Category Archives: San Diego

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 8th, 2021

This is a COVID case update. New case numbers for the US, California, and San Diego County continue to steadily drop. In particular, San Diego County has seen fewer than 100 cases in a single day reported 15 times in the last 2 weeks. Also, California has had several days with less than 1,000 cases, and the US has had several days with less than 10,000 cases.

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, June 8, 2021
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 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 presented in a logarithmic format to emphasize small numbers. Note that each number on the left is 10x higher than the one below it.
San Diego County Media Briefing, June 8th, 2021

Things feel like they’re getting back to normal all over. As I’ve mentioned before, I still haven’t been vaccinated, and am often the only weirdo wearing a mask in an indoor environment. It doesn’t bother me. I know at least 60% of the people I encounter have been vaccinated, and I’m also used to being a weirdo.

Internationally, case numbers are down, but not everywhere. Cases in India are coming down, but cases in Brazil are persistent. There are still countries in Southeast Asia that have very high new case numbers.

Graph is by me, from data collected from Johns Hopkins University COVID site.
New Cases from India, from Johns Hopkins University COVID site.
New Cases from Brazil, from Johns Hopkins University COVID site.

I will probably have another post later today or tomorrow regarding the Lab Leak hypothesis and all the stuff swirling around that issue right now.

Don’t fear, but be smart!
Erik

Case Update: May 7th, 2021

This is a late COVID update! I’ll also offer a correction on my April 20th post regarding vaccination numbers in San Diego County.

New case numbers continue to trend downward in the US, California and San Diego County. A few hot-spots persist in the Northwest, Colorado, and parts of the Rust Belt, but the situation in Michigan is improving.

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

I was overly optimistic in my April 20th report of vaccination in San Diego County, because I didn’t read the fine print! On their press briefing slide deck, they report the percentage of people with either 1 or both doses of vaccine. As it turns out, however, this is not of the total County population, but only of their target of 75% of residents over 16! Yesterday, they reported that 83.9% of the target population has received 1 dose, and 59.2% has been fully vaccinated. This actually corresponds to roughly 50% and 35% respectively of the estimated 3.3 million SD County residents.

San Diego County Media Briefing, May 6, 2021

All SD County residents over 16 can now get the vaccine if they so choose. My guess is that in the next few weeks, more restrictions will continue to drop. California has stated a goal to fully reopen on June 15th.

Don’t fear, but be smart!
Erik

Case Update: April 20th, 2021, Vaccination in SD County, Herd Immunity

This is a case update. I’ll also discuss vaccination in San Diego County and herd immunity in general.

New cases may have plateaued in the US, but new outbreaks are apparent in some states. Michigan was the standout state for new cases, but endcoronavirus now suggests outbreaks across the Rust Belt, Northeast, Northwest, Colorado, and Florida. In most counties, actual numbers are small, but are obviously much larger in urban areas. If we are in a 4th wave, it appears to be much smaller than Wave 3, probably impacted by increased vaccination.

Graph is by me, from data collected from Johns Hopkins University COVID site.
Endcoronavirus County Level Map, April 19th, 2021
Endcoronavirus State Level Map, April 19th, 2021

New case loads remain low in California and San Diego, likely at least partially because cases were so high during Wave 3 in the Fall and Winter.

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

Internationally, new cases are very high worldwide. The new high cases numbers are likely impacted by the new variants such as B.1.1.7 (the UK variant) which is more infectious than the original Wuhan strain, and now dominates in many countries. Brazil and India are particularly hard hit. Canada’s current wave is as high as their Winter wave, but the numbers there are in general much lower than for the US.

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

Vaccination in San Diego County: According to the County, about 37% of County residents are now fully vaccinated, with 60% having had at least 1 dose. Vaccination is now available to anyone 16 and up who wants to be vaccinated. If you want to be vaccinated, you can find a location on their website.

San Diego County Media Briefing, April 14, 2021

Herd Immunity: First, just a reminder that I am not an epidemiologist. Early in the pandemic, many recommended herd immunity as a way out of the pandemic. At the time, I argued that exposing a lot of people to a disease to protect people from a disease was counter productive. Now that we have a vaccine, herd immunity is a viable option for moving forward. For a population, herd immunity can be effective, although the percentage of people who need to have immunity to reach this is dependent on the disease and usually surprisingly high. On an individual basis, if you’re concerned about catching the virus, it’s far better to just get vaccinated at this point than to worry about if we’ve reached herd immunity.

Don’t fear, but be smart,
Erik

Case Update: August 23rd, 2020; New study on transmission from masks.

Friends,
Sorry for the long wait for a new update, I’ve been helping put together a new COVID lab, and I’ve been working long days for the past week. Today, I’ll give the update, then talk about a new study concerning masks.

Update: New confirmed cases continue to go down for the US, California and San Diego County.  For California, the numbers are kind of flat.  The reporting system in California was broken for much of last week, but the state says it’s working again.  Death rates are coming down from their second peak.  Comparing the new daily case numbers and the new death numbers make it clear that the virus has become much more survivable than it was in March and April.

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.
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. Some data points of “Active Confirmed Cases” are from SD County, others are calculated.
From Rt Live.

New study on droplet transmission from various masks: A study was pre-published a few weeks ago that studied droplet transmission from various popular masks (Fischer EP, et al., Low-cost measurement of facemask efficacy for filtering expelled droplets during speech, Science Advances, pre-released August 7, 2020).  The study used a system in which a speaker wearing a mask would say a prescribed phrase several times into a box through which a laser was shining.  A camera would then capture droplets that were illuminated by the laser. The study used a relative scale for mapping mask benefit, with the N95 getting a relative score of 0, and no mask at all getting a score of 1.  See the results in the photos.

Fischer EP, et al., Low-cost measurement of facemask efficacy for filtering expelled droplets during speech, Science Advances, pre-released August 7, 2020
Fischer EP, et al., Low-cost measurement of facemask efficacy for filtering expelled droplets during speech, Science Advances, pre-released August 7, 2020

Surgical masks did the second best after the N-95, and a 2 ply cotton mask with a sheet of polypropylene (like blue Shop Towel) fabric did third.  I’m particularly happy to see the cotton and poly mask do so well, because that’s what I use!  Performing poorly are knitted masks, bandanas, and especially the neck gaiter, which actually did worse than nothing! The authors speculate that this is because the fleece material may break up larger droplets into smaller ones instead of stopping them.

Shout out to my sister-law Penny who has made hundreds of masks in her home.  The 2 ply cotton masks she makes have a pocket for inserting a filter or piece of poly like I use, and these masks did very well in this study! For extra credit, say the phrase “masks she makes” ten times fast.

I have never been a fan of the surgical mask because of the large side spaces that allow air to pass easily into and out of the mask from the side.  I was surprised to see these masks do so well in this study.  The answer may be in the experimental design, which captured droplets coming from the front of the mask, but excluded ones from the side. I would like to see a study that captures that too!  This just shows that experimental design matters, and just because a study shows something, doesn’t mean the study was designed to detect all relevant things!

Mask wearing has become controversial, but the data supports the idea that masks reduce viral transmission, and that lower viral load on exposure leads to better medical outcomes!

Don’t fear, but be smart,
Erik

Case Update: August 11th, 2020

Here’s the weekly update.  The US, California, and San Diego County continue to improve.  New confirmed cases continue to drop.  I have to qualify this however, since California had a problem with their cases reporting system for much of last week.  It’s back working normally, but cases may still be erratic in number for the next few days.  This may impact the San Diego numbers as well. 

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 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. “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.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Some data points of “Active Confirmed Cases” are from SD County, others are calculated.

Death rates are climbing to some degree, but this was expected to lag behind the large spike in cases we had in June and July.

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.

According to Rt Live, more than half the states in the US now have an Rt of below 1.0 again.  This suggests that those states are on the downslope of the last peak, and virus is slowly going away in those states.  This is great news.

From Rt Live.

I spoke to testing professional this week who said that viral load, the number of viruses in a patient’s test sample, started coming down in April, when mask wearing became common place.  This supports my claim that even if a person gets exposed to the virus, they receive less virus if they’re wearing a mask. This may also be why the virus has been more survivable in the past few months.

Keep up the good work, and stay positive!
Erik

Case Update: August 4th, 2020, KN95 masks, D614G mutation, where do outbreaks happen?

I have a grab bag of things to discuss today, starting with the weekly update, a note about the new KN95s, a new version of the Coronavirus (D614G), and where outbreaks are located, at least in San Diego County.

The positive trend continues! Cases are dropping in the US and San Diego, and are flat in California, which is actually better than it sounds, since the state has been steadily increasing in cases since mid-April.  Active cases continue to decline in San Diego. Even in Los Angeles County, the epicenter of new cases in the entire country for the last few months, new daily confirmed cases are finally coming down.

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 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. “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.
Graph is by me, from data collected from San Diego County Public Health. See also regularly updated slides from SD County. Some data points of “Active Confirmed Cases” are from SD County, others are calculated.
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.
From Rt Live.

KN95 masks: I’ve started to see a new kind of mask being worn, the KN95.  They are rated to filter out 95% of virus particles, but are made and certified in China and carry the European CE mark. The FDA has allowed their use in the US as an emergency measure.  They fit a little less snugly than an N95. Perhaps their greatest benefit is that they’re available.  If you’re still using a surgical mask consider upgrading to the KN95, which will be an improvement! 

A KN95 mask.

New strain D614G: A new strain appeared in the US and worldwide probably in May or June.  Called D614G, it carries a mutation at the 614th position of the Spike protein.  This mutation makes the virus more infectious by 4-5 times, and may have contributed to wave Ib of the virus that we saw in June and July.  Dr. Deborah Birx, White House Coronavirus Response Coordinator, has speculated that this mutation may be why we saw more widespread virus outside urban areas during the last jump in cases.

Coronaviruses are RNA viruses.  Enzymes that replicate RNA tend to be very error prone which is why RNA viruses change so rapidly.  This is true for Coronaviruses as well as for the flu and for HIV.  We can continue to expect more naturally occurring mutations in the future.  The good news is, over the course of years, viruses generally become less virulent and more mild.

The location of outbreaks in San Diego County: San Diego Public Health has published a graph on the locations of outbreaks as part of their regular slide package.  Out of 134 the top most common places for outbreaks are restaurants with a bar (40), businesses (27), the healthcare environment (15), and residences (9), further down the list, faith based organizations and government offices are tied at 5. As a business traveler myself, I’m happy to see that hotels are only at 3. Restaurants without a bar only had 5 events.

From San Diego Public Health.

Another graph shows some of these outbreaks during June and July.  You’ll notice that July had about twice as many events.

From San Diego Public Health.

Things are starting to get better!  But remember that an epidemic is like a wildfire, getting containment doesn’t mean it’s over!  We need to remain diligent in order to put it down for good. Keep up your efforts!

Don’t fear, but be smart,
Erik

Case Update: July 28th, 2020

Some more good news this week.  The United States has unambiguously reached the peak of wave 1b, and daily new confirmed cases are slowly going down.  Daily deaths have risen slightly, trailing the higher new cases by a few weeks, but are still relatively low.  

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 situation is much the same in California and San Diego, with new daily cases coming down and daily deaths rising slightly.  Active cases are probably starting to go down as well.

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.
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. Some data points of “Active Confirmed Cases” are from SD County, others are calculated.

Testing continues to rise and it is having some impact on the increasing confirmed numbers.  The higher testing is definitely a positive thing and will help us get a more accurate picture of what’s going on.

Don’t fear, but be smart,
Erik

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: July 7th, 2020; Antibody Dependent Enhancement

Dear Friends,
This is a case update. I’ll also have an important message about antibody dependent enhancement.

Cases continued to rise unchecked in the US, California and San Diego County in the last week, although the long holiday weekend did have impacts on reporting. Some good news is that the number of deaths reported in the US has been slowly declining despite the case increase. Keep in mind however, that deaths will lag behind cases by as much as 2 weeks, so we may yet see an impact from the higher caseload. The number of deaths have been trending flat in California.

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 San Diego County Public Health. See also regularly updated slides from SD County.
From Rt Live

Rt Live is reporting that all but 8 US states or territories have Rt values above 1.0, meaning that the virus is expanding in those states.

I’m going to bring up an issue that I’ve been avoiding talking about for some time. I’ve been avoiding talking about it because it’s not a certainty, and also because the possibility will be scary for some. The reason I feel compelled to talk about it now is that many are having a hard time understanding why I am still so concerned about the virus when the fatality rate is low and dropping, and folks want to get back to normal life. I’m even hearing about young people having COVID parties in which people gather with a sick individual so they can all get infected and be immune from the virus thereafter.

Before I share this, I’ll also say that the medical community is doing a better job treating patients with COVID, and the disease is becoming more survivable. In addition, we now know a lot about how the virus is spread, and if a person wants to remain uninfected, they can do that, while still getting together with friends and family, and still working and getting on with life. You can be reasonably certain you will not get infected if you do the following:

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.

Antibody Dependent Enhancement: Several years ago, scientists were developing a vaccine against Dengue Fever, a mosquito borne disease which causes debilitating joint pain in patients. Some time after trial vaccination, several vaccinated patients died suddenly of Dengue Fever. This became the most studied example of Antibody Dependent Enhancement (ADE). Normally, for the annual flu let’s say, a person gets infected by the flu, is sick for a few days, and the immune system develops a response by creating antibodies against that specific strain of the flu. If they are exposed again in a month, nothing will happen. If the patient is exposed to a different strain the following year, they may still get sick, but the antibodies they developed the year before may help them have less severe disease and recover more quickly. Part of the immune response is that some immune cells display antibodies on their surface to capture new invaders.

With Dengue and some other viruses, the first stages are normal. A person gets infected and develops a response. If they get re-infected a month later, nothing happens. But if they get infected with a slightly different strain months or years later, instead of being protected, the virus attaches to antibodies displayed on immune cells and uses the antibodies as a site of entry into the immune system. The immune system is quickly infected, and the patient has a more severe disease with the second infection. Some estimates are that disease may be 3-4 x more severe in these patients.

As it turns out, SARS-1, which arose in 2002, and MERS, which has small outbreaks every year, are both Coronaviruses and both appear to be able to use the ADE pathway. This raises the possibility that SARS-2, the current virus, can also use the ADE pathway. This means that a person infected for a second time with a different strain of SARS-2, or any other Coronavirus for that matter, may be at much higher risk for severe disease.

This is why I’m not in favor of pursuing herd immunity as a pathway out of this crisis, because it will prime people for ADE related problems if a similar strain should strike next year.

This is not a new idea. If you search for “ADE” or “Antibody Dependent Enhancement”, you will see many articles, some peer reviewed from respected journals, on the phenomena. Dr. Fauci has even referenced it using the term “enhancement” when talking about vaccine development.

Why haven’t the government public health departments been more open about this? They tend to make statements only based on what they can be reasonably certain of, which is why they have been so slow to react to many aspects of the current crisis.

Again, it’s not certain that ADE will play a role next year. It’s too early to know. I’m informing you of the possibility so you can make wise decisions for you and your family.

More than ever, don’t fear, but be smart,
Erik


A selection of relevant papers:

ADE and it’s potential impact for SARS-2:



ADE in SARS-1:



Overlapping symptoms for SARS, MERS, and SARS-2:



Is COVID-19 receiving ADE from other coronaviruses?



Possible mechanism for ADE: