Vaccine Q&A, 12Mar2021
Georgia COVID-19 Updates
I’m sure you may have heard by now that the President announced last night that all adults will be eligible for COVID-19 vaccines starting May 1. In addition, the federal government is coming up with a centralized appointment scheduling system that should help too. Another thing that will help is that a whole host of new health professionals just got added to the list of people who can administer vaccinations. All of this is good news and will help us get back to normal.
Getting back to normal
A question I am asked often is when and how do we get back to pre-pandemic life. The key is that we get the disease burden down to something that doesn’t overwhelm our hospitals and doesn’t result in lots of death. We can get there through two mechanisms that shift in importance as time goes on. The first is non-pharmaceutical interventions (NPIs). These consist of all the things we’re tired of doing like wearing masks, social distancing, limited gatherings, proper ventilation. The second mechanism is immunity. We can get there through natural infection or vaccination. The US saw >500,000 deaths in a year and that was when we were trying to limit transmission. Even with >29 million cases (natural infection) in the US, we are nowhere close to herd immunity and we have >500,000 deaths to show for it. It’s far safer to get to herd immunity through vaccination. The good news is that the vaccination numbers are improving every day. Georgia has a lot of room for improvement, but we will get there. Right now, because relatively few people are immune through natural infection or immunization, our primary tool against disease spread is the non-pharmaceutical interventions (NPIs in the graphic below). However, as more people get vaccinated, then the NPIs become less necessary. So if you’re tired of wearing a mask (as we all are), then get your vaccine as soon as you’re eligible and help those around you to do so also.
If we subtract out non-Georgia resident infections, there have been 1,000,347 infections in Georgia (those who have natural immunity) and 936,451 people have been fully vaccinated. Combined, that means that 18% of the Georgia population has some immunity to COVID-19. Note: this is not a perfect analysis and it is very likely that the number of infected is higher, but I’m going with what we know for sure in this example. But with 18% of the population immune, we are somewhere between the first and second boxes in the graphic below. It’s actually a video, but Substack won’t allow me to place it here. If you click on the graphic below it will take you to the video. In the center of each box is a black dot that is meant to represent a sick individual. Blue dots around that black dot represent non-immune people. Yellow dots represent those who have immunity. When you click on the video to see the animation, you’ll see how disease can spread within a community depending on how much of that community is immune. Remember, Georgia is somewhere between the first and second boxes.
What you’ll see when you watch the video is that the boxes where most of the dots are blue see disease transmit rapidly and overwhelm a population. The more dots are yellow, the less the disease has an opportunity to spread. Eventually, you reach a point that enough of the dots are immune that they shelter or protect those who are non-immune (blue dot). This is called herd immunity and it is our finish line for this pandemic. For COVID-19, herd immunity is estimated to be somewhere between 70-90% immunity in a population. So for now, Georgia and the US more broadly is very much still in the left side of the scales graphic I showed above. But hopefully by summer, we will reach 70% of the population with at least one dose of the vaccine on board. The reason I mention summer is based on the seasonal trends we’ve observed for COVID-19 surges. They tend to happen when weather makes people want to spend time indoors. So the heat of summer and the cold of winter are our points of vulnerability. So it is my fervent hope that we reach the bottom end of the herd immunity estimate by then.
Georgia is on the way there too but it is not a for sure thing. The US Census Bureau has done some surveys among those who have not yet received a COVID-19 vaccine, asking them about their likelihood to get a vaccine once it is available to them. The national average is 52.5% of respondents saying “definitely yes.” If you combine that with the portion of the nation that has already initiated the vaccination process (19.3% of the total population), then you can predict that the US is on track to reach 71.8% immunity. That’s just with the “definitely yes” crowd. We might be able to push that number higher as vaccination is normalized and people start to see the benefits of doing so. “Slow yes” or maybe might become “definitely yes” eventually. But the US is on a good path. For Georgia, 44.6% of respondents said they would definitely get the vaccine. So add 44.6% to 18% of the population already immune to COVID-19 and we are predicted to reach 62.6% based on current trends. So as of now, Georgia will fall short of the herd immunity goal unless the state starts taking education and messaging seriously. We can drive that number higher, but it means giving people time and opportunity to ask their questions and address their concerns about vaccination (if they exist).
So the bottom line is that for the time being we need for people to continue to do the annoying things like wearing a mask, remaining socially distant, and limiting their gatherings or prioritizing them outdoors. Be sure to get your vaccine as soon as you are eligible and follow up if you’re getting the two-dose series (Moderna or Pfizer). You are considered “immune” 2 weeks after the final dose. There are 3 doses authorized for use in the US -Moderna, Pfizer and Johnson and Johnson. They all achieve the goal of ending the pandemic - they either prevent infection altogether or they reduce its severity to nothing more than the common cold. And honestly, I suggest you take whichever one is offered to you first. There really is no need to “shop around.” However, there are differences or tradeoffs between them and maybe those tradeoffs matter to you. Johnson and Johnson’s advantages include a single dose (one and done!) and fewer side effects. However, with the Johnson and Johnson vaccine it’s possible that you may still get infected with COVID-19, but the symptoms will be mild - certainly nothing that requires a hospital stay like natural infection can cause. With the Pfizer and Moderna vaccines you are less likely to have a symptomatic infection in the first place. But they do require two doses which can be inconvenient and it takes longer to achieve immunity (5-6 weeks compared to 2 weeks for the Johnson and Johnson). In addition, these two vaccines are more likely to induce reactogenicity - the headache, fever, malaise, fatigue and other symptoms that are part of an immune response.
You can search for a vaccine at retail pharmacy locations using Vaccine Spotter. You can also schedule an appointment with your local health department or a GEMA mass vaccination site. If I can answer questions about the vaccine to help you move from a “slow yes” or maybe to definitely yes, then please email me. You can see previous editions of the Vaccine Q&A newsletters from 12Feb, 19Feb, and 26Feb.
Long term effects of the vaccine
We just marked the 1 year anniversary of the COVID-19 pandemic’s arrival in the US. And a year later we are very fortunate to have not just one but three safe and effective vaccines.
I’m getting questions regarding potential long term effects of these vaccines on health. Typically, if we’re going to see adverse reactions to a vaccine, we will see it right away or within the first 2 weeks. With over 64 million doses administered in the US so far, we aren’t seeing any safety signals that would cause us to think that the vaccines are unsafe. I suppose anything is possible, but based on the safety of these vaccines so far, I am doubtful that there will be deleterious long term effects. The ultimate long term impact of these vaccines is that you don’t die of COVID-19.
Part of the reason I’m doubtful about the vaccines having long term impacts when they don’t seem to have short term ones is their minimalistic components. For the RNA vaccines (Pfizer and Moderna) the RNA inside of them is an unstable molecule that is prone to falling apart and it has a short half-life inside of the body. The other ingredients are all there to form the liposome shell and keep it stable. The liposome is made of the same materials as your cell membranes. Remember, mRNA is meant to be a temporary message. So it’s gone and processed, recycled into other molecules, probably after the first day. The proteins that were made using the vaccine-supplied mRNA will be displayed on the outside of your cells for your immune system to recognize. But they too will turnover and be recycled out of the cell membrane. In the meantime, your immune system has a chance to recognize that protein, develop antibodies against it, and create lots of memory B cells (these produce antibodies) that will be ready to be activated quickly the next time that the protein is seen in your body. I mean, anything is possible, I suppose. But I can see no biological reason to expect that the mRNA vaccines would cause long term side effects.
For the Johnson and Johnson vaccine, I’ve provided the ingredient list below from the FDA briefing document. One of the most important words here is “replication-incompetent.” This vaccine is constructed of a dead-end adenovirus. It’s dead-end because it can no longer make copies of itself, even if it is inside one of your cells with all the tools your cells have available. Adenoviruses cause the common cold - your body most likely already knows what this looks like. But it works a bit like a Trojan Horse. It looks like an adenovirus, but in its non-replicating DNA genome, scientists have inserted a gene for the SARS-CoV-2 spike protein (SARS-CoV-2 is the virus that causes COVID-19 disease, in case you didn’t know). So the adenovirus can’t replicate, but it delivers the instructions to make the spike protein. Once inside the cell, this virus does need to go to the nucleus of your cell (where your DNA is held) in order to find the enzyme that can convert DNA into RNA. From there, it functions much like the RNA vaccines.
So it’s a dead-end virus that can’t replicate. As such, its genome will eventually be broken down for parts and recycled (your cells are very efficient!). Again, I don’t see a potential for long term impacts. If we look at the inactive ingredients we see a lot of electrolytes and buffers that keep the dead-end virus from degrading rapidly as it might in pure water. The ethanol is probably there in trace amounts and is unlikely to cause any intoxication in your cells, if that’s what you were worried about. I’m not part of the manufacturing process for these vaccines. But in my past work we use ethanol to extract (technical term is precipitate) DNA and RNA from a solution. So it could be there due to that process. These are largely inert ingredients or things that are already present in your cells. They keep biological molecules in their comfort zone.
So to summarize, there haven’t been a lot of short term impacts and biologically it’s hard to see how there would be long term ones either. The simpler a design is, the less chance for something to go wrong. And these are simple designs. The volume of liquid that is being injected into your body is really small and the material inside degrades quickly. Compare that to the volume of sugar that one eats of the amount of alcohol one drinks. If you’re concerned about long term impacts of things you put inside your body, the vaccine might not be the most important thing to worry about, all things considered.
Is there antifreeze in the vaccines?
The short answer is no. The vaccines do not contain antifreeze, which is toxic to humans. I’ve pasted the vaccine ingredients for Moderna below. I’ve discussed what the ingredients do here. Both this vaccine and the Pfizer vaccine include an ingredient called polyethylene glycol (PEG for short). That sounds a lot like the chemical ethylene glycol (antifreeze) but they are not the same thing. PEG is found in a variety of cosmetics, lotions and creams, food products, toothpaste, etc. It is used in the vaccines to form the liposome that holds the RNA.
There is some speculation that the PEG is the trigger for the rare anaphylaxis reactions that have been observed following vaccination for COVID-19. But I don’t think that we have enough evidence to know for sure. And the anaphylaxis reactions are pretty rare considering how many people have been vaccinated. However, if this is a concern for you, then perhaps the Johnson and Johnson vaccine makes the most sense for you since it does not contain PEG.
Would it be beneficial to get vaccinated, even if people in my family are not currently eligible?
Absolutely! This is actually the basis for the cocoon strategy in vaccinations. As much as we can immunize the people around a vulnerable person, the safer that vulnerable person is. We usually discuss this in the context of pertussis (get your Tdap booster!!!), but it works here too. Remember that infections don’t just spring up out of nowhere. A person has to be infected and then transmit the virus to you. So if we can avoid infections in the people you’re most likely to contact, that means fewer opportunities for you to get sick at all.
So it absolutely makes sense to get vaccinated in order to protect the people you live with who cannot be vaccinated. This is not an all or nothing thing here. We lower the risk with each person who is vaccinated.
Should I wait and let other more vulnerable people get vaccinated first?
If you’re relatively healthy and want to take that altruistic path, I think that’s fine. But honestly I would encourage you to get the vaccine as soon as you’re eligible. I mean, unless you’re going to go find someone to go take the shot that was made available for you, it does no one any good in a freezer. If you’re currently prioritized for eligibility, please just go ahead and make that appointment. Because when eligibility opens to everyone in April, it will be every man, woman and child (over the age of 16 for the Pfizer vaccine) trying to get a vaccine all at once. From a logistics standpoint, just get your first dose on board now before things open up. And if you’re immune, that’s one less chain of transmission to others in your family or community. Getting to herd immunity is a team effort.
How long does immunity last?
When we’re exposed to something our immune system doesn’t recognize, a really complex sequence of events results in B cells producing antibodies against that new thing. The graph below helps us see how antibodies are produced both in terms of timing and concentration (or how much is there). Where it says 1oAg on the lower left is the first time you’ve seen an antigen (foreign thing). It takes a bit of lag, but eventually your body starts to produce antibodies. The first batch is called IgM, but later that transitions to IgG, the main antibody type that circulates in your blood stream. It takes about 14 days to reach peak antibody concentration and then concentration starts to diminish because it’s being used up to control and remove that antigen. It takes about 21 days from start to finish.
The next time you see the antigen (see 2o Ag in the middle) your immune system has memory of what it saw before. So there isn’t so much of a lag or training period to teach your cells what to do. Instead, they go to work right away and they go to work in ABUNDANCE. Not only is the second immune response bigger but it is also faster than the first time around. It is mostly IgG antibodies that are made in the secondary response. This is the basis of antibody tests to test for recent versus distant past infection or immunity: they look for IgM and IgG. There’s a couple things to take away from this. First, the antigen can be natural (i.e. you inhaled a bunch of viral particles) or it can be artificial (i.e. a vaccine). Different antigens can drive a bigger or smaller immune response. Second, notice that even though the antibody concentration diminished between the 1st and 2nd antigen exposures, antibodies were produced rapidly and in abundance right away. That’s not because antibodies came out of thin air. It’s because there are memory B and T cells (the main cell populations of your adaptive immune response) that are sort of a stockpile of learned experience and materials that can spring into action right away.
On average, antibodies last ~90 days. However your immune response is not a one and done sort of thing because of those memory cells. The question we don’t know yet is how long the memory B and T cells last in your body. For some vaccines or infections, one exposure is sufficient for lifelong immunity. For others, we need boosters to remind our immune system, for example needing a tetanus booster at least every ten years. The memory cells likely last a lot longer than 90 days, possibly years. We know for sure that the antibodies produced will circulate for ~90 days. But we are too early in the process to know for sure how long the memory cells remain. But because of the disease burdens in our communities now, after vaccination your immune system may have natural reminders, simply because you are exposed to others who may be infected. As we get closer to herd immunity, that natural reminder system may diminish. It is at that point that we may need to think about boosters to really put COVID-19 down to minimal levels. So when you hear that the immune response lasts at least 90 days, PLEASE STOP READING THAT AS THE MAXIMUM. It is not the maximum. It says “at least” right there. It is a cover-your-butt, really conservative guess because we don’t have enough data to know for sure how long immunity lasts. With more time, we will be more confident extending that timeline out.
Will COVID-19 become endemic?
What we’re experiencing now is a pandemic, when disease is above epidemic threshold on multiple continents. This is why it’s redundant to say “global pandemic.” Pandemic already implies global. But there is another state of disease burden called endemic. “En” might remind you of the word intrinsic or “part of.” That means that there is just a known amount of disease that is just expected. A lot of times, disease can be endemic to a specific region, especially if a particular insect is involved in transmission (i.e. ticks or mosquitos) that is native to that area. If disease burden spikes above the expected/endemic level, then we have an epidemic.
I have no crystal ball here, but to me the most likely outcome of the pandemic is that it does become endemic. The opportunity for eradication became less likely the more we let the virus burn through our communities unchecked. Essentially, we let the problem get too big to eliminate it all together, at least for a while. Perhaps it becomes something that we immunize against periodically like seasonal influenza. Perhaps eventually we vaccinate enough people globally that eventually we can talk about eradication. But that takes a lot of effort and public buy-in. A vaccine for polio was authorized for use in 1955. Over the decades, the disease burden of polio decreased a lot and in the late 1980s a global health effort was begun to eradicate polio all together. In 2021, we still haven’t fully eradicated polio and it remains endemic in Afghanistan and Pakistan. You can read more about this global effort here.
Polio is an attractive target for eradication because it doesn’t have an animal or insect vector (a reservoir of infection). If we can eliminate it in humans, we can eliminate it all together. Coronaviruses are trickier because we do have non-human reservoirs. But if polio is considered an “easier” target for eradication and we still haven’t done so 30 years after dedicating a lot of resources to do so, then I think eradicating COVID-19 will be an even bigger challenge.
Not to add to your worries, but COVID-19 is the third scary coronavirus we’ve seen emerge this century and may not be the last. The other epidemics of SARS and MERS were able to be controlled. For a variety of reasons, that didn’t happen with COVID-19. But just understand that public health is important not just for managing this pandemic but for preventing the next one too.
Georgia Data
Testing: today there was a net increase of 21,486 newly reported PCR tests reported and 4.8% of them were positive. For antigen testing, there were 9285 new tests reported and 3.9% of them were positive. It is likely going to be a low test output week when I do that analysis on Sunday, based on current numbers.
Cases: there was a net increase of 1185 newly reported PCR cases and 382 antigen cases for a combined total of 1567. The 7-day case rate per 100,000 for the state is now only 47% above the pre-surge baseline. We’re heading in the right direction!
Hospitalizations: today there was a net increase of 77 new confirmed COVID-19 admissions and 16 admissions to the ICU. The confirmed admissions are low for a weekday. Only one hospital region is in the red zone for ICU bed use (region L) and there are two regions in the orange zone for COVID-19 patient census (regions F and N).
Deaths: today there was a net increase of 47 newly reported confirmed deaths and zero probable deaths. As we see for cases, the 7-day death rate per 100,000 is only 44% above the pre-winter surge baseline. So more good news, even as we grieve those we’ve lost, that things are getting better.
I’ll be back on Sunday with the week in review!
References
https://www.fda.gov/media/146217/download
https://www.sciencemag.org/news/2020/12/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions
https://dph.georgia.gov/covid-19-daily-status-report
https://covid-gagio.hub.arcgis.com/
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My Ph.D. is in Medical Microbiology and Immunology. I've worked at places like Creighton University, the Centers for Disease Control & Prevention and Mercer University School of Medicine. All thoughts are my professional opinion and should not be considered medical advice.