CME INDIA Presentation by Admin.
WHY only one dose of Covishield dilemma?
The highly-talked news now is findings of the pre-print paper, although not peer-reviewed paper which appeared on 02.02.2021 online. The preprint is currently under review at “The Lancet.”
It has definitely supported Britain’s decision to extend the interval between initial and booster doses of the shot to 12 weeks. Should we do the same in India too? Its a big gamble at present. CME INDIA tried to understand the science behind it.
Let us see what Pre-print study says
- It shows sustained protection of 76% during the 3-month interval until the second dose.
- The dose efficacy from day 22 to day 90 post vaccination of 76% with protection not falling in three-month period.
- After the second dose vaccine efficacy from two standard doses is 82.4% with the 3-month interval being used in the UK. (82.4% effective, with a 95% confidence interval of 62.7% – 91.7% at 12+ weeks).
- Thus, data supports the 4-12 week prime-boost dosing interval.
- Interestingly study suggests vaccine may have substantial effect on transmission of the virus with 67% reduction in positive swabs among those vaccinated.
We cannot ignore the Glamourous Findings
- “The effect of dosing interval on efficacy is pronounced, with vaccine efficacy rising from 54.9% with an interval of less than six weeks to 82.4% when spaced 12 or more weeks apart.”
- “A single standard dose of the vaccine is 76% effective at protecting from primary symptomatic COVID-19 for the first 90 days post vaccination, once the immune system has built this protection 22 days after the vaccination. The protection is significant.”
Chief Investigator of the Oxford Vaccine Trial says
- ‘These new data provide an important verification of the interim data that was used by more than 25 regulators including the MHRA and EMA to grant the vaccine emergency use authorisation. It also supports the policy recommendation made by the Joint Committee on Vaccination and Immunisation (JCVI) for a 12-week prime-boost interval, as they look for the optimal approach to roll out, and reassures us that people are protected from 22 days after a single dose of the vaccine.’ – Professor Andrew Pollard.
CME INDIA Discussion
Dr Ambrish Mithal, DM Endo., Delhi:
- Exceedingly important paper from Oxford. We should delay our second shot to 12 weeks!
- 1st shot gives protection after 3 weeks. For HCW we should be checking antibodies and prioritising those with negative antibodies even for 1st shot. Ideally. For 2nd shot definitely if we have a decent titer at 3 weeks we should wait for 2nd shot.
Dr Awadhesh K Singh, DM Endo., Kolkata:
- While deeply dissecting the data of 3 papers of Covishield all published in Lancet – I have a feeling that 2nd dose might attenuate the antibody response triggered by the first dose (unlike other Covid vaccines) 🤔
- The question is why UK and EU that approved this vaccine in 2 dosage didn’t look in to it?
Dr Shashank Joshi, DM Endo, Mumbai:
Very much needed answers for these questions:
- Do a neutralizing igG antibody on day 21 and 27
- See the titres.
- Dose, timing, frequency are all unanswered questions.
- Immunogenicity is it variable or consistent?
- Data in public domain and data with regulatory and innovators also needs to be looked at.
- Primary question is, will delaying the dose actually boost the antibody response? Most UK docs feels delaying up to 3 months may increase response by 10 percent.
That’s what is the big debate.
With most HCW getting Covishield and new and old Oxford data suggesting that delaying the second dose possibly may be more immunogenicity may be conferred.
Dr Rajan Chaudhary, Radiologist, Patna:
- I heard something about half the normal dose on the 2nd vaccination proving more efficacious?
Dr Manisha Singh, Nephrologist, USA:
- There was a Mistake during the trial – a few lots were given at half dose (first time Round) they generated better response post second dose. That’s why the efficacy went up from 60-70% to 90%.
- One dosing regimen (n=2,741) showed vaccine efficacy of 90% when AZD1222 was given as a half dose, followed by a full dose at least one month apart, and another dosing regimen (n=8,895) showed 62% efficacy when given as two full doses at least one month apart.
- The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%.
- All results were statistically significant (p<=0.0001).
Dr Awadhesh K Singh, DM Endo., Kolkata:
- 2nd dose was never half dose. It was either half dose (first) – full dose or full dose – full dose. Intriguingly half dose – full dose was more efficacious.
- However, approval has been given for full dose – full dose!
- These studies have been done in COVID-19 negative patients!
Dr Sanjeev R Pathak, Ahmedabad:
- People who’ve had COVID-19 and then receive the vaccine mount higher antibody responses after one dose than COVID-19-naive people mount after two doses, suggests a study posted on the preprint server medRxiv.
- Researchers studied 109 vaccine recipients, 38% of whom were seropositive for SARS-CoV-2 at the time of vaccination. They found that median antibody titres among seropositive vaccines after their first dose were over ten times higher than titters among seronegative vaccines after their second dose.
- Seropositive vaccines also had more systemic side effects, like fatigue and headache. One of the researchers told “I think one vaccination should be sufficient (in those who’ve had COVID-19)
- Do we have analysis of patients who had already COVID-19?
Dr Awadhesh K Singh, DM Endo., Kolkata:
- This is not a newly conducted study This is a derivation and modelling which has been derived from previous published phase 2 and 3 study.
- For the last 2 days I raised similar question of single dose, no sig increases in antibody after 2nd dose if given at short interval etc .
- My Q is still unanswered on Twitter directly asked to UK approval committee, Editors of BMJ and Lancet 😊
- Someone from UK approval committee commented we backed the wrong horse.
- Even the lancet phase 3 publication found better neutralising antibody if 2nd dose injected at 8-12 weeks gap.
- Don’t know where from 28 days emerged. In fact, in phase 1 study peak antibody developed in 91-100% at day 28 and therefore it is logical that 2nd dose should have been given not at day 28 but when there was falling antibody – say at 8-12 weeks.
- Previous data (UK and Brazil) plus South African cohort together reanalysed.
|Summary of this study:|
1. Vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination = 76%. Protection did not wane by 90 days.
2. Efficacy after 2nd dose when taken at >12 week – 82%.
3. Efficacy after 2nd dose when taken < 6 weeks – 55%.
Dr Basab Ghosh, Sr. Diabetologist, Agartala:
- Govt of India in their initial letter to states mentioned that 2nd dose will be given AFTER 28 days, but since then no further intimations initiated regarding 2nd dose. Are we planning the 2nd dose in India after 28 days?
Dr Shashank Joshi, DM Endo., Mumbai:
- Let’s all do our own neutralizing antibody after 21 days; I will share it in the ग्रुप (group).
- Need for IgG neutralizing antibodies to make some decision .it looks unlikely that the current booster time will be changed How logical or scientific will that be? There is no clarity on the serums Indian data it’s not at all in public domain as well. We are told that the secretary of DCGI also kept asking them for data of the 1600 case of which only 1200 were done and only 100 cases immunogenicity data was apparently presented.
Dr Manoj Chawla, Mumbai:
- Dr Shashank, you were the first one here for the 1st dose and then we followed. For all the controversy surrounding the second dose, we shall wait to see your pic with the 2nd dose and then decide 😀
Dr Shashank Joshi, DM Endo., Mumbai:
- Yes, Manoj agree.
Dr Sanjeev R Pathak:
- So, need to change the national vaccine strategy?
- ICMR may consider if experts like you and so many experts in this group strongly suggest.
Dr N K Singh:
- Very essential points raised. But, at 28 days, all are going the schedule dose?
Dr S K Goenka, Physician, Begusarai:
- Till date it is a tradition to space two vaccine doses by 28 days to avoid interference. In covid case, since the vaccine was introduced in emergency, probably 28 days was accepted for the time being. May be later on, after many data coming in, the spacing period might be increased.
Dr Mridul Das, Diabetologist, Agartala, Tripura:
- We have no option but to respond to call from Govt. and to take 2nd dose as scheduled after 4 weeks as obedient student of class 😶If we miss it, we shall not be called later for 2nd dose as informed.
Dr B B Rewari, Sr. Internist, Delhi:
- And there is no reason as of now not to take second dose.
CME INDIA Learning Points
- COVISHIELD efficacy is higher at longer prime-boost intervals, and that a single dose of the vaccine is 76% effective from 22- to up to 90-days post vaccination.
- The exploratory analyses presented in this preprint suggest that it is the dosing interval and not the dosing level which has a great impact on the efficacy of the vaccine.
- Single dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine is under immense debate now.
- Efficacy estimates now include data from all four studies of the vaccine from 3 countries, and a breakdown by the interval between the two doses is provided.
- These analyses show that higher vaccine efficacy is obtained with a longer interval between the first and second dose, and that a single dose of vaccine is highly efficacious in the first 90 days.
- The University of Oxford sponsored studies were initially planned as single dose studies but were amended to incorporate a second dose after review of the phase 1 immunogenicity data which showed a substantial increase in neutralising antibody with a second dose of vaccine.
- After initially providing consent to participate in a single dose study, some participants chose not to receive the second dose, providing a self-selected cohort of single dose recipients.
- Additionally, due to the time required to manufacture the second dose, there were delays in administration of the second dose for a large number of trial participants who received the two-dose schedule.
- These two situations, provide an opportunity to explore the immunogenicity and efficacy of a single dose of vaccine, and the impact of an extended interval before delivery of the second dose.
- Till things are well analysed in Indian perspective, Dr BB Rewari opinion is very appropriate – “And there is no reason as of now not to take second dose”
CME INDIA Tail Piece
(By Dr H D Sharan, Ranchi)
- Scientists are now looking at the reasons for the plummeting Covid cases in India even before the start of vaccination program. The simplest answer to it is GOK (God only knows; used humorously to indicate that an answer to a question or problem is impossible to give).
- Two things that helped are the age of the population and innate immunity. 0nly 6.5 percent of Indian population is above 65 yrs. And more than half the population is under 25. So, even if they acquired infection, it went unnoticed.
- We, who are living beyond 65, in spite of multiple co-morbities are really tough and hardened by multiple infections and poor-quality drinking water.
- Masks may have been a factor in big cities like Mumbai. In rural areas and states like Bihar, they will make fun of you if you go out with a mask.
- The message from this pandemic is “दाग अच्छे हैं।”
- Let the small kids roll on the floor and enjoy, let them walk and play barefoot, let them travel in trains without reserved seats.
- Bet – 10 yrs. from now, this will be the final conclusion of the epidemiologist.
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The 3 month routine is gaining ground
.The yet unanswered question is how long will the immunity last after the second dose spaced either 4 or12 weeks apart.Will a 3rd dose be needed?Only time will tell
Govt or icmr cannot be persuaded unless we have long term data regarding 28 days and 3 months
Vaccine roll out on a mass scale has not been long enough. We may have more definitive answers a few months down the road.
We also have to consider significant vaccine hesitancy especially in India, USA, Brazil, SA, and some other countries of African continent. If the 2nd dose is pushed to 12 weeks, compliance will go down greatly, risking resurgence of the pandemic after initial decline.
Very much informative. Highly enriching discussion. Hopefully as days passes by we will get clearer picture about the efficacy data & the proper time line for greater efficacy.
What was the original strategy in UK? A gap of 28 days or 90 days? If it was 28 days, who had primarily suggested a gap of 90 days, for the trial subjects and on what basis?