On January 16, large-scale vaccination of healthcare workers began across India. Two vaccines are in use — Covishield and Covaxin — both rolled out under emergency use authorisation (EUA) by the Drugs Controller General of India (DCGI), with the condition that all information on adverse reactions following immunisation (AEFI) be collected. For Covishield, the responsibility of AEFI monitoring is with the Government of India, since the authorisation for restricted use is at the discretion of the government. The government has defined who should be prioritised for vaccination — the first priority is healthcare workers.
Since the epidemic was transitioning to the endemic phase (when, on average, each infection reproduces another and the effective reproduction number or R0=1) from the third week of January, the vaccination is not expected to impact on the epidemic, but offer protection to healthcare workers since repeated exposure to infection is an occupational hazard. The vaccine roll-out is without a need assessment and includes those previously infected. It is essentially a token of appreciation to the healthcare workers who stoically faced the brunt of the epidemic and efficiently managed infected individuals.
Longer interval
The Lancet has just published a paper (that is not yet peer-reviewed) describing the clinical protective efficacy of the Oxford-AstraZeneca vaccine (called Covishield in India) in Phase 3 clinical trials conducted in the U.K., Brazil and South Africa. The critical lesson is that the efficacy after the second dose was only 54.9% when given 4-6 weeks after the first dose but 82.4% when the second dose was delayed to 12 weeks. It is an accepted principle in vaccine immunology that the second dose of a vaccine administered after 28 days functions as a booster and the longer the time interval between the two doses — upto six months — the higher the booster response. The results of the Oxford vaccine trial are therefore no surprise.
For the vaccine roll-out in India, the due date of the second dose will begin from February 13 to 27 if at 4-6 weeks, but April 10 if delayed for 12 weeks. Which is preferable for India under the present endemic phase of infection (by our estimates) — early low efficacy or delayed but high efficacy? This is a question that the government must answer immediately, so that the due dates for the next dose can be revised in case the longer interval is chosen.
Had we begun the vaccine roll-out in the middle of the epidemic, early protection by two doses would have been preferred in order to accelerate the decline of the epidemic curve. But now that we are in the endemic phase, the 12-week interval between doses would be more appropriate. If the longer gap is chosen, a larger number of persons would be able to access the first dose and this would ensure better community coverage.
The present COVID-19 vaccination roll-out in India has completed first dose administration of vaccine to 43.9 lakh (47%) out of 92.6 lakh registered healthcare workers from the public and private sectors by February 3, 2021. It is important to understand that in this group, the earlier infections would have been much more than in the general population figure of about 60% at endemicity — may be 70%-80% already.
The vaccination centres are achieving only 50%-60% of their potential (50-60 vaccinations per day as against the possible 100). These slots are sought to be filled by other essential workers like the police and those in public service.
Slots for the elderly and vulnerable
It would be important to start registering the empty slots for the elderly and vulnerable and to administer the first dose of the vaccine to these subjects who are at high risk of serious disease and death from the novel coronavirus infection. After all, a single dose of the Covishield vaccine has some degree of protective efficacy starting about three weeks after the vaccination lasting up to 12 weeks. Delaying the second dose to 12 weeks and starting the first dose of the vaccine for the elderly and vulnerable will ensure that vaccination centres run to full capacity and the elderly and vulnerable are protected against serious disease or death. This is very important because, with relaxation of curbs on assembly and reopening of schools, these so far cocooned subjects will be exposed to the infection. The U.K. is already following the schedule of delaying the second dose of the Oxford vaccine by 12 weeks. It is important that India does the same and ensures that serious disease and death are prevented in elderly and vulnerable subjects.
Dr. M.S. Seshadri is Medical Director, Consultant Physician and Endocrinologist, Thirumalai Mission Hospital, Ranipet, Vellore; and Dr. T. Jacob John is retired Professor of Clinical Virology, CMC Hospital, Vellore
