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Antibody Dependent Enhancement

Note, March 26th, 2022: The first part of this post was written on July 7th, 2020. Since that time, there has been evidence that appears contradictory in the ADE story. Reading the entire post will help you understand how ADE and COVID are related, but it is a complex and evolving issue, so things may still change.

Originally posted July 7th, 2020

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.

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Update: November 20, 2020

Since writing the above post, things have changed a little. There have been a handful of known cases of people being re-infected with SARS-2. In some of these patients, symptoms were worse, while in others, symptoms were less severe. In all of the well characterized cases, the 1st and 2nd strains that infected them were different, suggesting that it’s not a re-infection by the same strain, but a new infection by a different strain.

We’ve had at least 2 main strains in the US, SARS-2 which arrived in January or February, and a strain called D614G which probably arrived in April or May and likely caused the 2nd wave in June and July. The D614G strain is likely more infectious than the original SARS-2 strain, but is perhaps less virulent, since the fatality rate during the second wave appears to have been lower. In fact, there may have been several strains circulating around the world and the US for much of the pandemic.

How does this all relate to ADE? The fear with ADE is that a 2nd infection will cause worse symptoms than with the first infection. This may still be true. But we’ve had several circulating strains and so far, no real evidence the re-infections have universally been worse. So it appears for now that the ADE experiment is already going on, and that perhaps the phenomena will not have as great an impact as I feared. I am currently cautiously optimistic that ADE will not cause significant additional mortality.

This also has some impact on the vaccine discussion that is currently ongoing. If ADE will not have a significant impact, than the vaccine may be safer that I previously thought, and I have become cautiously optimistic about the success of the vaccine.

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Update: December 12th, 2020

More on ADE and Vaccines: Some potential very good news for me on the vaccine front. For months I’ve been warning about ADE, the phenomena that some viruses can be even more dangerous in a second infection than the first. Karen Parrott, a former colleague at Quest Diagnostics, often provides me with interesting COVID related stuff. This week she sent me a podcast featuring Paul Offit, the developer of the first Rotavirus vaccine and an author of many books on immunology and vaccine production. I am not an immunologist but he is. More importantly, he’s the first authoritative person that I’ve heard in the media speak at length on the ADE issue and how it relates to COVID. He claims in the attached clip (time stamped at 14:40) that the current vaccines do not appear to trigger the ADE pathway in animal models, and human trial subjects never displayed the signs that ADE was involved in secondary exposures. This difference from SARS-1 and MERS may be related to the fact the SARS-2 is much less virulent than these other 2 viruses.

This makes me more optimistic that the vaccine will be safe from an ADE perspective. I won’t be able to get the vaccine for some time, but I am more willing to get it now than ever before. Several physicians I know are eager to get it as soon as it is available. This is great news!

In the interest of full disclosure, I will point out the some patients receiving the vaccine the UK have experienced some injection site irritation, especially in those with allergies. This is actually somewhat normal for vaccines, and appears to pass within a few days.

Now that mRNA vaccines have been produced for the first time, future development of this new kind of vaccine should be even faster than this time!

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Update: April 13th 2021

ADE and the next SARS virus: I wanted to explain a little more about my continued concerns about ADE. As the pandemic progresses and we have numerous variants circulating around the world and the US, ADE does not appear to have had an impact on the current situation. This is certainly good news. If it did have an impact, we would be seeing additional deaths from the new variants, which we do not.

My continued concern comes because ADE impacts our ability to fight the NEXT virus. SARS viruses (SARS, MERS, SARS-2) have the ability to easily infect the immune systems of those previously infected with closely related but different strain of the virus. If a future strain of SARS comes out, let’s call it SARS-3 for now, ADE may become a big deal. I stress that this is only theoretical at this point. SARS was moderately infectious, but also very pathogenic, giving all known patients severe symptoms and killing 10%. It was actually less dangerous globally, since outbreaks tended to be detected early and quickly snuffed out. SARS-2 is highly infectious, but much less pathogenic. It’s greater global impact came from it’s very high infectiousness and very long incubation time, being passed even from pre-symptomatic patients. The tendency of all viruses is to become more infectious and less pathogenic over time, a pattern followed by SARS and SARS-2. If we have a SARS-3 someday, it will likely be even more infectious than SARS-2, but less pathogenic. On the other hand, MERS is more pathogenic than SARS, so this pattern doesn’t always follow. The next time another SARS coronavirus breaks out, we will need to be very careful initially until we understand the parameters of the new virus.

So what do you do if you had COVID or had a COVID vaccine if a SARS-3 comes out? If that happens, vaccine production will likely be much faster than this time. Be very careful with the virus initially, and get the new vaccine as soon as it is available to you, because you may be at greater risk for severe symptoms. I know some of this is confusing and counter-intuitive! Feel free to ask questions below!

Update: August 30th, 2021

Delta already using the ADE pathway? A doctor friend of mine sent me a pre-print paper from a lab in Japan. Please note, this is a pre-print paper and has not yet finished peer review! The paper describes experiments using antibodies derived from patients infected with the Wuhan strain, as well as with the Delta Variant. They then studied binding of these antibodies to artificial viruses. The paper argues that Delta variant viruses are less neutralized by vaccines against “wild-type” or Wuhan strain vaccines. While the “wild-type” antibodies against Wuhan can neutralize a region of the Delta Spike protein called the Receptor Binding Domain (RBD) (Figure 1C), other antibodies binding to another region of Delta Spike protein actually enhance infectivity. Figure 1D from the paper shows negative levels of “neutralization” for antibodies that bind the N-terminal domain of the Spike protein. The paper calls this “enhanced”. Yes, this is the ADE I’ve been talking about.

Figure 1 from Liu et al 2021.

They suggest that with rapid changes in COVID variants, a new version of Delta is going to be able to use the ADE pathway in the near future, when Wuhan era antibodies will no longer be able to neutralize a mutated Delta strain.

To sum that all up in simpler language, it basically says that Delta is more infectious because it is partially using the ADE method of infection. Future versions may be less prone to be neutralized by Wuhan antibodies, making them fully enhanced. If this happens, we may have more severe disease in those who get infected with this new enhanced Delta.

They conclude by saying a booster against the Wuhan strain will not be effective in improving protection from Delta, and that a new vaccine against Delta will be required.

The material in the paper may help to explain why we have been seeing lowering levels of vaccine effectiveness in some countries.

Just to be very clear, they are not saying that this new enhanced Delta exists now, just that it may exist in the future.

I will pay close attention to this issue. If you have already been vaccinated or had COVID, a new Delta vaccine will be your best defense against possible ADE arising from a possible enhanced Delta.

If an enhanced Delta arises, and you have had Wuhan COVID or a Wuhan vaccine, and you haven’t had Delta, then you may be at greater risk for severe disease.

If you have had COVID since July 2021, you are likely already immune to the Delta variant, and this will not be an issue for you.

I am fully aware this complicated. Also, the CDC has rarely if ever discussed this possibility, so unfortunately, most of the people you talk to about this will not believe it. I am sharing this with you so you can make wise decisions for you and your family.

Some companies are already working on Delta versions of the vaccine. If you have had the current vaccines, or had COVID, you should get the Delta vaccines as soon as they are available.

Of course, discuss your medical history with your doctor before making medical decisions.

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Updated: January 29th, 2022

The “Final” Verdict on Antibody Dependent Enhancement: As most of you know, ADE has been a major concern of mine from almost the beginning. I’m finally willing to give an assessment of how ADE impacted the pandemic. There were a smattering of cases in previously infected people who may have had more severe cases because of possible ADE, but not more than a smattering. It’s also becoming well acknowledged that Omicron infected everyone regardless of vaccination status and may have even preferentially infected vaccinated people. I know MANY people who are double vaxxed and boosted who got Omicron.

All that being said, I never saw any evidence that conclusively suggested that ADE was causing more severe symptoms because of natural or vaccine mediated immunity. In fact, even during Omicron, during which ADE was most likely to be operating, those with previous immunity clearly fared better than those without. Because I think Omicron is the death rattle of the pandemic, I’m willing to say that ADE never became the threat I was concerned about. For this reason, IF I didn’t already have natural immunity because of Omicron, I might actually get vaccinated IF I could find someone who would aspirate before injecting (see the post from earlier this week)!

I never saw any paper that dealt with the issue of ADE, not even a little. Those that mentioned it did so only in passing.
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Updated March 25, 2022

Certain vaccinated individuals are more likely to be infected by Omicron than the unvaccinated:  A UK surveillance report shows that vaccine effectiveness against symptomatic Omicron infection goes from around 65% effective soon after 2 doses of vaccine, to around 5% 6 months later.  Protection from hospitalization goes down to just 35% after 6 months. These findings suggest that to maintain full protection against Omicron, a vaccinated person will need to get a booster every 3 to 6 months.

From UK Surveillance Report, March 17, 2022, Table 1b. Effectiveness of Pfizer vaccine at preventing symptomatic COVID infection after 2 doses, and after a Pfizer or Moderna booster.
From UK Surveillance Report, March 17, 2022, Table 2b. Effectiveness of Pfizer vaccine at preventing hospitalization after 2 doses, and after a Pfizer or Moderna booster.

In another finding from the report, people with 3 doses of vaccine are 3x more likely to be infected with Omicron than unvaccinated individuals.  This is the clearest evidence yet that Omicron may be using Antibody Dependent Enhancement (ADE) to infect people. The Lewnard et al paper from a few months ago has a similar finding.  For both studies, a certain number of vaccine doses are more likely to increase the chance of infection.  If viruses are using the ADE pathway, this effect would be explained more by the timing than by the number of doses per se.  For ADE to work, a person needs to have a mediocre immune response to an agent, not a strong or weak one. Since we know vaccine mediated immunity goes down over time, then a person becomes more likely to be reinfected as their immune response goes from strong to mediocre.

From UK Surveillance Report, March 17, 2022, Table 13. New case rates among UK residents with at least 3 doses of vaccine, and with no vaccination. Numbers are normalized for the percentage of people in each group.

So should you get a booster? Again, if you have risk factors like age, obesity or respiratory problems, you might want to get a booster every 3 – 6 months. Otherwise, you may choose instead to just take extra precautions as Omicron cases continue to fall in the US. If you choose to get a booster, ask them to aspirate before injection. Talk to your doctor when making medical decisions.

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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-and-sars-2 Download



ADE in SARS-1:ADE and SARS-1 Download



Overlapping symptoms for SARS, MERS, and SARS-2:ade-sars-mers-sars-2-liu_et_al-2020-journal_of_medical_virology Download



Is COVID-19 receiving ADE from other coronaviruses?ADE_and_COVID Download



Possible mechanism for ADE:ade-mechanism-jvi.02015-19 Download

Case Update: October 13, 2020; Voting, Re-Infection, 3D Structures

I’ve been traveling a LOT recently and just skipped last week’s update. Sorry for the long delay.

The US continues a slow trend upward in new confirmed cases. According to endcoronavirus, most of these new cases are arising in the Northern states, although the upward trend seems to be creeping south. This seems to confirm my suspicion that the new uptick in cases is caused by colder weather, and people being indoors together more often. If this suspicion is correct, we may be in for a long broad 3rd wave of cases this winter. You may remember that the Southern states (California all the way to Florida) drove new cases this summer. During the summer of course, people in Southern states tend be indoors with their air conditioners more often. This is my theory for the time being.

Graph is by me, from data collected from Johns Hopkins University COVID site.
Endcoronavirus County Level Map, October 13th, 2020

After the end of the 2nd wave, California is experiencing a persistent 3000 new confirmed cases a day, and San Diego County has a persistent 300 new confirmed cases a day. Unfortunately, I’m firmly convinced at this point that COVID may be with us at least until next Spring. As you know if you’ve been reading my posts, I think we will need to adapt to this situation, and open up our economy and normal life as much as possible, while still taking precautions.

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.

As I’ve mentioned before, I am doing a lot of traveling these days, and get tested almost every week, and I’m always negative so far. I use air travel and go into all kinds of gas stations and stores. I do the following:

1) Wear a mask or face covering in public. Avoid places with unmasked people.
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.
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.
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.

Voting: If you haven’t heard, there is an election coming up. As with many issues, mail-in voting has become a politicized issue. The New York Times recently had a story expressing reservations about mail in voting, claiming that mail in ballots are more likely to be disqualified than in person voting. This is because filling out and mailing in these ballots can be complicated and prone to errors that disqualify these ballots. Some stories even claim that people have been sanitizing their ballots, ruining the ink and disqualifying be ballot. It is therefore my recommendation that everyone vote in person if possible. Follow the above precautions, and I’m confident you can do so safely. Dr. Fauci claims that in-person voting is safe if proper precautions are taken.

Reinfection: There is a recently published study of a confirmed case of re-infection in an American man. Apparently, this is the first confirmed and well characterized case in the US, although there have been other suspected cases. His symptoms were more severe with the second case, suggesting that my fears of ADE may be warranted. However, there have been only 22 confirmed cases of reinfection world wide, so it’s still apparently a very rare phenomena. The paper also states the 2nd infecting strain is distinct from the first, consistent with the ADE model.

The paper suggests that there may have been dozens of circulating strains since the beginning of the pandemic. While this case of re-infection appears consistent with ADE, the rarity of the re-infection phenomena along with the many circulating strains suggests that ADE, while theoretically possible, may not have large real-world significance.

New 3D structure: Last, for those of you who want a deep dive, the New York Times has a nice story with a collection of 3D structures of the virus from different sources.

Don’t fear, but be smart!
Erik

Masks: What’s the Deal?

The messaging on masks has been very confusing.  For several weeks, the CDC said the public doesn’t need masks, then finally, the surgeon general was demonstrating how to make a mask out of a T-shirt. I’m convinced that the CDC was so slow to recommend masks simply because they have been so hard to come by.  But the delay in recommending masks has caused a lot of confusion. 

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Section added 2/22/21: Masks have produced a lot of controversy, but I am a big fan of mask wearing indoors. This does several things, it usually prevents infection if you’re wearing an N95 or KN95. However, studies suggest that even if you get infected, a masks will help you have a lower initial viral load on exposure, greatly reducing your symptoms! I personally always wear a mask indoors, and I rarely eat indoors right now.

Outdoors are a different story. Unless you are in a tightly clustered large group of people, you probably do not need to wear a mask outdoors! Some municipalities encourage or require mask wearing outside, but this is usually unnecessary. I am not saying you should ignore local requirements! I’m just saying that when you are going for a walk, a hike or a bike ride, a mask is not necessary.
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First, let’s talk about the words you’re hearing now!

Cloth Face Covering: A “cloth face covering” (I’ll say CFC for short here) is not technically a mask as the CDC defines it, and is not considering Personal Protective Equipment (PPE) from a medical perspective.  This a t-shirt, bandana, buff, or anything else that can be used to cover your nose and mouth.  The virus can still get both into your nose or mouth, or leave your body through these coverings, but it’s much better than nothing.  A lot of people who are trying to be responsible, but can’t find a mask to buy, are using these coverings.  If you hear someone saying they don’t work, they mean that they aren’t completely effective, but they are much better than nothing! Even if you sneeze, a face covering will capture larger droplets, slow the velocity of the sneeze, and help protect those around you.  If all you have is a CFC, you should still wear it when you go out!

According to Fischer et al, gator style masks may be even worse than wearing nothing at all, since they may break up droplets into a smaller size that stays in the atmosphere longer! So avoid a neck-gator style mask!

A surgical style face mask.

Face mask: A “face mask” is a filtering mask that covers the nose and mouth, but does not seal around the nose and mouth.  This includes the blue surgical mask that you see a lot of today.  These masks are designed to prevent material from medical worker’s  face and nose from getting to a patient during a procedure, while still allowing somewhat normal breathing.  They filter incoming air to some degree, but there are large gaps at the sides of the mask, so there are not very effective at preventing infection by SARS-2.  Coughing, sneezing and singing will still expel air from the sides while wearing these masks!  They aren’t completely effective, but they are certainly better than nothing, and will prevent transmission through simple talking. If you have one, please wear it!

UPDATE: Now that KN95 masks and some N95s are available (see below), I can no longer recommend wearing these masks.

Respirator: These masks seal against the sides of the face cover at least the nose and mouth.  They are designed to filter the air and prevent particles from entering the nose and mouth.  N95s prevent 95% of viruses from getting through and are the preferred mask for medical workers in most situations right now.  Unfortunately, they have been in very short supply since the beginning of the pandemic, so the public is being asked not to purchase these for now.  Doctors tells me that N95s are not adequate protection while performing certain procedures on COVID patients!  One told me a story about 14 medical workers being infected by a single patient during a procedure!  This work requires a Powered Air-Purifying Respirator (PAPR).  These masks cover the entire face and also blow air into the mask, pushing virus out.

An N95 with a valve.

If you have an N95 with a valve in the front, these masks will still vent air when you cough or sneeze, so be aware that it will not protect others from virus coming from you! N95s with no valve are the best choice for protecting both you and those around you. Again, hold off on purchasing these until there are in greater abundance.

An N95 with no valve.

I see a lot of very nice looking fitted masks with a little round filter in the front.  These filter out large particles like dust or large droplets, but not necessarily small virus particles.  While much better than nothing, these are not necessarily N95 masks! Read the product information carefully when buying these masks.

KN95 Masks: A new style of mask is being sold in the US now, labeled KN95. These masks are made in China and designed to filter out 95% of viral particles, like N95s. However, they are certified by a Chinese agency, and not by the FDA or CDC. They have been allowed to be sold in the US on an emergency basis. Users say they fit more loosely than N95 masks.

KN95 mask.

There are lots of studies showing the effectiveness of these masks, and unfortunately I don’t have one ultimate study to share with you.  Suay, a clothing company in LA, did a study suggesting that normal blue shop towels (like Tool Box Shop Towels or Zep Industrial Towels) do a much better job at filtering than cotton, and are a cheap and available alternative to an N95 when sewn into a mask. My sister-in-law Penny is part of a team that makes masks for the local hospitals in Bozeman.  These are homemade masks with a pocket for a HEPA filter. She’s sending me some, and I’m going to add a Shop Towel to mine! Both designs are posted below.

Here’s a few tips for wearing your mask:

  1. Your CFC or mask must cover your mouth and nose.  Leaving your nose hanging out, or simply wearing it as a chin mask is not adequate! 
  2. When adjusting your mask assume both your hands and the mask are contaminated.  Wash your hands before AND after adjusting.
  3. 30 min of UV light effectively kills SARS-2 virus.  In the bright sunlight, it may only take a few minutes.  I sterilize my mask by leaving it in the sun for a half hour after a shopping trip.  If you have a cloth face covering or mask, machine washing is a better choice.

In addition to preventing infection, masks appear to reduce the viral load in newly infected patients, leading to less severe symptoms! So even if you get infected while wearing a mask, your symptoms are likely to be less severe!

As we think about re-opening the economy, face coverings, even the bandana type, will really help keep new infections low.  So wear a mask when you go out in public! Any improvements will hasten the day when businesses can re-open. I am awaiting data to see what the infection rate is at businesses in which employees wear masks. Hopefully, this data will come out soon.

Don’t fear, but be smart!
Erik

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Update, February 23rd, 2023,

Cochrane Report on the Effectiveness of Masks:  Jefferson et al released a meta-study through Cochrane Reviews on the effectiveness of medical masks (surgical masks) and medical respirators (N95) in public settings.  A meta-study is a study in which the authors gather information from published articles and try to draw conclusions from a large body of data. They do not gather a new set of data.

The Jefferson et al study reviewed 78 different studies, including data from pre-COVID flu outbreaks.  Their conclusions are sobering.  First, the authors suggest that there is virtually no benefit to wearing a medical surgical mask over not wearing a mask in most settings.  If you’ve been reading my blog for long, you will know that this conclusion does not surprise me.  Blue surgical masks have large gaps in the sides and do not filter air leaving the mouth and nose.  They were designed to prevent droplets from a medical worker from contacting a patient, not to prevent transmission of aerosol based agents.  This is a problem, since most mask wearing people in public during the pandemic were wearing surgical masks.  These people thought they were protected from aerosols, but they were not.

The study also concludes, however, that N95 masks didn’t perform much better.  In fact, for lab tested COVID, the difference was statistically insignificant, meaning that the difference between wearing N95s or surgical masks was so small, it could not be proven to be a real difference statistically. 

I have to point out that the Jefferson meta-study points out that many of the studies they reviewed had various failings that may have made them unreliable.  Much of the data was collected through self-reporting of participants, which is a source of inaccuracy, and participants were often non-random, making application to the general population difficult.  So some of the conclusions may have suffered from these kinds of errors.

As you know, I’ve been a proponent of wearing N95, KN95, or KF94 masks when indoors during the pandemic.  Unfortunately, N95s are tight and intolerable for most people for long periods, so most people didn’t want to wear them at all.  Those that did were not careful to make sure the mask fits properly, making the mask ineffective.  This is part of the reason I wore a KF94 (Korean) during the later stages of the pandemic when I had choices.

So have I been wrong this whole time?  Well, yes and no.  I wore a KN95 in all kinds of environments while traveling during the pandemic.  When I finally got COVID in January of 2021, I was not wearing my mask, working in a “gray area” environment with people that I later found out had COVID.  I was technically indoors, but the room had a lot of ventilation, so I thought I would be OK. Obviously, I was incorrect.  All this to say, I think my KN95 was effective for much of the pandemic.  On the other hand, I am a scientist in the infectious disease field, and have had a lot of experience wearing and fitting these masks to myself, so I am not a typical user.  It may certainly be that my experience does not translate to non-scientists.

If you still have not had COVID and are not high risk, I might say that the current version has an extremely low fatality rate, and it may now be worth the risk to say good-bye to the mask.  I know the large majority of you have done this already.

If you are at high risk, I still think an N95, KN95, or KF94 can be effective for you.  In order for it to be effective, however, you need to make sure it is properly fitted, making sure you don’t have gaps between your nose and cheek.  The mask should filter the air coming into your nose and mouth.

Since I had COVID last January, I no longer wear a KN94, and enjoy eating indoors in restaurants again.  I’ve basically been back to normal for a long time.

Dr. Visay Prasad has an excellent video describing some of the details of the meta-study.  He is an epidemiologist from UCSF. 
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CDC report on filtration.

Masks effective in protecting healthcare workers, Bartoszko et al.

Study on the best masks, Fisher et al.

Mask may reduce symptoms and even provide some immunity, Ghandi et al.

Science Communication, and Being Persuasive

Originally posted on April 27th, 2020 on Facebook

Friends,
This post doesn’t have much science in it, it’s about why I started posting about the virus, and something about my philosophy on communication. If you’re not interested in that, feel free to skip it.

Much of the reason stems from how scientific information is often communicated to the public. So often a scientist or public official shows up on a news show, and basically gives a conclusion, but no real data. Instead of giving a persuasive case, they just make a claim without much support. Because of this, many in the public have been confused or lost trust in what they learn from the media.

On March 9th, I started posting to Facebook, since I don’t yet have a blog. If you’ve been one of my Facebook friends for a long time, you know that I rarely post, really only to change my profile picture for Talk Like a Pirate Day! I felt it was important to give some data in a digestible way, so people would have some understanding of what was going on. I just wanted to show some data so people could understand why SARS-2 was not like the typical flu.

I started out by giving my credentials, since many of you, especially my high school friends, may not have even known I was a scientist. And yes, it might have helped me get my foot in the door with some of you. However, one of the things I don’t like about our public discourse, is how many scientists expect that their credentials means that they must be believed by the public. Being an expert isn’t enough to automatically be believed. You still have to show your data and show why it supports your conclusion. Anyone who has been to a scientific conference or even a journal club knows that experts often disagree. You can’t just say “I have a PhD” to a room full of PhDs. So when experts try to make a case to the public, they still need to show data, and how they came to their conclusion. Unfortunately, because they often just have 60 seconds on a news show, they don’t have time for that. What too often happens, is that they just make a claim without support, and say that if you don’t believe them, you’re just a <news anchor, YouTuber, insurance salesman> or you’re just anti-science or racist or whatever. This is just lazy, and ironically, is anti-science. Scientists must make observations, show data, and be persuasive. Taking short cuts like name-calling isn’t persuasive, and it just makes your opponent irritated and unwilling to listen. In fact, if your opponent knows how to argue, you’ve just clearly told them that you can’t make your case. You lose.

Here’s what I do: I show a piece of data, then say what it means. I’m prepared to tell you where the data come from, and how I manipulated it if I did. If I quote a source, I give a reference. This shows I have reliable information, and also relieves me of some of the burden, since I’m just reporting what someone else said. I also think graphs are much easier to digest than tables, and tables are much easier than numbers in a paragraph, so I make content visual when I can.

If a news story makes a scientific claim, I try to find the original source, since journalists often oversimplify, misunderstand, or misrepresent scientific information. Politics and science make a terrible combination. As soon as a scientific issue gets politicized, it becomes difficult for scientists to figure out the truth, and nearly impossible for the public to. If you want to understand a scientific issue that has become political, you’ll have to read widely on all sides of the argument. Most people just don’t have time for that.

Here are a few of my rules for being persuasive. If you’re one of my lunch buddies from Quest, you know I did this well sometimes, and also failed sometimes!

  1. If you can’t support a claim, don’t talk until you can. Go study and come back.
  2. If you do speak, don’t just lean on your credentials or criticize someone else for not having any. You both need to be persuasive. And if you have data and can support your claim, you don’t need a degree, although training certainly helps to develop these skills. I am a molecular biologist, specializing in medical testing. I am not an epidemiologist or a physician*.
  3. If someone asks you to support your claim, and you find that you can’t, you may need to change your position!
  4. Ask clarifying questions. This may give you time to think, and also helps you learn their position. It’s OK to have an entire discussion in which you only learn their position.
  5. Don’t accept the burden of proof. When someone makes a claim, many will just offer an opposing claim. When you do that, you’re accepting the burden of proof! Don’t do that! Just ask them where they heard it, or why they believe it. A lot of people can’t tell you either of these things.
  6. If you don’t know something, say you don’t know. Making something up undermines your credibility! You may lose a discussion in the short term, but you’ll build trust.
  7. Don’t hide important information. This of course is a favorite trick of media and politicians. It’s a handy way to deceive your audience without technically lying. However, if you’re caught doing this, you completely undermine your credibility. Plus, you can’t really hide the opposing facts, you just bury them alive. They’ll eventually come out like a zombie and eat your brain.
  8. Your job is not to “win”, it’s to be persuasive. Jerks aren’t persuasive. Play the long game! It’s OK to lose a discussion if you can earn another discussion by being respectful.
  9. Find common ground and build from there. If you can show your opponent that you’re on the same team, you have a head start.
  10. If you find that someone is more interested in being insulting than seeking truth, it’s OK to disengage. Some also give you a burden of proof so great, it’s impossible to meet it. They may not be seeking the truth, and there are some people that you will never convince. Relax! It’s not your job to convince everyone!
  11. Don’t post angry! Take a walk, have lunch, maybe even sleep on it, and think before you respond to something obnoxious. You will lose credibility if you say something destructive. While live conversations are always better, social media allows you to think before you post!

Don’t fear, but be smart!
Erik

*A medical license grants the legal right to order tests, interpret results, prescribe medication, and give medical advice. Also, your doctor knows your medical history, and the particular tests and medication you’ve taken. So always consult with your doctor when making medical decisions!

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Update: October 26th, 2021
This past few years have become incredibly contentious and polarized in the US on many important topics of public life. So many times, the default response to disagreement has become to break off discussion and even relationships. This is a tragedy. In addition to above points, I’m adding a new one:

12. When discussing a controversial topic with someone with whom you disagree, do your best to at least understand why your opponent would hold the opinion they do, rather than just assuming they are crazy or evil. This has 2 functions, it allows you to consider points that you may have not considered before, and it also allows you to better understand their view so you can know how to address it. You may still disagree, but you’ll be better equipped to address their view, and may also be able to preserve the relationship.