CME INDIA Presentation by Dr. Rajeev Jayadevan, MD, DNB, MRCP, ABIM (Med) ABIM (Gastro), NY. Vice Chairman, Kerala state IMA Research Cell. Member, National IMA Task Force on Corona Epidemic, Cochin; and Admin.

More Doses of Covid Vaccine may not be the answer

"More Doses of Covid Vaccine" Isn't the Solution?
  • Symptomatic breakthrough infections by Omicron despite 3 doses of Pfizer vaccine & high antibody levels in recently “boosted” young adults shows its immune evasion capability. Symptoms were cough, chest pressure, fever etc.
  • No one was hospitalised.
  • Fact: “More doses of vaccine” isn’t the solution.
  • It’s time to work harder on those mucosal vaccines, and stick to standard public health measures.

The Omicron Immune Attack

  • Immune evasion potential has been predicted by genomic data since its inception.
  • Preliminarily confirmation by observation of increasing incidence of re-infections was brought in notice by (Pulliam et al., 2021).
  • Worldwide new triggered calls to intensify vaccination programmes has been intensified.
  • Omicron also strengthened the concept of   provision of vaccine booster doses (Dolgin, 2021).

The Big News is not good at present

  • As per  report by Kuhlmann & Mayer, A group of German visitors after receiving three doses of SARS-CoV-2 vaccine went to Cape Town Africa in late November / early December 2021.
  • Their vaccination included at least two of a messenger ribonucleic acid (mRNA) vaccine.
  • In spite of booster doses, 7 experienced breakthrough infections with the Omicron variant.

Vaccination status

  • Six cases: fully vaccinated with BNT162b2 (Comirnaty; BioNTech, Mainz, Germany).
  • Five cases:  received a third (booster) dose of BNT162b2 in October or early November 2021.
  • One case: received a full dose (0.5 mL, 100 mcg) of mRNA-1273 (Spikevax; Moderna, Cambridge, MA, USA) at the beginning of October.
  • Seventh case: received an initial dose of ChAdOx1-S (Vaxzevria; AstraZeneca, Cambridge, U.K.), followed by a dose of BNT162b2 for completion of primary immunization + a booster dose of the same vaccine.
  • None of them had a reported history of a SARS-CoV-2 infection.
  • Booster doses were administered between 5 and 10 months after the second vaccine doses, and breakthrough infections occurred one to two months thereafter.

How they presented?

  • All patients were managed by domestic isolation.
  • Daily symptom diary to document the course of disease was initiated.
  • All individuals had symptoms compatible with COVID-19.
  • Initial symptoms:
    • Sore throat (85.7%).
    • Fatigue (71.4%).
    • Headaches (57.14%).
    • Dry cough (42.9%).
    • Chest pressure, sinus pressure, rhinitis and nausea (all reported by 28.6%),
    • Night sweats – in one patient within the first three days after symptom onset.
    • All individuals developed a dry cough (85.7%).
    • Sinus pressure (71.4%).
    • Rhinitis (71.4%).
    • Anosmia and dysgeusia were observed only temporarily (on day 3) in one patient.
    • Fever – 14.3 % of patients.

Important Symptoms Day-wise

Day 1Sore Throat 85.7%Fatigue-71.4%Fever-14.3%Shortness of breath-(SOB)-0%
Day 3Sore Throat 85.7% Dry Cough-85.7%Fatigue- 57.1%Fever-14.3%SOB-28.6%
Day 5Dry Cough 100%Fatigue- 57.1%Fever-14.3%SOB-42.9%
Day 7Dry Cough 100%Fatigue- 57.1%Fever-14.3%SOB-42.9%

Viral loads/Anti-spike antibody Co-relation

  • 5 of the cases were confirmed to be due to infection with the SARS-CoV-2 Omicron variant (PANGO lineage B.1.1.529, Nextstrain clade 21K);
  • 2 cases sequencing failed but they are inferred to be Omicron, too, based on their very close epidemiological links to the others.
  • Viral loads range:
    • 1.41 x 10E4 to 1.65 x 10E8 (mean 4.16 x 10E7) viral RNA copies per mL of swab eluate,
    • Highest averages (mean 6.69 x 10E7) on day 4 after symptom onset.
    • Viral RNA loads in Omicron variant infections have not yet been reported. It is thus unknown whether the viral loads observed in our group are different from those in unvaccinated, or differently vaccinated, individuals.
    • In this case series –There is higher viral loads in samples from patients infected with the Omicron variant but should be regarded as preliminary.
  • Anti-spike antibody levels:
    • 15,011.2 to > 40,000 with a mean of approximately 23,000 arbitrary units / millilitre (AU/mL) of serum.
    • All individuals experiencing breakthrough infections had high levels of viral spike protein binding antibodies.

Why this case series is hot news?

  • This case series  of 7 cases only but shows the importance of clinical medicine ever increasing importance
  • This is the first case series to report, and characterise, breakthrough infections with the Omicron variant in individuals fully vaccinated and having received a vaccine booster dose.
  • Cases  with heterologous booster doses in line were studied
  • This is what is now marching as global practice.

Travel Boon

  • South Africa has yet to introduce booster vaccinations for individuals immunised with two doses of BNT162b2. The presence of this group from Germany presented a unique opportunity to study Omicron breakthrough infections in individuals with mRNA vaccine boosters.

A booster dose still provides good protection against severe COVID-19

  • During the first week after onset of symptoms a mild clinical course was observed.
  • This suggests that full vaccination followed by a booster dose still provides good protection against severe COVID-19.

Omicron variant is able to evade immunity

  • This case series proves that the Omicron variant is able to evade immunity induced by mRNA vaccines in vivo.
  • Vaccine is insufficient to prevent symptomatic infection and emphasises the need to maintain CAB (Covid appropriate behaviour).

CME INDIA Learning Points

  • The recently emerged SARS-CoV-2 Omicron variant is predicted to evade immune responses to some extent.
  • In spite of symptomatic COVID-19, clinical manifestations have been restricted mild to moderate in vaccinated individuals.
  • Even three doses of mRNA vaccines may not be sufficient to prevent infection and symptomatic disease with the Omicron variant.
  • We do need updated vaccines to provide better protection against symptomatic infection with the Omicron variant

CME INDIA Tail Piece

"More Doses of Covid Vaccine" Isn't the Solution?
Dr Eric Topol – Founder and Director of the Scripps Research Translational Institute, Professor of Molecular Medicine, and Executive Vice-President of Scripps Research.

"More Doses of Covid Vaccine" Isn't the Solution?
Epidemiologist @UKHSA, PhD student.


  1. Kuhlmann, Constanze and Mayer, Carla Konstanze and Claassen, Mathilda and Maponga, Tongai G. and Sutherland, Andrew D. and Suliman, Tasnim and Shaw, Megan L. and Preiser, Wolfgang, Breakthrough infections with SARS-CoV-2 Omicron variant despite booster dose of mRNA vaccine (December 9, 2021). Available at SSRN:
  2. WHO. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. Statement 26 November 2021. sars-cov-2-variant-of-concern (last accessed 6 Dec 2021)
  3. Pulliam JRC, van Schalkwyk C, Govender N, von Gottberg A, Cohen C, Groome MJ, Dushoff J, Mlisana K, Moultrie H. Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa. Pre-print. medRxiv 2021. Doi:
  4. Dolgin E. Omicron is supercharging the COVID vaccine booster debate. Nature. 2021 Dec 2. Doi: 10.1038/d41586-021-03592-2. Epub ahead of print. PMID: 34862505.
  5. Cele S, A. SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. Pre-print. (last accessed 9 December 2021).
  6. Wilhelm A, Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies. medRxiv 2021.12.07.21267432; doi:
  7.  Pfizer. Pfizer and BioNTech Provide Update on Omicron Variant. Press release. Wednesday, December 08, 2021 – 06:54am.

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