Vaccines – Because of this week’s announcement about vaccines, lots of folks are asking me about it. I’ll give you my thoughts. I am not an immunologist, I’m a molecular biologist specializing in infectious disease testing, so my thoughts on vaccines are informed, but not expert.
As I’ve discussed before, I’ve been pessimistic about COVID vaccines, mostly because of the phenomena of Antibody Dependent Enhancement, or ADE (link below). This is the phenomena in which some virus can use antibodies against a similar but not identical virus to infect the immune system and cause more severe disease. As this relates to a vaccine, a person given a vaccine could gain immunity against virus very similar to the vaccine given, but less similar strains may still infect and cause more severe illness. This has been my concern about both vaccines and the herd immunity approach.
In the past few months, however, a trickle of known cases have come out about people who have been reinfected with SARS-2. Some of these patients have had worse symptoms, and some more mild. It’s also evident that they are not being infected with the same strain they had before, but by a different strain. If all this is true, then the ADE experiment is already being done. And it looks like while some experience more severe illness, not all do, and reinfection appears to be rare, despite several circulating strains.
This week Pfizer announced that studies with their vaccine show 90% effectiveness in preventing COVID infection. My hesitation with vaccines has always been about ADE. It’s still not well known if ADE will play a significant role, but if it doesn’t, then perhaps there is reason for hope.
All medications and vaccines carry the risk of side-effects and harm. However, I’m actually becoming cautiously optimistic about a COVID vaccine.
Some technical info about vaccines. There are actually several kinds of vaccines. Various developers tried different pathways to a COVID vaccine, and several kinds are in trials right now.
Killed vaccines – These are vaccines that have been deactivated or broken down into various parts and then injected into the body. They cannot replicate and degrade in the body, so parts are attached to molecules called adjuvants that serve to boost their visibility to the immune system.
Attenuated vaccines – These are live viruses that have been engineered to cause infection, but with no or mild symptoms. Some are other viruses like Adenovirus which are symptom free, but produce viral proteins that your body can recognize and raise a response against.
RNA vaccine – This a brand new kind of vaccine that has been in testing for years. Several SARS-2 vaccines are of this kind, and are the first potential viable candidates ever. The patient is injected with a piece of RNA that codes for a viral protein. The RNA enters a cell and temporarily causes the cell to make the viral protein. RNA naturally degrades rapidly in the body and does not persist or permanently change the patient’s genetic material. This promising technique has the potential to generate new and more effective vaccines in the future.
Personally, I’m still taking a wait and see approach. Vaccines will probably not be available to the general public for few months. By then we may know more about how people are responding.
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.
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.
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!
This is a case update. The US is experiencing a third peak in cases. This is likely being driven by cold weather, driving people indoors where the virus spreads more easily. The 3rd peak is already almost 2x as high as the 2nd peak in July and August, and it’s still going up fast. Some states are experiencing record hospitalizations.
California has been trending up for the last several weeks, and San Diego is trending up this week for the second week since the 3rd wave began.
I been seeing new ads in California, talking about benefits of mask wearing. The ads have several shots of people wearing masks in small groups outdoors. As you know, I am a big fan of masks in indoors environments, and wear a mask a lot when at work in a lab or when traveling. However, wearing a mask outdoors is almost always unnecessary unless you are in a large group of people. I’m am not saying that you should ignore local guidance if they require mask wearing outdoors! I am saying, however, that as far as getting infected is concerned, you don’t need to wear a mask while you’re jogging, hiking, or riding a bike.
I have the weekly update, and I’ll also talk about a promising new treatment regimen and a surprising paper about children and COVID.
Update: Unfortunately, the US is experiencing a 3rd wave. This is driven by new confirmed cases in the Northern states, likely because colder weather is driving people indoors. I traveled to Anchorage and Minneapolis in the last few weeks, and I will tell you first hand that eating outside at a restaurant is not an option in those places, but the restaurants have lots of people in them. They’re not full, mind you, they are following the current rules, but lots of people are indoors without masks on. I’ve also been in plenty of airports, in “red” and “blue” states, in which people are filling the restaurants in between flights, with seemingly no regard to the virus. No, I can’t tell you for certain that people are being infected in restaurants, but this is consistent with the idea that indoor activity is driving the increase in new cases. Several European countries are also experiencing 2nd or 3rd waves at this time.
California has had a flat but persistent new case load for the past several weeks, but new cases are starting to increase here too. This is likely most driven by new cases in LA County (18k), which has by far the most confirmed cases in California (308,000), and indeed has almost twice as many confirmed cases as the next highest county, Cook County, the home of Chicago (185,000). Yes, counties in Northern California are experiencing the big upticks in cases right now, but the population and actual case numbers of these counties is so low that they cannot drive the increase in California. Incidentally, Cook County currently has the most confirmed new cases of any US county at 24,000.
San Diego County continues to have a stable but persistent new case load of about 300 new confirmed cases per day. There may be just a hint of 3rd wave starting in San Diego County right now.
Air Travel: When I travel by air, I pretty much never take off my mask on the plane. On layovers, I grab lunch to go at restaurant or convenience store, then go find an isolated spot to eat it.
Delta and Alaska are currently keeping middle seats open. United and American are not. The airlines claim that the air on the plane is filtered by industrial grade HEPA filters every 4 minutes. A pilot friend tells me that this is true. The intake vents are on the floor, and output vents are in the ceiling, like your personal vent, so air is constantly moving to the floor during the flight. If all this is true, then a commercial airplane is a relatively safe place to be!
New Treatment:Doctors in India have developed a treatment combination that has shown great success. Ivermectin is a drug that is commonly used for parasite infections, but is now being used for COVID. It is being used in combination with Doxycycline, Zinc, and Vitamin D. In a study, 93% of confirmed patients do not move on to severe disease while using this regimen, as compared to 58% who developed severe symptoms in the control group.
I’ve said before that Vitamin D has protective effect against the virus, so consider supplementing daily with Vitamin D, or getting out in the sun 30 minutes a day. This is especially important if you have darker skin. Also, supplement with Zinc and Vitamin C.
Less severe symptoms in households with small children:A pre-published study from Scotland claims that adults in households with small children get less severe symptoms if infected than those without small children! This is a counter intuitive result of course. We have known for some time that a low viral load on exposure can lead to less severe symptoms. Also, it appears that most infected children carry a low SARS-2 viral load. This paper puts these pieces together. It suggests that adults with infected children are getting exposed to a lower viral load and having less severe symptoms that adults getting exposed to a higher viral load. In fact, the paper suggests that the more children a household has, the less likely adults are to have severe symptoms!
Friends, Just a short update today. For the US, new case numbers continue to rise. Most new cases are centered in the Northern states, and new cases are spreading South. My guess is that the cold weather is driving these new cases, as people are spending more time indoors. Despite this, new cases are so far not producing an increase in fatalities.
California and San Diego continue to have a persistent number of new daily confirmed cases.
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.
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.
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.
Here’s an update for today. The US, California, and San Diego County seem to have reached a “new normal” after the 2nd wave is over. All have a persistent rate of new cases, unfortunately higher than when the 2nd wave started. The US in fact is increasing in cases a little, with the Northern states having the largest new confirmed case load.
India now has 6.1 million cases as compared to the USs 7.2, and they are just reaching their first peak now, so they will probably surpass our case load soon. This is confirmed cases of course, and there’s no telling now many non-detected cases they have. Of the countries with the top 10 number of confirmed cases, 4 are in South America, Brazil, Colombia, Peru, and Argentina. Mexico is also in the top 10.
This is a weekly update, but I’ll also talk about apparent existing immunity in some people, reinfection, and the 2nd wave of cases and what this all may mean about Coronavirus strains.
The 2nd wave of cases is apparently over in many places in the US, although not all. The US new confirmed case numbers have risen slightly in the past week. While the southern part of the country, California all the way for Florida, was the epicenter of cases for several weeks, new cases are primarily arising in the North Central part of the country. I might speculate that this might be related to the coming Fall weather, but of course it’s too early to say for now. The US also crossed a threshold of 200,000 total COVID deaths, outpacing a prediction I made several weeks ago that we would have 100 – 200 thousand deaths. California is back down to pre-2nd wave new case numbers, but is not sinking below that. In San Diego County, we had a small wave of cases related to a series of outbreaks at SDSU, but we’re back to a lower persistent new case rate.
Internationally, India now has the second most cases in the world, with 5.6 million cases as of this posting. Of course India’s very high population and densely packed cities are likely a contributing factor. Brazil and Mexico have managed to slow the rate of new confirmed cases, having peaked in late July. While things are improving in the US, many countries are experiencing first or second waves right now, including France, the UK, Israel, and Austria.
Existing Immunity: I’ve resisted talking a lot about existing immunity because the information is complicated and may have phenomena with overlapping and opposing impacts. Also, I’m not an immunologist! Be aware that what I say next may change. There is data suggesting that the reason many, especially children, are asymptomatic is that there may be some existing immunity to Coronavirus in those individuals. Coronaviruses is a large family of viruses which includes the SARS and MERS viruses, but also several viruses that cause the common cold. As such, many may already have some kind of immunity to Coronaviruses as a group. This is good news of course.
Reinfection: On the other hand, I listened to a story on the September 2nd episode of the Nature Podcast about several cases of SARS-2 reinfection. These cases appear to be rare, and most are not well studied. In one case in Hong Kong, however, both the 1st and 2nd strains which infected a patient were sequenced and were found to be different strains. This has several implications. It suggests that immunity to a single strain may persist at least for a few months, but also that several strains are circulating, and immunity may not apply to other stains.
If you’ve followed my page for long, you know that I’m concerned about Antibody Dependent Enhancement (ADE). In some cases of reinfection, symptoms were worse the second time, but in others, they were less severe. So unfortunately, these don’t necessarily provide clarity on whether ADE will be an issue, although if this is ambiguous now, it may be the issue will at least not be as serious as I feared. We’ll have to see more of these cases to know for sure.
Strains and Vaccines: I’ve written about the D614G strain that arose in April and May. When I first heard about it, scientists were saying it may be several times more infectious than the already very infectious SARS-2. I suspect that the 2nd wave we saw in the US may have been so large partially because of this strain. All of this, as well as the reinfection story above, highlights that we have several strains moving around at once, and will likely have more. Like HIV and Flu, Coronaviruses are RNA viruses. RNA viruses use a RNA dependent polymerases to copy their genomes, and these enzyme tend to be VERY error prone as compared to DNA dependent polymerases. Because of this, RNA viruses mutate quickly, and are resistant to the use of vaccines. This is why we need a few Flu vaccine every year, and part of why we still don’t have a vaccine against HIV. This of course also complicates the prospect of a vaccine against SARS, along with concerns about ADE. I’ll keep you posted as I learn more.
Avast! This be Talk Like a Pirate Day! So if you be havin’ a question below, use your favorite dialect of the high seas!
The New England Journal of Medicine foisted a flag regardin’ mask wearin’. It appears masks reduce scurvy and COVID symptoms even in infected seafarers. This may be explainin’ why even with the large number of cases during the second wave, fatalities were low.
Friends, This is a virus update. I’ll also have a few comments regarding the recent Bob Woodward book. New confirmed cases continue to drop for the US, California, and San Diego. California new case numbers are back down to what they were before the 2nd Wave hit in mid June.
San Diego had a moderate sized outbreak at SDSU in the last few weeks which created a spike in new confirmed cases for the County, but those numbers are coming down as well.
Endcoronavirus.org’s county view map now shows mostly yellow across much of the South, including California, Arizona, Texas, Louisiana, and Florida, which was perhaps hardest hit by the 2nd Wave. It looks like that region is now recovering, and the Mid-West is now the region of greatest concern, with increasing numbers in many Mid-Western states.
Bob Woodward comments: If you’ve been reading my posts for long, you know that I try to keep these posts as politics free as possible, referring to policies, but not to people. You also know that my recommendations sometimes support those commonly from the “left” and sometimes from the “right”. I do my best to pass along the science as I see it, since I believe politics and science are terrible together.
If you’ve read my July 7th post, you know that a major concern of mine is Antibody Dependent Enhancement. This phenomena is still not discussed openly in the media, and the only other commentator I hear discussing it is Chris Martenson of the Peak Prosperity YouTube channel. Tony Fauci has mentioned it only in passing. I have been concerned about this phenomena since February when I started studying the SARS-2 virus.
Why did I wait until July to post about it? In any crisis, there are people who are anxious about it, they are the first to react, and some overreact. There are others who are unconcerned, and react slowly if at all. Many are somewhere in between. Anyone who communicates to the public has to aim somewhere in the middle of these perspectives. My goal from the beginning has been to communicate adequate concern while being as positive as possible and not cause the anxious to over-react. As I’m sure you’ve heard, there have been many mental health issues attached to recent events, and I have friends in the mental health field for whom this is a great concern. I struggled for a long time before my July 7th post. I wanted people to be adequately concerned, but I didn’t want to cause needless anxiety. The ADE phenomena is still poorly understood, and it’s not certain if it will play a roll in this crisis. I finally decided to discuss it because I had a lot of friends who I felt were not taking the virus seriously enough, and I began to feel it was wrong of me to not inform them. To this day, I wonder if I waited too long, or maybe shouldn’t have mentioned it when I did.
All this to say, Bob Woodward’s discussion with the President was in February, if my understanding is correct. In February, the virus had still not come to the US, except for a few small clusters. Little was still known about how it would behave in the US, and the opinion of medical professionals regarding how to deal with it has changed many times since then. If President Trump was wrong to downplay the virus in February, then I was wrong too. I hope you will have some understanding for the difficult decisions to be made.
The CDC continued to treat the virus like it has always treated epidemics somewhere else, deep into March. Only in Mid-March did they allow other entities to do SARS-2 testing in the US, responding to the President’s request. Large scale testing did not start until early April. In my opinion, the CDC is most responsible for reacting too slowly to the virus.