Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the Omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.


Objectives: To estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after applying a homologous or heterologous third-dose (booster) in individuals who had previously received primary vaccination schemes with rAd26-rAd5, ChAdOx1 nCoV-19, BBIBP-CorV or a heterologous combination, during the period of Omicron BA.1 predominance. Design: Retrospective, test-negative, case-control study, with a matched analysis. Setting: Province of Buenos Aires, Argentina. Data were extracted from the National Surveillance System and VacunatePBA, a system developed in the province, between 12/1/21-4/1/21. Participants: 422,144 adults older than 50 who had received two doses of COVID-19 vaccines and were tested for SARS-CoV-2. Main outcome measures: Odds ratios of confirmed SARS-CoV-2 infection, hospitalisations and death after administering a booster, compared to a two-dose primary scheme. Results: Of 221,933 (52.5%) individuals with a positive test, 190,884 (45.2%) had received a two-dose scheme of SARS-CoV-2 vaccines and 231,260 (54.8%) a three-dose scheme. The matched analysis included 127,014 cases and 180,714 controls. The administration of a homologous booster after a primary scheme with vectored vaccines provided a large protection against hospitalisations and death (OR 0.30 [0.26-0.35] and OR 0.29 [0.25-0.33] respectively). However, this effect was lower and waned earlier compared to heterologous boosters (OR 0.59 [0.47-0.74] and OR 0.51 [0.41- 0.64] respectively). The inoculation of a heterologous booster after a primary course with ChAdOx1 nCoV-19, rAd26-rAd5, BBIBP-CorV, or heterologous schemes, provided some protection against infection (OR 0.70 [0.68-0.71]), which quickly decreased after 60 days (OR 1.01 [0.98-1.04]). Notwithstanding this, there was a clear protective effect against hospitalisations (OR 0.26 [0.22-0.31]) and deaths (OR 0.22 [0.18-0.25]) that persisted after 60 days (OR 0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Conclusions: This study shows that, during Omicron predominance, heterologous boosters provide an enhanced protection and longer effect duration against COVID-19-related hospitalisations and death in individuals older than 50 compared to homologous boosters.

Competing Interest Statement

NK, LC, TV, AG and SP declared being involved in the decision making process of the vaccination campaign in the Province of Buenos Aires, Argentina. All other authors report no competing interests.

Funding Statement

This study did not receive any funding.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.


The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Central Ethics Committee of the Ministry of Health of the Province of Buenos Aires evaluated and approved the protocol of the present study on 21 September 2022. The report number is 2022-31701807-GDEBA-CECMSALGP. Informed Consent.This study was exempted of informed consent due to its retrospective nature, and given it is a public health-related official program. Anonymisation of data. Data were anonymized by the following procedure: the personal ID number was used to link the databases of follow-up and of vaccination. After this process, the personal ID number was removed and an ID reference number for each individual was created. This reference number is not associated with any personal information.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.


I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).


I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.


Data Availability

All data produced in the present study are available upon reasonable request to the authors

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