CME INDIA Presentation – Compilation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh, India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.

A Covid Update meeting was held on the aegis of East Delhi Physicians Association on 12 October 2021 at 8.30 pm on Zoom to discuss the Third Dose Booster in India, especially for Health Care Workers. The expert panel consisted of Dr. Vijay Yeldandi from the University of Illinois, Chicago USA, who expressed his original ideas; Dr. Atul Patel from Sterling Hospital Ahmedabad, Dr. S K Gupta from Max Hospital, New Delhi and Dr. Alok who deliberated upon Childhood Covid Vaccination. The meeting was moderated by Dr. Pankaj Choudhary and Dr. Ruby Bansal.

Excerpts of the meeting

Dr. Vijay Yaldandi made an outstanding presentation and said:

• Booster Dose Studies mainly coming from Israel and USA, have a serious limitation of small size and short term follow up.
• These studies have Robust Data recommending Third Booster dose in Immunocompromised people and transplant recipients. But the same can’t be applied to Health Care Workers and the general population. However, because of the high risk of exposure, HCW may be accorded Third Dose Booster.

Boosters don’t come without adverse events

• Immune-mediated myocarditis with mRNA vaccines, Guillain Barre syndrome, and Vaccine-induced thrombocytopenic Thrombosis with Vector-based Vaccines are serious side effects.
• Society shouldn’t be exposed to such serious adverse events based on the sheer abundance of caution in the absence of definite evidence of proven benefit by the third dose booster.

Declining Anti Body levels and Need for 3rd dose Booster

1. Anti-Body levels measured after vaccination consist of Anti-Spike antibodies and not Neutralising Antibodies.
2. Protective correlates of neutralizing antibodies have not been established. 
3. Trained innate immunity, Memory T cells can mount a reasonable defence upon fresh challenge by the virus even when the antibody levels are low. Stimulated memory B cells can start the production of neutralizing antibodies immediately after a new infection. 
4. Tests to measure T cell responses are not commercially available.

So, the physicians should not get into a mad rush or panic demand for a third dose booster with declining antibody levels in healthy immunocompetent subjects.

Third Dose Booster – When should it be taken?

• Usually, five to six months after the primary vaccination.

A. Covaxin – In the case of Covaxin, the timing may not be an issue because both the primary doses were given 28 days apart.

B. Covishield – The majority of the population has been inoculated using the AstraZeneca Covishield vaccine with different interval schedules between two primary doses like 0- 4 weeks, 0-6 weeks, and 0-12 weeks. Hence, the optimal timing of the Third dose booster may not be uniform for all the subgroups. And the best interval duration of the third dose booster may be inferred only after comparative studies. And the data of mRNA vaccines may not be extrapolated to vector-based vaccines.

Which Vaccine could be the best as the Third Dose Booster?

• Covaxin as Third Dose Booster after primary series by Covaxin would be the right choice. The Bharat Biotech has conducted studies in India with the Third Dose Booster. The study results were expected to be available in August but are now likely to be out by November 21.
• Covishield’s third dose booster timing may have certain concerns. It is noteworthy that Covishield uses chimpanzee adenovirus vector (not human adenovirus vector) to code for SARS Cov-2 spike protein. It was suspected if the human adenovirus vector is used, the body might neutralize the Vector in Vaccine and render the Vaccine ineffective by preformed antibodies against the human adenovirus developed during repeated infections.
• It is also possible that after two primary doses of the AstraZeneca vaccine, the human body might have developed antibodies against the chimpanzee adenovirus. These antibodies may render the third dose ineffective. However, it remains an unfounded fear because the adenovirus vector in Covishield is a non-replicating virus. Also, no studies have so far proven the development of such antibodies. Also, it is again reiterated that no studies with the booster dose of vector-based Vaccines are available. And it may not be appropriate to extrapolate the data of mRNA vaccines to Vector based vaccines.

What about heterologous mix match Third dose booster?

• Trials in the UK have shown that a third dose booster with Pfizer is safe after primary vaccination with Vector-based AstraZeneca Vaccine. Small trials by ICMR in India using heterologous prime-boost as the second dose (Mix and match of Covaxin and Covishield) showed better antibody responses. But a definite answer can come only when properly designed trials are conducted.

How to decide if Health Care Workers in India need a Third Dose Booster?

• The only way to answer the question is to look for breakthrough infections in (fully) vaccinated population. In countries that have completed vaccination for masses, the breakthrough infections are mild and don’t need hospitalization. In India, new cases have dropped drastically, hospitals do not have much cases hence, HCWs are not being exposed, and it may not be possible to find the correct incidence of breakthrough infections.
• Israel and the USA had a fresh surge of cases in the fourth wave by Delta infection, which had already wreaked havoc in India during the second wave. Second wave data from various hospitals in India showed the incidence of breakthrough infection from 2 to 17%, mainly affecting young doctors and nurses. Still, most of these infections were mild and did not require hospitalization.
• Good five months have passed since the peak of the second wave in India, and it is possible that the immunity levels might have dipped, so the concern of HCW can’t be outrightly rejected. But we will need to wait for the trial data from Bharat Biotech. The resurgence of Delta infection in India could be a remote possibility, however further mutations in the virus can play spoilsport.   

Are HCWs being denied Third Dose Booster for lack of vaccines?

• India is the largest producer of vaccines in the world. With more than 960 million doses of Vaccines already administered in India till 13 October 2021. The government of India has restarted the export of vaccines to neighbouring Nations like Bangladesh, Myanmar, Nepal, and Iran. So, the scarcity of vaccines does not seem to be the concern. One crore dose for HCWs in the current scenario are not likely to strain the system anyway. Probably, the Govt is waiting for the results of Indian studies to confirm that the booster dose vaccination is the need of the hour. The government of India is likely to accord top priority to Health Care Workers in the case need for a third dose booster is confirmed.

What do experts say on the need for the third dose Booster of HCWs in India?

• Dr. Vijay Yeldandy believed that the Healthcare workers could be vaccinated, but it may not be appropriate to extrapolate data of the Pfizer vaccine to the Indian scenario. The best way would be to have trials here in India before embarking on the Third Dose Vaccination of HCWs.
• Dr. Atul Patel was of the opinion that in India Health Care Workers should be accorded third dose booster vaccination based on current data. Still, he maintained that the priority should be the primary vaccination of masses since it leads to a decrease in caseload, essential for containing the pandemic.
• Dr. S.K. Gupta was categorical in saying that the booster dose trials in the Healthcare workers have not been done in India, and HCWs cannot be exposed to the side effects of the third dose booster out of the abundance of caution. And, it may not be wise to extrapolate data of Pfizer mRNA vaccine to Vector-based vaccines. mRNA vaccines primarily induce antibody responses, while Vector-based vaccines like Covishield have a higher effect on cell-mediated immunity, and Covaxin is likely to have a balance of the two. So, it will be best to wait for our own trials’ results rather than blindly following the West.

Covid vaccination among Children?

• India has a vast population of nearly 40 crore Children less than 18 years of age who are yet to be vaccinated. Vaccination of children is essential for opening up of the schools.
• Though children have mild disease, nevertheless, children serve to transmit the infection to adults and the elderly. So, it is essential to vaccinate children to control the pandemic.
• Govt. of India is keenly considering to start vaccination of children. Approval of Covaxin in children more than 2 years to 17 years by Subject Expert Committee DCGI should be seen as the first step in this direction. India already has ZyCov-D approved for 12 to 18 years of age.  India might start the vaccination of children soon after completing 1 billion doses of adult vaccinations, and the milestone is likely to be achieved in 3 to 5 days.

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