CME INDIA Presentation by Dr Rajeev Jayadevan, Senior Consultant Gastroenterologist and Deputy Medical Director, Sunrise Group of Hospitals, Member, COVID Task Group, National IMA, Kochi.
Even if the thief gets past the gate, how to make our house still secure?
B.1.1.7 rose quickly in February, but is slowly being replaced by B.1.617
- Monthly genomic analysis of multiple districts in Kerala shows that over 5 months, the B.1.617 has had a steep growth, now standing tall at ~60% of genomes.
- In the beginning of 2021, there were very few variants; the bars are almost flat. Then came the rise of B.1.1.7 (UK), and the B.1.617(India) in April. But now the “India variant” B.1.617 is fast-replacing all other viruses in circulation, accounting for ~60% of genomes.
- The B.1.617.2 (which has lost the E484Q mutation from the so-called “double mutant”), is now fast-growing in many countries, also in UK
- While the rise can seem scary, one must remember that B.1.617 has no extra powers to damage our health. Its hospitalisation rate is the same as the “old virus”. (so far) It has also been effectively stopped by existing vaccines. The chief problem is, it is faster spreading.
- When a virus spreads faster it does two things:
- Affects more people in the same timeframe
- When more people fall sick at the same time, healthcare systems get overwhelmed When healthcare systems are under strain, mortality rates go up. We have seen that elsewhere.
- One concern about B.1.617.2 is whether it will evade vaccination protection. There is no clear evidence that it will happen. Theoretically in lab neutralisation studies we can see, as in the case of other variants, there’s slight reduction in “power of the serum” against it.
- The “reduction in neutralising power” itself is relatively small for the B.1.617 at this time. Besides, vaccine protection is multipronged and our T cells (the heavyweights of our immune system) are expected to take care of most variants.
What this means?
- Vaccines are expected to protect on two levels. First, they stop the virus from entering our body, and then they stop our organs from being damaged as a result of the dysregulated excessive immune response that occurs in some people. Both are different entities.
- The first process is like closing our gates so that a thief cannot enter our premises. However, a smart thief (variant) might still jump over the gate and get into the premises. The second part is stopping the thief from breaking into our house and inflicting harm on us.
- All vaccines are considered equally good at the 2nd part. i.e. Even if the thief gets past the gate, our house is still secure, and the thief can’t break in. In other words, even if the virus enters our body, our vital organs are safe. For this, T cells are the main players.
- T cells have an extraordinary ability (more than antibodies) to remember and attack more and multiple parts of the virus, called epitopes. Even the most advanced variant is unable to change ALL its epitopes, therefore they cannot fully escape detection from our T cells.
(These graphs have been provided by @vinodscariagenomic scientist http://genescov2.genomes.in)
Can the virus add more mutations endlessly so that it can escape our T cells?
- Unlikely. Why?
- Remember that every mutation puts the virus at risk for its own survival because it may damage its own mechanisms in doing so. Many experts in this field believe that the repertoire of mutations for this virus is this limited. In other words, this virus might not really have an endless number of tricks (super-clever mutations like E484K) up its sleeve – that can help it escape more from T cells.
- It is worth remembering that the predecessor of this virus, that is the SARS virus of 2003, disappeared from earth after about two years, most likely because of such deleterious mutations that threatened its own survival.
As of now there is NO direct evidence that these variants can:
- Cause more damage to our body than the past virus or
- Have become smart enough to evade our T cells. The fact that vaccines prevent hospitalisation is proof of protection by T cells.
Vaccine efficacy data against B.1.617.2 is just coming in.
- Two doses are good. Note that some vaccines take longer to build full adaptive immunity. These are early data thanks to @PHE_uk
- 80.9% efficacy of vaccine against B.1.617.2 in UK. Includes Pfizer and Astra vaccine, 2 doses. Small numbers prevent accurate analysis of each subgroup. One dose has lower efficacy. These don’t represent severe cases, where efficacy is expected to be higher.
CME INDIA Learning Points
- Evidence is growing. One so called variant of Wuhan originated but first detected in India might be more transmissible and slightly better at evading immunity than existing variants.
- While only a small proportion of samples have been sequenced, B.1.617 lineages have dominated. B.1.617. It is the most commonly reported variant in the country from mid-April 2021.
- This Wuhan originated but first detected in India has spread to about 40 nations, including the United Kingdom, Fiji and Singapore.
- Genomic data show:
- B.1.1.7, first identified in the United Kingdom, was dominant in Delhi and the state of Punjab.
- A new variant dubbed B.1.618 was present in West Bengal. B.1.617 was dominant in Maharashtra.
- Now B.1.617 has overtaken B.1.618 in West Bengal.
- In UK Vaccines used are:
- Pfizer- BioNTech BNT162b2 mRNA vaccine
- Oxford- Astrazeneca ChAdOx1 adenovirus vector vaccine
- Moderna mRNA-1273 vaccine.
- There is now substantial evidence that levels of protection conferred by vaccination are similar to those observed in the clinical trials, with additional protection against severe disease.
- In this study recently estimated the effectiveness of COVID-19 vaccines against symptomatic disease with the B.1.617.2 variant.
- They found an absolute reduction of one dose vaccine effectiveness against symptomatic disease with the B.1.617.2 variant of approximately 20% when compared to the B.1.1.7 variant. However, reductions in vaccine effectiveness after two doses were very small.
- This was the case for both the BNT162b2 and ChAdOx1 vaccines.
- Using a TNCC analysis, estimated vaccine effectiveness against symptomatic disease with B.1.617.2 for a single dose of either vaccine is approximately 33%, for two doses of BNT162b2 is approximately 88% and for two doses of ChAdOx1 is approximately 60%.These findings suggest a modest reduction in vaccine effectiveness.
- Nevertheless, a clear effect of both vaccines has been noted with high levels of effectiveness after two doses.
- Vaccine effects after two doses of ChAdOx1 vaccine were smaller than for BNT162b2 against either variant. This is consistent with reported clinical trial findings.
- The recent studies show that Pfizer vaccine was 88% effective against the B.1.617.2 variant, first found in India, 2 weeks after the second dose. The Pfizer vaccine was 93% effective against the variant found in the U.K., known as B.1.1.7, two weeks after the second dose.
- Two doses of the AstraZeneca vaccine were 60% effective against the B.1.617.2 variant and 66% effective against B.1.1.7, the strain.
- It is now clear how important the second dose is to secure the strongest possible protection against Covid-19 and its variants.
- What about COVAXIN?
- It has demonstrated potential effectiveness against the Brazil variant of SARS-CoV-2 in a recent study published by the Indian Council of Medical Research (ICMR)-National Institute of Virology (May 3,21)
- Ocugen is a biopharmaceutical company based in the US that is developing Covaxin for the US market.Thus Indian made vaccine shines.
- In the recently shared second interim results of the Phase 3 clinical trial, Covaxin demonstrated 78 per cent overall efficacy and 100 per cent efficacy in severe Covid-19 cases.
- The risk of contracting COVID after 2 doses of Covaxin or Covishiled is minuscule. A study has found 0.03% of people caught COVID after the 2nd dose of Covishield and 0.04% tested positive after the 2nd dose of Covaxin.
CME INDIA Tail Piece
- European Centre for Disease Prevention and Control. Threat Assessment Brief: Emergence of SARS-CoV-2 B.1.617 variants in India and situation in the EU/EEA – 11 May 2021: ECDC; 2021
- medRxiv preprint doi: https://doi.org/10.1101/2021.05.22.21257658 Effectiveness of COVID-19 vaccines against the B.1.617.2 variant .Jamie Lopez Bernal, Nick Andrews et al.
- Nature 593, 321-322 (2021)doi: https://doi.org/10.1038/d41586-021-01274-7
- Public Health England: “Effectiveness of COVID-19 vaccines against the B.1.617.2 variant.”May 23rd 21
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