Are Australia’s current COVID-19 vaccines as effective against delta as they are against alpha?

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The emergence of the delta strain of SARS-CoV-2 (which causes COVID-19) earlier this year was not a surprise, and has resulted in an additional increase in morbidity and mortality across the world. Studies indicate a high effectiveness of many vaccines designed for the previously dominant alpha strain. But scientists are still waiting for the full story on the delta variant, and research results need to be viewed with caution.

English researchers recently published an observational study in the New England Journal of Medicine using a test-negative case-control design to estimate the effectiveness of the Pfizer and AstraZeneca vaccines against the delta strain compared to the alpha strain.

Test-negative case-control studies have been popularised in the last 10 or so years as a way to study effectiveness of different kinds of pneumococcal and influenza vaccines. The method looks at groups presenting with similar symptoms and compares those who test positive for the strain in question with those who test negative (but may have another strain of the same disease). In this particular study, authors compared people with COVID-like symptoms and confirmed delta infection (“cases”) and two separate symptomatic control populations - those with negative testing and those with the alpha variant.

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English patients with symptoms compatible with COVID were enrolled during a 7-week period, including a mix of people who were unvaccinated, partially-vaccinated, and fully-vaccinated with either an mRNA-based vaccine (Pfizer) or an adenovirus-vectored vaccine (AstraZeneca). Over 100,000 control patients who tested negative were included along with 19,109 patients who had positive COVID testing with gene sequencing confirming the presence of alpha or delta variant.

A week-by-week breakdown of the test status shows the percentage of COVID cases caused by the delta variant to grow from 0.5% in the first week to 63% by the 7th week of the study.

After only one dose of the vaccine, adjusted effectiveness was only 48% against alpha and 36% against delta for the Pfizer vaccine. For AstraZeneca the results were 49% and 30% respectively. Effectiveness improved significantly after the second dose for Pfizer (adjusted 94% against alpha and 88% against delta) and a little less so for AstraZeneca (75% against alpha and 67% against delta). Results were similar in a secondary analysis that estimated vaccine effectiveness against delta by aligning the proportion of delta cases with vaccination status, a method that relies on the assumption that if the vaccines were less effective against delta, delta strains would make up a higher percentage of cases.

In Australia newly published modelling from Melbourne’s Doherty Institute used a simplified model that assumed a national epidemic consisting of only the delta strain. Their vaccine effectiveness assumptions showed rates of hospitalisation dropped by 86% after two doses of AstraZeneca, compared with 87% for Pfizer. On intensive care risk, two doses of AstraZeneca cut admissions by 86% almost level with 87% for Pfizer. Deaths are reduced by 90% from AstraZeneca, compared with 92% for Pfizer.

Examining the detail of relative vaccine effectiveness has important policy implications. However comparisons should consider potential implications of collider bias, a type of selection bias that occurs in observational studies. Collider bias  is represented visually by variables colliding together and changing the linear path to an outcome. In a hypothetical example from this study, contracting the delta variant (more common with foreign travel) and getting the Pfizer vaccine (more common in healthcare workers) each may reflect a population with different characteristics than the general population. When these two factors occur together, vaccine effectiveness may also be different than if neither or only one of those risk factors were present. In this observational study restricted to symptomatic people, vaccination status and virus variant might “collide” at the outcome of those seeking medical care for symptoms, skewing estimates of vaccine effectiveness.

When present, collider bias limits the ability of a study to answer questions about the population as a whole (including asymptomatic patients and those who have symptoms but don’t seek medical care), and is a limitation of the otherwise useful test-negative case-control method.

For more information about COVID-19 and vaccines, see the topic COVID-19 (Novel Coronavirus) in DynaMed.

Adapted from the DynaMed EBM Focus

The EBM Focus is a weekly e-newsletter published by DynaMed, and available for all Queensland Health and QAS staff. It provides valuable, advertising-free information to the medical community. DynaMed editors monitor a large volume of research information on a daily basis through the process of Systematic Literature Surveillance. Articles are selected each week that are “most likely to inform clinical practice” and are highlighted in the EBM Focus with a brief and concise overview. The EBM Focus provides sufficient information to understand the outcome of the research as well as links to the study and relevant DynaMed topic should the reader want to know more.