CME INDIA Presentation by Admin.

An efficacious COVID-19 vaccine could reduce the likelihood of infection of an individual.

Efficacious COVID-19 vaccine
(Courtsey: Lancet Infect Dis 2021; 21: e26–35 Published Online October 27, 2020 S1473-3099(20)30773-8)

In spite of so many odds, uncertainties, gaps in knowledge, vaccines are the ultimate hope in a very desperate situation. Physicians need to understand the art and science behind these scenarios.

“Let not perfect become the enemy of good”

By Dr Rajeev Jayadevan, Gastroenterologist, Sunrise Hospital, Cochin

  • There are numerous practical difficulties in measuring whether a COVID vaccine is useful or not.
  • For instance, the choice of “primary endpoint” in a vaccine trial can substantially affect the sample size required. The ideal endpoint to study is either prevention of severe disease or death.
  • But if we choose ‘death’ as primary endpoint, enormous numbers of participants are required. That number will also depend on the age group, and also how active the pandemic is in that region over the study period. Since death is rare in the young, bigger numbers of participants are naturally needed to detect any difference between the vaccine and placebo groups.
  • For example, if the pandemic is slowing down, we need to study as many as 5 million young people to prove if vaccination reduces death rate.
  • But in an active pandemic zone, 619,000 will suffice.
  • Likewise, only 24,494 people are needed if >80-year-old people are theoretically selected as participants.
  • The ability of vaccine to reduce at least mild self-reported symptomatic illness is currently taken as the standard, so that the sample sizes are within reach. This outcome can also be studied across age groups, although it does not reliably foretell death in the young.
  • But whether prevention of asymptomatic / mild self-limiting disease can be equated to preventing severe life-threatening COVID-19 involves some speculation, particularly when we know that the immune signature for mild illness is different from that in seriously ill patients.
  • The importance of T-cell immunity in preventing severe disease is increasingly recognized. Unfortunately, this is not a readily measurable correlate of protection, and often we are left with checking antibody titers simply because that is the only thing we can measure.
  • Antibody titers decline quickly and are not a reliable surrogate of immune response in the long-term, as sterilising immunity is not achievable for this disease. Besides, there is heterogeneity in assays. Antibodies may be absent even when there is T-cell immune response.
  • Exactly how we will assess the efficacy of vaccines in actual field conditions (outside of clinical trials) is a big question, and whom to compare with is another issue.
  • The pandemic, like a thundershower, has been seen to mysteriously abate on its own in certain areas too, and reappear later.
  • In summary, there will be plenty of uncertainty about the true efficacy of vaccines for some time to come. This is not the fault of science – this is just the way the disease is.
  • But let not perfect become the enemy of good. (The phrase means that sometimes we lose valuable time waiting for the perfect solution, we forget what is truly practical and good for the society as a whole. As a result, we delay using something that was actually available and beneficial).
  • Vaccines are here now, and deserve our trust. There are no better alternatives at this time, as obtaining immunity by natural infection (instead of vaccination) is fraught with risk of severe disease and death.

CME INDIA Discussion

Dr Keyur Acharya, Intensivist, UK:

  • It very obvious that mutation rates in virus remains unpredictable if not high. Majority are harmless but there are few which can cause havoc.
  • E484K mutation originally identified in SA variant is also identified in UK. It’s an escape mutation and has been found in SA (B.1351) and Brazilian (B.1.1.28) variants. This might have different immune response and vaccine efficacy.
  • There could be many more such. Only Genomics and its sharing can identify such variants.
  • US has its own home-grown mutation S: Q677P and few sub types – Robin, Pelican etc.
  • We still need our guards against it by Masks, vaccines, appropriate social distancing and perhaps Vit D.

Dr H D Sharan, Ranchi:

  • What is important is that no mutation has so far made the vaccines totally ineffective.
  • The trial on combination of 2 vaccines is very important and so is the success of vaccines that have the whole attenuated or killed virus.
  • In view of the more than 4000 mutations so far, it seems that the labs will have to keep updating the vaccine and trial will have to involve hundreds and not thousands of volunteers like flu vaccine. In that case, vaccination will become an annual affair
  • Meanwhile proper masking is the only way to keep safe. Physical distancing appears very difficult in countries with huge population like ours. We have to continue to politely refuse invitations for marriages and family gatherings of more than 5 to 7 people and it should be organised in an open area.
  • As far as masks are concerned, how they fit is more important than the material used to make them.
  • We are safer in COVID-19 wards because we take all precautions. The maximum risk is with family and friends when we let our guard down.

2nd DOSE of Vaccination going on: What the Scenario tells

Dr N K Singh, Dhanbad:

  • Yesterday, I had to attend a marriage ceremony. I was wearing mask, rest were not. All were looking at me in surprise, as if some new animal they were seeing.

Dr Santosh Malpani, Nanded, Maharashtra:

  • We in Maharashtra are in phase of taking second dose. Precisely it started on Friday. Nothing, till date, has proven to be beneficial than what we followed Pre-vaccination time. No strategy practically is beneficial than mask, social distancing, washing hands, exercise, and taking healthy food. Still vaccine is to prove its efficacy. But one has to take it out of desperation. So, it’s better to rely on old time-tested measures. We saw a hike in social gatherings in last few days.

Dr H D Sharan, Ranchi:

  • Family gatherings and vacations have become the new super spreaders. Avoid marriages and puja. One of our family friends, a widow, stayed safe and indoors throughout the pandemic. Recently she attended a family puja. Now that lady, her daughter and 2 grand daughters have been infected. Mother and daughter have COVID-19 Pneumonia too. Now is the time for taking care for all of us. We treated Corona patients and remained safe. Let us not be careless now

Dr Praveen Kulkarni, MD, Medicine Miraj, Maharashtra:

  • True. Even I got same feelings and looks yesterday in a gathering.

CME INDIA Learning Points

  • Dr Anthony Fauci, MD, the White House COVID-19 Response Team’s chief medical adviser
    • Data ‘Favorable’ That Vaccines Limit Transmission (Medscape)
    • Researchers know by now the available COVID-19 vaccines prevent people from getting COVID around 95% of the time. But the million-dollar question remains: Are people less likely to spread the illness after they get the vaccine? According to preliminary data, the odds are good.
    • Fauci cited studies showing the amount of viral load — or the amount of the COVID-19 virus in someone’s body — is significantly lower if someone gets infected after they’ve been vaccinated, compared with people who get infected and didn’t have 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: A new study shows-
    • 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, providing further support for current policy.
    • Vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination was 76% (59%, 86%), and modelled analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 day (GMR 0.66, 95% CI 0.59, 0.74).
    •  In the SD/SD group, after the second dose, efficacy was higher with a longer prime-boost interval: VE 82.4% 95%CI 62.7%, 91.7% at 12+ weeks, compared with VE 54.9%, 95%CI 32.7%, 69.7% at
    • ChAdOx1 nCoV-19 vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3-month period is an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term.

  • Assessment of the efficacy of a vaccine is complex for many diseases but particularly so in the case of SARS-CoV-2, where the fundamental understanding of the pathogen is evolving.
    • These data offer evidence that 40 SARS-CoV-2 variant B.1.1.7 may cause longer infections with similar peak viral concentration 41 compared to non-B.1.1.7 SARS-CoV-2. This extended duration may contribute to B.1.1.7 SARS42 CoV-2’s increased transmissibility

CME INDIA Tail Piece

Q. A friend had his 2nd injection of the vaccine at the vaccination center and began to have blurred vision the whole way home, he called the vaccination center for advice. Immediately, He was told to come back to the vaccination center. Explain the possibilities!

Dr Kapil Sud, Internist, Delhi: He was told to come back to the vaccination center as a matter of urgency to take back his forgotten glasses 😂.

Dr Santosh Malpani, Nanded: चश्मा भुले भैया!


  1. Voysey M, Clemens S, Madhi S, et al. Single dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1nCoV-19 (AZD1222) vaccine.
  2. Voysey M, Clemens S, Madhi S, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021. Jan 9;397(10269):99-
  3. Kissler, Stephen, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Mallery I. Breban, et al. “Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2.” Preprint, 2021. Citable link
  4. MedRxiv: “Initial real world evidence for lower viral load of individuals who have been vaccinated by BNT162b2.”
  5. The Lancet: “Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study.”
  6. News briefing, White House COVID-19 Response Team, Feb. 17, 2021.

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