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COVID-19 antibodies: Should we worry about reducing levels?

COVID-19 antibodies: Should we worry about reducing levels?


COVID antibody going down


Written By:

Mr Devi Prasad V.,

PhD research scholar, CSIR-CCMB, India


In the past few weeks, we have been hearing of studies showing that antibodies against SARS-CoV-2 decrease in patients who recover from COVID-19, and the levels might even become undetectable within a few weeks after recovery. Reports also say that humans might not be acquiring long-term immunity against SARS-CoV-2.

This is indeed frightening because if we cannot become immune to the virus, then

  •  Recovered patients can get re-infected,
  •  Health complications and deaths will increase,
  •  Vaccines will be ineffective,
  •  We will never be able to achieve herd immunity,
  •  We will rely solely on new drugs for a momentary cure, and
  •  The disease cannot be easily eradicated.


This could also mean that COVID-19 will become COVID-20, COVID-21, and so on. But let’s calm down a bit. If we can understand for ourselves how the immune system works and what recent research has actually found, it might not seem so bad after all!

Human beings are one of the most highly evolved creatures on the planet, with very complex organ systems in the body, and our immune system is no exception. Every day, we are attacked by foreign substances, starting from microscopic bacteria, viruses, fungi, toxins, to macroscopic insects, worms, pollen, etc. Nonetheless, not only have we individuals survived till today but so has humankind, for millions of years. Thanks to our body’s immune system.


Types of cells in immune system
Image: Types of immune cells.
Image Source: Medical gallery of Blausen Medical 2014". WikiJournal of Medicine.


We have two major arms of the immune system – innate and adaptive. The innate immune system consists of cells that are like local vigilantes. They attack any suspicious foreign material in the body and kill, incapacitate, or eat them, to prevent them from thriving further. But, although they have the weapons, these cells are not very intelligent. They can even go beat up a wrong target, causing damage to our own body (which is what happens in severe cases of COVID-19).


Image: A neutrophil (purple) eating a bacterium (yellow).
Image source: National Institute of Allergy and Infectious Diseases (NIAID).

On the other hand, the adaptive immune system comprises very specialised cells called the lymphocytes. These are of two types – B lymphocytes (from the bone marrow) and T lymphocytes (from the thymus). These are like trained intelligent cops, who verify using fingerprint scanners, photo identification, etc., before trashing up a suspect. Sometimes, these cops also outsource the killing job to the innate immune cells.

What are antibodies?

Each cell type has a different style of attacking foreign matter. One category of B lymphocytes, called plasma cells, makes large quantities of unique custom-made proteins, called antibodies (Abs). These Y-shaped proteins have tiny structures that can sense several different shapes on the foreign body, such as a virus. Among the millions of plasma cells in the body, only a small subset can make Abs that can bind to SARS-CoV-2 virus.

When several of these Ab molecules stick to a virus, they “neutralise” the virus and prevent it from infecting the cells in our lungs. In order to visualise this, consider the virus as a ball of dough. When you place it on the table, it sticks to the surface. But if we coat the dough with dry flour, the dough is not sticky anymore. Similarly, a virus coated with numerous Abs cannot “stick” to and infect lung cells. Furthermore, our local vigilantes, the innate immune cells, will see this Ab-coating as a tasty flag and eat up the virus.


Antibodies binding coronavirus

Image: Graphical depiction of antibodies binding to the virus. Antibody icons made by Flat Icons from www.flaticon.com
 


Abs are very important for fighting infections. In fact, people with severe cases of COVID-19 have been reported to have much higher quantities of Abs produced than those with mild symptoms.

However, recent studies have also shown that the levels of Abs sharply decrease within weeks after a person recovers from the disease. Does this mean that there is no readymade protection from the virus anymore? Is a cured person as susceptible to the disease as a new person who has never seen the virus? Well, I think not. We know our body is a very complex evolved machine. Do you think it would so easily give up on a virus?

Our bodies can “remember” past infections

When there is an infection for the first time, the body takes time to even realise that there has been a security breach. Then, it sends its innate immune army to the site. Next, the B lymphocyte troops reach the spot and then start making plasma cells. These plasma cells then make Abs against the virus. This whole process can take 1-2 weeks from the start of the infection, by which time the virus would have happily multiplied and sometimes caused enough damage.

However, when the virus revisits in the future, the body responds within a few days and launches a strong attack. But how? There is a second category of B lymphocytes, called the memory B lymphocytes, which persist for years. As soon as a familiar virus is detected, there is a fast-track production of plasma cells and Abs, and the virus is quickly eliminated before it can even establish a home.

This is how vaccines also work – vaccines are nothing but inactivated viruses or viral components that train the body to make memory cells for future attacks by the real virus. This memory is the reason why people who have been administered polio or measles vaccines do not develop the disease. Moreover, such immunity is also acquired naturally, like in the case of chickenpox; most people do not get re-infected and hence the immune adults are able to take care of the infected kids.

Oh, we forgot about the “T” party

Remember the T lymphocytes we talked about? There is a class of them called the cytotoxic T lymphocytes. These are the major adaptive immune cells that respond to viral infections. Viruses cannot live independently; they thrive inside our own cells. And as the name suggests, cytotoxic T lymphocytes cause toxicity to virus-infected cells and kill them, thereby preventing further spread of infection. Sounds cool, right?

But as you already guessed, these cells have a job only during an active infection. Once the viruses are cleared from the body, these cells also die. So, what happens when the virus comes back later? Surprise, surprise! These cytotoxic T lymphocytes also have a memory compartment that is alive in the body for years, as seen in the case of the 2003 SARS-CoV outbreak. During a subsequent infection, these silent cells turn violent and start attacking virus-infected cells again. Interestingly, in some COVID-19 patients where even Ab responses were absent, T cell responses have been detected.

So, should we still be worried?

Coming back to our Abs, why is the decline in Ab levels alarming, given so many other layers of protection? Well, for many diseases, the plasma cells that make the Abs are long-lived. Although, this is not a rule; some diseases (like COVID-19, apparently) generate short-lived plasma cells, that last only for weeks. But we would not have to worry if the memory cells are made against this virus.

Since Abs are protein molecules abundantly flowing in the blood, it is easy to detect them using methods such as Rapid Ab testing or ELISA. On the other hand, detecting memory B and T lymphocytes in everyone is not as easy. First of all, we are still learning how these cells look and how they can be identified using specific tags on their surfaces. Also, T lymphocytes do not make Abs, making their detection even more difficult. Secondly, these cells do not all flow freely in the blood; they are mostly stored in the spleen, lymph nodes, and lungs. Thirdly, their numbers are very less and hence can be easy to miss. Lastly, these tests are complicated, expensive, and time-consuming.

Although it is human nature to first do what is easy, we must not forget the reality. If memory lymphocytes are not easy to detect, how do we know they exist? The straightforward and robust test is to wait for several months and closely monitor recovered patients to see if any of them gets re-infected. However, that is not pragmatic, given the severity of the pandemic.

But not to worry, we can look to our primate ancestors for help. We already know that monkeys that have been infected once, do not get re-infected. Although there is a decline in Ab levels, they again increase if the animals are given a second dose of the virus during the decline. This means that there could be some kind of memory B cells that are responding to the secondary infection. Such experiments could also be done over a longer period to see if monkeys are protected from re-infection even after several months.

A very recent study in humans has shown that memory B lymphocytes are detected in convalescent COVID-19 patients and long-term protection is anticipated. Additionally, it has also been observed that people infected with SARS-CoV in 2003 still possess memory T lymphocytes against the old virus, that may help in the fight against SARS-CoV-2 as well.

Does that mean we are invincible?

No, not really. On the flip side, there are some diseases against which our immune system cannot create lifelong immunity. For example, the tetanus toxoid can trigger immunity that persists only for several months to a few years. Also, some viruses, like HIV, attack the immune cells themselves, thereby preventing the formation of immunity. Even in COVID-19, the T lymphocyte population temporarily declines during the infection. Recently, it has also been shown that the virus can infect macrophages, one of the major innate immune players. But these cells are restored to their original state after the infection subsides, indicating that there might not be permanent damage to the immune system.

Additionally, the virus is a continuously evolving entity. If the immune system is trained for a particular strain of the virus, and it encounters a mutated version in the future, the older Abs and memory cells might not work as efficiently. We know for this to happen with the influenza (flu) virus, thereby necessitating the discovery of new vaccines every year. Fortunately, in the case of SARS-CoV-2, the mutation rates are much lesser, and so are the chances of the virus escaping any pre-formed immunity. But since it is a novel virus, we are yet to observe the long-term effects of accumulated mutations.

Therefore, until further studies prove the absence of any kind of long-term immunity, we can and should remain hopeful that some of the aforementioned mechanisms will keep us protected from re-infections. Nonetheless, this in no way means that we can be careless and let evolution or vaccine/drug companies fight the battle for us. We need to be responsible as a species and watch out for our collective well-being.

About the author:

Mr Devi Prasad is a PhD research scholar at CSIR-Centre for Cellular and Molecular Biology, India. His research is focused on immune memory in B lymphocytes. He is a “corona warrior” and has been involved in testing patient samples from Telangana, for the presence of SARS-CoV-2. He was also in the team that recently developed an inexpensive and sensitive assay for COVID-19 testing.

You can reach him here or here.  

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