folks are abusing science, trying to make you agree with them.  Hopefully I’ve given you a few tips on how to discover the truth.  Here’s an article on how to communicate scientific things!

Don’t fear, but be smart,
Erik

Case Update: September 15, 2020; Bob Woodward and Communicating in a Crisis.

Friends,
This is a virus update. I’ll also have a few comments regarding the recent Bob Woodward book. New confirmed cases continue to drop for the US, California, and San Diego. California new case numbers are back down to what they were before the 2nd Wave hit in mid June.

Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site. “Active Confirmed Cases” numbers are calculated based on the assumption that patients confirmed to have SARS-2 virus at least 17 days ago have recovered.

San Diego had a moderate sized outbreak at SDSU in the last few weeks which created a spike in new confirmed cases for the County, but those numbers are coming down as well.

Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.

Endcoronavirus.org’s county view map now shows mostly yellow across much of the South, including California, Arizona, Texas, Louisiana, and Florida, which was perhaps hardest hit by the 2nd Wave. It looks like that region is now recovering, and the Mid-West is now the region of greatest concern, with increasing numbers in many Mid-Western states.

Endcoronavirus County View Map

Bob Woodward comments: If you’ve been reading my posts for long, you know that I try to keep these posts as politics free as possible, referring to policies, but not to people. You also know that my recommendations sometimes support those commonly from the “left” and sometimes from the “right”. I do my best to pass along the science as I see it, since I believe politics and science are terrible together.

If you’ve read my July 7th post, you know that a major concern of mine is Antibody Dependent Enhancement. This phenomena is still not discussed openly in the media, and the only other commentator I hear discussing it is Chris Martenson of the Peak Prosperity YouTube channel. Tony Fauci has mentioned it only in passing. I have been concerned about this phenomena since February when I started studying the SARS-2 virus.

Why did I wait until July to post about it? In any crisis, there are people who are anxious about it, they are the first to react, and some overreact. There are others who are unconcerned, and react slowly if at all. Many are somewhere in between. Anyone who communicates to the public has to aim somewhere in the middle of these perspectives. My goal from the beginning has been to communicate adequate concern while being as positive as possible and not cause the anxious to over-react. As I’m sure you’ve heard, there have been many mental health issues attached to recent events, and I have friends in the mental health field for whom this is a great concern. I struggled for a long time before my July 7th post. I wanted people to be adequately concerned, but I didn’t want to cause needless anxiety. The ADE phenomena is still poorly understood, and it’s not certain if it will play a roll in this crisis. I finally decided to discuss it because I had a lot of friends who I felt were not taking the virus seriously enough, and I began to feel it was wrong of me to not inform them. To this day, I wonder if I waited too long, or maybe shouldn’t have mentioned it when I did.

All this to say, Bob Woodward’s discussion with the President was in February, if my understanding is correct. In February, the virus had still not come to the US, except for a few small clusters. Little was still known about how it would behave in the US, and the opinion of medical professionals regarding how to deal with it has changed many times since then. If President Trump was wrong to downplay the virus in February, then I was wrong too. I hope you will have some understanding for the difficult decisions to be made.

The CDC continued to treat the virus like it has always treated epidemics somewhere else, deep into March. Only in Mid-March did they allow other entities to do SARS-2 testing in the US, responding to the President’s request. Large scale testing did not start until early April. In my opinion, the CDC is most responsible for reacting too slowly to the virus.

Don’t fear, but be smart,
Erik

America’s Frontline Doctors Video

A quick note, I posted an update yesterday, but I accidentally only sent it to one person, so for the weekly update, check your feed for yesterday morning, or check my timeline.

Many people have asked me about a video that was posted yesterday by a group called “America’s Frontline Doctors”.  The original video has since been removed from Facebook, YouTube and the group’s website has even been dropped by the host, Squarespace. All this to say, you may have a hard time watching it if you want to.  I found a different version.

As I’ve said before, politics and science should never go together.  Whenever a scientific issue becomes political, it becomes very difficult for free scientific inquiry to move forward, and nearly impossible for non-scientists to figure out what the truth is. So I’m sorry to those of you who are confused and are trying to pursue the truth. The video was put together by the Tea Party Patriots and Breitbart News, 2 right leaning organizations.  This is a red flag for me because I know that the message will have a political angle, and that I’ll need to watch with extra care.  As I said in my July 14th post, however, just because you disagree with someone in general doesn’t mean they have nothing good to contribute to the discussion.  Especially with politically charged issues, we need to get information from a variety of sources in order to be as informed as we can.  I know for many of us, it’s nearly impossible to have time for that, so we often just pick someone we trust to get our information from.  I definitely have political opinions, but whenever a scientific issue comes up, I do my best to set those aside and look at the evidence.  I hope this has been valuable to you.  You may have noticed that some of my thoughts about the Coronavirus have been “left-wing” and others have been “right-wing.”  I’m doing my best to be objective.  And yes, I consider it a tragedy that opinions on scientific issues can be categorized as either left or right.

I want to discuss some of the main points of the video and offer my informed but not expert opinion.  I am a Ph.D. molecular biologist specializing in infectious disease testing.  I am not a physician or an epidemiologist. I will give my opinion and also why I think that way.

Hydroxychloroquine (HCQ): The video focuses to a great degree on HCQ as a potential “cure” for the Coronavirus.  As soon as President Trump mentioned it as being potentially helpful for treating Coronavirus, it became a subject of immediate and hot controversy.  Democrats seemed to reflexively dismiss HCQ, and Republicans seemed to reflexively support it.  President Trump dug in his heels and seemed to support its use before all the evidence was in.  Obviously, this is not how science should be done.  Careful and well-reasoned studies should be done, and conclusions made based on evidence. Early studies seemed to support both conclusions. Opponents claim that HCQ doesn’t work and is even harmful to patients, causing heart problems in some.  Supporters claim that HCQ works when given early in the disease, and with Zinc and perhaps azithromycin.

Dr. Immanuel made an impassioned case for the use of HCQ, having successfully used it to treat over 300 patients.  This kind of evidence is what scientists call “anecdotal”.  Anecdotal evidence, basically stories, is often not considered scientific because in a large pool of people, you can find stories supporting all kinds of claims.  Anecdotal evidence also usually does not carefully consider other factors that may contribute to a conclusion.  An example would be “I ate ice cream and then I got attacked by a shark, so eating ice cream leads to shark attacks.”  This is obviously a silly example, but many pieces of anecdotal evidence you hear suffer from the same lack of critical thinking.  However, this is not at all to say that anecdotal evidence is not useful!  These kinds of stories may not be scientific per se, but can often trigger more rigorous studies that prove the claims of a story.

Several scientists I’ve heard from will point out that HCQ is useful when given early and given in combination with Zinc, and also in appropriate dosages.  I actually agree that some of the studies arguing against HCQ use have given it too late or in inappropriately high dosages.  I would like more rigorous studies to be done, however at the moment, I think HCQ is well worth consideration by the medical community. Other treatments also exist and may actually be better, such as the MATH+ protocol I described in my summary post on June 22nd, Dexamethasone, Remdesivir, and perhaps Budesonide.  For the HCQ protocol, it appears that Zinc is actually most responsible for anti-viral activity, with HCQ mostly helping Zinc enter cells to interact with the virus.

Some have pointed out that Dr. Immanuel has some beliefs that are well outside accepted scientific views.  As I pointed out before, even folks who you generally disagree with can bring helpful information to the table.  Her HCQ experience may be true despite her unorthodox beliefs. So even if you justifiably don’t consider a person reliable, you should resist the urge to dismiss them outright.

Lastly on the issue of HCQ, physicians have the right to use drugs “off-label” meaning they are granted by their medical degree the right to try medications in ways that are not necessarily supported by the literature or guidelines.  This right is granted in the interest of patients, because careful studies can take a prohibitively long time to be published, and to encourage the development of helpful new protocols.  In my opinion, government agencies should not be restricting the use of HCQ by doctors at this time.

School reopening:  In some ways, there is reason to re-open schools in the Fall.  It appears to be true that children under 10 do not get infected at high rates, do not carry a high viral load when infected, do not get severe disease, and do not seem to spread virus to others.  So there is a case to be made for reopening schools for young children.  However, because of the ADE issue I’ve written about before, I am not currently in support of re-opening schools in the Fall.  Just to recap, ADE (Antibody Dependent Enhancement) is the phenomena in which some viruses can use antibodies presented on immune cells to infect those cells and cause more severe disease.  So a second infection with a similar strain can lead to much worse symptoms.  SARS-1 and MERS, cousins of SARS-2, can both use this pathway, so with current evidence, it seems likely that SARS-2 will as well.  But we won’t know for sure until another SARS strain develops and we see how people respond to it. I will point out in full disclosure, that almost no-one is talking publicly about ADE.  Dr. Fauci has mentioned it, but just in passing.  So I could be out to lunch about this, but it is a major concern of mine. I have had a few epidemiologists mention in private conversations that they think ADE is a real issue, but they aren’t comfortable talking publicly about it either. 

Sweden and Herd Immunity: Dr. Dan Erickson, who made a video back in April, also spoke.  I was critical of his original video because his analysis of the death rate used the wrong number for total cases.  This time he spoke mostly about the lock-downs, and most of his comments were more measured.  He argued against lock-downs and suggested Sweden as a model.

I am also critical of lock-downs as they were done in much of the US, with people asked to stay home at all times.  However, I am not supportive of the Swedish model either, in which few precautions are taken.  While I am not for people staying at home, and I think people should find ways to get back to work, I also think people should wear masks while indoors in public.  Small outdoor meetings are fine, even without masks, but large outdoor gatherings with closely packed people are dangerous in my opinion.  Again because of the ADE issue, I am not in support of the idea of obtaining herd immunity as a way out of the crisis.

Masks: Some have taken away from the video the idea that we should not wear masks.  I didn’t get this from the video. Dr. Gold explicitly said she thinks masks should be worn indoors, but not necessarily outside. I agree with this approach.

As you can see, I agree with some aspects of the video, and disagree with others. When possible, study all sides of the issues, and make the best most reasoned choices for you and your family.

My basic rules are as follows:

1) Wear a mask or face covering in public. Avoid places with unmasked people.
2) Keep 6 ft away from others.
3) Avoid indoor gatherings, especially ones in which singing or shouting is likely.
4) Small outdoor gatherings are fine, even without masks, if everyone maintains a distance. Have guests bring their own food.
5) While many restaurants are open for limited indoor seating, I personally am still not comfortable eating indoors at a restaurant. I enjoy eating outdoors at restaurants, however.

Don’t fear, but be smart!

Erik

A version of the America’s Frontline Doctors video:
NOTE: The below video was removed by YouTube a day after this blog posted.

My recent summary post.

My comments on Dr. Erickson’s original video.

Masks

Antibody Dependent Enhancement

Science Communication

July 28th Update

Case Update: July 14, Budesonide

This is a case update. For the US and California, cases continue to rise. The number of daily deaths have begun to rise as well in the last week, running about 3 weeks behind the rise in daily confirmed cases.

Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.
Graph is by me, from data collected from Johns Hopkins University COVID site.

The news is better in San Diego. Daily new cases has flattened and may even be going down. A caution is always that Sunday and Monday are always low days of the week in terms of new cases, so you have to be careful about saying things are getting better on a Tuesday! The number of active cases in San Diego may be flattening as well.

Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.

After a spike in cases in Imperial County, east of San Diego, hospitals in El Centro have become overwhelmed and COVID patients are being sent to San Diego, Orange and other counties. This stresses the importance of keeping case loads low so as not to overwhelm hospitals and ICU deparments.

Texas Medical Association Chart: The Texas Medical Association released a very helpful chart giving the relative risks of different activities.

If you’ve reading my posts, you won’t be very surprised by the entries, they are pretty consistent with what I’ve thought myself.

The information was obtained by polling Texas doctors, so the data probably reflects what they know about their own patient’s histories, and also probably some opinion.

Budesonide: A very interesting video was posted last week featuring Dr. Richard Bartlett. He claims to have a very effective new treatment, using a nebulized anti-inflammatory normally for asthma, Budesonide. It will be very interesting to watch if others have success with this method.

The video introduces another topic that is very timely. If you watch the whole video, you’ll notice that Dr. Bartlett has some views about the virus that I don’t share. However, I think the video is still worth watching. Often these days, people dismiss people with whom they disagree on any topic. In reality, it’s very common to be able to take at least some truth from those with whom we disagree. In fact, on complicated topics, I find that with almost anyone I read or watch, even people I respect highly, there is often some topic that I think they’re wrong about. If I refuse to learn from people that I disagree with, I’d have to quit listening to most of the people I respect! With all that’s going on in the US right now, we will need to listen to and learn from all kinds of people to move forward. Even if you disagree, learning a person’s position will help you understand the topic better.

Don’t fear, but be smart!
Erik

Case Update: June 9th

Here’s the weekly update on the virus. As I predicted in my June 2nd post, we’ve started to see an increase in cases, at least for areas that I closely monitor. For the United States as a whole, the increase has been subtle, really just a flattening of a steady downward trend. For California and especially San Diego County, there has been a pronounced uptick in cases during the last week. The City of San Diego had some protests last weekend, but not nearly as much as in other cities like Minneapolis, NYC and LA. If the pattern for San Diego holds for other cities, they will experience more severe increases in cases. Oddly, many in the media strongly discouraged protests in favor of re-opening, but are seemingly promoting protests about police brutality without regard to precautions like mask wearing. Even the WHO is encouraging mass protests. Of course there are good reasons to attend a peaceful protest. If you go to a protest, please wear a mask. Of course, I have to discourage you from attending a riot.

I do have to point out that there are many factors that contribute to these increases, such as the ongoing re-opening, and no single factor can be blamed.

Graph is by me, from data is collected from Johns Hopkins University COVID site.
Graph is by me, from data is collected from Johns Hopkins University COVID site.
Graph is by me, from data is collected from Johns Hopkins University COVID site.

Endcoronavirus.org has introduced a new feature in the last week, a county level map showing the recent change in new cases. Clicking on a county will give you a plot of new cases for that county. High caseloads for urban areas is a well known pattern, but I’ve also noticed hot-spots of cases in certain rural areas. A new article in the Wall Street Journal may suggest a reason. Large families living in the same house may present an opportunity for rapid spread should someone be infected who lives there. As we discussed on May 27th, the virus spreads much more quickly in indoor venues than it does outside. This suggests that if you have a large family, members will need to be extra cautious to not bring virus in from the outside.

From endcoronavirus.org Counties map.
From endcoronavirus.org Counties map.
From endcoronavirus.org Counties map.

Don’t fear, but be smart,
Erik

JP Morgan Study on Lockdowns, The Moral Matrix and Pandemic, and the Viral Upsurge in the Southern Hemisphere

Today I’m going to discuss the JP Morgan study on transmission (among other things), how the Moral Matrix effects how people see the fight against the virus, and the boom stage in many Southern Hemisphere countries.

JP Morgan has produced a study suggesting among other things that lockdowns are ineffective in fighting Coronavirus (see also a summary from Daily Mail).  The reasoning for this is primarily that transmission is most common in households if a member becomes infected. 

Frankly, when I think about anti-coronavirus efforts, I have tended to lump lockdowns and social distancing together, especially since many use these terms interchangeably.  Notably, the study separates these 2 concepts and suggests that will social distancing (staying a distance away from people in public) may be valuable, lockdowns (staying in your home) is not. 

You might say there have been 2 primary models for dealing with the pandemic in the last month after we’ve flattened the curve, but have not brought the numbers down, at least not in the US.  I’ll call those models the Lockdown and the Re-opening models.  Some want to continue the lockdowns to keep everyone safe from the virus, others want to re-open right away without restrictions.  For several weeks, I have been gravitating toward a third Adaptive model.  Of course, there can be many flavors of this model.  Personally, I think masks, even bad ones, are far better than nothing, especially when worn by everyone, and can help us get back out of our houses and help us re-start the economy with reasonable safety.  So I’m very open to the idea that the lockdowns have not been beneficial.  Some of you will disagree.

The JP Morgan study is at odds with the endcoronavirus.org study, which recommends brief, very strict lockdowns.  It could actually be that these 2 studies actually agree, depending on the time frame you’re talking about.  I do think the lockdown was very helpful in the initial “boom” stage of the epidemic here in the US, but may have lost its usefulness later.

The Moral Matrix: ZDoggMD is a physician and medical YouTuber with a very silly screen name, but who posted VERY interesting video on how different people see the pandemic we are all facing.  Using Jonathan Haidt’s work on the Moral Matrix, he talks about how different people’s moral framework shapes how we are viewing different efforts to address the issue.  I was aware of Haidt’s work, but not had yet applied it to the pandemic in my mind.  As someone who is sometimes exasperated with people who disagree with me (as they are with me I’m sure), this video is helping me remember to see their point of view.  If you’re exasperated with your friends or family, I HIGHLY recommend you watch this video.

Upsurge in the Southern Hemisphere: Lastly, I just want to mention that many countries which have been relatively little effected until now, are now experiencing a big upsurge in cases.  These countries include Russia, Brazil, and Mexico, and many are in the Southern Hemisphere, which is in the late Autumn months right now.  Let’s hope they are able to get things under control quickly.

Don’t fear, but be smart!

Erik

PS. We went hiking in nearby Calaveras Park today for the first time in months, without our masks. There were a lot of people on the trail, and most were well behaved. When I can’t avoid someone on a narrow trail, I use an old SCUBA diving trick for ascending without getting the bends. Just close your mouth and blow slowly out of your nose as you pass someone. You’ll gently move any virus away from your nose! To maintain my friendliness, I greet people early, with plenty of time to start this little maneuver!

Re-opening, How Many New Cases?, endcorona.org Compares Responses, Viral Spread

I have a variety of resources to share with you today. 

Re-opening: First, after many states have started to re-open, Rt Live is showing that all but 3 states have an Rt value below 1. This means that for most states, each infected person is passing the virus to less than 1 other person, and the virus is slowly disappearing in that state.  The states with an Rt above 1 are Minnesota, Maine, and Nebraska.  After a poor initial response, I’m happy to say that New York State is doing very well now, and daily new cases are low in New York. In California, my home state, the number of new cases is flat, approximately 1700 cases per day since the middle of April.

How many real new cases?  This is going to be a little mathy!  I told you I was going to start tracking the number of tests, and I have been doing that since April 27th.  This will help us know how many of the new cases are just because of more testing, and how many are actual new cases.  I’ve plotted the new cases against the new tests.  For each day, a point comparing the new cases and new tests is shown. If new testing matters, then a day with a high number of tests will also have a high number of new cases. To find out if this pairing exists, we can do a statistical test called the R2 test (pronounced “R squared”, also called the correlation coefficient).  This test creates a best fit line with the data and that creates an R2 value.  This value is a measure of how well the 2 parameters (new tests and new cases) are correlated.  I show a hypothetical graph in which the 2 sets of data are well correlated.  A perfect correlation will have a score of 1.0, while a set of data with no correlation at all will get a score of 0.0.  For scientists (at least the ones in diagnostics, like me) a correlation is considered “true” if the R2 value is above 0.95.  You could also say that the correlation is 95% likely to be true.

Now on to our data. I started plotting on April 27th.  5 days later, the graph for the United States got an R2 value of 0.6559.  This suggests that new cases and new tests are 66% likely to be correlated for this time period.  In real world terms, this probably means that some new cases are because of new testing, but some aren’t.

Interestingly, as of yesterday, a graph like this for the US gets an R2 value of just 0.0117.  This is very low and suggests that there is now no correlation between new testing, and new cases.  This means that new cases we see now are probably “real” new cases, and not just pre-existing ones that are just being found because of new testing.  For California, the correlation between new cases and new testing was never very high.  Right now, the R2 value is only 0.0039 for California, suggesting that most new cases discovered are “real” new cases.  What this means going forward is that we probably have enough testing now to locate new cases.  As we go forward, I expect we will start to see a steeper decline is new cases.

Good news!  This good news comes with a warning, however!  Those living in the West will easily understand a comparison to a brush fire.  Right now, we are in the “containment” stage.  We have the fire surrounded, and were at the beginning of the end, but if we walk away now, the fire will start to spread again.  We need to stay on task and keep fighting the fire!  I am all for re-opening, but we need to remain diligent.  Wear a mask when you go out into public, and continue to keep your distance from others!  If your workplace re-opens, you will probably want to wear a mask, wash your hands frequently, and sterilize your workspace often. I am probably going to start traveling for work again soon, and I’m very glad that everyone will be wearing a mask on the plane!

Endcorona.org compares responses: I discovered a new website the other day, endcorona.org, from the New England Complex Systems Institute.  The group compares the responses and results from different countries.  First, “green” countries responded very well, and were able to get the virus under control quickly.  Aside from the good response, I also notice that most of these countries have relatively small populations.  You may notice that China also appears on this list.  Most experts agree that the data coming from China is not reliable, and they probably have many more cases than they are reporting. After intermediate cases in yellow are countries in red that need more action.  This includes the US.  If you’ve been reading my posts, you’ll recognize the “flat” curve of the US.  Yes, we’ve flattened the curve, but we haven’t been able to knock down our case load yet.  Other countries with similar flat curves include Canada, Finland, Indonesia, Panama, Poland, Sweden, and the UK. Other countries had low cases at first, but are now experiencing explosive growth in new cases, including Brazil, Mexico, and Russia.

After analyzing the responses of these countries, endcorona.org recommendations include the following, many of which you’ll recognize:

  1. Lots of testing to identify new cases.
  2. Isolating infected individuals, even from family members!
  3. Strict lockdowns.  The stricter the lockdown, the shorter it will be.
  4. Travel restrictions, even within the same country.
  5. Adequate health care capacity.
  6. Safe practices for essential services.
  7. Masks in public for everyone.

Viral spread: Erin Bromage, an Associate Professor of Biology at U Mass Dartmouth, has a very nice article on his blog describing how the virus spreads. It is well written for non-scientists and has lots of links to original research.  The take home lesson is that the virus spreads particularly well in-doors.  In addition, cough, sneezing, and to a lesser degree shouting, singing, and even talking are all risk factors in spreading virus.

That’s all for now!

Don’t fear, but be smart!

Erik

Case Update: May 2nd, Video: Simulating an Epidemic

The number of news cases has been erratic in the last week, but at least in the US, it continues to trend downward. I’ve started collecting the number of new cases in the US and California, and while I’m not sure how to integrate that data into my Excel spreadsheet yet, I can tell you that more tests definitely mean more new confirmed cases. So some of the erratic graphs were seen are definitely because of more testing. In the long run, I expect to see new cases come down drastically as we continue to increase testing.

Rt.live is showing that 45 of 50 states have an Rt value below 1 yesterday. This is great news, as it shows that in most states, the virus is slowly disappearing. I’m watching with great interest to see how the states that have started re-opening do. Keep up the great work! We are having an impact!

Also included is a very interesting video I ran across, Simulating an Epidemic, showing a non-scientific computer model of possible epidemic outcomes given different approaches. Keep in mind, this model is NOT attempting to show what will happen in the COVID epidemic, just some theoretical things that might happen given different approaches. He does NOT attempt to prove that any of these things are what’s happening.

The most interesting parts for me were when he compared 2 methods that have been used in different places. At 6:00 minutes, he talks about the Detect and Isolate method, which I favor. This is were you find an infected person and quickly quarantine them until they have recovered. He argues that this is the most effective method in an epidemic like the current one. We haven’t been able to do this, really, because of our lack of testing in the beginning. My fervent hope is that if we get a second wave in the Fall or Winter, we will be ready for this approach.

At 16:50, he talks about a method that I think we are kind of using, the shelter in place, but with trips to central locations. He says that without other measures, these locations become a source of new infections. This is probably not happening as badly in real life because so many are wearing masks to the store!

Don’t fear, but be smart!

Erik