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Given emerging evidence of immune escape in the SARS-CoV-2 Omicron viral variant, and its dominance, effectiveness of heterologous and homologous boosting schedules commonly used in low-to-middle income countries needs to be re-evaluated. We conducted a test-negative design using consolidated national administrative data in Malaysia to compare the effectiveness of homologous and heterologous BNT162b2, CoronaVac, and AZD1222 booster vaccination against SARS-CoV-2 infection in predominant-Delta and predominant-Omicron periods. Across both periods, homologous CoronaVac and AZD1222 boosting demonstrated lower effectiveness than heterologous boosting for CoronaVac and AZD1222 primary vaccination recipients and homologous BNT162b2 boosting. Broadly, marginal effectiveness was smaller by 40–50 percentage points in the Omicron period than the Delta period. Without effective and accessible second-generation vaccines, heterologous boosting using BNT162b2 for inactivated and vectored primary vaccination recipients is preferred.

Malaysia rolled out a diverse portfolio of predominantly three COVID-19 vaccines (AZD1222, BNT162b2, and CoronaVac) beginning 24 February 2021. We evaluated vaccine effectiveness with two methods, covering 1 April to 15 September 2021: (1) the screening method for COVID-19 (SARS-CoV-2) infection and symptomatic COVID-19; and (2) a retrospective cohort of confirmed COVID-19 cases for COVID-19 related ICU admission and death using logistic regression. The screening method estimated partial vaccination to be 48.8% effective (95% CI: 46.8, 50.7) against COVID-19 infection and 33.5% effective (95% CI: 31.6, 35.5) against symptomatic COVID-19. Full vaccination is estimated at 87.8% effective (95% CI: 85.8, 89.7) against COVID-19 infection and 85.4% effective (95% CI: 83.4, 87.3) against symptomatic COVID-19. Among the cohort of confirmed COVID-19 cases, partial vaccination with any of the three vaccines is estimated at 31.3% effective (95% CI: 28.5, 34.1) in preventing ICU admission, and 45.1% effective (95% CI: 42.6, 47.5) in preventing death. Full vaccination with any of the three vaccines is estimated at 79.1% effective (95% CI: 77.7, 80.4) in preventing ICU admission and 86.7% effective (95% CI: 85.7, 87.6) in preventing deaths. Our findings suggest that full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in Malaysia has been highly effective in preventing COVID-19 infection, symptomatic COVID-19, COVID-19-related ICU admission, and death.

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IntroductionCOVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. While primary series vaccination rates are generally high in Southeast Asian (SEA) countries, various factors have limited the rollout and impact of booster doses. Areas coveredWe reviewed 79 studies in the publicly available International Vaccine Access Center (IVAC) VIEW-hub platform on vaccine effectiveness (VE) after primary immunizations with two-dose schedules. VE data were reported for SARS-CoV-2 infection, COVID-19-related hospitalizations and deaths, and strati ed across variants of concern (VOC), age, study design and prior SARS-CoV-2 infection for mRNA vaccines (BNT162b2, mRNA-1273 and combinations of both), vector vaccines (AstraZeneca, AZD1222 "Vaxzevria") and inactivated virus vaccines (CoronaVac). Expert opinionThe most-studied COVID-19 vaccines provide consistently high (>90%) protection against serious clinical outcomes like hospitalizations and deaths, regardless of variant. Additionally, this protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222, as supported by our analysis of local Asian and relevant international data, and by insights from SEA experts. Given the continued impact of COVID-19 hospitalizations and deaths on healthcare systems worldwide, encouraging vaccination strategies that can reduce this burden is more relevant than attempting to prevent broader but milder infections with speci c variants, including Omicron. Article highlights-VE was high and comparable for both AZD1222 and mRNA vaccine types (91%-93%) in protecting against hospitalization and death from COVID-19, regardless of age.-VE against symptomatic infections trended higher (though not signi cantly) for mRNA-based vaccines compared to AZD1222.-Waning of VE since time of vaccination was observed for symptomatic infections but was limited for serious COVID-19 outcomes. A sub-analysis of studies with comparative arms evaluating the VE of different vaccines in the same settings also con rmed these observations for all VOC assessed, with all vaccines conferring a high level of protection against serious outcomes.-For Omicron, there is limited comparative data within the IVAC dataset, however, expert review of emerging data suggests that VE against all outcomes is lower for all COVID-19 vaccines, than for the Delta variant.-Data from the UK indicate that VE improves with a booster dose and that VE continues to be very similar, irrespective of the type of vaccine used.-Importantly, all COVID-19 vaccines evaluated here have favorable bene t/risk pro les.-Although many SEA countries have high rates of primary vaccination, there are still challenges to achieving high booster dose coverage. The results of this analysis suggest that the most effective way to achieve vaccine booster targets, particularly in resource-limited settings, would simply be to consider any vaccines which have good safety and comparable effectiveness pro les, particularly against severe outcomes, and that are accessi...