COVID-19 “ANTIBODIES” has been a popular buzzword since 2020. It all started with media bombarding every channel about importance of antibodies in fighting COVID-19. Since then, everyone wants to grab whatever information they can so that they can eventually have antibodies against COVID-19!
Unfortunately, there are more myths than facts about antibodies.
Actually, there is nothing new about antibodies. We have scores of textbooks existing since decades that outline clear facts about antibodies. Yet, it’s astonishing to see how even the experts are ill- informed about the facts around antibodies. Armed with this media driven disinformation several decision makers in families, schools, housing societies, offices etc. across continue making utterly foolish decisions and policies. Their intentions are noble. But their actions are led by myths. Such actions lead to imposition of insensible restrictions that do not help in any way to stop COVID-19, but just add to unnecessary costs and discomfort.
So, this post is an attempt to dispel all these common myths about COVID-19 antibodies.
For Audio Lovers: Audio-Narrative on Antibodies
For those who would like to listen to the entire post, rather than reading– please use the below audio link:
Others may simply read along from below!
For Readers: Facts About Antibodies
Imagine viruses to be like terrorists. Each such terrorist is wearing a protective shield. This shield is very strong and protects this terrorist from being killed by defending soldiers. However, each shield has a lock. If you can open the lock, the shield will open up and fall off, exposing the terrorist naked and vulnerable. Now the defending soldiers can kill of this vulnerable terrorist easily.
Also, shields of terrorists from a specific group will have similar locks. So, all terrorists from “alpha group” will have similar locks specific to alpha group. Let’s call these locks as “alpha locks”. Similarly, all terrorists from “beta group” will have similar locks (the “beta locks”) specific to beta group. But the alpha locks will always be different from the beta locks. The difference in the structure might be very little. Or sometimes they can be exceedingly different.
Now let’s imagine a scenario where terrorists from alpha group (we will call them alpha terrorists) attack a country (let’s call this country as “Zel”). Soldiers of Zel will have a very hard time to fight against alpha terrorists so long as these terrorists have their shields on. So, at the very early stage of the battle Zel defense starts making large keys in the hope that these will help opening the alpha locks of the shields. The structure of these keys are based on initial information collected by Zel intelligence. However, since the information is limited at this early stage, the initial keys are designed to work like master keys (we will call them “M- alpha keys”). These “M-apha keys” are large, heavy and don’t open up the locks quite efficiently. However, as the battle proceeds, Zel intelligence finally is able to fully gather all the information needed to make an accurate key specific to the lock that keeps any alpha terrorist shielded. These specific keys are very good (we will call them “G- alpha keys”), and now the Zel defense starts making these “G- alpha keys” in huge quantities. The Zel soldiers use these keys to open up the locks on the shields worn by alpha terrorists. Stripped off their shields, the alpha terrorists are now sitting ducks simply to roasted dead by Zel’s soldiers.
Note that it took some time for Zel defense to develop the “G- alpha keys”. This delay allowed alpha terrorists to push their way in and penetrate deep inside Zel’s territory. Here they could now capture many of the houses and start occupying those houses. Once inside such a house, the terrorists lock the doors from inside. They start using resources from these captured houses to heal their wounds, keep themselves warm and well fed. Once they are ready, they start their attack again.
Once any terrorist has penetrated and taken shelter inside any house within Zel’s territory, it is a difficult task to kill such terrorist. Zel soldiers do not have any weapons to break open the doors and fight these terrorists out. Hence, the “G- alpha keys” are useless here. That’s why, the only option left for Zel defense is to simply bomb these hijacked houses and destroy them completely. But they cannot simply bomb any house- they need to be sure that the houses they are targeting are the ones in which terrorists are hidden. If targeting is inaccurate, such bombing will end up killing a large number of civilians.
Remember, earlier we noted that all these terrorists from alpha group wear shields that bear similar locks. That’s how, using alpha keys, Zel soldiers were able to strip off these shields and kill the terrorists. In this situation where alpha terrorists are hiding inside a house, the alpha keys are useless. But the terrorists are still wearing shields that bear alpha locks. So Zel defense then start creating “targeted” smart bombs such that these bombs will blow only those houses that have anyone inside carrying the alpha locks. Let’s call these smart bombs that can specifically target alpha locks as “T- alpha bombs”.
In summary any alpha terrorist not inside the house will be attacked using “G- alpha keys” and any terrorist inside the house will be destroyed using “T- alpha bombs”.
Let’s now imagine that eventually the Zel defense is able to kill all the terrorists and win this battle. Once the battle is over its important to do a good analysis and learn. The first thing Zel defense concludes is that while their soldiers were shooting and throwing bombs at the terrorists, a lot of innocent citizens of Zel were also killed. This is expected as collateral damage in any war. Collateral damage can be prevented if you can specifically target your enemy. Since at the start of the war very little information was available, it was difficult to make targeted attacks on alpha terrorists. This was the main reason for collateral damage. Later, when Zel defense learnt how to make the specific “G- alpha keys” and “T- alpha bombs” collateral damage was minimal. Zel defense quickly starts archiving the information about making these “G- alpha keys” and “T- alpha bombs” in a book called “Fighting Alpha”. This book is kept in their central library.
So if, several months later, the terrorists from alpha group attack Zel again, the Zel defense would simply refer to the book “Fighting Alpha” in the library and start making “G- alpha keys” and “T- alpha bombs”. They don’t have to wait and gather all the information and then figure out anything- they have all the needed information in that specific book.
We now fast forward to a future time point for Zel, 10 years later. In these 10 years several different terrorist groups attempted attacking Zel. Few attacks were formidable. Many were just weak futile attempts. Let’s take example of alpha terrorists. They attacked 90 times till now. They are moderately formidable opponents and can’t be ignored. But whenever alpha terrorists attacked, they were easily destroyed using “G- alpha keys” and “T- alpha bombs”. Since the attacks for alpha terrorists are quite frequent, the book that contains information on how to make “G- alpha keys” and “T- alpha bombs” is kept at the front shelf of the library and everyone knows about that book.
Similarly in these past 10 years, another terrorist group called “beta” had also attacked Zel. They attacked 3 times till now. During the first attack Zel defense quickly realized that the beta terrorists are weak and can never be a formidable threat. As a rule, Zel defense did make “G- beta keys” and “T- beta bombs”. As a rule, Zel defense did archive the information in a book. They named the book “How to Fight Beta” and kept the same in the central library. But they hardly referred to that book again. Beta terrorists did not attack frequently. And anyways they were not so dangerous. There were so many other more dangerous opponents like alpha group that kept attacking Zel, that there was hardly any focus on this book “Fighting Beta”. Hence this book was delegated to a corner shelf at the back of the library and soon was forgotten.
This is where I will stop asking you to imagine any further and start coming straight to the main topic of this article.
In the above story, Zel is our own body. Zel defense is our immune system. Terrorists are the viruses. T- bombs are the T cells and keys are the antibodies!
When any virus invades our body for the first time (in the above story this correlates to alpha terrorists attacking Zel for the first time), our body’s immune system launches a generalized attack. This initial generalized attack is not specific to the virus that has attacked, and the response remains similar irrespective of whether the attacker is a virus or a bacteria or a fungus. It is this generalized attack that manifests in the form of fever, pain, runny nose, loss of taste etc. Since this attack is not specific, it does end up causing some damage to the surrounding human cells. However, our immune system keeps collecting information and tries making its attack more specific. In its attempt to make attack specific, based on initial limited information, it starts creating large “keys” which can specifically attack the invading virus. These initial large keys are known as “IgM antibodies“ (in the above story these were the “M-alpha keys”). IgM, although specific, is not quite efficient in killing the virus since it is manufactured based on limited initial information about the virus. With time, finally our immune system gathers enough information to make highly efficient IgG antibodies (in the above story these were the “G-alpha keys”). IgG antibodies are smaller than IgM, and are extremely specific in targeting the virus against which it has been designed.
It’s obvious to conclude at this point that if any virus has invaded our body for the first time, initially there are no antibodies and then after some delay there are lots of IgM antibodies. Later, IgM levels go down and are replaced by IgG antibodies. Hope this is logical and you are not getting confused.
However, viruses are quite smart. They start penetrating inside our cells and take over the cellular machinery. And antibodies cannot go inside any cell. Hence, the more the time it takes for our immune system to generate antibodies, more number of viruses will get chance to penetrate into our cells and hide. Once the virus is inside the cell, neither IgM or IgG can do anything against that virus (In the above story, this is similar to terrorists hiding inside Zel houses and the keys are then ineffective). However, we have a very evolved immune system. Apart from antibodies, our immune system is armed with another set of weapons called T cells. There are various types of T cells, but that discussion is beyond the scope of current discussion (I have tried discussing about T cells in another article- click here if you want to read more about T cells). Based on information gathered by our immune system, T cells can accurately locate cells harboring these viruses and destroy only those cells. When such cell is destroyed by the T cell, the viruses hiding inside such cell also get destroyed.
This also means that if a large set of our cells have been invaded by viruses, all these cells will be killed by the T cells. So, if let’s say 75% of your lung cells have been penetrated by viruses you will end up losing 75% of your lungs and can cause respiratory failure followed by death. This is a scary conclusion- and has couple of implications:
- Either prevent the invading viruses from hijacking large number of your cells (this is the basis of vaccination, as we will see later) or
- Prevent T cells from killing all these cells if such killing will eventually lead to organ failure (this is why immune silencing medicines are used in critically ill patients. For further details, click here).
So, antibodies destroy the viruses lying outside the cells and T cells destroy those which are hiding inside the cells– and together they completely eliminate the invading viruses. Once this is achieved, our body also prepares for future battles with the same invader. The knowledge on how to make antibodies and T cells specific to this particular virus is stored in special cells called “memory cells“. These memory cells store the signature of the virus and the corresponding structures of antibodies and T cells that specifically act against this virus (In the above story, the books in the library- “Fighting Alpha” and “Fighting Beta”- are the memory cells).
Next time, when the same virus starts invading our body, our immune system captures the viral signature of that virus, and tries matching that with the database of existing signatures stored in the memory cells (This beautiful signature matching mechanism has been discussed in another article in quite detail- you may click here to read the same). Once the signature matches, the corresponding memory cell immediately triggers production of IgG antibodies. Though some amount of IgM is produced to provide initial cover, this time IgG antibodies are produced rapidly with literally no delay and IgG antibodies dominate the attack. As you can imagine, the initial non- specific generalized attack is also quite limited in magnitude. This is why the symptoms are quite limited when the same virus attacks you again.
Also, this time viruses don’t get enough time to penetrate large number of our cells. Consequently, very few cells are required to be destroyed by the T cells. This results in much lower rates of complications.
Till now you must have noticed that when any virus (or for that matter any pathogen) attacks us for the first time, our response is more generalized. Antibodies come a bit later, and are dominated by IgM in the initial stages. This response from our immune system for the “first time invaders” is called as primary immune response. Primary immune response can cause lot of damage to our own cells. A large number of cells can get penetrated by viruses during primary immune response. Consequently the T cells end up damaging lot of our cells. Hence patients suffer most during this stage. (Remember, in most patients the immune system is mature enough not to cause exceeding damage to our own cells. This maturity depends on how healthy the immune system is. I have explained this concept in quite detail in another article- you may click here to read the same).
However, when the same virus (or any invader) attacks again our body, this time we are quickly able to produce antibodies. This time these antibodies are predominantly of IgG type. This response from our immune system for the “repeat invaders” is called as secondary immune response. Since this time the attack on the virus is quite focused right from the start, the initial generalized response is quite minimal. Due to same reason, this time, the virus is able to penetrate only a limited number of human cells. Thus, compared to primary immune response, secondary immune response results in very minimal damage to our own cells.
Vaccines make our body go through the primary immune response stage without actually facing the virus or the bacteria against which vaccine is designed. Vaccines do this by just introducing the signature of the virus/bacteria. So, when the actual virus/bacteria bearing that specific signature attacks our body, our body responds as if it already faced this invader and mounts the efficient secondary immune response. If you have read everything in this article carefully, it’s easy to conceive that vaccine can reduce the chances of hospitalization caused by excessive damage done by our own immune system. By the same logic, when you get the first shot of vaccine the primary immune response can cause excessive damage in rare cases. This, although rare, is the reason why you hear people getting hospitalized or dying after taking vaccine.
Through vaccine we attempt to train body create antibodies and T cells against the target virus/bacteria. Unfortunately, this attempt is not 100% accurate. The signatures introduced by a vaccine partially mimics the entire pathogen. Hence, in most cases, the actual infection is the best vaccine if you can survive that infection.
Also, we must remember that viruses like COVID-19 keep changing their structures, resulting in different strains. Each strain will have signature with some difference compared to signature of any other strain. Since antibodies are produced by matching these signatures, antibodies are strain specific. If the signature of the virus changes, the same antibodies might or might not work depending on how massive is the change in signature.
Every lock has a specific key. If some serrations inside the lock change, still the key might work- but there is no guarantee. And if there are significant changes to the lock, you will need an altogether a new key- the old key will not work.
Hence, antibodies against one strain of virus might or might not work against another strain of same virus. Vaccines manufactured in 2020 against alpha strain of COVID-19 virus may have very low efficacy against Omicron strain, if there are huge differences in the structures of these two strains. More the similarity between 2 strains, better will be the effect of the vaccine against the second strain although it was designed against the first strain. Hence, technically speaking, use of different types of vaccine for first and second dose might lead to better protection against COVID-19.
About passive immunization
We saw that for our body to generate efficient antibodies against a virus/bacteria, our body needs be either infected by that particular virus/bacteria or we must be vaccinated. Obviously, this takes time. But, what if I want these antibodies right now- immediately? Maybe I have contracted a potentially dangerous infection, and I fear this infection will kill me before my immune system makes antibodies. Is this possible?
Of course it is possible. There are actually 2 ways of doing it. One is to simply collect antibodies from the blood of people who have recently suffered and recovered from same infection. The blood of such an individual will be rich with efficient IgG antibodies. Blood of such individuals can be filtered into a concentrate rich with antibodies. Such concentrate is known an as convalescent plasma which can be then injected into me if I need immediate protection against the infection I am so afraid about.
The other way is to create such antibodies in laboratories using genetic engineering. One such example is Roche’s antibody cocktail (Casirivimab and Imdevimab).
Because these antibodies are not primarily produced by recipient’s body, this way of introducing antibodies from outside is also known as passive immunization.
Question is- are they effective? Let’s talk about viral infections like COVID-19. Remember, antibodies work only against those viruses which haven’t entered the host cells. Once the cells have been infested by a virus, antibodies won’t work. They will have to be destroyed by T cells. So, these antibodies administered from outside work best only when given earlier during the infection. Once a significant number of patient’s cells have been hijacked by the viruses, there is nothing much these antibodies can do. Later complications and deaths are not because of virus anyways. Complications and deaths result from the excessive force and destruction wrecked by immune systems of few unfortunate patients that end up critically damaging internal organs.
So, if you want to use antibodies from outside use it earlier in the infection (maybe within first 4 days). Also, there is no guarantee that these outside antibodies will always work. They are designed to work against a specific strain of virus. And if you have been infected by a different strain of that virus, these antibodies just might not work. Remember what we said earlier- if a lock changes the structure of the serrations inside, the key might not open such lock and you might need a new key specific to this changed lock.
About Immune Memory
Post primary immune response, once the invading virus/bacteria has been completely neutralized, blood remains flooded with antibodies. But they slowly disappear since there is no virus/bacteria left to fight against. It’s really waste of resources to keep producing these antibodies in absence of the corresponding pathogen. So, the knowledge of how to create these specific IgG antibodies and T cells are stored in special cells called memory cells. Slowly the existing antibodies and specific T cells disappear. However, memory cells remain for a very long time– some research show evidence that some memory cells can live life long. So later, when the same virus/bacteria attacks our body again, these memory cells allow immediate production of IgG antibodies and specific T cells against the invading pathogen, leading to the efficient secondary immune response.
Immune memory is very much like our own brain memory. For example, I will definitely forget about a tiny scratch that I got my fore-arm a year back. But I definitely remember the serious accident that I suffered 20 years back, and I remember it very vividly. Similarly, I can’t remember a phone number that I noted yesterday. But if I read that number again and again repeatedly, soon I won’t forget. In short, we remember recent events better; we remember significant events better; and remember better what’s repeated.
Immune memory follows a similar path. Immune memory is more efficient for recent infections. Immune memory is more efficient for infections which keep happening repeatedly. And, immune memory never forgets an infection that caused significant damage earlier. Since the whole point of giving vaccines is to create memory cells, these facts are true for vaccines as well. More painful the vaccine (it can be intense pain, body ache, fever), more efficient is the generation of memory cells. More frequently you take the vaccine shots, better will the secondary immune response.
However, there is a big catch here. Immune memory stores signature driven information; it stores information to produce specific antibodies against a particular signature. If the signature changes, there is no way to predict how these specific memory cells will behave. Even if they produce antibodies, the same antibodies might or might not work, depending on how massive the change in signature is. As discussed earlier, if some serrations inside a lock change, the key to that lock might work- but there is no guarantee. And if there are significant changes to the lock, you will need an altogether a new key- the old key will not work.
So, if you have taken vaccine against a virus, it will create memory cells against that particular virus signature. If then, that virus attacks, body will immediately make specific IgG antibodies and T cells against that virus. However, if the virus changes its structure (we call this as mutation), and the new signature is completely different from the earlier one, the training given by the vaccine will be useless. Our immune system will have to resort to primary immune response and learn to deal with this new signature. If the signature is not very different, it might invoke the earlier memory cells- but the antibodies and the T cells might not work efficiently as the keys might not open the lock this time.
So, vaccine and their boosters are fully effective against the virus they were originally designed for. As the virus mutates the efficacy of vaccines keep going down- more the mutation less is the efficacy of original vaccine. The only way out is to then keep making new vaccines specific to new mutations. But, at any given point (especially in a pandemic), several mutants of the same virus cause infections. So, in reality, the hope lies in the chance that keys will still be able to open the locks, although the serrations of the locks are different!
My personal belief is that the newer variants of COVID-19 virus will keep getting milder than previous variants in terms of lethality. We will keep getting infected, no matter how many vaccines or boosters we take. But hardly anyone will die (death rate should be similar to one we see with common cold). And each such infection will act as booster more efficient than any vaccine booster. And that is the end-game!
I have explained about this end- game for COVID-19 in another post- click here if you want to read further on this
I hope this post is simple enough for any layman to understand all the relevant facts about COVID-19 antibodies. While keeping the explanations simple, the intention is also to make this post useful to even doctors so that they can help me in my quest to fight against media driven disinformation regarding antibodies.
Please note that this blog is specifically designed to make you understand the facts about antibodies. But antibodies constitute just a small component of our amazing immune system. What you have learnt in this blog will be of little value if you do not understand the whole context. I would highly recommend you read the article I had written on our immune system. In that article, have tried to paint the larger picture of our immune system in simple words. Please click here to read that article.