It has been a remarkable scientific feat that within one year of the outbreak of the COVID 19 pandemic, we have vaccines available against it. However, unlike many vaccines known to us it has to be given twice in quick succession. It has still several issues like; Why 2 doses? Are 2 doses enough to increase the immunity sufficiently? What is the best time of having the 2nd dose and is a booster dose again required after the 2nd dose?
When the COVID 19, vaccines were first tested the first dose gave rise to a relatively low level of immunity in a few weeks. This was substantially strengthened by a 2nd dose. This led to the 2nd dose becoming a part of the protocol by the researchers. The trials therefore started to look at the immunity conferred after the 2nd dose of vaccine which was administered after 3 to 4 weeks. The results showed very convincingly that the immunity was strong enough to prevent symptomatic COVID 19 infections. However, since the trials were giving 2 doses, it is hard to comment on how much immunity was conferred by the single dose alone.
Is 2nd dose actually required:
The production of the vaccine in sufficient amounts is a challenge especially when millions of people have to be vaccinated in a short period of time. There is thus a case for delaying the 2nd dose till most of the population has received the first dose. Since the immunity after first vaccine as judged by the antibody titres in the blood, after a few weeks is low the next set of trials looked at the ability to prevent COVID-19 infection after receiving the 2 doses of vaccine. These vaccines were highly effective in preventing infections that cause symptoms after both the first and second doses. However, in these trials, a second dose was always given. It is therefore not known how well the vaccine works if only 1 dose is given.
It is possible that people who get only 1 dose will have only partial immunity to COVID-19 infection, resulting in a higher risk that vaccine-resistant variants will develop. At present there is no evidence that people who get only 1 dose have adequate long-term protection against COVID-19 infection.
Timing of the 2nd dose:
The information we have regarding this is largely based upon the Pfizer and Moderna vaccines, mRNA-based vaccines, which are not available in India (because of a number of reasons mainly the cost and very fastidious storage needs) and the Oxford Astra Zenica’s “Covishield” vaccine. For the mRNA-based vaccines the centres for Disease Control and Prevention of USA, has recommended that the 2nd dose be given within 3 weeks of the first dose for Pfizer and within 4 weeks for Moderna vaccine. Under no circumstances should the 2nd dose be delayed beyond 6 weeks.
The data regarding the Oxford Astra Zenica vaccine which is also being bulk manufactured by Serum Institute of India at Pune, recommends that the 2nd dose be given after 28 days. This protocol is being followed in our country where the vaccine at present is being given to frontline workers. Till date more than 4.5 million doses have already been given. This pace however, is not adequate to meet the target of 300 million people by August 2021. The second adeno-virus based vaccine from India COVAXIN, from Bharat Biotech is currently in Phase 3 of clinical trial, but has been launched prematurely.
The new data from United Kingdom, the country of origin of the Oxford vaccine, now suggests that the dosage interval of 12 weeks should be preferred. The researchers found vaccine efficacy reached 82.4% after a second dose in those with a dosing interval of 12 weeks or more. If the two doses were given less than six weeks apart the efficacy was only 54.9%. A single standard dose of vaccine provided 76% protection overall against symptomatic covid-19 in the first 90 days after vaccination. However, how long protection might last with a single dose after 90 days is not known.
This additional data has come from trials involving 17 177 participants in the UK, Brazil, and South Africa. The analyses suggest that it is the dosing interval and not the dosing level which has the greatest impact on the efficacy of the vaccine. This is in line with previous research supporting greater efficacy with longer intervals with other vaccines such as influenza and Ebola. If we take all this evidence together, the 12-week gap between first and second dose seems to be a better strategy as more people can be protected quickly and the ultimate protective effect is greater. It is hoped that with mass vaccination and a large population already having been infected, a herd immunity would develop making the community free of COVID-19. Whether a booster dose would be needed at some stage during the follow up is a moot question? This would need a longer follow up and research.
It is very important to remember that the vaccines increase the immunity to face the infection and do in no way prevent the transmission of the virus. There will therefore be very few symptomatic infections. It is the symptomatic patients who are far more infectious than asymptomatic ones. The hygienic measures for prevention need to continue for times to come.
What about the side effects after 2nd dose of vaccine?
Some people who have received the COVID-19 vaccination report they feel ill after getting their first shot. It is usually fever, chills, body aches, malaise and soreness at site of injection. These symptoms are transient and not life threatening and subside by taking drugs like paracetamol etc. Many say the second shot can be followed by symptoms more often. These common symptoms are signs that the vaccine has triggered an immune response, which it is supposed to do. It’s usually very short-term and is much better than actually, getting COVID and being sick for 2 weeks or more, needing hospitalization, oxygen use with frank pneumonia which in some cases can be fata
What about new variants?
The data suggests that the new variants seem to increase the ability of COVID-19 to spread but do not influence the degree of sickness. The current vaccines appear to work against the new variants. When vaccines are created, they are designed to create different antibodies to various components of the virus. That means even if one part of the virus mutates, the antibodies may recognize another part of the virus. It is possible that there will be a variant that reduces vaccine efficacy but researchers and the companies that make vaccines are creating modifications that should work against new strains of SARS-CoV-2.
Learning points:
We are fortunate to have effective vaccines against COVID 19. At present all the vaccines need two doses in succession. The success rates after 2nd dose are very high. The timing of the 2nd dose is still evolving and data and recommendations are likely to change for COVISHIELD to 12 weeks or more from the present 28 days. We should not be shy of getting vaccinated twice against this very infective virus.
Prof Upendra Kaul is a renowned cardiologist. He is a recipient of Padma shri and Dr B C Roy Award