. Covishield or Covaxin ? .
RAMA PRASAD T.
Dr. T. Rama Prasad,
Formerly: Medical Superintendent (Special) of RTS & IRT Perundurai Medical College and Research Centre, Perundurai, Tamil Nadu, India. www.rama-scribbles.com
Presently: Director of ‘PAY WHAT YOU CAN’ Clinic, Perundurai, Erode District, TN – 638052. drtramaprasad@gmail.com
A MONTHLY JOURNAL OF MEDICINE AND SURGERYSN
Vol. 118 No. 4 April 2021 ISSN 0003 5998
Indexed in IndMED Email: admin@theantiseptic.in www.theantiseptic.in
Covishield or Covaxin ?
RAMA PRASAD T.
Dr. T. Rama Prasad,
Formerly: Medical Superintendent (Special) of RTS & IRT Perundurai Medical College and Research Centre, Perundurai, Tamil Nadu. Presently: Director of ‘PAY WHAT YOU CAN’ Clinic, Perundurai, Erode District, TN – 638052. drtramaprasad@gmail.com ; www.rama-scribbles.com
Specially Contributed to “The Antiseptic” Vol. 118, No. 4
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“What’s in a name ? That which we call a rose By any other name would smell as sweet.”
-- Romeo and Juliet (II,ii,1-2); Shakespeare
Preamble
What if it’s called Covishield or Covaxin, so long as they are safe and efficacious ? But, media won’t allow them to ‘smell as sweet’ resulting in hesitancy and distrust ! Hence, in India, this question “Covishield or Covaxin ?” is circulating like a virus, because of the media reports of serious side effects of AstraZeneca vaccine (Covishield). Causal link is not clearly established. Indian medical doctors are also caught in the quagmire. The quintessential Covishield is under cloud now on March 16, 2021 which marks two months since the roll out of the Covid-19 vaccinations in India and as well the ‘National Vaccination Day’. Also known as ‘Immunisation Day’, March 16 was celebrated in 1995 when the first Polio vaccine was administered in India.
Key words: Covishield, Covaxin, Adenovirus vector-based vaccines, Inactivated virus vaccines
Introduction
One year on, we couldn’t see the light at the end of the ‘Covid tunnel’. Making the battered, bruised and fatigued people wear masks and keep distance from others lifelong is impossible. Vaccinating people around the world may be an alternative, but may prove to be wildly optimistic. Seemingly orchestrated by powerful nations, the Covid-19 vaccination is universally accepted as the saviour of humankind now, albeit uncertain. About 194 vaccine candidates are in the field out of which two are being used in India since January 16, 2021 – Covishield and Covaxin.1 Covaxin was not rolled out much and not preferred much, perhaps, due to some academic objections on the ground of lack of ‘full’ data on safety and efficacy. Added to this is the glamour and trust in the “British developed” vaccine (Oxford-AstraZeneca which is manufactured in India under the name ‘Covishield’) which the “native” vaccine (Bharat Biotech’s ‘Covaxin’) lacked. Hence, Covishield was mostly (90% of about four crore doses) used during the past two months of India’s vaccination drive.
When the ‘Covid vaccine drive’ was initiated in India on January 16, 2021 with Covishield and Covaxin, the ‘Tamil Nadu Government Doctors Association (TNGDA)’ advised its members to opt for Covishield, not for Covaxin.2 And, the government in Chhattisgarh (a State in India) said in January 2021 that it will not allow Covaxin vaccination in its State until the clinical trials prove it to be safe and effective. That had been the acceptability status of the two available vaccines until mid-March 2021.
Then, in mid-March 2021, about 20 countries (Norway, Denmark, Iceland, Bulgaria, Italy, Romania, Austria and numerous European countries) suspended the use of the AstraZeneca’s Covid vaccine (called ‘Covishield’ in India) following sporadic reports of blood clots (37 out of 17 million vaccinated across the EU and Britain), bleeding and allergies. More countries halted the vaccine while the World Health Organisation (WHO) and the European Medicines Agency (EMA) have said they had no evidence of an increase in dangerous blood clots related to the shots.
Following this, the EMA reassessed the situation, and, on March 18, 2021, the EMA’s highly consequential “verdict” said that the link to “rare blood clots” (with thrombocytopenia or clots in cerebral veins or in multiple organs, with or without bleeding) in some cases cannot be ruled out, while declaring AstraZeneca vaccine to be safe and effective to continue its use, and saying that its benefits continue to be far greater than its risks.3 However, the agency indicated a need to display a warning. Out of the 20 million who were given AstraZeneca vaccine, at least nine died due to rare types of blood clots (one type affecting multiple blood vessels and another the blood vessels in brain only); most were in people under 55, and the majority were women. The EMA also said the overall number of clotting events of various sorts reported after the roll-out of the vaccination campaigns was lower than what could be expected in the general population (1,500 every day in the US). The WHO opined that there was no evidence to suggest that the vaccine was to be blamed and that the benefits far outweigh the potentially small risk. Indian authorities said that there was ‘no signal of concern’ in India with regard to Covishield. It remains to be seen as to which countries would stop using AstraZeneca vaccine (Covishield) and which do not.
Almost at the same time, a publication had come up in The Lancet of the impressive safety and efficacy profile of Covaxin in the phase 2 trial.4 Equally impressive are the phase 3 results of Covaxin announced in advance of the publication, indicating that Covaxin may be better than similar vaccines, being more effective and safe, sans serious adverse effects.4,5
While the media have been spreading the news – negative about Covishield and positive about Covaxin, people, including medical doctors, in India faced a dilemma as to which of the two vaccines is to be preferred now. Thus, the tide turned and the Covaxin is in the limelight, bringing the question “Covishield or Covaxin ?” to the fore. Promptly, the government of Chhattisgarh made a U-turn, welcoming Covaxin ! If Indian doctors too welcome, people would also fall into the line.
Meanwhile, further confusion and divide among scientists descended when a group of experts from diverse fields including public health, ethics, medicine and law has written an ‘open letter’ to the Indian authorities demanding a ‘time-bound and transparent’ investigation into the 65 deaths that are supposed to have occurred following Covid-19 vaccinations in India. Covishield was used mostly (90% of about four crore doses). The signatories to the letter included Dr. T. Jacob John, former professor and head of the department of clinical virology at Christian Medical College, Vellore and Dr. Amar Jesani, editor of Indian Journal of Medical Ethics. This is a very consequential issue. Now, the trust in the two vaccines can be earned only by the government’s zealous attention to allaying concerns.
A brief review of the facts connected with these two vaccines along with the projection of an idea of giving a combination of the available vaccines is presented in this paper. In India, Covishield and Covaxin, both manufactured in India, are the only brands available until now (mid-March 2021). Pfizer vaccine (94% efficacy) and Moderna vaccine (95% efficacy), rated as the best in the world, are clearly out of reach for India due to the high cost and the very low storage temperature requirements. Some information and comment on ‘Covid vaccines’, in general, may be found in my article published in ‘The Antiseptic’ of January 2021 under the title “The Conundrum of COVID-19 Vaccines” – Vol.118; No.1.6
Covishield
COVISHIELD is the Indian version of the ‘British’ vaccine, Oxford-AstraZeneca / ChAdOx1 nCoV19 (AZD 1222). It uses ‘live Chimpanzee adenovirus type 5’ on a ‘tried-and-tested’ recombinant platform (adenovirus vector-based vaccine), showing a claimed efficacy of about 80 %. Storage temperature requirement is 2 to 8 degrees Celsius. The supply was prioritised to India -- 10 crore doses by January 2021. It is manufactured in India by Serum Institute of India, Pune under license and is priced at around Rs. 300 per dose. It has the international presence under the brand name of ‘AstraZeneca’. A part of the virus (spike protein) is used. As such, the spectrum of activity may be narrower for variants – in contrast to Covaxin which is of whole body virus.
While it is not exactly a live attenuated vaccine, it is an engineered simian (Chimpanzee) adenovirus vector-based vaccine. It is called ‘replication deficient’ as some genes required for replication are deleted. The genome of ‘Covid Spike Protein’ is inserted instead. After injection into the body, it produces ‘Spike Protein’ of SARS-CoV-2 which triggers immunological reactions to produce antibodies against SARS-CoV-2. Simian adenovirus has been used because many people already have antibodies against human adenoviruses acquired from the recurrent ‘common cold’ which may prevent the development of adequate antibody response to the vaccine. This is the first ever non-human adenovirus vector-based vaccine licensed to be used on a large scale, though it may trigger anti-vector response which is likely to dilute its efficacy during revaccination.7 Of course, one adenovirus vector vaccine was granted emergency use authorisation for Ebola previously which was used in small numbers only and subsequently was found to be not of much value. Various platforms like ‘inactivated’, ‘viral vector’, or ‘mRNA’ are being used by various developers.
Normally adenovirus vector-based vaccines are superior in producing T Cell response and inferior in producing B Cell antibody response. B Cell antibodies are normally good in preventing the intrusion of virus into the cell and thereby neutralising the virus in the extracellular space. T Cell response is good for mainly destroying the infected host cell. This may be the cause for the slightly decreased efficacy of Covishield in preventing the infection. All the same, it seems to be very good in preventing development of severe illness, hospitalisation and death as inferred from the studies. However, results of ‘bridging studies’ in Indian subjects have not yet been made public. Some adverse events, transverse myelitis and deaths were reported following vaccination with AstraZeneca / Covishield, though a clear link to the vaccine is not yet in sight. Serious blood clotting events and deaths occurred abroad following AstraZeneca vaccination which led to halting of the vaccine in many countries in March 2021. The cases are under investigation to know whether they are related to the vaccine or not.
Covaxin
COVAXIN (BBV152) is an indigenous vaccine developed at Bharat Biotech, Hyderabad / Indian Council of Medical Research (ICMR)’s National Institute of Virology, Pune. This is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor (TLR) 7/8 agonist molecule adsorbed to alum (Algel-IMDG). It is made on a traditional whole cell inactivated (killed) virus platform (inactivated virus vaccine), fully locally developed from a strain isolated by ICMR-NIV, Pune. With a claimed efficacy of around 80%, it is priced at around Rs. 300 per dose with a storage temperature requirement of 2 to 8 degrees Celsius. Whole virus is used. As such, the spectrum of protection may be wider which may include variants.
Covaxin is a killed vaccine. Conventionally, killed vaccines produce weaker immunological reactions and that is why adjuvants are added to enhance the immunological effects. In the case of Covaxin, a new adjuvant called IMDG along with ‘alum’ (Algel, an aluminium salt) is used which makes it a superior vaccine in its class. Phase 2 trial results of 380 participants were published in The Lancet on March 9, 2021, indicating that Covaxin may be better than similar vaccines, being more effective and safer, sans serious adverse effects.3 Chinese players, Sinopharm and Sinovac, are using alum adjuvant (but not along with IMDG) in making BBIBP-CorV and CoronaVac. Multiple booster doses may be required as the immunity may not be long lasting. They are more stable and generally more safe.
The only negative aspect of Covaxin at present (mid-March 2021) is that it is not yet widely used in populations and that the peer-reviewed phase 3 trial results are not yet documented, though Bharat Biotech and the ICMR announced preliminary results of 81% efficacy, much more than that of Covishield (52%).4 No major adverse events like anaphylaxis, transverse myelitis or blood clotting are reported so far in the small number of people who were vaccinated so far. And, Covaxin has the advantage of being possibly effective against some variants to some extent, as it is designed on a whole cell virus platform. The theoretical superiority in efficacy and safety of Covaxin over Covishield can be confirmed only after the phase 3 trial results are finally published and a large population is inoculated.
Some studies showed that two weeks after the second dose, the efficiency of Covaxin was around 81% and that of Covishield was 52%. But the antibodies produced by Covaxin may not last as long as those of Covishield, and as such a third dose of Covaxin may be necessary. In contrast, ‘Johnson & Johnson’ vaccine (Ad26 human adenovirus viral vector vaccine, approved in the US on Feb 27,2021) may be given as a single-dose vaccine whose overall efficacy is 66% (100% against hospitalisation / death). It is touted to be effective against some variants in South Africa and Brazil.
A blend of Covishield & Covaxin
Covishield is an adenovirus vector-based vaccine. Covaxin is an inactivated virus vaccine.8 Many mild adenoviral infections (like common cold) produce antibodies which are called ‘pre-existing adenovirus antibodies’. These adenovirus antibodies reduce the efficacy of adenovirus vector-based vaccines like Covishield. The pre-existing antibodies against adenoviruses prevent the adenovirus particles in the vaccines from gaining entry into body cells and making the SARS-CoV-2 spike proteins which in turn make the immune system to produce antibodies against SARS-CoV-2. A second dose of the same adenovirus vaccine may also meet the same fate. This may be the reason for the lower efficacy (55.1% when the second dose of Covishield was administered less than six weeks after the first, but 81.3% when the gap between the two doses was over 12 weeks). The long gap may facilitate a fall in the pre-existing adenovirus antibodies produced by the first dose. Based on this, some countries increased the dosage interval. A long gap between the doses may mean that the anti-vector immunity (‘pre-existing adenovirus vector antibodies’ which may interfere with the entry of the injected adenovirus particles) caused by the earlier dose could wane by the time the subsequent dose is administered. The longer gap between the doses may be beneficial even when inactivated virus vaccine (non-adenovirus) like Covaxin is used for all the doses.
The pre-existing antibodies to Chimpanzee adenovirus are not common in the human population, except in Sub-Saharan Africa. This is the reason why Chimpanzee adenovirus was chosen in the making of Covishield. If it was made from a common adenovirus, the efficacy would have been very much lower. Even then, when the same Chimpanzee adenovirus is used for the second dose, the antibodies formed by the first dose may act as pre-existing antibodies and lower the efficacy of the second dose.
To obviate this problem, the second dose may be made from a different adenovirus to which pre-existing antibodies may not be present to a significant extent. This is the wisdom used in the making of the ‘Sputnik V’vaccine in Russia. They used Ad26 and AD5 subtypes of the adenovirus so that the antibodies developed by the firstdose would not interfere with the different subtype in the second dose.
Hence, a good plan might be to give an inactivated virus vaccine (Covaxin) or mRNA vaccine (Pfizer), which use non-immunogenic lipid vesicles, as a second or third booster dose to those who had Covishield as the firstdose (mRNA vaccines are known to produce more anaphylactic reactions, compared to other vaccines). Another alternative for the second dose is to use Sputnik V’s Ad26 component (unlike other vaccines, Sputnik V has two different components -- different subtypes of the adenovirus – Ad26 & Ad5, in the two doses) after the first dose of Covishield.
In India, as most of the people (90% of about four crore doses), so far, had Covishield (an adenovirus vector-based vaccine) as the first dose, if authorities permit, it may be better to take Covaxin (an inactivated virus vaccine) as the second dose. It would be beneficial if the drug regulatory body gives the choice of having Covaxin as the second dose to the people who already had Covishield as the first dose. A third dose after an interval of four months might give a very long-term protection. Studies are already in progress using a combination of AstraZeneca vaccine with Pfizer and Sputnik V vaccines.
Best way forward
The above theory of interference by ‘pre-existing antibodies to the adenoviruses’ does not apply to inactivated virus vaccines like Covaxin. Rabies vaccine and inactivated polio vaccine are examples. The second and third doses of Covaxin would only raise the height of immune response as there is no possibility of production of adenovirus antibodies. Theoretically, if three doses of Covaxin are taken with an interval of 12 weeks between the first and the second dose and 16 weeks between the second and the third dose, the immunity may last for a very long time, even for years. Studies are to be conducted to prove this to be true in the real-world situation. But, I am sanguine to say that, in view of the emergency, there is enough scientific justification to try this regimen straightaway in the Indian population in a ‘modified clinical trial mode’. It may sometimes be better to come out of the ‘iron-clad’ science and take calculated risks.
Covaxin better ?
As in mid-March, 2021:
COVISHIELD (Oxford-AstraZeneca) enjoys: (1) the international brand reputation; (2) the credit of studies of longer duration; (3) endorsement and approval by many developed countries. But, it suffers from the reports of occurrence of dangerous blood clots and neurological side effects in a few cases following the vaccination which are under investigation. And, results of ‘bridging studies’ in Indian subjects have not yet been made public.
COVAXIN enjoys: (1) the status of “double blind controlled studies” in Indian subjects; (2) the higher efficacy record (81% compared to 52% of Covishield) which partly may be due to better B cell antibody response compared to Covishield; (3) the absence of severe adverse side effects so far; (4) the prospect of protection against variants to some extent, by virtue of its whole cell virus platform; (5) the freedom from the problem of ‘pre-existing adenovirus antibodies’, unlike Covishield. But, it suffers from lack of data of large numbers in studies of long duration, and from low confidence as it has not yet been widely used among populations.
Overall, considering these findings, it may be right to prefer COVAXIN in India, at this point of time (mid-March 2021). But as the preference might be based partly on theoretical considerations, for practical purposes, both the vaccines may be ranked as equally good. We are not talking about politics here, nor about ‘vaccine nationalism’. Too much of it is going on around the world -- a nation is denying entry into its country without being vaccinated by its vaccine abroad before undertaking travel ! Science is global, but some nations made it local !
COVISHIELD or COVAXIN ?
People often ask for opinion as to which of the two to choose from when there is an option. The following is my default answer:
“The final outcome of the vaccination in an individual depends on a multiplicity of factors (including viral load, strain of the virus, pre-existing adenovirus vector antibodies, inherent immunity, herd immunity, herd effect, environment, lifestyle, etc.), not just on the projected ‘PERCENTAGES’. As such, one may take any available vaccine at any inter-dose interval as advised by the local health authorities. Covid vaccines provide ADDITIONAL protection for SOMETIME – additional to the “Social Vaccine” (face mask, physical distance & hygiene) and the inherent / acquired immunity. One should not relax with the false assurance of TOTAL protection FOREVER, what with the presence of mutants / variants and the resurgence in some places. Vaccination is not a license to throw away masks, distancing and hygiene. And we don’t know how long the protection by the vaccines lasts – may be eight to 12 months. Indians are LUCKY to have the UNEXPECTED benefit of the availability of the vaccine earlier than many countries and it is also free of cost to some ‘high-risk’ groups. The opportunity should be availed to protect oneself and the nation, to some extent and for sometime."
Speed is the keyword
In future, we are likely to get more vaccines – Sputnik V, ZyCov-D, Johnson & Johnson, Novavax, Sinovac, etc. Fortunately, India does not face shortage of vaccines. The problem is about the inability to administer the available abundant stock of vaccines speedily, partly due to hesitancy, and partly due to the prioritisation of eligible groups and registration formalities. We have an enviable stock of vaccines -- the stark factoid is that India has exported more doses (481 lakh) than it has administered at home. As on March 12, 2021, the planned vaccination capacity was 54 lakh whereas the total doses administered were 20 lakh ! What is worse is that during this one week, the registrations for vaccinations have yo-yoed from a peak of 19.7 lakh to 3.5 lakh. The problem is about how to vaccinate the entire eligible population quickly. So far, we could give only about four crore shots while 60 crore doses are to be given to the 30 crore of the priority groups by now. Assuming an average of 20 lakh doses a day, it would take 285 days to administer the remaining 57 crore doses. Then, how about the remaining humongous eligible groups out of the 1.3 billion people ? So far, just 0.35% of the population in India is vaccinated. At this rate, it would take 18 years to complete the vaccination process !
If the ‘vaccination drive’ is not done speedily, the second and third waves with variants would engulf a huge chunk of the homo sapiens and drive us into permanent penury, gloom and doom. We are sitting on a time bomb. There should be a health education blitzkrieg to make people come forward fast to get vaccinated. Generally, all the approved Covid-19 vaccines are very safe.
And, there is an urgent need to restructure the strategy by massively deploying mobile vaccination units working 24/7, inoculating whoever is reachable and eligible, if necessary even by mobilising the army personnel. The vaccine should be taken to the working places and residential areas for a speedy cover up. And, even younger healthy groups, with or without comorbidities, working in private or public commercial establishments, teaching institutions, service enterprises, and those exposed to the public, etc. must urgently be inoculated now itself in tandem, if the economy of the country is to be put back on track in the near future. Flexibility and improvisation is the need – ‘one-size-fits-all’ can’t address the diversity of consumers and providers. With all this effort, if 70% of the population gains immunity through vaccination and natural infection, there would be a possibility of surmounting this invincible scourge.
Reality in the real world
In the field of vaccines, analysts always hark back to history and build mathematical models which may not always be real in the real-world. Real world cohorts and algorithms on vaccines are still in the process of evolution. The available information is founded on the application of Bayesian principles in health care – best probabilities and guesses. Vaccines may not work to our expectations, but in every adversity lies an opportunity.
Most of the opinions on the Covid vaccines are based on limited studies of small number of people (for example, there are only 380 participants in the phase 2 study of Covaxin). A study of 10 years is compressed into 10 months ! As such, the jury is still out on many aspects. The pandemic is far from over. We are not out of the woods. Delusions of grandeur may just vanish. Then, we shrug our metaphoric shoulders. Double mutation variants – E484Q and L452R have emerged in Maharashtra. The present surge in Maharashtra and elsewhere teaches us the consequences of complacency and systemic stasis. Ergo this brings us back to the basic non-pharmacological preventive measures !
Five-finger formula
“There are 5 fingers. The first 3 important fingers represent 'Social Vaccine' (1. Mask. 2. Hygiene. 3. Distancing). The 4th finger represents 'Covid Vaccine'. The 5th one represents 'Timely Treatment'. But, no single finger can do the job of all the five. So, only if all the 5 factors are taken care of simultaneously for sometime, our planet would be free of the pandemic. Otherwise, it would be a gloom and doom forever.” -- Dr. T. Rama Prasad, Perundurai, India
REFERENCES
1. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
4. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00070-0/fulltext
5. https://www.clinicaltrialsarena.com/news/covaxin-india-vaccine-covid-19-lancet/
6. Rama Prasad, T., Versha Rajeev. The Conundrum of COVID-19 Vaccines. The Antiseptic. 2021 January; Vol.118; No.1; pp 10-17; Indexed in IndMED; www.theantiseptic.in
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189890/
A short list of some of the published articles in The Antiseptic (a premier Medical & surgical journal),
The Hindu (a national Newspaper), etc. authored by Dr. T. Rama Prasad
1. DIGITAL CLUBBING and HYPERTROPHIC PULMONARY OSTEOARTHROPATHY - Pathogenesis --
The Antiseptic, Vol. 76. pp. 213-215, 1979.
2. CHILDHOOD TUBERCULOSIS - Part I -- The Antiseptic, Vol. 76, pp. 449 - 504, 1979
3. CHILDHOOD TUBERCULOSIS - Part II -- The Antiseptic, Vol. 76, pp. 567 - 574, 1979
4. STEVENS-JOHNSON SYNDROME and THIOACETAZONE -- The Antiseptic, Vol. 77, pp. 99 -102, 1980
5. HIGHLY PURIFIED INSULINS - An Assessment -- The Antiseptic, Vol. 77, pp. 3455-347, 1980
6. IS THE "LOCKDOWN MEDICINE" TOO TOXIC ? -- The Antiseptic, Vol.117, No.10, pp. 13 -15, 2020
7. ANTISEPTICS, DISINFECTANTS and COVID-19 -- The Antiseptic, Vol.117, No.11, pp. 26 - 28, 2020
8. 40+15 HYPOXIA TEST in COVID-19 -- The Antiseptic, Vol.117, No.12, pp.13 –17, 2020
9. THE CONUNDRUM of COVID-19 VACCINES – The Antiseptic, Vol. 118, No. 1, 2021
10. COVISHIELD or COVAXIN -- The Antiseptic, Vol. 118, No. 4, 2021
11. HEALTH CHECK-UP: how healthy is it ? - The Hindu, Open Page, January 15, 2012 --
……http://www.thehindu.com/opinion/open page/article2801701.ece
12. THE ‘GOOGLE EFFECT’: may be good, may be bad - The Hindu, Open Page, April 22, 2012 --
...http://www.thehindu.com/opinion/open-page/article3340116.ece
13. OF TEA, COFFEE and COMMERCE - The Hindu, Open Page, January 12, 2014 --
… http://www.thehindu.com/opinion/openpage/of-tea-coffee-and-commerce/article5567951.ece.
14. A BAD PATCH - The Hindu, Open Page, March 15, 2020 --
https://www.thehindu.com/opinion/open-page/a-bad-patch/article31069356.ece
15. YELLOW NAIL SYNDROME - Chest (U.S.A.), Vol. 77, p.580, 1980
https://journal.chestnet.org/article/S0012-3692(16)40458-7/fulltext
16. YELLOW NAIL SYNDROME - The Indian Journal of Chest Diseases & Allied Sciences, Vol. 22, pp. 69-72, 1980.
17. DRUG RESISTANCE in TUBERCULOSIS - Journal of the Indian Medical Association, Vol. 64, pp. 264-267, 1975.
References to more articles by Dr. T. Rama Prasad may be found in: http://drtramaprasad.blogspot.com www.rama-scribbles.com
Developments that took place after the publication of the above article in April 2021
June 10, 2021
Since writing the above article, to date, the question still persists – “Covishield or Covaxin ?” Unfortunately, the Covaxin (developed by Bharat Biotech, with support from ICMR) has become “suspicion-laden” from the beginning when the ICMR chief stated that it must be ready by August 15, 2020, giving the colour of “vaccine nationalism.” Then, it was “hurriedly” approved by the Central Drugs Standard Control Organisation for public use in “clinical trial mode” while still under efficacy trials on 25,800 people and introduced in January 2020 along with Covishield. About 194 vaccine candidates are in the field out of which two are being used in India since January 16, 2021 – Covishield and Covaxin. Covaxin was not rolled out much and not preferred much, perhaps, due to some academic objections on the ground of lack of ‘full’ data on safety and efficacy. Even today, after about five months, it is intriguing that the phase 3 final data are not even submitted (? Intentional delay) to the Indian drug regulatorwhich has recently approved Covaxin trials for kids and adolescents aged 2-17 years who should not be subjected to any experiment until the vaccine’s protection in adults is fully understood and analysed. Is the delay due to ‘not praiseworthy findings of lower antibody response’ compared to Covishield ? Is Bharat Biotech/ ICMR getting extraordinary privileges while science is taking a backseat ? A bit of maturity would have put the Covaxin in a better light. After all, ‘being an inactivated virus-based’ vaccine, Covaxin may confer better immunity through ‘cellular’ response.
June 29, 2021
The ‘Phase 3 Trial’ data of COVAXIN was approved by Subject Expert Committee of Indian authorities. The data show an efficacy of 77.8%. The COVAXIN was not approved by the WHO, and the US FDA rejected its ‘emergency use’.
AstraZeneca’s COVISHIELD vaccine was approved by the WHO on February 15, 2021.
Till June 12, 2021, only 2.8 crore doses of COVAXIN were made available for use in India, whereas about 30 crore doses of COVISHIELD were used. Though the Central government placed orders and provided funds, Bharat Biotech could not manufacture enough quantity in time.
The Oxford Vaccine Group (that developed the AstraZeneca Covid vaccine) said in a pre-print publication (June 2021) that two doses of the AstraZeneca vaccine, administered 44-45 weeks (nearly one year) apart, generated nearly four times the level of antibodies than when the doses were given 8-12 weeks (two to three months) apart. The Indian authorities had already extended the dosage interval to 16 weeks (four months).
A study published in the Lancet Infectious Diseases journal (June 2021) said that a higher dose of the Chinese vaccine, CoronaVac was well tolerated and effective in children and adolescents aged 3-17 years.
December 2021
OMICRON variant which has numerous mutations that may make it ‘escape’ the presently available vaccines is reported to be present in a couple of patients in India in the first week of December 2021. In this context, a debate is going on about the relative efficacy of the Covid vaccines against Omicron. With the currently available evidence, it may be said that the indigenous Covaxin is likely to be more effective against Omicron by virtue of its ‘Whole-virion’ inactivated virus platform compared to the ‘Spike Protein–based’ vaccines like ‘mRNA’ vaccines (Pfizer / Moderna) and ‘adenovirus-vector-based’ vaccines (Astra-Zeneca / Covishield / Sputnik).
Eight months ago, I wrote in an article published in a medical journal (The Antiseptic of March 2021): “Overall, considering these findings, it may be right to prefer Covaxin in India, at this point of time (mid-March 2021)”.
At the face value, the stellar reputation of Oxford University, AstraZeneca and Serum Institute of India is daunting enough to prefer Covishield if a choice is between Covishield and Covaxin. However, an objective comparison of properties, attributes and available information indicates that Covaxin is better placed to receive a recommendation.
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ReplyDeleteIndeed it was amazing for me to be of practical consideration of your imagination on correlating the five fingers and tuning the prose and cons of covishield & covaxin to arrive at the efficacy based recommendations of covaxin should be of acceptance as for me , hence opted to wait for !
ReplyDelete