The Nuts and Bolts of Vaccines Against SARS-CoV-2

The groundbreaking cooperation between medical experts across the globe has made a return to normal possible thanks to the COVID-19 vaccines. Many people are skeptical or concerned about side effects, and we hear you. Good, evidence-based information about the vaccine has been hard to come by, so we've put together the following FAQs to cut through the uncertainty.

Returning to this page? New topics from the last update on December 1, 2021 are marked with a plus sign.

General vaccine information

What is an mRNA vaccine?

Short Answer: This is a newer vaccine technology that uses the genetic material for a virus's most crucial protein. A considerable advantage of this technology includes producing the vaccine directly and rapidly in the lab, rather than first cultivating large amounts of the actual virus as starting material. It is harder to distribute the vaccine because the genetic material has to be frozen, but the advantage is that there is no need to add any antibiotics or preservatives. Thus, mRNA vaccines are safer for people who are allergic to these things in other medications or vaccines. The mRNA breaks down in several hours, after which there are no traces of the vaccine other than the antibodies we are now able to produce because of the vaccine.

Expanded Answer: Messenger RNA, or mRNA, is the genetic material that tells our cells how to make a specific protein. If we were to simply inject the spike protein into people, enzymes in our bloodstream would break it down, preventing us from making protective antibodies against it. Instead, we first make the genetic material that holds the spike protein code. Our blood would also break down plain mRNA that gets injected into us, so we have to wrap it up in material that helps it get into our cells. Once inside, the mRNA tells our cells how to make the spike protein. The muscle cells making this protein show it to our immune system, which recognizes that it is a foreign protein and starts to produce antibodies against it. Messenger RNA doesn't last a long time, so after our cells have used it for a day or so to make the spike protein, the mRNA just breaks down inside the cells, and our cells recycle its parts as part of our day-to-day life.
'Genetic material' sounds scary. Does it get into our DNA?

Short Answer: Absolutely not. That is not what mRNA does, and the claims we hear about mRNA vaccines changing our DNA are nothing more than an uninformed scare tactic.

Expanded Answer: Our cells make proteins coded by our DNA in the cells' nucleus. When our cells want to make proteins, parts of the DNA code are copied into mRNA. The mRNA moves out of the nucleus, where little organelles called ribosomes read the mRNA code using transfer RNA to make the correct proteins. After a few days, the mRNA is broken down and recycled by the cells. This process is a one-way street, because our cells don't have the machinery to go backwards - mRNA does NOT go back into the nucleus to get back-translated into DNA. Ever.

Recent studies have examined people in whom the PCR test remains positive long after the infection, and it has been shown that this is due to small pieces of viral genetic material getting incorporated into the patient's DNA. The evidence indicates this is due to current infection with other viruses that do have the machinery to do this, and with the widespread replication of virus RNA throughout the body during an infection, some of that RNA gets accidentally reverse translated into the human genome. Of course, reverse transcription can only occur with RNA, which is what comprises the genome of the intact virus to which one is exposed during an infection. Messenger RNA, the genetic material in the vaccines, cannot undergo what would have to be a two-step process, reverse transcribing it first into RNA and then again into the patient's DNA. There is no cellular mechanism for translating mRNA back into RNA. So the risk of viral RNA showing up in a person's DNA is only after an actual infection, not a vaccination, adding to the reasons for getting vaccinated. The reports of bits of COVID DNA showing up in our DNA only happens in people who have been infected with the actual virus; this doesn't happen from the vaccine.

In general, how do we know vaccines work?

Short Answer: In a vaccine study, half the people are given the vaccine, and half are not. If the people given the vaccine get sick less than half as much as those who got the vaccine, we consider that the vaccine worked.

Expanded Answer: The obvious way to prove a vaccine works is to vaccinate people, expose them to the virus, and see if they get sick. But that's unethical. Instead, we recruit people for whom the vaccine is appropriate and give half of them the real vaccine. The other half receives a placebo injection that contains no active vaccine (some trials use two-thirds vaccine and one-third placebo). Then everybody is monitored to see if they get sick. Statisticians can tell us how many people need to get sick in the placebo group before finding out if the vaccine worked.The FDA's standard of efficacy is 50% - people who received the vaccine need to get sick no more than half as often as those who did not receive the vaccine for it to be considered effective. Among the 43,448 participants in the Pfizer trial, the first COVID-19 vaccine trial to be completed, the half who received the vaccine experienced only nine infections. Those who did not receive the vaccine suffered 169 infections, showing a vaccine effectiveness rate of 95%. The FDA would have considered the vaccine effective if as many as 84 vaccinated participants became infected, but only nine of them actually did.
What does the COVID-19 vaccine do?

Short Answer: The vaccine helps us make our own antibodies against what's called the 'spike' protein of the virus, which makes it much harder for us to get infected.

Expanded Answer: What makes the SARS-CoV-2 virus (the name of the virus that causes the disease we know as COVID-19) unique is its spike protein, which are the red things you see in the depictions of the coronavirus. They attach to a protein on human cells called the ACE2 receptor, allowing the virus to gain entry to our cells, where it takes over our cell machinery to make more copies of itself. So the strategy is to get people to make antibodies against this spike protein without getting infected. Once we have our own antibodies against the spike protein, if we then get exposed to the virus, our antibodies latch onto the spike protein. Once the spike protein is covered with antibodies, it can't attach to the ACE2 receptor and can't infect our cells. Unable to make more copies of themselves, the inactivated virus particles can be quickly eliminated by our immune system.

COVID-19 vaccine development

This new technology was developed awfully fast - is it really safe?

Short Answer: It is true that there are no other mRNA vaccines previously manufactured, but the technology is not new. mRNA technology has been used for fifty years, and efforts to use mRNA specifically for vaccines have been ongoing for the past twenty years.

Expanded Answer: The first time a cell made a foreign protein from injected mRNA was in 1971. The first time we induced living mouse muscle tissue to make foreign proteins from mRNA was in 1993. The first mRNA vaccine was developed against rabies and entered clinical trials in 2013, but this was a proof-of-concept trial and was not used to make a commercial vaccine. We started to develop mRNA vaccines against SARS and MERS, but those viruses were so lethal that they burned themselves out, and there was no need to bring the vaccines to market. SARS-CoV-2 very rapidly showed that it would be a significant threat to the planet, so we picked up where we left off with mRNA vaccine development and hit the ground running. The first clinical trial of an mRNA vaccine started just 66 days after the genome of SARS-CoV-2 was sequenced - you can't move that fast if you're not well prepared for it.
The trials were completed in only nine months or so - didn't they cut a lot of corners to do it so fast?

Short Answer: The time it takes to develop a vaccine depends on the population who needs it and how common the disease is. These vaccines are intended for all adults (initially) for a disease striking 60,000 to 100,000 people per day (in summer and fall 2020). That makes it easy to generate a lot of important information very quickly without cutting corners.

Expanded Answer: Many of the vaccines we use were developed for children, and that process can take a decade or more. That's why it's easy to think that the COVID-19 vaccine trials were rushed. But as we discussed how we find out if a vaccine is effective, that is a function of the disease. There are several reasons why childhood vaccines take so long. First off is the slow recruitment rate - we can't enroll babies into these trials any faster than they're born. Secondly, many parents will not enroll their newborn in a clinical trial of a vaccine. So the trials are slow to enroll, and the diseases we're trying to prevent aren't very common in this country. So it takes a very long time to get enough infections in the placebo group to see if the vaccine did anything at all. But for COVID-19, practically anybody over age 17 who wasn't infected with SARS-CoV-2 at the time, didn't have any significant, unstable medical problems, and who wasn't pregnant or nursing was eligible. And instead of studying a vaccine for a relatively uncommon disease, we saw over 50,000 new cases in the US every day during these trials. In fact, that was a strategy for recruitment - the people running the trials specifically looked for parts of the country where the disease was most active. You'll get the required number of infections in the placebo group much faster if you conduct the trial in an area getting 1,000 new cases a day rather than 20. AASC was actually selected as a clinical trial site for the Moderna vaccine, but before our site was initiated, COVID-19 started spreading like wildfire in Florida and Texas. Spread of disease in the Milwaukee area was not nearly as fast as many areas in those states, so Moderna moved their trials to those regions, knowing that they could reach their endpoints faster where the disease was most active without comprising data integrity.
Why did it take so long after the EUA to get full approval? Were there problems with the vaccine?

Short Answer: The EUA allows use of unapproved treatments in situations in which the benefits of using the treatment are reasonably known to be worth the risk, so the vaccines reached EUA as rapidly as possible. But knowing that the public needed to have confidence in the safety of the vaccines, the FDA knew it needed to perform the full data analysis for approval - no shortcuts. It did place the vaccines under Priority Review and marshalled additional resources, but did the full safety and efficacy review. There is no compromise on this, which is why the Moderna and Janssen vaccines still aren't approved at the time of this writing.

Expanded Answer: Several things were done to expedite the data generation and analysis. Based on previous data with the mRNA technology, it was reasonable to combine phases 1 and 2 of the clinical trial process, and phases 2 and 3 were run concurrently as well. Then, due to selecting sites in areas of high transmission, trial endpoints were met in just a few months. Given the dire need to balance vaccine efficacy with the need to slow down the pandemic since health systems around the planet were being overrun with COVID-19 cases, HHS invoked the Emergency Use Authorization rules that were part of the Public Services Act that was enacted on June 12, 2002 in response to 9/11. Another unusual aspect of this program was that due to the previous work done at DARPA and other organizations over the previous decade, it was known that the mRNA vaccines had a highly likelihood to be found safe and effective, so both Moderna and Pfizer received support to start producing the vaccine well before the trials were concluded - something that never happens in ordinary circumstances. Production usually starts only after FDA approval, but we needed to be able to start vaccinating as soon as possible to protect our first responders, health care workers, and people at high risk, as well as slow down the spread of the pandemic. But it was also known that many people would be reluctant to receive the vaccine until it was fully approved. Thus, it was put in Priority Review status, the FDA reassigned some people from other departments to help analyze the data, and more analysts were hired to help move the process along as rapidly as possible. In addition to reviewing the data submitted for the EUA, additional safety data continued to come in from the clinical trials, which are still ongoing. Thus far, the process has been completed with the Pfizer vaccine, which has demonstrated its safety and efficacy to meet the standards for full FDA approval, which was granted on August 23, 2021 for people 16 years of age and older. All previous Emergency Use Authorizations remain in effect.

Concerns about adverse effects of the vaccines

Can the vaccine make me sick? What about all the side effects I've heard about?

Short Answer: No. The vaccine is not made from live virus particles, so there is no possible way to get infected by the vaccine. Many people have some symptoms of a robust immune response to the vaccine, but this is expected, is typically mild, and lasts only one or two days.

Expanded Answer: You cannot get infected from the vaccine. There is no virus in the vaccine, only the mRNA for the spike protein, and not anything else required for viruses to cause an infection. However, what is critically important is that most of the symptoms that people associate with viral infections are symptoms caused by the immune system in its response to the vaccine, not the infection itself. Not everybody experiences these symptoms, but it is expected that many people will notice a mild fever, muscle aches, fatigue, chills, or joint pain that can last for 1-3 days after vaccination. This is only a sign that your immune system is doing what it is supposed to do. The reason this is important enough to use bold type is that there is a concern that people who experience these symptoms after the first dose will think that the vaccine made them sick, and they won't go back for the second dose. This would be a critical mistake. The studies have shown that while there is an antibody response after the first dose, that first dose "primes the pump" for the second dose, after which antibody levels soar to levels so high that the vaccine is 95% effective at preventing infection. You can't expect the vaccine to work that well after just one dose, so please be sure to go back for the second.
I've heard about reactions to the vaccine. Is that worrisome?

Short Answer: Adverse reactions to the vaccine are rare, because of the way the vaccine is prepared. The only people advised to be cautious about getting the vaccine are those who have had severe reactions to injectable medications in the past. If you have had a severe reaction to an injectable medication that required treatment, talk to your doctor or allergist/immunologist about whether to get the vaccine. As we got more experience with these vaccines, we've found that almost everyone who has a reaction to the first dose is able to tolerate the second dose, sometimes with premedications. It is safe for virtually everybody to get vaccinated.

Expanded Answer: The mRNA in the vaccine is essentially the same as the mRNA for the spike protein in the virus. The main difference is the wrapper that is used to get the mRNA into our muscle cells. It does contain polyethylene glycol, which is known to cause allergy-like reactions in some people. Allergies to other common allergens like pollens, molds, dust mites, foods, or latex do not put people at increased risk of vaccine reactions. The vaccine is distributed in a deep freeze, so there is no need for any antibiotics or preservatives. Since we don't have to grow the viruses in the lab to make mRNA vaccines, there is also no egg or gelatin in the vaccine. So the vaccine should be used with caution in people who have reacted to other vaccines or medications containing polyethylene glycol or polysorbate 80, or if they have conditions such as mast cell activation syndrome that put them at greater risk of severe reactions to a variety of things. For these people, various precautions can be taken to ensure that vaccination will be safe and reasonably tolerated.
I've seen reports on social media that the vaccines have caused thousands of deaths. Where's the outrage?

Short Answer: This refers to VAERS, the Vaccine Adverse Event Reporting System. All of these reports have been or are being investigated, and to date none of these deaths have been shown to have actually been caused by a COVID-19 mRNA vaccine. There have, however, been 4 reports of death due to cerebral venous sinus thrombosis after the Janssen vaccine.

Expanded Answer: The VAERS is a voluntary reporting tool - anyone can submit an adverse event report to VAERS. This means that non-medical people who do not have the knowledge base and experience to truly know whether a death was related to a vaccine can make a report anyway, and once it's been submitted, it's counted. It also means that anyone out to discredit the vaccines can go ahead and report a death that occurred for any reason as having been related to the vaccine. But even at that, with over 437 million doses administered thus far in the US, only 0.0016% have been reported as having died some time afterward, a bit lower than the risk of being struck by lightning.The Advisory Committee on Immunization Practices continued to recommend that the benefits of vaccination outweigh the risks as of November 19, 2021. Additional information about adverse events is also available from the CDC.
I've heard a lot about myocarditis after vaccination, which is a big deal, so why are we still telling people to get vaccinated?

Short Answer: As with most viral infections, the symptoms people experience are due in large part to our immune response to it. In some people, antibodies we make against the virus spill over and attack the heart. In fact, myocarditis occurs about 16 times more often in people infected with COVID-19 than in people without COVID. Fortunately, myocarditis from the vaccines goes away quickly, yet people still get the protective immunity from the vaccine. So it's still a good idea to get vaccinated.

Expanded Answer: Inflammation of the heart as a consequence of COVID-19 infection was observed early on, when hospitalizations soared in Italy and Spain in early 2020. Reports were published in summer 2020 documenting the persistence of heart muscle inflammation as much as two months after COVID-19 infection. Since it has been known for quite a while that COVID-19 infection is associated with autoimmunity against the heart, it is no surprise that in susceptible people there is some myocarditis associated with vaccination. But the encouraging thing that we're seeing is that since the mRNA from the vaccine is broken down so rapidly (it lasts only about a day), this autoimmunity against the heart after vaccination is also transient. So rather than being a bad thing, myocarditis after vaccination is reassurance to the patient that they did the right thing by getting vaccinated - if their immune/genetic makeup is such that they get the transient myocarditis from the vaccine, they know that they would have been in a whole world of hurt had they come down with COVID-19 and had a full-blown immune response raging for several days, rather than several hours.

Natural immunity versus vaccination

I'm young and healthy, and COVID-19 doesn't seem to be a big deal in my age group. Shouldn't I just get it over with, and develop better immunity by getting the infection?

Short Answer: No. The mRNA in the vaccine helps us make antibodies against the spike protein, just like we do with COVID-19 infection. But with infection, the virus forces us to make ALL of its proteins and make more copies of the virus itself. That's what triggers the severe illness many people get with COVID-19, and the risk of long-term complications. None of that happens from the vaccine.

Expanded Answer: A major feature of SARS-CoV-2 is that it is so unlike any other viruses before it that essentially none of us are immune. That's why it's called a 'novel' coronavirus. If we are significantly exposed, we will get infected. Almost everybody will likely have to develop immunity either the hard way (getting infected) or the easy way (getting vaccinated). So it is useful to compare the risk of the vaccine with the risk of getting infected. That makes it easy - with vaccines for the spike protein, we start making the spike protein to show to our immune systems just like we would if we were to get infected - but without all the other proteins and without the genetic material of the virus as a whole. So it is far safer to get vaccinated instead of wait to get infected. And we see that in the numbers: more than one in 46 people with COVID-19 worldwide have died from the infection, but only about 1 in 100,000 people has significant reactions from the vaccine. These are all treatable, so these folks do carry on with their lives. As of this writing, there have been 216 million COVID-19 infections resulting in over 5.2 million deaths, killing people of all ages as young as two months. Of the 3.3 billion people fully vaccinated worldwide with over 7.8 billion doses administered so far at the time of this writing (November 27th), there have been zero deaths attributable to the mRNA vaccines. Protecting yourself with the vaccine is clearly the best way to go, so please roll up your sleeve!
I take vitamin C, vitamin D and/or other supplements to boost my immune system, so I don't have to worry about getting COVID-19, right?

Short Answer: There is no such thing as "boosting" the immune system. And although these supplements might be helping the immune system to work at peak performance, they do nothing about preventing infection in the first place, as the antibodies produced by the vaccine do.

Expanded Answer: The immune system knows what it's doing, and it does it very well. However, the immune system, along with other systems and enzymes in the body, needs cofactors such as vitamins and minerals in the diet to keep everything working normally. So all you need to do is give the immune system the tools it needs to do its job - giving it more than it requires won't help it work any better. Your Honda Civic will run great if you keep the air filter and oil changed as often as recommended and filled with gas - but more gas or a better grade of oil still won't get you winning the Indy 500 with it.

But if a well-functioning immune system were enough, we wouldn't see appreciable case fatality rates. That's because once an infection starts, our immune system is often not powerful enough to stop it. So we have to prevent the infection in the first place. That starts with distancing and masking to reduce the chances of getting exposed to the virus and getting vaccinated to generate enough antibodies so that when we do get exposed, these antibodies latch on to the virus and prevent it from infecting us, which is something that only antibodies can do - vitamins and immune supplements cannot do this.

I had COVID last year, so I have my own natural immunity and don't have to get vaccinated, right?

Short Answer: Not really. Now more than a year into the pandemic, we're starting to see studies done in people with prior infection, and the protection from that natural immunity is not as consistently strong as the protection we get from the vaccines.

Expanded Answer: Recent studies have looked at the Delta variant because of how rapidly it is expanding across the planet. The mRNA vaccines (Moderna and Pfizer) are highly effective against the Delta variant at 88% protection (compared to 90-95% against the original strain), although only about 33% effective after just one dose. The Johnson vaccine is about 60% protective against the Delta variant, and about 66% against the original strain. Importantly, some preliminary laboratory studies showed that antibodies from fully vaccinated people are much more effective at blocking the Delta variant than antibodies from partially vaccinated people. In fact, the additional protection after the second vaccine dose is much greater with the Delta variant than the Alpha variant, underscoring the need to get both doses. Lastly, studies with antibodies from people who recovered from COVID-19 a year earlier showed they did not do a good job at blocking the Delta variant, but after these people were vaccinated, their immunity against the Delta variant was just as strong as other vaccinated people.
Can I get the COVID vaccine even though I have a sinus infection?

Short Answer: If you have the opportunity to get vaccinated, or have significant potential risk such as exposure to the public with your job, go ahead and get the vaccine. But if you have low exposure and it is reasonable for you to wait, then it'll be best to wait until you're over the infection.

Expanded Answer: Our immune system works best when it can focus. Just like we do a better job when we're focused on one objective rather than multi-tasking, our immune system works best when it is focused on one thing. If your immune energy is occupied with fighting off a sinus infection, it can't do as good a job processing the vaccine. It will, so you can go ahead, but you might get a better immune response if you don't have any other distractions for your immune system to divide its attention. But also be aware that the COVID vaccines strongly activate the immune system, and many people do experience symptoms of a robust immune response for 24-48 hours after the COVID vaccine. If you already have an active immune response to the sinus infection brewing, the additional response to the vaccine might make you pretty miserable for a couple of days while theoretically also helping you fight off the sinus infection.

Pregnancy, fertility, and children

I am pregnant or planning on getting pregnant. Should I get the COVID vaccine?

Short Answer: This question really boils down to the mother's risk of infection. If she is able to avoid public exposure and have minimal risk of getting COVID-19 for the entire pregnancy, it could be reasonable to wait. But if mom is not able to minimize her risk of getting infected, it would be best to get vaccinated. Both the American College of Obstetrics and Gynecology (ACOG) and the Society for Maternal and Fetal Medicine (SMFM) recommend that pregnant women be vaccinated.

Expanded Answer: Because of the way the new vaccines work, there is no reason to expect that there would be any complications from the vaccine that wouldn't occur with an infection. Of course, the symptoms of an infection would be much worse, and COVID-19 infection carries significant risk of long-term complications for mom. A study done in Mississippi found 1,637 COVID-19 infections in pregnant women between March 1, 2020 through October 6, 2021; 15 of these women died due to the coronavirus infection. The majority (nine) of these deaths occurred during the period of Delta predominance in the last three months of the study. Importantly, these 15 deaths in 1637 pregnancies mean that 0.9% of all pregnancies in Mississippi during that period of time resulted in maternal death due to COVID-19. In contrast, there are only about 700 maternal deaths in the United States during pregnancy or within six weeks after giving birth; given the roughly 3.75 million births each year, only 0.018% of pregnancies end in maternal death. We can infer that a pregnant woman may be at up to 50 times the risk of death in pregnancy if she gets infected with COVID-19.

There is limited information about the effect of COVID-19 infection on a fetus and newborn, and of course, this disease has not been around long enough for us to have any idea about possible long-term complications for the baby if mom gets COVID-19 while she is pregnant and the baby then gets infected from mom. Because of the long-term complications we are seeing in adults, it is likely best to do what we can to avoid the baby getting infected. We have long known that antibodies from the mom do cross the placenta; that is a major source of immunity in newborns that helps prevent infections in the first few months of life. Limited studies in pregnant women done thus far have shown that the antibodies stimulated by the COVID vaccines also cross the placenta and can be found in the baby, helping prevent the baby from getting infected if exposed after delivery.

Will getting vaccinated hurt my chances of having a baby in the future?

Short Answer: Both the American College of Obstetrics and Gynecology (ACOG) and the Society for Maternal and Fetal Medicine (SMFM) find there is no suggestion of any effect of the vaccine on fertility.

Expanded Answer: The vaccines are too new for us to have prospective, observational data on fertility. However, since the vaccines essentially do nothing other than a subset of what happens during coronavirus infection (ie, using viral mRNA to make the spike protein to induce an antibody response in the same way that happens during an infection, but without the other viral proteins and the rest of the viral genome), it is appropriate, reasonable, and reassuring to note that after at least 216 million infections worldwide, there has been no observable effect on fertility among those who survived the infection. Further, we can think of death as the ultimate adverse effect on fertility. Coronavirus infection itself poses a substantial risk to women of child-bearing age; as of this writing, there have been 6,831 deaths from COVID-19 among women in this age group, while there have been only 239 deaths due to influenza in this group over the same period of time.
Even though it's authorized for emergency use now, giving my kids a new vaccine is still scary. Should I do it?

Short Answer: Yes. With over 262 million doses of the Pfizer vaccine (the only vaccine authorized for 5-11 years olds) given thus far, we now have overwhelming evidence that the benefits of vaccination outweigh the risks. The 'Under 10 years old' is the only age group in Wisconsin that is now contracting COVID at a rate even higher than the peak we saw in Nov/Dec 2020. The pathway out of this pandemic lies in the trifecta of vaccination, masking, and distancing, and the Omicron variant is simply the most recent reminder that we have to slow the spread of the virus so we don't give it more opportunity to mutate. Everybody eligible needs to be vaccinated to make this happen.

Expanded Answer: Everything in life is a risk/benefit analysis. Because the mRNA vaccines stimulate protective immunity the same way the virus does (using mRNA), the vaccines cannot produce any adverse effects that would not occur as part of an infection. While it may have been reasonable last year to take the position of waiting it out, that ship has sailed. We will not be eradicating this virus, and with the return of in-person school, many of which are not enforcing masking, the risk of contracting COVID-19 is increasing. And the risks of infection are not fully understood. As of November 1, there have been over 5,500 cases of Multisystem Inflammatory Syndrome in Children, which have resulted in 48 deaths. Even more concerning is the unknown risk of developing autoimmunity that results in long COVID, and what the implications of an autoimmune syndrome might have as a child goes through puberty. Less than two years into the pandemic, we have no idea what these risks might turn out to be, but we have abundant data about the safety of the vaccines. So it makes sense to vaccinate and prevent infection, so we don't find out the answers to these other questions the hard way.

The threat of variants

What is the problem with the new variants and the vaccine?

Short Answer: We use the term variants to describe new strains of the virus with altered spike proteins, which might make our vaccines less effective.

Expanded Answer: One way to think of the immune response to a virus would be to think of it as a lock, which holds back the floodgates of an effective attack against the virus. The vaccine tells our immune system how to make the lock by showing it the spike protein (the key). Then, when the same virus comes back - that is, the key unlocks the floodgates - our immune systems react strongly and swiftly to hopefully prevent infection, or at least keep it less severe. Over time, as the key gets banged up (variants emerge), the key will still work, but maybe not as well - it doesn't turn smoothly, or it takes more force to turn it. Eventually, the shape of the key becomes so different that it no longer opens the lock. That's where the concern is. As the SARS-CoV-2 spike protein mutates into new variants, the antibodies we've made in response to the vaccine might no longer recognize the new spike protein, and a preventive immune response won't be triggered.
I keep hearing about variants - what does that mean?

Short Answer: Variants are new strains of a virus that come about when mistakes are made while copying the genetic information. The importance of the variants to the COVID-19 pandemic is that the ability to infect human cells may change if the spike protein is altered.

Expanded Answer: During an infection, when the coronavirus takes over our own cells' machinery and forces our cells to make new copies of the virus, errors are made when the genome is copied or transcribed. Many of these are minor and don't seem to make any difference. Some are catastrophic - a single change might code for a protein that takes a wrong turn at a given point, for example, and the protein can't do its job anymore. These mutations just die out because the virus can no longer cause itself to be replicated. The concern for the pandemic is twofold: 1) With regard to the lock-and-key analogy above, mutations and variations in the spike protein could change the shape of the protein so much that the antibodies we're making in response to the vaccine can no longer bind, and we lose that protection. We already see a decreased effectiveness of our current vaccines to some of the new variants. 2) These same variants (the banged-up key in our analogy) might actually bind more tightly and more strongly to the ACE2 receptor. This can make the virus more contagious since it wouldn't take much exposure to get past our bodies' defenses, and it can also potentially make the illness more severe.
What do I need to know about the Delta variant?

Short Answer: It is more contagious than the original strain, and symptoms are more likely to be headache and fever than the loss of smell and taste with the original strain. Importantly, it is twice as likely to cause hospitalization in unvaccinated people, and in just three months after it emerged in India it became the predominant strain in the UK and caused well over 50% of all new infections in the US, half way around the planet! It is a serious error in judgment to lose respect for how dangerous this virus is and how rapidly it can spread.

Expanded Answer: An important feature of the Delta variant to keep in mind is that it first emerged as COVID-19 was spreading rapidly throughout India in April of 2021. In just a few months, it spread across the globe and became the prominent strain in the UK and had been identified in all 50 states by July. The Delta variant is 60% more contagious than the Alpha variant, which itself is 50% more contagious than the original Wuhan strain. It was announced in June that it was expected that the Delta variant would overtake the Alpha variant in the United States. Fortunately, although the vaccines do not seem to be as effective against the Delta variant and its related Delta-plus variant, they still offer good protection.
We keep hearing about variants "escaping our immune protection" - what does that really mean?

Short Answer: Protective antibodies recognize the surface contours of proteins. Mutations change the shape of proteins, so the antibodies can no longer latch on - like the old adage, "you can't put a square peg in a round hole." The concern is that we're continuing to let the virus multiply so quickly, it will keep on making mutations and change the shape of the spike protein so much that our antibodies will no longer neutralize the virus to prevent infection.

Expanded Answer: Interactions between antibodies and the proteins to which they bind are complex, and the strength of binding depends on how well they match - and the stronger the binding, the tighter the antibody latches on to the protein, and in the case of the coronavirus, the antibody gets in the way so that the virus can't attach to the cells in our respiratory tract and infect us. You can think of a hand and glove - lots of surfaces that interact with each other to form a strong bond that doesn't fall apart if you shake your hand around. So if you have a tight-fitting leather glove (antibody) that latches on to your hand (virus), your fingers won't be able to open your phone with the touchscreen (infecting human cells). Some mutations don't matter much; if you lose a finger, the glove will still fit, and you still won't gain access to your phone. Some will affect the strength of the binding but still allow some interaction - it would be easier to shake off the glove (looser fit) if you lost a thumb rather than a little finger. If your hand can shake off the glove, you'll be able to open your phone. Some mutations make it harder for our antibodies to protect us - grow an extra finger coming straight out of your palm, and now the glove isn't going to work so well. Sure, you might have some gloves around that have a tear through the cuff such that you can get the glove partway on, but that sixth finger will still be sticking out and can be used to open your phone. So now our current gloves are essentially useless, and we'll have to go back to the drawing board and design a whole new six-fingered glove that will fit the mutated hand completely, covering up all of the fingers so the hand can no longer be used to open our phones again. That's what we've been trying (ineffectively) to do with distancing, masking, and vaccination - slow down the spread of the virus because each person who gets infected is another opportunity for a mutation to happen that weakens the ability of our antibodies to neutralize the coronavirus and prevent infection.
So isn't this a losing battle? If we already have variants that can get past the immunity we get from the vaccines, why bother?

Short Answer: Viruses mutate by moving through people. The more we do to limit the spread - including vaccination, masking, and distancing - the more we decrease the ability of the virus to mutate, keeping our vaccines more effective.

Expanded Answer: As above, viruses mutate in the process of replication. So when we are not taking precautions, sharing the virus freely, and see infections sweep through a community or a country, the high rate of virus replication increases the chances that mutations will occur. So the more we do to limit the spread of the virus - vaccination, mask-wearing, hand-washing, social distancing - the slower the virus will mutate, and the longer our current vaccines will be effective. So it is true that our vaccines are less effective against some of the new variants, but vaccination remains an essential part of limiting the spread and giving the virus less chance to mutate.

Boosters, treatment and autoimmunity

Now that boosters are available to all adults, should I get one?

Short Answer: Yes. Surveillance studies have shown that antibody levels decline over time - both from vaccination and from natural immunity following infection. Also, we have shown that antibody levels go up after a booster dose. So yes, you are improving your protective immunity by getting a booster dose.

Expanded Answer: While booster doses do substantially increase protective antibody levels, we want to be careful about messaging - breakthrough infections are occurring NOT because of waning immunity, but because of pandemic fatigue. People are tired of all the precautions, so it's easy to think that once we're vaccinated, the pandemic's over and we can get back to life as we want to live it. But vaccination does not mean bulletproof - it is certainly possible (and clearly happens) to overcome our protective immunity with significant exposure. That is why we aren't seeing breakthrough infections just in healthcare workers and the elderly, who received the vaccines in Jan/Feb 2021; we're seeing them across the board as people relax their masking and distancing and overcome their protective immunity with massive exposures. We have further evidence that the vaccines are still working from the fact that people with breakthrough infections have much milder disease, and are dying from COVID-19 at less than a tenth of the rate at which COVID-19 is fatal in the unvaccinated. So while everyone eligible for a booster should get one, it is important to remember that we still must take steps to limit our exposures through masking and distancing to not overcome our protective immunity, whether from the vaccines or from prior infection.
Are we going to continue to need booster vaccinations, like we do with influenza?

Short Answer: Likely, but we don't know enough information yet to know how often we might need boosters, and whether we will need to change the vaccines from time to time.

Expanded Answer: We continue to gather data about how long the immunity lasts and how well the antibodies produced by the vaccines protect us from the new variants. The original Moderna and Pfizer studies are two-year studies in which the participants - who were vaccinated in summer 2020 - come back periodically to have their blood drawn to check their antibody levels. So by the end of 2021, we'll have good data on how well protective antibody levels last for the first year after vaccination, and that will give us an idea of whether and how often we'll need boosters. Studies are also ongoing as to how well the antibodies we make in response to the vaccines protect us from the variants. The beta variant (formerly B.1.351) seems to not be well covered by the current vaccines, and Moderna already has a study underway of a modified vaccine specifically for this variant. Delta seems to be reasonably well covered by the current vaccines, but we have a lot to learn about omicron at the time of this writing. We'll have to monitor how well we stop the spread and limit the emergence of new variants to see whether we'll need to re-vaccinate with modified vaccines from time to time. (See the hand-glove analogy in the FAQ about escaping from our immunity).
I hear a lot about long COVID, which we don't hear about with any other respiratory viruses. Why is that, and what does it mean?

Short Answer: Because of the way it attacks our respiratory tract, COVID is able to provoke an autoimmune process in which it causes us to make antibodies that attack our own tissues. The long-term consequences of this are still unknown.

Expanded Answer: No other respiratory viruses cause symptoms that last many months after the infection itself - we're now seeing reports showing that as many as 30% have shortness of breath and fatigue a full year after the infection is gone - and no other respiratory viruses interfere with an important regulatory system (angiotensin/bradykinin) like COVID-19 does. From that, it was inferred early on that long COVID is a form of autoimmune disease, and we're now seeing evidence that supports that. A major concern becomes what might happen if we get infected, don't maintain our immunity with vaccination and stop masking and distancing, and get infected a second, third, fourth time. Will the autoimmune effects sharpen and intensify with subsequent infections? Will the brain fog, heart troubles, and shortness of breath keep getting worse each time? We don't know the answer to any of these questions, and some questions are better left unanswered! The problem with autoimmunity is that there is no do-over; if we ignore the possibility of autoimmunity, act like the pandemic is over, and start seeing long-term adverse effects from it, there is no walking it back. The safer course is to take all available steps to minimize infections to prevent any long-term complications from multiple infections.
We now have good treatments for COVID-19 - a few different antibodies against it, and some inhibitors of coronavirus replication, among others. Why don't we just leave those who don't want to get vaccinated alone, and make sure we treat everybody who gets infected rapidly?

Short Answer: This approach doesn't do anything to prevent infection, which is the main goal of the pandemic response. The only way to limit the long-term consequences of this disease is to do what we can to not get infected in the first place.

Expanded Answer: Three reasons to continue to try to prevent infection rather than treat the disease once it takes hold: 1. We cannot predict who will have rapidly progressive, severe disease. We would likely still see many people suffer severe disease up to and including death, particularly if people were to first "see how it goes" for a while and delay treatment. 2. This approach still allows people to get infected, possibly leading to the autoimmune complications we know as long COVID. We have no idea whether these treatments would prevent people from getting long COVID once they are infected, even if these treatments did decrease the severity of the infection. 3. A main purpose of responding to a pandemic is to limit the spread of disease, since viruses can only mutate when they replicate. Taking a wait-until-infected-and-then-treat approach does not limit the development of new, potentially more problematic, variants.

Perspectives and next steps with the pandemic

People die of respiratory illnesses every year - did COVID-19 really make that big a difference?

Short Answer: Yes. Between March 1, 2020 and January 2, 2021, there were 2.8 million deaths in the US, about 23% more than expected. Most of these were due to COVID-19.

Expanded Answer: The excess deaths in 2020 (23%) is substantially more than in recent years (<2.5%). Of those, 72% were attributed to COVID-19, and these deaths reflected racial disparities in COVID-19 (highest among non-Hispanic Black). Many of the excess deaths not due to COVID-19 were due to heart disease, dementia, and diabetes, and these excess deaths were associated with surges in COVID-19 activity. It is widely believed (though difficult to prove) that many of these deaths were due to delayed care during surges - people reluctant to go to the hospital for fear of being exposed to COVID-19 patients. for more information: Woolf SH, Chapman DA, Sabo RT, Zimmerman EB. Excess Deaths From COVID-19 and Other Causes in the US, March 1, 2020, to January 2, 2021. JAMA. 2021;325(17):1786-1789. doi:10.1001/jama.2021.5199
I look around, and almost nobody is wearing masks - the pandemic must be over. Why vaccinate now?

Short Answer: No, the pandemic is far from over, with less than 45% of the world's population vaccinated as of this writing (November 2021). Vaccination protects against infection, protects against severe disease, and protects our children - both those ages 5 to 11 who are unvaccinated, as well as those under age 5 who are not yet eligible.

Expanded Answer: Infections have slowed down, but enough people remain at risk of infection that it is important to continue efforts to limit the spread. Even more importantly, hospital systems across the globe are reporting that more than 90-95% of people getting hospitalized or dying from COVID-19 are unvaccinated. Although no vaccine is 100% protective against getting infected, people who get infected after vaccination almost never get severely ill. The current vaccines are highly effective at preventing severe disease.
I've waited a year for the vaccine to finally come out so I can get back to my life. But now that I'm vaccinated, some people are saying we should keep on mask-wearing and social distancing anyway, even though these restrictions are being relaxed! Why?

Short Answer: No vaccine can be 100% effective, and because the vaccine does make illness less severe, it is possible for vaccinated people to get asymptomatic infection and be able to spread the disease to others. Limited data we have suggests this risk is very low, but not zero.

Expanded Answer: It is the antibodies secreted into respiratory secretions, not in the bloodstream, that are protective. If you get exposed to respiratory droplets that contain virus, it is the antibodies in the fluid covering the eyes, nose, mouth and lungs that have to latch onto the spike proteins to prevent all those virus particles from infecting us. So if you have a huge exposure (for example, an infected person suddenly sneezes on you), you might not have enough antibodies lining your respiratory tract to prevent infection. But if you get infected, the antibodies in the bloodstream will limit the infection, so you might not even know it. We don't know how asymptomatic infection in vaccinated people happens - to find out, we have to go out and randomly test many people who have been vaccinated, and we just don't have the resources to do that. But in certain circumstances (for example, the mandatory testing required prior to elective surgery), we have seen very low numbers of vaccinated people testing positive. So continuing to reduce your exposure after vaccination helps to prevent getting infected, prevents you from unknowingly infecting others, and helps to encourage everybody to keep taking care to prevent the spread, whether vaccinated or not.
What's the deal with omicron?

Short Answer: Omicron is the latest variant of the SARS-CoV-2 virus to earn the Variant of Concern status from the World Health Organization. That means it has evidence to suggest it is more transmissible, causes more severe disease, or gets past our defenses such as vaccines and other public health measures intended to contain the spread. How bad this variant will turn out to be is as yet unknown as of this writing (November 30), but we should have much more information in a few weeks.

Expanded Answer: The Omicron variant is known to have a few dozen mutations, that potentially affect important aspects of the virus. It might bind more tightly to human cells, increasing its infectivity and transmissibilty. Some of these properties might allow it to cause more severe disease. Of particular concern is that these multiple mutations might change the outside shape of the spike protein so much that the antibodies we have produced from our current vaccines might not effectively prevent infection. This does not look at this time to be a particularly bad problem, but more information is needed. In the meantime, the best strategy is for as many people as possible to either get vaccinated or get a booster, so we are in the best possible situation to fend off infection.

Considerations for gatherings

What can we do to get together with friends and family, but still remain safe?

Short Answer: The pandemic is far from over, and we have seen ample evidence over the past few months that vaccinated people who unnecessarily expose themselves to potentially infectious people can overwhelm their protective immunity and still get infected. We also have evidence that vaccinated people can be infected and spread virus even without having symptoms, and can therefore be a risk to others around them, especially other people who are unvaccinated. So the basic principles of vaccination, masking, distancing, and hand-washing all still apply. More specific recommendations in the Expanded Answer.

Expanded Answer: Vaccination remains our best defense to pull ourselves out of this pandemic. Specific steps to use include:

• Encourage all family members to get vaccinated

• Consider limiting your exposure to family and friends who are not vaccinated, as they present the biggest risk of transmission

• Even if there is not enough time to get fully vaccinated, even one dose of an mRNA vaccine before holiday gatherings, as much in advance as possible, will help

• Consider promoting vaccination among your family by letting everyone know that your home is only open to vaccinated people. This is a very reasonable request, especially if vulnerable people will be there, such as the elderly, unvaccinated children (especially those under 5 years of age who cannot be vaccinated yet), and people with conditions that put them at high risk of severe COVID-19 such as diabetes and high blood pressure

• Zero tolerance for people with symptoms. Hopefully anyone with symptoms of a viral infection such as runny nose, sneezing, cough or fever will have enough respect for others and decline participation, but if anyone with symptoms of any viral infection shows up, they should be turned away

• It is not unreasonable to ask all guests to take an at-home, rapid antigen test on the morning of the gathering. Many people with family members at high risk of severe disease do this, now that these tests are readily available

• Masking when not eating is a good idea, even though it's awkward. If people will be present who are not vaccinated or ignore the risks and often go to places like bars or concerts where there are a lot of unmasked people, this is not an unreasonable request

• Ventilate. Even if it's cold outside and you can't have a lot of fresh air coming in, just cracking open a few windows so there is some air exchange in the home can help

• Spread out. Having people eat in the kitchen, the dining room, and at the coffee table is better than crowding everyone around a single large table in one room

• Limit traditions that involve hand-to-hand contact or passing things from one person to the next, or have plenty of hand sanitizer

• Handling things with intact skin (no cuts or open sores on the hands) is not a problem, but remind guests to wash their hands or use hand sanitizer before touching their face

• Consider designating someone to serve food to everybody, rather than passing serving plates around the table

• Minimize exposure. Have everybody plan to arrive just as dinner is served, exchange presents and honor other family traditions, then call it a night