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In a recent study posted to the medRxiv* preprint server, researchers assessed the efficacy of the coronavirus disease 2019 (COVID-19) second booster vaccine compared to the first booster vaccine and the protection conferred by prior COVID-19 infection.

Study: Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France. Image Credit: Fit Ztudio/Shutterstock


Since December 2021, the SARS-CoV-2 Omicron (B.1.1.529) variant and its following sublineages have been driving the ongoing COVID-19 pandemic. Due to its inherent increased transmissibility and immune evasion capabilities, this variety has led to the most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections ever documented worldwide.

Research has revealed a quick decline in the efficacy of COVID-19 vaccines against this variant and its sub-lineages, prompting recommendations for a fourth vaccine dose. More extensive knowledge of the impact of the second booster dose is required to curb further SARS-CoV-2 transmission.

About the study

In the present study, generic tribulus toronto researchers utilized a test-negative design to determine the efficacy of the COVID-19 second booster vaccine compared to the first booster, along with the protection elicited by a prior COVID-19 diagnosis against Omicron BA.2 or BA.4/5 infection.

The team performed a retrospective test-negative study on individuals aged 60 years and older having COVID-19-like symptoms. The eligible individuals had a SARS-CoV-2 positive reverse transcription–polymerase chain reaction (RT-PCR) assay or an antigen test diagnosed between 21 March and 30 October 2022. Individuals were deemed eligible if vaccinated with a minimum of three vaccine doses, comprising a two-dose primary immunization series and one booster vaccine. The team also obtained data related to SARS-CoV-2 vaccination and diagnosis.

Eligible individuals included those having a positive SARS-CoV-2 test result, whereas controls were those with a negative result. The team matched the cases and controls in a ratio of 1:2 based on the week they were tested for SARS-CoV-2, test type, and geographic location. Demographic parameters and past infection status information were also obtained. Also, prior SARS-CoV-2 infection was described as a reported SARS-CoV-2 positive antigen test, or PCR, reported a minimum of 60 days before the inclusion diagnostic test, regardless of the symptoms.

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The probabilities of testing SARS-CoV-2-positive with one or two booster vaccine doses, with or without prior infection, were compared between cases and controls using conditional logistic regression. The odds ratios (OR) were calculated based on the period since (1) the last booster dosage, (2) the prior infection, and (3) the dominant SARS-CoV-2 variant when the prior infection was diagnosed.


The study comprised 9,33,491 people, including 4,56,657 SARS-CoV-2 positive cases matched with 4,76,834 SARS-CoV-2 negative controls. Most individuals were aged between 60 and 79 years and were vaccinated with one booster dose. In addition, 92% had no recorded history of SARS-CoV-2 infection.

Almost 51% of SARS-CoV-2-positive cases were attributable to the Omicron BA strain. On the other hand, 36% of the infections were detected during the transitory period from BA.2 to BA.4/5, whereas 13% were assigned to Omicron BA.4/5. Almost 74% of the participants were vaccinated with the BNT162b2 messenger ribonucleic acid (mRNA) vaccine as the first booster, while 26% had received mRNA-1273. Similarly, among individuals who had received a second booster vaccine, 85% were administered BNT162b2, while 15% received mRNA-1273.

Compared to participants vaccinated with the first booster dose approximately 181 to 210 days before testing, the relative protection observed seven to 30 days after the first booster was 64%, and after the second booster was 39%. For booster doses 1 and 2, a statistically significant reduction in relative vaccine effectiveness (rVE) was found across periods since the last immunization.

Nonetheless, at comparable vaccination time points, the rise in protection estimated by the rVE for the second booster was less than that provided by the first booster. This was noted as the second booster rVE in the previous 91 to 120 days was 8%, while the first booster rVE was 33% during the same period.

Compared to those without a history of COVID-19, the team noted that the more recent the infection was, the greater the resistance to symptomatic illness. For example, the adjusted protection observed for an infection that was 61 to 112 days old and occurred during the BA.2-dominant period was 95.6%. In contrast, the protection linked with a 321 to 467-day-old infection that occurred during the Delta-dominant era was 61.7%. Additionally, five months after a prior infection, protection was greater if the infection occurred when BA.2 was dominant as opposed to when BA.1 was dominant.


The study findings indicated that a second booster vaccine dose of SARS-CoV-2 Wuhan strain-like mRNA vaccines provided greater protection than the initial booster dose administered six to seven months earlier. However, the protection elicited by the second booster vaccine was weaker than that found with the first booster vaccine administered at the same interval after the first vaccine. Moreover, in an Omicron-driven pandemic, immunization in conjunction with recent previous infection provided remarkable protection against subsequent SARS-CoV-2 Omicron infection.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Cynthia Tamandjou, Vincent Auvigne, Justine Schaeffer, Sophie Vaux, Isabelle Parent du Chatelet. (2023). Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France. medRxiv. doi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antigen, Assay, Coronavirus, Coronavirus Disease COVID-19, covid-19, Diagnostic, Efficacy, Immunization, Omicron, Pandemic, Polymerase, Polymerase Chain Reaction, Research, Respiratory, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Transcription, Vaccine

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Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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