CME INDIA Presentation by Dr. N. K. Singh, Admin.

Currently, there is no known difference in clinical outcomes associated with SARS-CoV-2 variants. The major concern is that it will lead to a higher rate of transmission, more cases and more deaths. The burden and fear on an already strained Indian population will be devastating. Well, second wave is a reality but will there be a significant change in outcome with availability of COVASHIELD and COVAXIN vaccines? The Game Changer is already here(?) and you need to get vaccinated at the earliest opportunity at your door.

Nectars available:

Even if variants of SAR-CoV-2 penetrate Indian population, we must be extremely vigilant on 3 factors:

  1. The increased transmissibility of the variant SARS CoV-2 requires an even more rigorous combined implementation of vaccination and mitigation measures (SMS)
  2. These measures will be more effective if they are instituted sooner rather than later to slow the initial spread
  3. Higher the vaccination coverage more will be the level of disease control to protect the public.

Lessons Learnt from Emergence of SARS-CoV-2 B.1.1.7 Lineage — USA

Lessons Learnt from Emergence of COVID in USA

  • December 14, 2020- UK reports SARS-CoV-2 variant of concern (VOC), lineage B.1.1.7(referred to as VOC 202012/01 or 20I/501Y.V1.)
  • The B.1.1.7 variant is estimated to have emerged in September 2020 and has quickly become the dominant circulating SARS-CoV-2 variant in England.
  • B.1.1.7 has been detected in over 30 countries, including the United States. As of January 13, 2021.It is learnt that over India has 38 cases of ‘highly infectious’ UK Covid-19 strain.
  • Now it is well known that B.1.1.7 is more efficiently transmitted than are other SARS-CoV-2 variants.

What are Projections by March 2021

  • The modelled trajectory of this variant is expected to become the predominant variant in March.
  • Increased SARS-CoV-2 transmission might threaten strained health care resources especially in Indian subcontinent
  • Although we require more rigorous implementation of public health strategies at present time but mood of Indian population is now to enjoy the social life without social distancing and Masking and hand washing(SMS). It appears that now people are not going to follow these instructions as they are almost fed-up with the restrictions.
  • To tide over the expected SECOND WAVE, we have a very critical window left over. All depends on how effectively we are able to increase vaccination coverage.
  • Enhanced genomic surveillance combined with continued compliance with effective public health measures, including vaccination, physical distancing, use of masks, hand hygiene, and isolation and quarantine, will be essential to limiting the spread of SARS-CoV-2.

How Vaccination Can Alter the Second Wave?

How Vaccination Can Alter the Second Wave?

The D614G mutation in the spike (S) protein: why in focus?

  • Enhanced transmissibility can rapidly dominate other circulating variants.
  • Variants of SARS-CoV-2 containing the D614G mutation in the spike (S) protein increases receptor binding avidity which is essential for binding to the host cell angiotensin-converting enzyme-2 (ACE-2) receptor to facilitate virus entry.
  • Mutations found in these variants might confer not only increased transmissibility but might also affect the performance of some diagnostic (RT-PCR) assaysand reduce susceptibility to neutralizing antibodies

CME INDIA Discussion

Dr Manish Ranjan, Cardiologist, Asansol asks:

By theory covaxin is safer option than covishield. I need opinions from esteemed members.

Dr T Rekha, MD Med., Salem, TN:

Technologies available are-

mRNA response against one Protein

1. Pfizer

2. Moderna

Plasmid DNA

1. Zydus Cadilla

Non-Replicating Viral Vector

1. AstraZeneca Oxford Covishield gives Response against

a. Spike Glycoprotein

2. Sputnik

Whole Virion Inactivated

1. Covaxin: gives IgG responses against

a. Spike (S1) protein,

b. Receptor-binding domain (RBD) and

c. Nucleocapsid (N) protein of SARS-CoV-2 along with

d. Strong cellular responses

So, what is the state of affairs

  • Covaxin must be much better in efficacy
  • Covaxin is Inactivate Virus – Which is a tried and tested…

Dr Jagdeeshan, Med Suptd, CGHS, Chennai:

  • Covaxin can be the best too, let the data come. But it has to wait for mass roll out.
  • That’s why it is approved as clinical trial mode. And people who are taking that are part of phase 3 trials. Unlike drugs vaccines are administered on health individual and also in mass. Definitely needs data before going for mass role out.
  •  Is there any other vaccine in the world approved before phase 3?? (Russia and China are different world).
  • It is not about safety and all. It is about procedure, there should not be any short cuts / assumption / guess n all in mass role out.
  • Covaxin is available. It is up to the beneficiary to decide whether to go head or not. For that data should be made public first. The so-called phase 1&2 at least.
  • Once again, I clear my stand. I am not against covaxin. I am for data to be made public for everyone to understand. All approved vaccine trials are there in public domain.

Dr Subrahmanyam Karuturi, Rajahmundry, AP:

  • They have published phase 1 and phase 2 data. You can go through it
  • Phase 2 Covaxin:
  • Phase 1 covaxin:
  • COVAXIN used a time-tested platform. It’s safer than covishield. We Indians don’t trust anything which is made my Indians. 🤦🏻‍♂️
  • Covaxin got emergency approval only. Emergency approval requires only phase 1 and phase 2 trials. I have seen many arm chair experts ask why it is approved without completion of phase 3 trials. These so-called experts don’t know what is emergency approval and its rules. 🤦🏻‍♂️

Dr Jagdeeshan:

  • Covaxin approved in clinical trial mode. Means people who are taking it are part of phase 3. Bharat biotech is a reputed company. They made many vaccines. No question about that.

Dr H D Sharan, Ranchi:

  • This raises another question. If phase 3 is not required for EUA, why was the vaccination delayed?
  • There is nothing like, ” I said so” in science.
  • The most important question is, The need for EUA of Covaxin.
  • The SII had 50 million doses ready. At the rate, the vaccination is planned, it would not have fallen short.
  • Vaccination needed full transparency.

Although the number of new cases on Sundays( projected on Mondays) is always much less than on week days, a figure of 10000 cases with a positivity rate of 1.8 is very encouraging.

Testing has gone down considerably in the last few weeks and it should concern the policy makers. This Sunday only 580000 tests were done. Even on week days between 8 to 9 lac tests are being done. Is it because of the fact that all attention now is on vaccination ? Both have to continue with equal vigour.

We have to track, trace and isolate all those who have brought the UK variant to our country. After sometime it will become the dominant strain all over the world

Efficacy of the available vaccines against the new strain should be studied and remedial action should be taken as early as possible.

Studies have not shown any advantage of plasma therapy in treatment of CoViD but it interferes with the vaccine. So let us stop using plasma.
The faster the vaccination program, the better will be the chances of avoiding second wave caused by the UK strain.

Dr P R Parthasarathy Chest Physician, Chennai:

  • Covaxin being an inactivated vaccine, it’s unlikely to cause severe adverse events & again immunogenicity is likely to be less as it’s likely to provide only passive immunity. but any value above 50% will be good enough for WHO & other health bodies as well as for us. Some amount of transparency at least for the medical community would have been better.

Dr Kapil Sud, Internist, MD Delhi:

  • Vaccine issue pe ek gaana yaad aa gaya …. Milo na tum toh hum gabhrayein,Milo toh aankh churayein, Humne kya ho gaya hai, Humme kya ho gaya hai…

  (On a lighter note)

One of our members, who got vaccinated asks:

  • *Post vaccination my thought.
  • Vaccines won’t prevent disease isn’t it. It only prevents severe disease.
  • If so, why are we thinking that vaccination provides herd immunity*???

One answer could be-

You develop proper antibodies. If in a society more than 60 to 70 percent develop such antibodies as per epidemiology prediction model, transmission slowly diminishes to significant proportion and virus will be wiped out

Dr Anupama Ramkumar, Physician, Clinical Researcher, Ahmedabad:

  • Just makes us realize that in spite of our advances in modern medicine – there are just so many things (such as herd immunity or ethnic predispositions to disease etc.)  that we still have very little understanding of! I hope science takes advantage of this social – medical experiment that is currently in at a global level!!
  • I have been studying patterns of the death rate due to COVID-19 (not absolute numbers) across the world. One strong association that is coming across is that countries where flu vaccine is very prevalent are suffering a higher death rate! 
  • I don’t know if it is only an association or an effect!! And would be interesting to study. leads us further to wonder if an immune system trained by vaccination vs naturally (through infection) behave differently and if so, how does it affect the herd immunity???

Dr Keyur Acharya – intensivist, UK:

It’s very nice to see vaccines rolling out. It will speed up as we go along. Going forward challenges are

1) Dealing with long COVID . Apart from Binary outcome of life and death there are many unknowns here. Would it have any long lasting impact on lungs , heart, kidney or even brain? Spanish flu was followed by mysterious epidemic of enchephalitis lethargica although link was not proven conclusively but what is known is that they both occured in same time frame.
2) Viral Drift- By very nature RNA is less chemically stable than DNA. Hence copying mechanism is not as good. This sloppiness is the key to flu’s notorious instability. Errors in genetic material will have effects on structural proteins and new variant will escape host’s immunity.
3) Viral Shift- two different viruses meeting in single host, exchange genes and produces entirely new virus. Every new flu pandemics of last century was triggered by new H in Flu A. H1 in 1918, H2 in 1957 , H3 in 1968. Will we see shift and drift here?
4) Are nfectious diseases genetically passed on ? Certainly when genome of 2 year old girl with annual glu was sequenced in 2011( Sick Children Necker hospital in Paris) they found she was not able to produce interferons and she bypassed 1st line of defence
and relied on cytokines making her prone to cytokine storm causing ARDS. Although rare, it opens a new ways of approaching these diseases.
It just makes sense to get on with vaccines!!

CME INDIA Learning Points

  • Buying critical time to increase vaccination coverage – CDC’s modeling data show that universal use of and increased compliance with mitigation measures and vaccination are crucial to reduce the number of new cases and deaths substantially in the coming months.
  • A more highly transmissible variant of SARS-CoV-2, B.1.1.7, has been detected in 10 U.S. states.
  • Modelling data indicate that B.1.1.7 has the potential to increase the pandemic trajectory in the coming months
  • “Enhanced genomic surveillance” will be necessary to track its spread.
  • This variant is more transmissible. Not only is the virus more transmissible, but it may cause false negative results on COVID-19 diagnostic testing via PCR assays, and could be less susceptible to neutralizing antibodies, such as monoclonal antibody therapy and convalescent plasma.

Source: Galloway SE, et al “Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021” MMWR 2021; Published on Jan. 15, 2021.

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