COVID-19 Notes
By Dr Satish K Gupta*
A 4th booster dose at this time in India makes no sense
Do we need a new booster dose with every new wave?
Israel and the United States have started propagating the idea of the 4th dose Covid vaccine. And many nations in Europe are following the line. Joe Biden himself having taken the 4th dose has fueled the fire.
Where does India stand for the idea of 4th dose?
Before we take up this question, let’s first analyse why America and Europe decided to opt for a repeat booster or 4th dose.
In the month of March 2022, many countries in Western Europe saw a significant 2nd Omicron wave attributable to the BA.2 variant, and some of them were accompanied by a substantial rise in hospitalizations and deaths. Denmark, Netherlands and Austria had particularly more pronounced BA.2 wave superimposed over BA.1
BA.2 wave lead to a fresh surge in the number of deaths in Austria, the UK, Italy and Belgium causing panic leading to a rethink.
Who tossed the idea of 4th dose/second booster?
Israel has been the pioneer of the second booster. There are only 3 studies of the 2nd booster to date. All these were initiated back in December 2021 for people aged 60+ during the Omicron wave in Israel. Initially, studies were started for the immunocomised, but now boosters are administered broadly to all adults who have completed 4 months from their 3rd shot.
- The first small study looked at safety and vaccine effectiveness in preventing infections in health care workers. While the neutralizing antibody response from the 4th shot was good, the effectiveness vs symptomatic infections was quite low, only 31% for Moderna and 44% for Pfizer.
- The second study was in a million people age 60+ with either a 4th dose of at least 4 months out from the 3rd dose (1st booster). Follow-up was only 12+ days but a >4-fold protection against severe disease was demonstrated.
- The most important, 3rd study, was performed at Clalit Health, one of the 4 large healthcare organizations in Israel. It was also among people age 60+ and showed a 78% reduction of death for 4 shots vs 3 shots (post 4 or more months).
This is remarkably similar to the Clalit Health report in people age 50+ with their first booster compared both only 2 shots (> 4 months out) for whom there was a 90% reduction of mortality.
Note that the absolute reductions in death are pretty small in these studies (Y-axis), but the huge number of people in these age groups may translate into an important benefit at the population level.
For whom does FDA recommend the 4th Shot?
FDA says that 4th shot (Pfizer and Moderna) is to be provided for people age 50+ as an option.
US Experts recommend the second booster to people who are more than 4-6 months from 3rd shot, are age 50+, who tolerated the previous shots well, and who are concerned about the BA.2 as per risks of their profession or BA.2 spread.
Ex-United States Food and Drugs Administration (FDA) Deputy Director speaks out against unnecessary boosters
Dr Philip Krause who is presently a consultant to the World Health Organization and who had been deputy director of FDA’s Office of Vaccines Research and Review, 2011-21 is much against offering boosters to the general population.
If you’ve had two doses of the vaccine, you have a lot of protection against severe Covid. Likewise, if you’ve been infected with the virus, including with Omicron. If you’re over 65 or otherwise at high risk of severe disease, it’s reasonable to get a third dose.
A fourth dose is already authorized for the immunocompromised
For everyone else, the data haven’t shown a meaningful benefit of three doses, never mind four.
Vaccine-induced protection against ‘infection’ is short-lived and doesn’t get much of a boost from extra shots. Yet the initial two-dose regimen is enough to provide most patients excellent protection against severe disease mediated by durable cellular responses, not the neutralizing antibodies that rise and wane quickly after vaccination.
Indian scientist dissects deep into Israel study
Rajeev Jaydevan from Kochi dissected deep into the Israeli study to dig out the truth. He made startling observations “Israel 4th dose study has been reported in an exaggerated manner by several media (and western ‘Twitter celebrities’)”
His chief observations are
1. They studied people over the average age of 70. This is important, as severe COVID outcomes are more likely to occur in this age segment. However, deaths were very very rare in both 3 and 4 dose groups.
2. He further points out that “when we look at raw numbers, it is clear there is no difference between the 3 or 4 dose groups”.
3. There was a high rate of infection, even after three doses of vaccination.
This is a very important finding, up to 22.9% of tests were positive. This shows that boosters, even 3 doses were not protecting against infection adequately during the Omicron wave.
And this crucial point is not even mentioned in the study results.
The infection rate in the 4 dose group was less than 3 dose. This makes sense because in the initial 10 weeks following a vaccine dose, there is a protective window of neutralising antibodies. Unfortunately with every additional dose, this window gets smaller. This is called the principle of diminishing returns.
The author reports that the additional protective effect of the 4th dose against infection dropped to 29% in only one and half months.
He goes on to say that the study tries to hide the truth behind statistical jargon – “If we tortured data long enough, it will confess to anything we want”
Do we need 4th booster dose in India?
It is noteworthy that several countries like India, Bangladesh, and Sweden slowly transitioned to ~100% BA.2 without experiencing an increase in cases or deaths.
Better protection among Indians can be attributed to higher run through infection by Delta during the second wave, better vaccination coverage among vulnerable age groups, superior long term efficacy of vector-based vaccines and Killed Virus vaccines used in India.
The positivity rate in India is presently 0.2%. The third dose booster is making advances in 60+ slowly. To call for 4th dose booster at this time in India makes no sense except blindly copying the West.
Nevertheless, the virus is as unpredictable as it is formidable. It may evolve further. So we need to keep a close watch and act as and when required.
Also read: Understanding COVID-19: Will there be a next wave?
*Dr Satish K Gupta is an MD in Medicines, a Visiting Senior Consultant Physician and Internist at Max Super Speciality Hospital, and a Clinical Assistant Professor at GS Medical College, Chaudhary Charan Singh University, Meerut. He is the author of Journey of COVID in India: A Doctor’s Perspective.
Well researched out of box article