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COVID-19 Vaccine Updates
With input from Dr Monica Vasudev
1299: HCFI Round Table Expert Zoom Meeting on “Consensus document on COVID-19 vaccine myths”
9th January, 2021, 11am-12pm
Participants: Dr KK Aggarwal, Dr Jayakrishnan Alapet, Dr Suneela Garg, Prof Mahesh Verma, Dr Anita Chakravarti, Dr Ashok Gupta, Dr DR Rai, Dr Balbir Verma, Mr Bejon Misra, Ms Upasana Arora, Dr KK Kalra, Dr Anil Kumar, Ms Ira Gupta, Dr S Sharma
Consensus Statement of HCFI Expert Round Table
- Several myths and concerns about the vaccine are circulating in society.
- A major concern is will the vaccine work on the mutant strain? Will it produce a new strain?
- Killed vaccines are safe; since they produce fewer antibodies, they require multiple doses (as also with rabies vaccine). E.g., Rabies vaccine (there are two types of rabies vaccine and both of them are killed vaccines), DPT vaccine (pertussis component is a killed vaccine).
- Phase 3 trial examines safety; the only vaccine which can be launched early is a killed vaccine.
- Vector vaccine and mRNA vaccines are being used for the first time. The only vector vaccine is dengue vaccine, which is not universally accepted.
- Each time a virus mutates, it takes away the unwanted amino acids. Deletion of amino acids causes the virus to increase its infectivity.
- The D614G is the strain which is prevalent all over the world. This mutation is in the S1 protein but after RBD and RBM. This mutation increases replication and infectivity of the coronavirus, while making it more vulnerable to neutralization antibodies.
- The virus will continue to mutate till it finds a gene of importance in the RBM. All monoclonal antibodies act against RBM.
- The Nigeria mutation P681H (proline to histidine) is an isolated mutation. This mutation is present near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. It has emerged spontaneously several times.
- The mutation N440K is in India (asparagine to lysine). This mutation is in the RBM and is ready for adoption by the virus. It is found in Andhra Pradesh (34% of genomes analyzed) and also in Karnataka, Maharashtra and Telangana. One case of reinfection with this mutant strain has been reported in Noida.
- Another mutation in India has been seen in Kerala; C1240Y and P84T. It is not in the RBD or RBM and hence this mutation will die out.
- Another mutation is in Australia - S477N (serine to asparagine); this is in the RBM and so is available for adoption by the virus.
- Cluster 5 mutation from Denmark, with 69/70 deletion. Since it was an isolated strain, it died out. But, this was adopted by the UK strain.
- Diagnosis of UK variant: S gene negative and the rest are positive on current RT PCR test.
- The UK strain is VUI (VOC) 2020-12/01; there are 23 gene mutations. The major substitution is N501Y (asparagine (N) has been replaced with tyrosine (Y). It has three deletions - Hi 69 histidine, 70 Vi Valine and 144. Other substitutions are A570 D, D614G, P681H (near the S1/S2 furin cleavage site), T716I, S982A and D1118H.
- A recent case report of an immunocompromised individual persistently infected with SARS-CoV-2 acquired around 10 mutations in the spike protein over 154 days, notably including N501Y. This mutation was due to killing of NSP 14; this mutation was also adopted by the UK strain.
- The function of NSP 14 (part of RdRP) is proof reading. If this function is defective, then mutations will occur. NSP 14 is killed by remdesivir and favipiravir. If resistance to antiviral drugs develops, mutations will occur.
- The UK strain has an affinity to 7-11 year age group.
- The South Africa variant 501.V2; there are three mutations (two are in RBD and one in RBM). N501Y is the main substitution (enhances binding affinity to ACE2). Other substitutions are K417N lysine with asparagine (would abolish key interactions with Class 1 Nabs and likely contributes towards immune evasion at this site) and E484K glutamic acid with lysine (enhances binding affinity to ACE2 and confers resistance to class 2 Nabs). About 90% of cases in South Africa are due to the new variant.
- The UK mutation is only a start; more mutations can be expected in the next few months. The virus will become more contagious. It may become chronic. Hence, this is the best time to take a vaccine.
- Both vaccines (vector vaccine and killed vaccine) have immunogenicity and are safe.
- There should be no controversy over the killed vaccine.
- Vector (non-replicating) vaccine and mRNA vaccine can be given to immunocompromised persons.
- In phase 1 trial of Bharat Biotech, 3 different combinations were used based on the adjuvants; phase 2 looked at immunogenicity and used two doses of adjuvants; one had 92% efficacy and another had 98% efficacy. On this basis, the expert committee gave its recommendation for permission. Phase 3 trial is nearing completion.
- Major trials of Oxford-AstraZeneca vaccine are done in the UK; in Bharat Biotech vaccine, all phases were done in India.
- Vaccine war is inevitable, but is not the need of the hour, especially when there is so much of vaccine hesitancy.
- Both vaccines are immunogenic, both are safe. Efficacy is awaited. Emergency use is the need of the hour; whichever comes first should be taken.
- There should be an increase in healthcare allocation in the coming budget. It was suggested that the members of the Round Table should meet with the Health Minister before the budget and have a discussion in this regard. This year, the allocation will be increased because of the expected increase in expenditure on vaccines. But there should a massive increase in allocation for strengthening the public healthcare services.
- Hopefully the vaccine roll out will start after the meeting of the Prime Minister with the Chief Ministers on Monday.
- The focus should be on bringing the right and credible information to the people. There is a need for transparency and accountability in the system.
- Doctors should be role models and be messengers of change to remove vaccine hesitancy.
Dr KK Aggarwal
President CMAAO, HCFI and Past National President IMA