Should I take Covaxin?

A medical worker inoculates a colleague with a Covid-19 coronavirus vaccine at the Rajawadi Hospital, Mumbai. Photo: Manoej Paateel / Shuttertock

This is a question that I have been asked frequently, and I will summarise my understanding on this topic. It is written in plain language for lay people to understand the big picture. I have also included a few insights on how the human mind takes decisions.

What is Covaxin?

It is a traditionally made inactivated virus vaccine for COVID-19.

What does traditional mean?

A vaccine is a technique to introduce a germ (pathogen) into the body in harmless form so that if that particular virus or bacteria attacks us in the future, we will be well-prepared - and escape without serious consequences. Vaccines work by tickling our immune system in several ways. Therefore, there are multiple methods of manufacturing them.

The traditional method is to kill the pathogen, mix it with an adjuvant and inject it.

Unlike live virus vaccines, the advantage of an inactivated vaccine is that there is no risk of actual infection. At the same time, the immune system gets sufficient training to recognise the pathogen. Rabies, polio (Salk) and hepatitis A vaccines are a few examples.

Has anyone else used this method to build a COVID-19 vaccine?

China has used this method extensively. Soon after they identified the cause of the pandemic, two Chinese companies Sinopharm and Sinovac started producing inactivated vaccines using the same traditional platform. Chinese citizens have been receiving these vaccines since April 2020. On 31 December, China gave approval for general use. As of 20 February, 43 million doses of the Sinopharm inactivated virus vaccine have already been administered worldwide – including UAE, China, Peru, Bahrain, Morocco, Egypt, Jordan, Brazil and Argentina.

How good are the results so far?

Although no phase 3 results are published on any of the inactivated virus vaccines, Chinese officials have stated on February 24 that Sinopharm’s Wuhan WIV04 vaccine has an efficacy of 72.5%. On December 30, Sinopharm had announced an efficacy of 79.34% for BBIBP-CoV, the Beijing version of the vaccine. These vaccines have been used in several countries, notably the UAE who found an efficacy of 86% for the BBIBP-CoV after testing it on 31,000 people.

What does the traditional inactivated vaccine contain?

The most effective way to tickle (stimulate) an immune system is to use a live virus. However, due to fear of COVID-19, such a method has not been used yet. Hence a dead version of the virus is used. A chemical called beta-propiolactone is used to kill the virus by bonding to its RNA. The proteins of the virus remain intact; they are needed for antigen recognition by our immune system.

The problem of using a dead virus is that on its own, it is not able to generate a strong immune response. Hence, an adjuvant is used. This will wake up the immune system, which will in turn detect and process the dead virus particles injected alongwith. In Covaxin, Alum-IMDG is used as an adjuvant, which is considered a better version of the old-fashioned alum that has been used for several decades. The three Chinese inactivated vaccines use alum. Alum IMDG is expected to generate a stronger immune response, in a safer Th-1 type direction.

What does the immune system do, once the vaccine is injected?

Specialised cells called dendritic cells gobble up the particles of the virus from the site of injection. They carry these particles to the nearby lymph nodes, which is the training center for our immune cells. By displaying the antigens in a special recognisable format (MHC-2), the dendritic cells initiate the training process of multiple immune cells to produce antibodies as well as to make CD4 T cells and CD8 T cells, some of which are stored away for later use.

A detailed description of memory cells is beyond the scope of this article, but they might prove to be the game changer for the long-term. The longest recorded survival of memory T cells for a closely related Corona virus is 17 years: for the SARS virus of 2003. For obvious reasons, we do not yet know the upper limit of duration of protection for the new virus.

How does that help protect against COVID-19?

The chief reason for the deaths and organ damage caused by the SARS-CoV2 virus is that the human race had never seen this virus before. Because of this lack of familiarity, those who got infected with this virus responded in various ways. The consequences ranged from asymptomatic illness to respiratory failure and death. Some individuals developed a dysregulated immune response, resulting in significant damage to their own body.

Vaccines provide the basic ID of the virus to our immune system. As a result, even if the virus invades the body later, the immune system is able to remember its training lessons, and respond appropriately.

Why not allow the virus to infect us once, so that we get immunity?

We know now that those who had SARS-CoV2 infection in the past are protected from future infections up to 90% of the time – for at least six months. However, getting infected with this virus involves the risk of severe disease and death. Vaccines provide the safer option to achieve immunity.

How do the numbers compare - for virus vs. vaccine for immunity?

To put the numbers in perspective, if 100,000 people get infected by the virus, there will be 15,000 hospitalizations and 1500 deaths. The survivors will receive immunity. (The deaths will vary depending on factors such as average age and access to quality healthcare) But if the same 100,000 people chose to take a vaccine instead, there will be only one person who needs hospitalisation, and zero deaths as a result.

When observed over a period of time, deaths and serious illnesses occur in any population - from multiple reasons. This occurs regardless of whether vaccines are used. Also called background rates, these are not counted as vaccine-related, unless it is specifically proved to be the case.

Which vaccine should I take?

Experts around the world are unanimous on this: the best vaccine to take is the first vaccine we can get hold of.

Which one is better? Covishield or Covaxin?

Covishield is developed by Oxford University-Astra Zeneca, manufactured in India by Serum Institute India. It is an adenoviral vector vaccine that carries the ID of the spike protein with it. Covaxin is a whole virus inactivated vaccine developed by Bharat Biotech in collaboration with ICMR and National Institute of Virology. Both vaccines are known to be safe, and are proven to activate our immune system in the right format. Deciding between the two is almost like deciding between a Toyota and Honda car.

Image courtesy: lakshmiprasada S / Shuttertock

Does Covaxin have any special advantage over Covishield?

All mainstream vaccines are believed to be effective in preventing severe disease; and that is basically because they provide an ID of this new virus to our immune system. As each one of them is built differently, they will have properties that differ from another. Whether these differences translate to actual clinical outcomes will only be known in the long -term. The adenovirus vector vaccine focuses entirely on the spike protein, which is considered to be the most vulnerable part of the virus.

A whole virus inactivated vaccine produces a wider range of (polyclonal) immune response against different parts of the virus. This might offer a theoretical advantage if and when major mutations occur in the future. Minor mutations are expected of any virus and are unlikely to affect the performance of the present-day vaccines.

The first major variant that captured the attention of the world is B.1.1.7 from the UK - due to the simultaneous occurrence of several mutations. Fortunately, there is evidence that antibodies generated by Covaxin in humans are effective against the B.1.1.7 variant. Astra-Oxford vaccine has also been found to be effective against this variant.

That being said, each vaccine will be some theoretical advantage or disadvantage over the other; hence the Toyota-Honda example given above.

Is there any evidence for Covaxin being effective? What determines effectiveness?

While none of the four widely-used inactivated virus vaccines have published their phase 3 trials yet, we do have statements from the manufacturers of near-identical vaccines from China that their efficacy ranges from 72.5% to 79.3%.

Real-life effectiveness of a vaccine depends on the immune response it brings about. This is multi-pronged. Although antibodies are discussed more frequently, those who have deep knowledge of immunology say that it is the T cells that really protect us from severe disease. According to Prof. Shane Crotty of La Jolla Institute for Immunology, California, “Among all the players of the immune system, it is the T cells that do the heavy lifting”.

Antibodies are certainly better known to the lay public, and are also easier to measure. However, they are not known to be reliable immune correlates. Their levels drop with time. Even those who do not have high antibody levels have been proven to have protection as a result of T cell immunity. Unfortunately, it is not possible to measure T cell immunity outside of research labs.

From a user’s perspective, I believe that Covaxin has all the qualities that I would want from a COVID-19 vaccine. There is published evidence that Covaxin generates adequate antibodies, and the right kind of T cell response.

Is Covaxin safe?

As it is a traditional inactivated virus vaccine similar to several others that have been used over the years, the safety profile of Covaxin can be predicted to a large degree. The concern about safety was primarily regarding the ‘new generation’ vaccines such as mRNA and adenovirus vector vaccines, simply because they had not been tried out much in the past. However, in the past year, these concerns have been erased.

The safety and immunogenicity data of Covaxin was published in The Lancet on 21 January. In the study I did on post vaccination symptoms in India, 55.6% of those who received Covaxin reported the usual self-limiting symptoms of any vaccination. This was lower than the average of 65.9%, but direct comparison was not possible because of relatively small number of Covaxin recipients in the study. No serious effects were reported in that study of 5396 participants.

Is it compulsory?

Deciding to take a COVID-19 vaccine is like choosing to wear a helmet while riding a two-wheeler. It does not stop accidents from happening, but improves our chance of being alive afterwards. Likewise, it is up to each individual to decide what is good for themselves and their dependants.

Image courtesy: Scott Cornell / Shutterstock

What is clinical trial mode?

Vaccine approval during the pandemic has been unconventional, unpredictable and unprecedented, with substantial variation between countries. Several confusing technical terms have been heard in this context. From a user’s standpoint, it involves signing a consent form to receive the vaccine. Such consent forms are commonly used for documentation purposes while visiting hospitals, getting an MRI scan or even opening a bank account.

Why are some people reluctant to take the vaccine?

There are several reasons for reluctance. If we discount those who are habitual anti vaxxers, there are several well-intentioned people who are concerned due to the numerous technical terms and dramatic news reports about vaccines. Paranoia created in social media groups and lack of background knowledge aggravates their confusion. Information overload and overthinking is a topic that I had written about a few years ago, which basically means that the quality of decision-making decreases when the quantity of available information increases.

An example to illustrate how information overload corrupts decision making is as follows.

Imagine that we go to a fruit shop to buy mangoes. In order to decide which mango to buy, let’s say that we decide to visit the library, check the encyclopedia and other available references on mangoes and other fruits, besides asking the opinion of a dozen people. In the end, we might decide to not buy anything, or even that we are better off buying apples instead of mangoes.

In addition to overthinking, there are those who believe that all the trial results must be published in medical journals before a vaccine is cleared for emergency use. While this is a valid thought process in an ideal world, it is noteworthy that about 43 million people in various countries have already received vaccination without the results of phase 3 trials being published. As far as vaccination goes, the earlier we can generate immunity among the vulnerable population, the lower the death rate will be, and the better it is for the world. Even when done one day early, vaccination saves lives.

Image courtesy: Anishka Rozhkova / Shutterstock

Opinion is divided about when exactly we go ahead with a decision based on trust, as opposed to hard evidence - while facing an unprecedented emergency and limited resource.

What exactly is meant by a decision made on trust?

Human decision making is not a black and white process, as we would expect from robots. In real life, even though we believe we are objective and evidence-based, many of the decisions we take are based on trust, heuristics, and in good faith. Decisions are influenced by several factors including cognitive biases. In fact, when we take healthcare as a whole, a large chunk of the decisions are based on belief and hearsay rather than hard evidence.

Let me quote a real-life example to illustrate a decision based on trust. When I was a teenager in 1984, bookings opened for the first Maruti car in India. My father, a mechanical engineer - decided to book a Maruti 800 car and paid an advance. He was immediately criticised by several of his colleagues and relatives. They said: “This car is made by a Japanese company, and you are getting one of the first cars. How do you know it will survive Indian conditions? What if you don’t get spare parts? Who will do the repair work? Ambassador and Premier Padmini are much better options - because these are the cars that are built for Indian roads.”

My father was firm. He said: “The Maruti 800 may not have been tested on our road conditions. But it is made by reputed car manufacturers. I trust their expertise, and I trust what I know about cars in general.”

Needless to add, we were happy owners of a lovely brown Maruti 800 that served us without any trouble for a long time. This was an example of how a decision is made on trust. The evidence came much later. If my father had hesitated after taking multiple opinions, we would have lost the chance to use a nice car for several years.

Approving a vaccine is obviously not the same as buying a car, but the principle outlined here is that trust is not a black and white (binary) entity, and that the amount of proof required to build it can vary between individuals and societies. What is acceptable for one person need not be so for another. In the example above, my father’s experience and superior knowledge of mechanics helped him cement his decision, and overcome the obstruction caused by doubters.

Deciding on a life partner is another example of a decision based on trust. That is, in spite of the shortcomings pointed out by critics at the outset, we trust that the relationship will be successful in the long-term.

Let not perfect become the enemy of good

While we wait for more scientific evidence, “we must not let perfect become the enemy of good” which means that sometimes we lose valuable time by waiting for the perfect solution. By forgetting what is truly practical and good for the society as a whole, we often delay something that was available - and beneficial. The contrasting approach and experience of several nations to the same pandemic is proof that a one-size-fits-all attitude will not work.

About the author:

Dr Rajeev Jayadevan MD, DNB, MRCP, American Board certification in Medicine, American Board certification in Gastroenterology; Vice Chairman, Research Cell, IMA Kerala State

Further reading

1. Summary of frontline vaccines, Nature, February 21

2. China says it will have vaccines ready for emergency use by April 2020

3. China’s human trials with Sinopharm’s inactivated vaccine started in April 2020

4. China started vaccinating their citizens before clinical trials are published

5. Chinese inactivated vaccine “PiCoVacc” (now known as CoronaVac) by Sinovac was effective in animals, and did not produce ADE upon re-challenge, even when antibody titres were low. Science, May 6.

6. Alum is not the cause for ADE as originally thought, experience from animal studies with the SARS 2003 vaccine

7. ADE not observed in an immunization-challenge model of monkeys using COVID-19 vaccine candidates, including 2 other inactivated vaccines: JAMA Sept 30

8. Wuhan inactivated vaccine by Sinopharm phase 1 study on 320 volunteers. JAMA 8 September

9. Beijing inactivated vaccine BBIBP-CoV by Sinopharm animal trials show safety and immunogenicity, no ADE in monkeys

10. Phase 1/2 results of Beijing inactivated vaccine BBIBP-CoV by Sinopharm, Lancet Inf Dis January 2021. The antibodies could neutralise multiple SARS CoV2 strains. Older people also had 100% seroconversion albeit at lower titres.

11. UAE reports 86% efficacy for Sinopharm’s BBIBP-CoV vaccine

12. Covaxin generates expected immune response

13. Safety and immunogenicity of Covaxin, Lancet 21 January

14. Antibodies generated by Covaxin are effective against UK variant B.1.1.7

15. Astra-Oxford vaccine is effective against B.1.1.7 variant

16. Survey of post vaccination symptoms in India: Dr Rajeev Jayadevan

17. How information overload corrupts our decision making: Dr Rajeev Jayadevan

18. The many factors involved in decision making: Harvard Business review

19. The neural basis of decision-making, including the Baye’s decision theory and variations that occur in real life.

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