All posts by Erik P. Johnson

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, August 19th, 2021, Is COVID Endemic?, Mandatory Vaccination.

This is a case update. I’ll also briefly discuss the future of the pandemic.

Numbers continue to rise in the US, but are definitely slowing in their increase. New cases are most prominent in the West and Southeast. New deaths are rising, but much more slowly than for other waves.

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Endcoronavirus County Level Map, August 19th, 2021
Endcoronavirus State Level Map, August 19th, 2021

For California and San Diego, it looks like we have crested the wave and new cases are starting to head down. In both of these regions, new deaths are not really increasing at all. This supports the pattern that in vaccinated areas, large numbers of new cases due to the Delta Variant are not followed by large numbers new deaths. I mentioned a few weeks ago that deaths can trail new cases by as much as 4 weeks, but we are now 6 weeks into the Delta Wave in California and San Diego without seeing a significant rise in new deaths.

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
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.

Internationally, new cases appear to perhaps have peaked world wide, but it will take some time to see if cases start to go down. As stated above, countries with vaccination programs are experiencing almost no new deaths due to Delta Variant. Numbers for the Netherlands are striking, and other countries like the UK, Sweden, Japan, and South Korea show a similar pattern.

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
New daily confirmed cases in the Netherlands, from Worldometers.
New daily deaths in the Netherlands, from Worldometers.

Several sources I listen to are now saying that SARS-2 is now or will be endemic. For some background, an epidemic is an outbreak of a disease in a small area or region. Avian influenza and the first SARS outbreaks were epidemics, since they didn’t leave Asia. A Pandemic is an outbreak in a large area including several continents. A disease becomes endemic when it becomes a constant feature of life in an area. I would include malaria, seasonal flu, and HIV in the list of endemic diseases. Interestingly, Wikipedia still considers HIV to be a pandemic.

I have resisted calling COVID endemic. I don’t think it fits the criteria at this point. While there have been several new variants that have caused additional waves of cases, they are all at least partially impacted by the available vaccines, and presumably by natural immunity as well. While this is the case, I still think it is possible that we can eradicate the virus from the world at some point.When might SARS-2 become endemic? For me, that would happen if either new variants arose that were not mitigated by natural or vaccine driven immunity, or if immunity in vaccinated or naturally immune people ceased to be effective in preventing new infection. Both of these would allow SARS-2 to continue to circulate indefinitely.

Some have argued that vaccine mediated immunity is not as long lived as hoped. This may be why there have been many “breakthrough” cases in the last few weeks. However, Youtuber Dr. Zubin Damania suggests that while protected from new infection wanes over months, vaccine protection against severe disease is persistent, at least against the Delta Variant. This may explain our current pattern of low deaths despite high cases in vaccinated regions.

So is COVID endemic? I still say no, and hope it can be eradicated. However, some municipalities, including Norway and the state of Iowa, have declared that is endemic and will be a permanent feature of the world. If I decide that the data shows that SARS-2 is endemic, then that is the day that I will get vaccinated. ‘Cuz I do want to go back to normal life someday, but I don’t want to actually get COVID. Obviously, many vaccinated and unvaccinated folks have decided to go back to living normally, despite official calls to maintain vigilance.

Vaccination mandates: I have not been in favor of requiring vaccination in order to return to work, fly on commercial aircraft, or other activities. While I am all for precautions and continue to wear a KN95 indoors while in public, healthcare is a personal choice and should not be coerced. Some have even claimed that it is illegal to coerce a measure that does not have FDA clearance. While vaccination is a good choice for many, it does have liabilities that have made many resistant to vaccination. This should be honored.

I know several people in the healthcare industry who have not wanted to be vaccinated, and have quit or been fired from technical or nursing jobs. While an argument could be made that those working with patients should be vaccinated, it seems misguided to be letting go of nursing staff when there has been a long standing nursing shortage.

Don’t fear, but be smart,
Erik

How Mutation Leads to New SARS-2 Variants

This is a brief post on the issue of new COVID variants and their cause. There has been a lot of confusion as how new variants arise. For small biological organisms that evolve quickly (bacteria, viruses, parasites, some insects), new strains can arise relatively quickly. I say relatively because it can still take many years in some cases. This is because small changes in genetic material can lead to important changes in function.

Point Mutation: There are 3 kinds of mutations that can cause this. One is a point mutation, a change in a single nucleotide (the basic unit of genetics, like a letter of the alphabet). Depending on the point mutation, this can lead to no change at all, or an important change that can have an impact on drug resistance, protein binding to target, or other effect. This is particularly likely in viruses whose genome are made from RNA, because the proteins that make RNA strands in these viruses are particularly error prone. This is why HIV, the Flu, and Coronaviruses can change so quickly.

Genetic Re-assortment: Another kind of change common in some viruses like the flu, is a re-assortment of chromosomes, or “antigenic shift”. The Flu virus genome comes in 8 pieces. If 2 viruses infect the same animal and the same cell, then that cell can produce new viruses that have a combination of pieces from both infecting viruses. This often happens when a pig on a farm somewhere gets infected with 2 flu viruses, and produces a new, novel form of the flu. This is why new flus are often called a “Swine Flu”.

From the Wikipedia page on Influenza.

Conjugation: Bacteria can donate genetic material to other bacteria, even those of a different species, in a process called conjugation. Yes, it’s more like that than you might imagine. In this fashion, bacteria may acquire large amounts of new DNA. These new DNA fragments are kind of like software downloads, encoding whole new abilities like drug resistance, iron scavenging, and the ability to bind and invade new cell types. In fact, it could be argued that many or even all disease causing bacteria are this way because they’ve inherited DNA from other bacteria!

So how does this all relate to SARS-2? COVID changes using the point mutation route, which it does quickly because it has an RNA genome. The probability of a new variant arising is dependent on the speed of mutation, the number of viruses that exist, and time. This means that the more viruses that exist at any moment, the more likely that a new strain will arise. In our present moment, this means that the more people in the world that have COVID, the more likely a new variant will arise. This is a concern at a time when new infections are high.

The very good news is that the vaccines we have appear to work on all the existing variants, at least to some degree. So while we do need to try to keep the number of infected people down to avoid new variants, we are not defenseless against them. But there is a possibility that a new variant will arise that is not neutralized by the current vaccines, and this should be avoided of course.

Don’t fear, but be smart!
Erik

Case Update: August 13th, 2021

This is a case update. For the US, cases continue to rise, although the rise in cases may be slowing just slightly. New cases are being driven by a few states with rocketing new case numbers, in states in the South, as well as Washington, Oregon, and Hawaii. Only Hawaii is experiencing a decline in cases after a sharp rise.

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 presented in a linear format.
Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format.
Endcoronavirus State Level Map, August 13th, 2021

For California and San Diego, new cases are still rising, but more slowly all the time. COVID related deaths are still only creeping up for the US, and still haven’t risen at all for California and San Diego, 6 weeks into the Delta variant peak. At least for now, it continues to appear that the Delta variant is less virulent, at least in the US and some other heavily vaccinated countries.

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 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.
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 Johns Hopkins University COVID site. Graph is presented in a linear format.

Incidentally, high infection rates in the South are likely caused by hotter weather causing folks to go inside for air conditioning. Just like last summer.

If the Delta wave isn’t over in the US by October, we are likely to see lots of cases in the North, just like last Fall.

Don’t fear, but be smart,
Erik

Case Update, August 2nd, 2021, Peak in New Deaths?, Breakthrough Cases.

This is a case update, and it will come with a big correction from last week.

New confirmed cases continue to rise due to the Delta variant in the US, California, and San Diego County, although at a noticeably slower rate.

I said last week that we may see the peak in US cases this week because Sunday’s number was the same as the previous week’s. This week’s numbers were erratic, but continues to show an upward trend, with yesterday’s new case number being higher than last week’s. So we are still on an upward trend, but it is slowing.

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 presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.
Endcoronavirus County Level Map, August 1st, 2021
Proportion of current cases from various SARS-2 Variants. The Delta/India variant (B.1.617.2) is in orange. From CDC data.

For California and San Diego County, new case numbers are definitely flattening, and we could very well start seeing a downward trend this week.

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

Correction on new deaths: Last week I said that new deaths were not rising at all as a response to the higher Delta peak case numbers. While this was true last week and is still true, I also have to say that I assumed that deaths generally followed cases by 2 weeks. After looking back at data from the US and other countries, deaths appear to trail new cases by anywhere from a few days to as many as 4 weeks. Since our current wave started at the beginning of July, it’s still too early to say if we will get a new peak in COVID deaths.

Several countries have indeed seen Delta peaks in cases without a peak in deaths so far. The UK and Portugal are both 6 weeks into their Delta variant peaks, without a substantial rise in deaths so far. My statements from last week may still end up being true. I will certainly keep you posted on this.

New cases and daily deaths in the UK. From Johns Hopkins University COVID site.
New cases and daily deaths in Portugal. From Johns Hopkins University COVID site.

How many breakthrough cases? There has been a lot of discussion around breakthrough cases, a new COVID case in a person who has been fully vaccinated. According to the CDC, there have been 6,587 hospitalizations or deaths in 163 million vaccinated Americans as of July 26. This is a proportionally small number, but is obviously not zero.

I could only find data until April 30th for any SARS-2 infection, 10,262 infections for 101 million vaccinated Americans from January 1st, to April 30th. Note that this is before the Delta wave started in the US (early July). There were 12,376,975 confirmed infections in the US during that time, so the proportion of infections in vaccinated individuals is 0.083% according to CDC numbers.

While the proportion of infections and deaths in vaccinated is very low, I hear persistent unconfirmed stories about vaccinated people being infected. Hopefully, given the politicized environment, we will someday get good data on this.

Don’t fear, but be smart,
Erik

Case Update, July 26th, 2021

This is a COVID case update. There were large increases in confirmed cases in the US, California, and San Diego County last week. Wave 5, the Delta Variant wave, can no longer be considered a blip to be sure. In all three regions, case numbers are significant, even matching last Summer’s wave. Most new cases are concentrated in the Great Lakes States, the South, and the West.

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 presented in a linear format.
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.
Endcoronavirus County Level Map, July 24th, 2021
Endcoronavirus County Level Map, July 24th, 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 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.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County.

For the US, I’ve noticed that the Friday numbers are always particularly high these days. This may be because labs are trying to report out all their cases before the weekend. Sunday continues to be the low reporting day. Last Friday’s number was very high for the US, 177k new cases. So we had a big upward trend for the week. However, Sunday’s number was about the same as last week.

I’m going make a very tentative point now that may very well be wrong. Since yesterday’s number was basically the same as last weeks, this MAY be an indicator that we’ve hit a peak for Wave 5. This next week will show if that’s true. In many nations, the Delta variant has created a sharp peak, with numbers quickly rising before the peak, and quickly falling after.

California’s numbers are very high was well, and San Diego County is the 9th highest county in the nation for new cases.

There is some good news. At least in the US and San Diego County, new deaths have not gone up with the number of new cases. In fact, in San Diego County at the time of this writing, new deaths are lower than they have ever been during the pandemic, with just 24 in June, and just 18 so far in July. California is experiencing a slight uptick in new deaths. This pattern appears to be true for many first world countries, including those in Western Europe, and Eastern Asia like Japan and South Korea.

World wide, cases continue to climb. In many countries including Indonesia, Russia, and India, new Delta Variant cases did result in a large number of new deaths. This suggests that vaccination in a country has resulted in better outcomes for infected people in that country.

Graph is by me, from data collected from Johns Hopkins University COVID site.
New daily confirmed cases and new deaths for Indonesia, Johns Hopkins University COVID site.

Don’t fear, but be smart,
Erik

Summary of the Pandemic, July 21st, 2021

This long post will be a summary of what we have learned so far about the Coronavirus, and I’ll make some predictions about what to expect next.  Since I’ll be sharing so much information, I won’t give references for everything here. I also have to make the disclaimer that new studies are constantly being done, and some of the below information may need to be revised later. To make my standard disclaimer, I am not an epidemiologist or a physician.  I have a Ph.D. in molecular biology, and my specialty is infectious disease testing. On much of the below, I have an informed but not expert opinion.

Coronaviruses: Coronaviruses are a large group of viruses unrelated to the flu.  What we think of as the common cold, are actually member of several classes of viruses like Adenovirus, RSV viruses, Rhinovirus, and several Coronaviruses.  Many Coronaviruses cause diseases no more virulent than the common cold.  However, just like novel flus can cause extra trouble, so can novel Coronaviruses.  The first SARS virus was much more lethal that the SARS-2 virus, but because SARS had a short incubation period and made almost every infected person sick, it was much easier to contain.  The Middle East Respiratory Syndrome (MERS) Coronavirus infects a few people every year, and is very lethal, with a fatality rate of 34%, but it also has not made a global impact.  The reason SARS-2 is so dangerous is that it’s VERY infectious (Ro of between 2.5 and 5.7) and has a VERY long incubation time (2-14 days), making it very hard to track.  Plus, it’s at least 2x as deadly at the annual flu.

Name: The official name of the virus is SARS-2-CoV (for Severe Acute Respiratory Syndrome-2 CoronaVirus).  The official name for the disease it causes is COVID-19 (for COronaVIrus Disease-2019).  You may notice that the term SARS actually sounds a lot like a disease.  You would be right.  So why did they need a different disease name than SARS-2, or SARS-19? I don’t know.

Origin:  Controversy over the origins of the SARS-2 virus began very early in the pandemic.  The most common theories were that the virus arose naturally at a live animal market in Wuhan China, where animals from a wide variety of species are sold.  The predominant theory is that the SARS-2 virus arose in bats, then transferred to another animal, perhaps a pangolin, before moving to humans.  This has been the most accepted theory for the majority of the pandemic, promoted by the WHO, the CDC, and American media. 

The lab leak theory, the idea that the virus arose from the Wuhan Institute of Virology, was present from the beginning, but was heavily disfavored by official channels for most of the pandemic.  On May 23, 2021, the Wall Street Journal published an article that gave evidence for idea, followed closely by an article from Vanity Fair.  The articles normalized discussion of the theory and as of this writing, polls show that a majority of Americans believe that the virus came from the WIV.

Emails between several virologists, public health officials and Dr. Fauci strongly suggest that this group believed that the virus may have come from the laboratory as early as January 31, 2020.  However, this same group published a scientific article on February 9th supporting the natural origin theory.  The paper was at odds with discussion in the email correspondence.  If investigations show that the group published claims they knew to be false, this would represent a significant case of scientific fraud.

Spread:  Early reports were that SARS-2 mostly spread like a flu, with droplets spreading from coughing or sneezing.  It became apparent later that the virus was also spread through aerosols by laughing, singing, shouting, or even just talking in close proximity for long periods.  As further study was done, it appears that most infected people don’t infect anyone else.  Rather, most infections come from “super-spreader” events, in which a single person infects a large group of people.  This usually happens indoors (at least 19 times more likely) during activities like fitness classes, funerals, concerts, and choir practices.  While outdoor activities aren’t completely immune to these events, outdoor transmission of SARS-2 appears to be extremely rare.

Viral load upon exposure appears to be an important determinant of how severe a case will be.  Basically, this means that if you’re infected by a “low dose” of virus, your disease is likely to be less severe.  I have several physician friends who have stated that it seems to them that cases in the hospital are less severe than they used to be.  One likely reason for this is that since more people are wearing masks in public than early on, those who are infected are being infected by a lower viral load.

Early studies demonstrated that viable viral can exist on objects for hours or days.  However, it does not appear that a substantial number of people are being infected because they have touched a contaminated object. 

The WHO made a confusing claim that asymptomatic people cannot spread the virus.  While this is technically correct, they were not clear that “asymptomatic” is a technical medical term meaning someone who does not have, and will never have, symptoms.  Another group is “pre-symptomatic”.  These are people who currently don’t have symptoms, but will develop symptoms in a few days.  As it turns out, pre-symptomatic people do spread virus, and are likely responsible for up to 80% of new cases. So yes, people without symptoms can and do pass the virus to others.

Risk Factors:  Many believe that only old people are at risk. While it’s true that age is a dominant factor, other risk factors are important, and younger people have also experienced severe symptoms.  Other risk factors include:

age
asthma or COPD
heart conditions
kidney conditions
liver disease
high blood pressure
diabetes
obesity
auto-immune disease
use of NSAID anti-inflammatory medications
being immunocompromised (HIV infected, undergoing cancer treatment, under medication for a transplant)
vitamin-D deficiency
type A blood (Type O appears to be protective)
inadequate sleep

Always check with your doctor before changing your medications. I have an auto-immune disease and take daily anti-inflammatories, but my doctor has advised me to continue taking these unless I experience COVID symptoms. Make sure your doctor is aware if you have any of the above conditions.

Symptoms: Many people who have SARS-2 experience no symptoms, or experience mild flu symptoms.  If you have ANY cold or flu symptoms, contact your doctor and see if you can be tested.  If you live in San Diego County, and your doctor cannot offer you a test, call 2-1-1 to get a free test from SD County Public Health.  If you have additional symptoms like shortness of breath (you just can’t seem to get enough air), loss of smell or taste, nausea or diarrhea, contact your health care provider or an urgent care immediately.

In severe cases, the virus can do wide spread and permanent damage to multiple organ systems.  Early treatment is necessary to prevent the most severe symptoms.

Precautions:  While lockdowns may have been effective in the US during the early stages of the pandemic, especially at a time when masks were hard to come by, recent evidence suggests that lockdowns provide only a moderate benefit over other means of control.  Here’s what appears to be beneficial:

Masks: Masks are not all the same and some are better than others.  Their main benefit is that they stop, reduce, or slow the travel of virus from infected people.  This prevents surrounding people from infection or lowers the viral load of exposure.  N95, KN95, and KF94 respirators are effective at filtering close to 95% of virus.  A good mask is well fitting and filters the air moving in an out of your mouth and nose.  The commonly used surgical masks and other loosely fitting masks do not filter air and I don’t recommend using them.

Social Distancing: Aerosolized virus can travel through the air. Staying 6 ft away from others helps prevent infection. Social distancing may be more important for droplet transmission, like the flu, than for aerosol transmission in which microdroplets can stay suspended for much longer and travel much further.

Handwashing:

Adequate sleep: Sleep is very important for a wide variety of body functions, including the immune system.  Get 7 – 8 hours of sleep per night.  A 26 minute power nap during the day is also beneficial if needed.

Vitamin D: Several studies have suggested that patients with the most severe cases of COVID also have the lowest levels of Vitamin D.  Because of our often indoor lifestyle, most Americans are Vitamin D deficient to some degree.  The best way of getting some Vitamin D is to make it yourself by going outside in shorts and a T-shirt for 30 minutes a day.  This is because Vitamin D is manufactured in our skin in response to sunlight.  If it’s not practical for you to do this, consider a Vitamin D supplement.  Darker skinned people are more likely to be Vitamin D deficient in the US. Supplementing Vitamin C and Zinc is also recommended.

Home isolation: If you have cold or flu symptoms, contact your doctor immediately and see if you can get a test.  Tests are much more available that early in the pandemic, and you should be able to get a test by request.  Also, if at all possible, isolate yourself from the rest of your family until you can be tested as negative.  Many new infections are taking place among family members.

I’ve been traveling all over the country, and have been in dozens of airports, gas stations, and stores.  I get tested regularly and have always been negative.  Here are the precautions I use:

1) Wear a mask or face covering indoors in public.  Now that vaccines are available, I no longer avoid unmasked people indoors, but as an unvaccinated person, I still wear mine.
2) Keep 6 ft away from others. (I basically ignore this one if other precautions are in place, especially on an airplane!)
3) Avoid indoor gatherings, especially ones in which singing or shouting is likely. This is now voluntary now that we have vaccines, as an unvaccinated person, I still follow this rule.
4) Outdoor gatherings are fine, even without masks, if everyone maintains a distance. I have hosted several outdoor gatherings.
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.
6) Wear an N95 or KN95 mask when going to more high risk areas like airports or public areas where people may gather. These masks are rated to filter out 95% of viral particles. In my opinion, surgical masks and especially neck gators are nearly worthless in these settings.
7) I never take my mask off on the plane, and find an isolate spot in the airport to eat or drink on layovers.

Vaccinated people can relax many of these rules!  Vaccines are 90-95% effective, so you still have a small chance of infection.

Testing: There are several kinds of tests, and they tell you different things.

PCR: These tests use material collected from the nose and need to go to a specialized laboratory for processing.  They are very sensitive and specific, and indicate whether the patient is currently infected. This is the most common kind of test. They can take longer to process because they need specialized equipment that most small labs don’t have, so most of the wait time is just for shipping to a specialized facility.

Antibody:  These tests detected antibody from a patient’s blood to see if the patient has been infected for at least a few days.  IgG tests may also tell if a patient was infected weeks or months previous, but are no longer infected.  Some patients do not mount an immune response that will provide long term antibody. These tests are cheap and fast, but are more prone to false positives and false negatives than PCR tests.

Antigen: These tests use a very similar technology to Antibody tests, but instead of detecting a patients antibodies against virus, they use antibodies to detect viral proteins in a sample. An “antigen” in immunology lingo is just a protein that can induce an immune response. So in this context, an “antigen” is a SARS-2 protein that can be bound by an antibody. Like PCR tests, these tests detect an active infection, because they detect viral proteins currently in the body.

Isothermal amplification:  The Abbott ID Now COVID tests uses this relatively new technology.  These tests are similar to PCR but more prone to false negatives. 

If you have cold or flu symptoms, contact your doctor immediately and see if you can get a test.  Testing is much more available than it was early in the pandemic.  San Diego County is encouraging anyone who wants a test to be tested.

Antibody Dependent Enhancement:  I’ve written about this a lot and I won’t describe it in depth here.  In short, this pathway allows some viruses to create more severe disease on the 2nd time infecting a person than the first.  It is theoretically possible, perhaps even likely with SARS viruses, which is why I have been careful to avoid infection and why I’m not going to get the vaccine unless perhaps my work requires it.

Treatments:  Treatment for COVID is complicated and not all patients can be treated in the same way.  Additionally, treatments are evolving rapidly, and your doctor many not treat you in the ways listed below.

Supportive care: Most treatment is supportive care, treating symptoms while the patient recovers naturally.  Anti-inflammatory medications are often used to prevent the immune system from over-reacting to the virus.

Ventilators/nasal cannula:  While widely used early on, some doctors now state that ventilators carry risks that may be unacceptable for COVID patients.  Many doctors now favor oxygen therapy using a nasal cannula, using ventilators only as a last resort breathing if labored. 

Remdesivir: This antiviral was used widely for much of the pandemic, but many sources now claim it has limited effectiveness.

Dexamethasone: Steroid used to treat patients with low oxygen levels.

Hydroxychloroquine, Azithromycin, Zinc: Several doctors from several countries have reported success with this combination.  Studies on the effects of these drugs have as yet still been non-conclusive.  Some positive studies suggest that Zinc is the main virus fighter of the treatment, with Hydroxychloroquine allowing better penetration of Zinc into cells.  Unfortunately, the debate on the efficacy of this regimen has taken on a strongly political tone, which almost always interferes with the scientific process.  Now pundits, as well as scientists, weigh in on this regimen.  Treatment with Ivermectin is likely more beneficial in a wider range of disease state than HCQ.

Ivermectin: A anti-parasitic medication used since 1981, Ivermectin has reportedly been used by doctors around the world, notably India and Mexico, to reduce COVID fatalities.  Reports claim that Ivermectin is beneficial in a wide range of disease state, from pre-disease prevention to late stage disease.  Like Hydroxycholoroquine, promising data was often labeled “misinformation” by outlets in Western countries, and western doctors were strongly discouraged from prescribing it.  Thus, experimentation with Ivermectin was hindered and the drug’s potential is still unknown. 

Vaccines: Each spring, scientists learn which flu is likely to be prominent by the following Fall.  They make some guesses and create a vaccine for the flu season.  The manufacture process takes a few months. But it’s only this short because they already know how to make a flu vaccine.  Development of a brand new type of vaccine takes between 4 and 30 years!  There are many methods to make a vaccine, and scientists must try many of them before finding one that works.  Then they must try the vaccine on patients and make sure they are relatively safe.  Every vaccine carries some risk of side effects.

Several vaccines against SARS-2 were finally released to the public in December of 2020.  The vaccines released to the public are in 2 types:

Attenuated vaccine: This type has been commonly used for decades for a variety of viruses. The technique makes a severely weakened form of the virus that still makes viral proteins that provoke an immune response.  With this type of vaccine, the patient is infected by a weak form of the virus that they quickly recover from, usually with no symptoms other than occasionally the flu like symptoms that are your body’s natural response to invasion.

mRNA vaccine: This is a brand new technology that has been worked on for years.  The SARS-2 vaccines are the first ones that have been introduced to the public using this technology.  The vaccine includes a piece of mRNA inside a lipid bilayer that mimics the cell wall.  The mRNA is inserted into the cell where it is translated into a copy of the viral Spike protein.  These vaccines are 90-95% effective against infection, and even those infected have less severe symptoms.  However, they are not 100% effective, so some infections of vaccinated individuals has occurred.

As has often happened, the vaccines have generated significant controversy.  As you know, I have been careful to avoid being infected and also getting the vaccine because of the potential of ADE.  My concern with the vaccine actually has nothing to do with the new mRNA technology, I actually have no reservations about the mRNA vaccines.  From an ADE perspective both the attenuated vaccines (Johnson & Johnson) and the mRNA vaccines (Pfizer and Moderna) produce Spike protein that may trigger an ADE response should a new strain of SARS virus appear, not a variant, a new SARS strain, like a “SARS-3”.

When the vaccines were released, rumors of side effects, sometimes severe, arose immediately.  For some time, I minimized these as a risk of any vaccine.  All vaccines carry the risk of side effects and even death.  However, a video podcast featuring Robert Malone, the inventor of mRNA vaccine technology, convinced me that the Spike protein itself has toxic properties of its own, separate from the vaccine technology used. This is because the Spike protein can bind to cells all over the body and may have wide ranging effects.

Despite ADE and issues with side effects, I actually still believe some will benefit from the vaccine.  These include the following groups:

Anyone over 60
Anyone with 1 or more risk factors:

obesity
certain auto-immune diseases
use of NSAID medications
heart, lung or kidney condition
immunocompromised patients (HIV, cancer and transplant patients)
respiratory condition such as asthma or COPD.

Frequently working with the public
Musicians who sing in indoor settings
Medical personnel

Again, I am not a physician, so check with your healthcare provider while making decisions about getting the vaccine or changing your medication.

If you’ve had the vaccine or had COVID and are concerned about ADE, remember that it will only become a factor if a significantly new strain arises (“SARS-3”). If this happens, then the procedure for you would be to be very careful initially, then get the “SARS-3” vaccine as soon as possible. The new vaccine will protect you from the new virus. In the future, vaccines against Coronaviruses will be produced even more quickly than this time.

The vaccines have pros and cons.  I’m in support of vaccines for some but not necessarily for others.  Each person needs to weigh the risks for themselves.  I am not for companies or government agencies coercing individuals to get the vaccine.

Herd Immunity:  The idea of herd immunity was popularized in pre-pandemic discussions on vaccines, promoting the idea that the more people are vaccinated, the more protection for those who can’t be.  The idea is useful, but in my opinion, efforts to push people into getting vaccinated to achieve herd immunity are misplaced. Before a vaccine is available, the only way to reach herd immunity is to expose large numbers of people to the virus, which is counter productive.  Now that the vaccine is available, those who are concerned should just get the vaccine themselves and not harangue others about getting it.  Gentle persuasion may be convincing, but haranguing rarely is. Given even the pre-pandemic resistance to vaccines, a forceful effort to vaccinate is likely to back-fire.

Variants:  During the course of the pandemic, several variants have arisen that have a slightly different Spike protein sequence from the original Wuhan strain.  Confusingly, naming conventions have changed several times, making it difficult to keep them all straight.  As a general rule, the variants have all been more infectious than the Wuhan strain, but have not been more pathogenic.  Fortunately, the vaccines have been effective against all of the variants, although are not as effective against some variants.

The Delta Variant: The UK/Alpha variant caused waves of new infections in some countries and was more infectious than the original Wuhan strain.  In late 2020, a new variant arose in India, the India/Delta variant.  This variant was significantly more infectious than other strains and has caused huge peaks in cases in several countries.  As of this writing, several countries are still experiencing waves of new cases most likely due to the Delta Variant, including the United States.

While the Delta Variant has caused large numbers of new cases and an increase in hospitalizations, data suggests it may be less pathogenic than the Wuhan or UK variants.

Current Status: In late Spring, at least in the US, life began to get back to normal, with approximately 50% of the US population vaccinated, much lower new case numbers, and reduced restrictions. Currently however (July 21, 2021) a wave of infections, likely caused by the Delta variant, is causing concern and some calls for new restrictions.  Several other countries scattered across the globe are also currently experiencing peaks in cases.

Graph is by me, from data collected from Johns Hopkins University COVID site. Graph is presented in a linear format and includes only the Fall/Winter 2020, Spring ’21, and Delta Variant peaks.
Endcoronavirus County Level Map, July 20th, 2021
Daily new confirmed cases in India, from data collected from Johns Hopkins University COVID site. The Delta Variant peak is the large one on the right. Notice the sharp upward and downward trends. The new persistent daily case numbers are higher than before the Delta peak began.

The Future: Since vaccination started in the US, there have been many fewer new cases.  This has led many to basically go back to behaving normally.  The Delta Variant is rightly causing concern, but I’m still hopeful that the current peak in new cases will be short lived. In other countries with Delta related waves, the peak has been very sharp, with quickly increasing, then quickly decreasing case numbers. However, I’ve started to be a little more cautious in public again, while we wait for the increase in cases to slow.

Several other countries are still experiencing an elevated case load.  The pandemic won’t be truly over until cases are low in all countries.  I’m hopeful that this will happen this year, but it’s certainly too early to know for sure.  So far, all new variants have been susceptible to the vaccines and natural immunity.  There is a small chance however, that we may see new versions that are not.  If this happens, SARS may become endemic, circulating seasonally like the flu does.  So far, I don’t see evidence that this will happen.

In the future, we may have a “SARS-3” a new virus from the SARS family that will be similar, but different enough to trigger the ADE pathway.  If this happens, those of you that have had COVID or been vaccinated should be very careful to avoid infection initially, then get the “SARS-3” vaccine as soon as it is available.

In a future post, I’ll give my recommendations for what should be done differently if a new pandemic should arise.

Don’t fear, but be smart,
Erik

Case Update: July 20th, 2021

This is a case update. We continue to see cases going up significantly in the US, California, and San Diego County. Frankly at this point, cases are going up further than I expected, although they still are not as high as our most recent small peak in April. These new cases are likely due to the more infectious Delta Variant. According to endcoronavirus, new cases are concentrated in the West, Midwest and South of the US.

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 presented in a linear format and includes only the Fall/Winter 2020, Spring 21, and Delta Variant peaks.
Endcoronavirus County Level Map, July 20th, 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 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 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.
Graph is by me, from data collected from Johns Hopkins University COVID site.

In the past I’ve seen that Sunday numbers are most consistent week to week and usually are an indicator of what we will see in the following week. This past Sunday, case numbers were significantly higher in the US than the previous week, although I might be optimistic and say that we may already reached the new peak in California. San Diego did not report Sunday numbers last week, so I can’t say what the current trend is for San Diego.

Happily, we have not seen a corresponding increase in deaths. A slow yet consistent downward trend in deaths in the US has apparently not been effected at all by the Delta Variant, but did rise a little in California.

A new study preprint by Bernal et al suggests that the Pfizer vaccine is 88% effective against the Delta Variant as opposed to 93% for the Alpha/UK Variant. The vaccines provide good protection when compared to others, but are not completely protective.

Don’t fear, but be smart!
Erik

Case Update, July 14th, 2021

This is a case update. We’ve been seeing a definite trend upward in cases in the past week for the US, California, and San Diego County. It’s not a huge number of new cases, but there is definitely an upward trend.

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 presented in a linear format and includes only the Fall/Winter 2020, Spring 21, and Delta Variant peaks.

In the graphs today, I’m showing a logarithmic graph for the US since the beginning of the pandemic, and a linear graph for cases since the start of the Fall peak last October. Logarithmic graphs are useful since they emphasize small numbers and are more useful when numbers become low, but they do make small numbers look deceptively high. So I’m showing both today so you can get a more full picture of the Delta Variant peak that we’re seeing right now. It’s significant, but not huge.

According to endcoronavirus, regions in the West and Midwest of the US are particularly impacted right now, with Arkansas, Louisiana, Nevada and Colorado perhaps being the most hard hit. Remember that in the endcoronavirus map, a red county means that cases are increasing, but total cases may still be low. For the Montanans reading this, new case numbers are still quite low in Montana, except for small rises in a few places, like Billings, Bozeman, and Missoula.

Endcoronavirus County Level Map, July 14th, 2021

Deaths are not increasing in the US yet, but are increasing in California.

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 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 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 presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.

Worldwide, numbers are far below the most recent India Variant peak, but are increasing in some areas scattered across the globe, like Russia, Cuba, Senegal, and Burma. The Delta/India Variant peak is over for many countries including India.

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

Don’t fear, but be smart,
Erik

Case Update: July 8th, 2021

This is a case update. Reporting has become erratic in the last few weeks. San Diego County in particular only reports new numbers on Wednesdays now, so we are no longer getting daily new numbers. Also, Johns Hopkins is no longer reporting Recovered Cases, so I can no longer give Active Cases. These disclaimers aside, there has been an increase in cases in the last few weeks. This is almost certainly because of the more infectious Delta/India variant.

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 presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.
Endcoronavirus County Level Map, July 7th, 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 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. Numbers are now reported only weekly. While total numbers are accurate, daily numbers are extrapolated from weekly reported numbers.
San Diego County COVID-19 Variant Case Summary, July 8, 2021.

I predicted last week that we wouldn’t see a major new spike in cases, and that’s arguably still true, but we are seeing increases in numbers. New cases are currently almost double what they were at this time last week for the US, California, and San Diego County. We’ll have to see how this progresses. I continue to believe at this point that we won’t see a major new peak, but what “major” means is still subjective.

In San Diego County, 79% of eligible residents have received at least 1 dose of vaccine and 68% are fully vaccinated. This represents 105 and 90% respectively of the Counties goal of 75% of the population.

Worldwide, new cases are a little higher than a few weeks ago. Countries with current outbreaks are scattered across the globe, with examples being Russia, South Africa, Indonesia, Tunisia, Cuba, and Columbia.

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.

Don’t fear, but be smart,
Erik