Does retrospective evidence show a decrease in COVID-19 mortality and infection associated with the use of the BNT162b2 booster in patients 50 years and older?

Comment by InpharmD Researcher

Retrospective data showed that participants who received a booster at least five months after a second dose of BNT162b2 (Pfizer-BioNTech) had 90% lower mortality due to COVID-19 than participants who did not receive a booster. However, being a retrospective study assessing electronic health records, the methods are not as reliable and may have a higher potential for bias. Furthermore, no adverse events were included in the study. This information is important in future trials as it could potentially impact a patient's decision to receive the booster.
Background

The Centers for Disease Control and Prevention (CDC) recommends everyone 12 years and older should receive the BNT162b2 (Pfizer-BioNTech) booster at least five months after completing the primary COVID-19 vaccination series. [1]

The National Institute of Health (NIH) COVID-19 Treatment guidelines state the following: For primary and booster vaccinations, the mRNA vaccines (i.e., BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) are preferable to the Ad26.COV2.S (Johnson & Johnson/Janssen) vaccine due to its risk of serious adverse events. A primary series of COVID-19 vaccinations is recommended for everyone aged ≥5 years in the United States. Everyone aged ≥12 years should also receive a booster dose at least 5 months after completion of the primary series of an mRNA vaccine (BNT162b2 or mRNA-1273) or at least 2 months after receipt of the primary, single-dose Ad26.COV2.S vaccine. [2]

The Infectious Diseases Society of America (IDSA) states the following: In the U.S., all adults aged 18 and older may receive a single booster dose of either Pfizer-BioNTech or Moderna COVID-19 vaccine under a revised eligibility policy that was FDA-authorized and CDC-recommended in November 2021. Single booster doses of either product may be administered at least five months after completion of a primary mRNA vaccination series or at least two months after primary vaccination with the single-dose J&J/Janssen COVID-19 vaccine. As of January 2022, Pfizer-BioNTech booster doses are also FDA-authorized for children and adolescents ages 12 and over. [3]

There are multiple, on-going studies assessing the role of a booster dose in COVID-19 mortality. Third doses of the vaccines developed by Moderna, Pfizer–BioNTech, Oxford–AstraZeneca, and Sinovac administered more than six months after vaccination can potentially boost the neutralizing antibody titers, including targets against the Delta variant. Vaccine related side-effects are similar to those experienced after the first and second doses. Current trials indicate that the third or booster dose of a vaccine may be beneficial in preventing COVID-19 mortality and infection, especially in older individuals and the immunocompromised population. [4], [5]

References:

1. CDC. Covid-19 booster shot. Centers for Disease Control and Prevention.



2. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of

Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed 02/11/22.



3. Idsociety.org. 2022. Vaccine Dosing & Schedule. [online] Available at: [Accessed 11 February 2022].



4.Fiolet T, Kherabi Y, MacDonald CJ, Ghosn J, Peiffer-Smadja N. Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review. Clin Microbiol Infect. 2022;28(2):202-221. doi:10.1016/j.cmi.2021.10.005



5. Shekhar R, Garg I, Pal S, Kottewar S, Sheikh AB. COVID-19 Vaccine Booster: To Boost or Not to Boost. Infect Dis Rep. 2021;13(4):924-929. Published 2021 Oct 28. doi:10.3390/idr13040084
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Does retrospective evidence show a decrease in COVID-19 mortality and infection associated with the use of the BNT162b2 booster in patients 50 years and older?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Table 1 for your response.

 

BNT162b2 Vaccine Booster and Mortality Due to Covid-19

Design

N= 843,208

Objective

To assess for any decrease in mortality associated with the use of the BNT162b2 booster

Study Groups

Booster group

Non-booster group

Inclusion Criteria

50 years of age or older on the study start date and had received two doses of BNT162b2 at least 5 months earlier

Exclusion Criteria

Patients with missing data on birth or sex, patients who had been infected with SARS-CoV-2 or had received a booster before August 6, 2021, and patients who received the booster and had a confirmed case of COVID-19 within three days before the effective-booster date

Methods

Researchers looked at electronic medical records of members of Clalit Health Services (CHS), a health system in Israel.

A specific database was created for this study that integrated patient-level data from two primary sources: the CHS operational database and the CHS COVID-19 database – allowing for the collection of sociodemographic, clinical, and vaccine data.

The study population was divided into two groups: those who had received a booster during the study period (booster group) and those who had not received a booster (non-booster group). Participants were included in the booster group on the effective-booster date to allow time for antibodies to build effectively.

Researchers compared the mortality due to COVID-19 in the booster group with that in the non-booster group.

Duration

August 6th, 2021, to September 29th, 2021

Outcome Measures

Primary outcome: death due to COVID-19

Secondary outcome: confirmed SARS-CoV-2 infection

Baseline characteristics

 

Characteristic

Booster (n= 758,118)

Non-booster (85,090)

Age - yr

68.9+10.5

64.8+10.9

Age > 65 yr – no. (%)

470,808 (62)

35, 208 (41)

Age 50–64 yr – no. (%)

287,310 (38)

49,882 (59)

Female sex –  no. (%)

400,300 (53)

47, 972 (56)

Diabetes

220,959 (29)

23,787 (28)

Chronic obstructive pulmonary disease

37,291 (5)

4,158 (5)

Asthma

49,198 (6)

5,162 (6)

Chronic kidney failure

47, 187 (6)

4, 449 (5)

Hypertension

358, 517 (47)

33, 137 (39)

Ischemic heart disease

131, 058 (17)

11, 684 (14)

Chronic heart failure

33, 524 (4)

3,773 (4)

Obesity

249,152 (33)

28,945 (34)

Lung cancer

5,132 (1)

529 (1)

History of cerebrovascular accident

54,328 (7)

6,015 (7)

History of transient ischemic attack

26,586 (4)

2,559 (3)

History of smoking

314,226 (41)

34,428 (40)

Results

 

Outcome

Booster (n= 758,118)

No./total

Non-booster (n= 85,090)

No./total

Adjusted Hazard Ratio (95% CI)

P-value

Death from COVID-19:

Age > 65 yr

 

60/470,808

123/35,208

0.09 (0.07–0.13)

<0.01

Death from COVID-19:

Age 50–64 yr

 

5/ 287,310

14/49,882

0.13 (0.04–0.40)

<0.01

Confirmed SARS-CoV-2 infection

2,888/758,118

11,108/85,090

0.17 (0.16–0.18)

<0.01

Safety 

Not included by researchers 

Study Author Conclusions

Participants who received a booster at least 5 months after a second dose of BNT162b2 had 90% lower mortality due to COVID-19 than participants who did not receive a booster.

InpharmDTM Researcher

Critique

The short duration, retrospective design, and lack of reported adverse events makes this study less reliable. Additionally, older patients in the study received the booster before younger patients – this could have introduced bias in the estimation of survival, resulting in higher mortality in the booster group as compared to the general population. Furthermore, bias could have arose from informative censoring as data was retrieved from electronic health records. Lastly, as this study was conducted in a study site in Israel, patient and cultural differences could play a factor when applying the results to American populations.

 

 

References:

Arbel R, Hammerman A, Sergienko R, et al. Bnt162b2 vaccine booster and mortality due to covid-19. N Engl J Med. 2021;385(26):2413-2420.