By Prof. Narendra Nayak
Mangaluru, Feb 11, 2021: With the confusion of a new strain of SARS2 alias covid19 virus with increased transmissibility and supposedly more deadly along with the release of the three vaccines in addition to some already there in the market has added to the scenario! So, a clear analysis of the state of affairs is warranted. The whatsapp university and face book colleges have also made their own contributions along with the religious lobby throwing in their hats into the ring to muddle up the affairs. Again a big fuss has been made about the contraindications for the two approved vaccines. But, it is conveniently forgotten that the same are applicable to almost every vaccine-even those in use since decades!
If you go back to your school days one can understand that a vaccine develops immunity to a disease. While getting infected and surviving it seems to be the best form of vaccination (including healing from dreaded diseases like plague, small pox etc of the good old days!) the heavy morbidity and mortality associated with it makes it a very inefficient and expensive method! The good old immune system of the human body develops immunity to infections by a number of mechanisms which for the sake of simplicity let us say the antibodies. These antibodies are formed in the body in reaction to what are called as antigens- usually foreign proteins- those of the bacteria, viruses etc. These antibodies bind to these and effectively neutralize them. These which are naturally causing deleterious effects on the body are also called as toxins- it is that all toxins are not proteins and also that all proteins are not toxins too. But, the body mechanisms look upon all proteins which are not constituents of the body as foreign and also form antibodies to them which is called as immune reaction. Well, this could sometimes be to one’s own body proteins too and in such cases it is called as an autoimmune reaction- those called as autoimmune diseases belong to this category. But, more discussion on these is beyond the scope of this write up. In rare cases allergies develop due to these reactions and sometimes a severe one called as anaphylaxis. These points are of relevance because some reactions to vaccines can be of this type too. The principles of vaccinations of the classic type are using a strain of the organism which confers immunity but causes a milder form of the disease or converting the various toxins of the organism to a form called as toxoid which while retaining the property of being able to produce antibodies does not have the toxic properties of the natural toxin. But the modern vaccines have now gone a step or two ahead of these concepts with the advance of science and technology. The immunity developed could be of various types as far as the transmission and effects of the disease are concerned. One can have what is called as he sterilizing type of immunity which means that though one gets exposed to the disease it will not find a foothold in the body and hence nothing will happen. On the other hand it could be protective immunity which does not prevent one from getting infected but is protected from severe effects of it. Whatever the type of immunity that may be developed to the covid vaccine, it would be certainly of use is preventing the transmission and the development of herd immunity. This concept when made simple just means that when enough number of people get infected, healed and develop immunity the transmission of the virus comes to a stop or becomes so low as to make it no more of a pandemic. Experts estimate the percentage of population anywhere from 60% to 90% to be immune to develop that. So how does one accomplish that? As already mentioned the good old method of getting infected and healed would be too much of a burden on the health care system as well as the society. Vaccination would be ideal but with a population of billions all over the world with at least 60% to be covered! So, now it looks like a judicious mixture of vaccinating the most vulnerable sections first followed by the universal coverage seems to be the only way out- provided the vaccine holds out against the possible mutations likely to happen, because the covid virus like all RNA viruses has a notorious reputation of mutations and some such RNA virus vaccines like the influenza vaccine needs tweaking every season.
All these advances have been made use of in the top three contenders of the race for the vaccine. The first ones released- the Pfizer and Moderna make use of a very recent concept.It depends of the property of the virus which uses the body’s own mechanisms for survival and reproduction. In fact the virus outside the cell is a strand of nucleic acids enclosed in a capsule of protein and lipid. This outside capsule facilitates the entry of the virus into the cells of the host. In case of the covid19 virus it is the protein called as spike protein which binds to AC2 receptors on the cell membrane causing its entry into the cell. Once the material enters the cell it utilizes the body cellular mechanisms to reproduce and also synthesize all the molecules needed for its survival and reproduction. These overwhelm the cell in such a way that it dies and the membrane ruptures releasing many copies of the virus into the blood stream from where it reaches all over the body. The vaccine made by these two consists of that part of the mRNA of the virus which codes for its spike protein. This mRNA is enclosed by a membrane by the help of which it enters the cells. Utilizing the body mechanisms the spike protein of the virus is formed using the mRNA as the template and this gets released into the circulation and antibodies get formed against that. These antibodies will protect against future infections by the virus by binding to its spike protein and inactivating it. Among these the Pfizer one needs refrigeration at a low temperature of-70*C while the other can be managed with refrigeration at -20*. These two are supposed to provide 95% immunity to the disease. These however have not been approved for use in India at the time of writing this. The one which is approved in India and also produced here by the Serum institute of India uses a similar technique by which the spike protein coding RNA of the virus is linked to an adenovirus which is harmless to humans. This virus infects cells and antibodies are produced to all its proteins which also include the spike protein of the covid 19 virus. This vaccine called as the Oxford vaccine is based on a proven technology of vaccines against many other viruses wherein they had used harmless viruses as vectors. Again, in its development a serendipitous error increased its efficiency to around 90%. The advantages of this vaccine are it is cheaper and does not require refrigeration at very low temperatures. With full faith in it, even before the approval millions of doses of this vaccine have been prepared and kept ready by Indian Company, the Pune based serum institute of India-the largest manufacturers of vaccines in the world!
While the new technologies are making their breakthroughs the old ones are not totally ruled out. In fact the good old method of using the inactivated virus is still being used. In this the virus is grown, inactivated and adjuvant is added to increase its potency and it is injected into the body where it develops immunity. The Russian, a Chinese one and with Russian collaboration an Indian one called as covaxine are all on the way. The processes of vaccination have already started in many countries. The process of this is an initial dose followed by a second one after 3 weeks. The first acts as an initiator to develop the immunity and the second acts as a booster. This product is still in phase 3 of clinical trials and those who are receiving it are in effect subjects for one such in which the conventional protocols of a control and placebo group are not being followed!
Coming to the present situation two vaccines have been approved for use in India- Covishield aka the Oxford vaccine and the Covaxine aka as the Bharat vaccine. While the first one has been approved in many countries including UK, the second one which is allegedly a desi product has not passed phase 3 of clinical trials even in the country of its origin- India. Though with all pride it is claimed to be Indian, the only Indian component seems to be the strain of the virus which was isolated from an Indian patient by the National Institute of virology Pune and the eggs used to cultivate it! The concept dates back to the time of Louis Pasteur who first devised them! When these vaccines are coming into use, the anti-vaccine lobbies and fringe elements have jumped into the fray to muddy the waters through half truths and plain lies. So, it is very important for us to understand the issues raised and counter the lies. As the vaccination drive has started and the option of two vaccines being given to the states the lobbies for and against each as well as against vaccines in general have all come forward to make claims and counter claims. Amidst this it has been reported that the Tata group is trying to get the Pfizer vaccine into the country after obtaining the statutory approvals for sale in the private sector. There are dozens of such vaccines under development too utilizing the old as well as new technologies. Despite of all efforts by the WHO and GAVI there have been attempts at what is called as vaccine nationalism by the developed nations trying to corner the doses of the available vaccines.
In conclusion, I can safely say the following: It is better to have some sort of immunity than none at all. So, if you have the eligibility, get the vaccine because, the chances of life threatening adverse reactions to the vaccine are far less than that of getting infected and the ensuing morbidity and mortality rates. For those who are not on the first list- that is that of the health care and frontline workers there is a lot of time to decide. As for myself I have not yet decided because I have already undergone the process of the vaccination with the live virus and lived through it! To take my decision I have plenty of time.
Interview with Dr. Srinivas Kakkilaya
The first ten days’ experience of the ‘world’s largest vaccination drive’ in India has given several insights. “Vaccine hesitancy” has emerged as the biggest roadblock while the operation as a whole presents a case of speeding up of its implementation.
Though the vaccination drive is underway, risks of new strain and other factors along with too much time to be taken in inoculation of the whole population, unrelenting vigilance against the pandemic and preventing its spread remains as important as ever. Awareness raising programs are necessary to dispel misgivings among the intended recipients of the vaccines. The initial experience suggests that people are under the grip of safety concerns.
The situation is evolving fast, and therefore everyone needs to be informed. Excerpts from the interview with eminent Physician and social activist Dr.Srinivas Kakkilaya:
Are the COVID- 19 Vaccines (Covaxin and Covidshield) safe? Are there any serious problems or side effects?
As the trials are not yet completed, there’s no clarity yet, nor is enough data available.
Covishield is nothing but the Oxford - Astra Zeneca vaccine, and several side effects have been identified during the trials conducted in Europe, Brazil and South Africa. These have ranged from simple side effects such as pain at the site of injection, body ache, fever etc., to a few cases of serious neurological problems. As per the product brochure for COVISHILD, and on the basis of the above mentioned trials, the most frequently reported adverse reactions were injection site tenderness (>60%); injection site pain, headache, fatigue (>50%); myalgia, malaise (>40%); pyrexia, chills (>30%); and arthralgia, nausea (>20%).
The brochure claims that the majority of adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination and that by day 7 the incidence of subjects with at least one local or systemic reaction was 4% and 13%, respectively. As per the product brochure, efficacy and safety data of Covishield are currently limited in individuals = 65 years of age and its safety and efficacy in children and adolescents (aged <18 years old) have not yet been established, and there is a limited experience with its use in pregnant women.
For Covaxin, phase III trials are not yet completed and only the data from initial trials are available, with only Phase I report now having been published. The government has allowed the use of this vaccine in clinical trial mode only, meaning, every recipient is taking the vaccine as a clinical trial participant. All those who are receiving Covaxin are made to sign a general consent form. The company released a fact sheet 2 days after the launch of the vaccination drive and enlisted certain conditions, such as pregnancy, use of blood thinners, and unspecified diseases as exclusion criteria. The brochure indicates that all the recipients will have to participate in the programme, being followed up for 3 months after the second dose.
It’s clear therefore that these vaccines are in evolution, and so is the information on their side effects.
There are reports of deaths after COVID19 vaccination in the country. However, authorities claim the deaths are due to other reasons. Can the Covid-19 vaccine trigger other problems like heart attack, organ failure or any other health problems?
At least 10 deaths have been reported among vaccine recipients, all of them healthcare workers and doctors, occurring within 1-5 days of vaccination. All these deaths have been attributed to heart attacks and stroke and the government authorities have stated, within no time, even before post mortem examination, that these were not related to the vaccination.
As mentioned earlier, it must be noted that the government has granted permission for Covishield vaccine for ‘restricted use in emergency situation subject to certain regulatory conditions’ and for Covaxin ‘for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, to have more options for vaccinations, especially in case of infection by mutant strains’. It’s therefore clear that the vaccination is being done under several restrictions, and in the case of Covaxin, as a clinical trial, virtually making every recipient a trial candidate.
None of the trials being exhaustive, it is really not possible to either link or delink these serious and fatal events to the vaccinations. It is well established now that COVID can trigger vascular events such as heart attacks, strokes, thromboembolism etc. Therefore, the onus of proving that these similar incidents following the vaccinations are unrelated to the vaccines lies entirely with the vaccine makers and the government.
There’s no information yet about organ failures or any other long term consequences of any of these vaccines.
There are reports of doctors refusing to take the vaccine. What could be reason?
The uptake of these vaccines have ranged from 10-50%, and among those who didn’t take the vaccines, there are not only doctors, but also healthcare workers at every level. If not for the pressures exerted, the uptake could even have been lower. There could be several reasons for this.
1.) Most important reason is the failure of the government to inspire confidence in the recipients.
2.) Hurried approvals that were questioned by many top scientists as well the media, lack of scientific information on the efficacy and safety of the vaccines, allowing a vaccine to be used in clinical trial mode, thereby making the recipients the subjects of phase III trial for that vaccine, inability of the authorities and vaccine makers to clear the doubts, lack of clear strategy for vaccination of those already infected, confusing statements on alcohol use after vaccination and many other such factors led to the refusal of vaccination.
3.) Reports of adverse events added to these concerns, and glitches in the CoWin app and other logistical issues compounded it. As the government had rightly made the vaccination an optional choice for the recipients, nearly half of the enlisted recipients chose to exercise that option not to take the vaccine.
Reports say that the vaccine may not protect from infection for long period? How long the vaccine can save anyone from infection?
For Covishield, phase III trials have been done on about 24000 volunteers, whereas Covaxin has only entered phase III trials. The available data is only from these studies and it is not long enough to comment on the duration of protection yet.
With so many uncertainties and side effects of COVID19 vaccination, is it prudent to stay away from vaccine?
That decision is to be taken by the individuals themselves, it’s unfair for anyone to advise either way.
The vaccines were developed so quick with minimum trial and put to use within a year of the virus outbreak. Does this mean a political urgency to save the face of the central government’s failures? Is there any possibility of political interest in the urgent Vaccine administration? Do you think it is political / publicity stunt?
There are three sides to this issue. One is the scientific and technological prowess of our times that has successfully demonstrated our ability to identify, sequence, recombine, and develop nucleic code based RT-PCR tests and also vaccines on many different platforms such as recombinant, inactivated, DNA, plasmid, and the most novel mRNA. Second is the interests of businesses and funding agencies in trying to make quick profits in quick time, trying to make profits out of human misery. Third, of course, is the political showmanship, trying to gain personal and/or political mileage out of the scientific feats and business deals.
It has been very clear from the very beginning, in every decision that was made with regard to this new pandemic, in most countries including India and the US, that political leaders took their own decisions and disregarded scientists and experts. Such decisions have cost our country and our people very dearly and for long term.
We see a very similar pattern with regard to the vaccines as well. When the vaccine makers of our country were asked to expedite the trials in June 2020, many top scientists opposed the move and questioned the intentions, and one senior scientist resigned. And now, when 3 meetings of the subject expert committee of CDSCO were held in 4 days, even without prior notice, and approvals were granted hurriedly, without even completion of phase III trials, very respected scientists and experts, such as Drs Gagandeep Kang, VineetaBal, Shahid Jamal, Jacob John, have openly questioned these decisions and have gone to the extent of declaring that they wouldn’t take these vaccines at this stage and have even compared it with Hitlerian methods.
All these facts indicate that the great achievements of science and technology have been trumped by business and political interests, completely sidelining scientific methods and ethical standards, and ignoring the safety and health of ordinary citizens. Such hijacking of science and technology and disregard of ethics and safety will result in loss of confidence and credibility of science itself and will do immense harm to the reputation of these very vaccine makers.
Such loss of credibility is already very evident in the fact that nearly half of the enlisted recipients among HCWs have not taken the vaccine and the Government has started threatening penal action against what it calls as rumour mongers; added to this, some supporters of the Govt, including some doctors, are invoking nationalism, patriotism, valour etc., to shore up support for vaccination and even spreading fake messages in the name of some top scientists to mislead the people to get vaccinated.
Leaving politics, what is your advice to public - to take or leave Covid-19 Vaccine?
As I have stated above, politics, nationalism, jingoism etc., have been brought into what should have been a purely scientific and medical effort by politicians and their cronies. If enough evidence was available about the efficacy and safety of these vaccines, and about the need for such emergency use authorisation, these questions and problems wouldn’t have arisen at all.
The government and its agencies have very clearly stated that the actual number of cases in India may be 90 times the reported cases, amounting to 65-70% of the population and that the transmission of corona virus has already declined in most parts of the country. That would mean that more than 100 crore Indians have been infected with the virus by now, meaning that the control measures didn’t work and the infection spread very widely. Yet in the same breath, the same government claims that India has shown to the world the way to control the spread of corona virus!
If indeed about 70% are infected, so many Indians would have developed immunity with the naturally acquired infection and at that level, as per all the literature, herd immunity would have set in, leading to natural decline in transmission, which is being witnessed now. If that’s the case, there obviously is no ‘emergency’ about corona virus transmission in India any more, but then, the government hurriedly grants approval for ‘emergency use’ of vaccines in a situation where the country is close to herd immunity according to the statements of the very same government!
Moreover, the government hasn’t been able to provide all the information on the safety and efficacy of the vaccines, nor has provided any firm opinion on the need for vaccination for those who are already infected, and it makes the vaccination optional, but in the same breath, threatens penal action!.
Under these circumstances, one needs to be sceptical about the entire exercise of vaccination and should remember that it is only optional and not mandatory to take the vaccine. As has been stated by the best scientists and virologists of our country, a safe and effective vaccine, so proved in multi-centric, large scale, ethically conducted trials, and approved for public use by the WHO, if and when becomes available, may be useful for those who are most vulnerable to severe COVID, such as the elderly and persons with co-morbidities, who have remained uninfected through community spread until then.