Meta-Analysis on Anticipated Efficacy of Vaccines Against Severe COVID-19 Over Time and Variants- Nature Communications

The COVID-19 pandemic has impacted communities worldwide, causing significant morbidity and mortality. The development of vaccines has been a crucial approach to combat this disease. However, with virus mutations and emerging variants, it is essential to examine how effective vaccines are over time and against various strains. In this article, we explore a comprehensive meta-analysis of vaccine efficacy studies, examining both time and variant effectiveness. This study provides critical insights into the long-term effectiveness of COVID-19 vaccines and the potential need for future booster shots to maintain immunity.


In a systematic review of 158 studies, researchers analyzed the vaccine effectiveness of various COVID-19 vaccines against severe SARS-CoV-2 infections caused by different variants. The studies included two randomised controlled trials, seven test-negative case-control studies, and six cohort studies. They focused on vaccines, including BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, and any mRNA vaccine, and their effectiveness against pre-Delta, Delta, and Omicron variants. The studies also reported vaccine protection against symptomatic infection and severe COVID-19.

Using a linear mixed-effects model, the researchers investigated the impact of vaccine type, variant, and time since vaccination on vaccine effectiveness against severe COVID-19. They found that vaccine effectiveness varied by vaccine, variant, and time. For instance, mRNA-1273 showed higher effectiveness than ChAdOx1 nCoV-19, and effectiveness against severe COVID-19 was lower against Omicron than against Delta or pre-Delta variants. The researchers also found that vaccine effectiveness declined over time since vaccination.

To understand the relationship between in vitro neutralisation titre and protection, the researchers aggregated data on neutralisation titre and effectiveness across all studies. They used vaccine regimen, time since vaccination, and circulating variant as predictors of neutralising antibody titres and found that this predicted neutralisation titre was associated with vaccine effectiveness.

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The correlation between the predicted neutralisation titre and reported vaccine effectiveness was strong, indicating that neutralising antibody titres might predict protection against symptomatic and severe COVID-19. The researchers also found that the reported vaccine effectiveness correlated strongly with neutralizing antibody titres, indicating that their findings were independent of the model developed by Khoury et al.

Finally, the researchers plotted the reported vaccine effectiveness against the estimated neutralising antibody titres and found that there was a strong relationship between neutralising antibody titres and protection from symptomatic and severe COVID-19. This suggests that neutralising antibody titres can be used to predict vaccine effectiveness against these infections.


In conclusion, this meta-analysis provides valuable insights into the ongoing effort to combat the COVID-19 pandemic. By analyzing data from multiple studies, we’ve learned more about how effective vaccines are against severe illness over time and against emerging variants. As new variants continue to emerge and vaccination efforts ramp up, continued monitoring and adaptation will be crucial to ensuring the best possible protection for individuals and communities. While there is still much to be learned about COVID-19 and its variants, this meta-analysis represents an important step forward in our understanding of vaccine effectiveness and sets the stage for further research and innovation.

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