Covid-19 vaccination booster – why, when, what?

23rd September 2021, Dr Chee L Khoo

Booster anybody?

You have to agree that the covid-19 vaccines have been pretty effective in reducing the case numbers of covid-19 worldwide. However, over the last few months, with the emergence of the delta variant, there have been resurgence of the virus. Is it because delta variant is more contagious? Perhaps, the efficacy of the vaccines has waned as it’s coming up to 6 months for those who had their vaccines earlier in the year. Maybe the vaccine is less efficacious against the delta variant. There are suggestions that the effectiveness of the vaccines (especially Comirnaty) starts waning after 6 months. For most of us, it is coming up to 6 months since our second jab. Do we even need a booster? If we do, when will the booster be needed and which vaccine should be the booster?

In Israel, the early initiation of a nationwide campaign resulted in the full vaccination in more than half the population by the end of March 2021 (1). Consequently, the incidence of Covid-19 infections dropped from approximately 900 cases per million per day in mid-January 2021 to fewer than 2 cases per million per day by June 2021. However, by the end of August, more than 10,000 PCR-confirmed cases were being detected daily, and more than 600 persons with severe cases were hospitalised.

There are 2 questions that need to be answered:

  1. Have the cases gone up because vaccine efficacy has waned? Or
  2. Have the cases gone up because of the vaccine is less effective against the delta variant?

Recent reports of large US studies (one from the US CDC’s COVID-NET (2) and two from major health maintenance organisations (3,4) demonstrate the continued high efficacy of full vaccination against severe disease or hospitalisation.

Initial results from an Israeli study may provide some answers. Data for the period from July 30 through August 31, 2021 from the Israeli Ministry of Health database were extracted. 1,137,804 persons who were ≥ 60 years of age had received two doses of BNT162b2 (Pfizer) vaccines at least 5 months earlier (5). They compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (non-booster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster.

At least 12 days after the booster dose, compared with the non-booster group, the booster group reduced the rate of confirmed infection by 11.3 times and rate of severe illness by 19.5 times. After 12 days, the rate of confirmed infection was reduced 5.4 times compared with 4-6 days after the booster dose. Mean follow-up was, however, only about 7 person-days. A very short-term protective effect would not necessarily imply worthwhile long-term benefit. 12 Since then, Israel has extended the booster program to the entire population.

Although the benefits of primary COVID-19 vaccination clearly outweigh the risks, there could be risks if boosters are widely introduced too soon, or too frequently, especially with vaccines that can have immune-mediated side-effects (such as myocarditis, which is more common after the second dose of some mRNA vaccines (6) or Guillain-Barre syndrome, which has been associated with adenovirus-vectored COVID-19 vaccines (7).

If unnecessary boosting causes significant adverse reactions, there could be implications for vaccine acceptance that go beyond COVID-19 vaccines. Thus, widespread boosting should be undertaken only if there is clear evidence that it is appropriate.

The result from the Israeli study is important for policymakers in other countries (including Australia) that are exploring strategies to mitigate the surge from the delta variant. If boosters (whether expressing original or variant antigens) are ultimately to be used, there will be a need to identify specific circumstances in which the direct and indirect benefits of doing so are, on balance, clearly beneficial. Additional research could help to define such circumstances. Furthermore, given the robust booster responses reported for some vaccines, adequate booster responses might be achievable at lower doses, potentially with reduced safety concerns.

Thus, the need for a booster is not certain yet. We still don’t know the optimal time for the boosters if indeed we need them at all and which vaccine will be the booster. Fortunately, we were late in the vaccination game and by the time, we are due for a possible booster, we should have more answers to the questions. Stay tuned.


  1. Ritchie H, Mathieu E, Rodes-Guirao L, et al. Coronavirus pandemic (COVID-19). Our World in Data. 2020. https://ourworldindata .org/coronavirus
  2. Havers FP, Phm H, Taylor CA, et al. COVID-19-associated hospitalizations among vaccinated and unvaccinated adults ≥18 years – COVID-NET, 13 states, January 1 – July 24, 2021. medRxiv. 2021; (published online Aug 29.) (preprint).
  3. Bruxvoort K, Sy LS, Lei Qian, et al. Real-world effectiveness of the mRNA-1273 vaccine against COVID-19: interim results from a prospective observational cohort study. SSRN. 2021; (published online Sept 2.) (preprint).
  4. Thompson MG, Stenehjem E, Grannis S, et al. Effectiveness of COVID-19 vaccines in ambulatory and inpatient care settings. N Engl J Med. 2021; DOI:10.1056/NEJMoa2110362
  5. Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N, Mizrahi B, Alroy-Preis S, Ash N, Milo R, Huppert A. Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. N Engl J Med. 2021 Sep 15. doi: 10.1056/NEJMoa2114255. Epub ahead of print. PMID: 34525275.
  6. Gargano JW, Wallace M, Hadler SC et al. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices – United States, June 2021. MMWR Morb Mortal Wkly Rep. 2021; 70: 977-982
  7. WHO: Statement of the WHO Global Advisory Committee on Vaccine Safety (GACVS) COVID-19 subcommittee on reports of Guillain-Barré Syndrome (GBS) following adenovirus vector COVID-19 vaccines.