Ireland’s testing and vaccination policies must be reviewed urgently

Kingston Mills: Our approaches to testing and vaccine mixing are at odds with recent studies

Is it discriminatory to confine older and vulnerable age groups to two doses of AstraZeneca vaccine with its higher risks of unusual blood clots and its poorer protection, especially against variants of concern?  Photograph: Getty Images

Is it discriminatory to confine older and vulnerable age groups to two doses of AstraZeneca vaccine with its higher risks of unusual blood clots and its poorer protection, especially against variants of concern? Photograph: Getty Images

 

Science has come to our rescue. Decades of biomedical research in the fields of immunology, virology and vaccinology have provided the groundwork for the rapid development of effective vaccines, treatments and diagnostic/screening tests that have been instrumental in controlling the Covid-19 pandemic.

We are not out of the woods just yet, and if we ignore the science the road back to normality could be very rocky. Many scientists are frustrated by a failure of our decision-makers to follow the science in formulating policy that affects our future activity and, potentially, our lives.

The failure to embrace rapid-testing approaches is unfathomable in the face of ever-growing international scientific evidence of their benefit in enabling a safe return to work, study, sport and cultural activities.

Rapid-testing approaches, including lateral flow antigen tests and loop-mediated isothermal amplification (LAMP) tests, can quickly identify people that are infectious and could spread the virus to others, allowing them to self-isolate and have the diagnosis confirmed by a PCR test.

Rapid testing is not a replacement for diagnostic testing by PCR, and should not be used to rule out infection and therefore suggest that an individual is safe to mingle with others. However, these rapid tests can detect infected individuals that may otherwise go undetected, and can potentially be used to discriminate virus variants.

Our authorities have also been slow to act on emerging scientific evidence on immunity to the virus. For example, we know that recovery from infection with SARS-CoV-2 generates strong antibody responses that persist for at least nine months. Therefore, people who have recovered from Covid-19 do not need to be vaccinated and certainly do not need two doses of a precious vaccine.

Antibodies

Covid-19 vaccines confer protection against Covid-19 disease, but the most effective vaccines also prevent infection with SARS-CoV-2 by generating antibodies that neutralise the virus and thereby stop it infecting human cells in the respiratory tract.

However, recent reports have demonstrated that Pfizer and Moderna’s mRNA vaccines and the Novavax protein vaccine are more effective at inducing neutralising antibodies than the adenovirus-vectored vaccines from AztraZeneca and Jannsen, and this correlates with their estimate efficacy against Covid-19 from Phase 3 clinical trials.

The problem with vectored vaccines is that the immune system also responds to the vector (such as an adenovirus) and antibodies to the vector reduces the capacity of the second vaccination to “take” and generate a booster effect. This phenomenon, called “anti-vector immunity”, has limited the more widespread success of this vaccine approach.

Anti-vector immunity will be an even bigger issue if individuals need to receive a third dose with new versions of Covid-19 vaccines specially designed to protect against the variants of concern.

An effective approach for overcoming the problem of anti-vector immunity involves heterologous vaccination, where a person is primed with one vaccine and boosted with another. Decades of fundamental scientific research support this approach, and there is already evidence that it is effective against Covid-19.

A recently-published study from Spain showed that boosting with the Pfizer vaccine dramatically increased (45 fold) neutralising antibodies in people given one dose of the AstraZeneca vaccine. In comparison, earlier studies showed that boosting with the AstraZeneca vaccine only increased neutralising antibodies by 3 to 6 fold.

A recent study in Canada “firmly validate(d) the value of the Pfizer-BioNTech vaccine in boosting immunity following initial Covishield (AstraZeneca vaccine) inoculation.”

Outweighs any risks

A UK study showed that mixing vaccines was associated with small increases in mild-moderate side effects which were short-lived. However, the benefit of boosting with an mRNA or protein vaccine in people given the first dose with adenovirus-vectored Covid-19 vaccine are likely to outweigh any risks.

Mixing vaccines was endorsed this month by a publication in the prestigious journal, Nature, and a number of countries, including Canada, France, Germany, Finland, Norway, South Korea, Spain, Sweden, Austria have or are about to adopt this approach. We should do the same.

In Ireland all in the 60-70 age group, some healthcare workers, people with underlying medical conditions, and some people aged 50-59 are considered the most appropriate groups to “use up” the stocks of the AstraZeneca vaccine.

Yet this vaccine was deemed unsuitable for those under 50 because of the supposed greater risks of unusual blood clots with low blood platelets in younger cohorts.

In Ireland all in the 60-70 age group, some healthcare workers, people with underlying medical conditions and some people aged 50-59 are considered the most appropriate groups to “use up” the stocks of the AstraZeneca vaccine. Photograph: Getty Images
In Ireland all in the 60-70 age group, some healthcare workers, people with underlying medical conditions and some people aged 50-59 are considered the most appropriate groups to “use up” the stocks of the AstraZeneca vaccine. Photograph: Getty Images

A report last week in Nature Medicine from a study in Scotland confirmed the association between the AstraZeneca vaccine and immune thrombocytopenic purpura, with an incidence of 1.13 per 100,000 doses, whereas there was no association with the Pfizer vaccine.

Recent statistics from the UK Medicines and Healthcare products Regulatory Agency revealed that of the 372 cases from suspected thrombo-embolic events with concurrent thrombocytopenia associated with the AstraZeneca vaccine, 185 of these were people over 50.

Even allowing for the greater use of the vaccine in the older population, the fact remains that there were 143 cases and 30 deaths associated with unusual blood clots with low blood platelets in the 50-69 age group.

The contention proposed by our authorities that the AstraZeneca vaccine is safer for the 50- to 69-year olds than other age groups is at variance with these findings.

Variations of concern

The emergence of variations of concern, especially the Beta, Gamma and Delta variants, first identified in South Africa, Brazil and India respectively, and the spread of the Delta variant in the UK, Northern Ireland and potentially Ireland raises yet another issue.

These variants of concern are more transmissible, infect young people as well as the old, and, most worryingly, can escape immune responses generated by vaccination or previous infection.

Public Health England (PHE) has reported that amongst 33,206 cases of Covid-19 caused by the Delta variant, 9,344 individuals had been vaccinated, including 1,785 with two vaccine doses.

An unreviewed paper from PHE reported that one dose of either the AstraZeneca or Pfizer vaccine was only 33 per cent effective in preventing symptomatic infection with the Delta variant. However, vaccine effectiveness against the Delta variant after two doses was 87.9 per cent for the Pfizer vaccine but only 59.8 per cent for the AstraZeneca vaccine.

Therefore, AstraZeneca vaccine breakthroughs in fully vaccinated individuals are unavoidable, and 40 out of every 100 would not be protected from Covid-19 caused by the Delta variant.

PHE later emphasised that two doses of either the Pfizer or AstraZeneca vaccine had 94 per cent effectiveness against hospitalisation with Covid-19; i.e. protected against severe Covid-19 disease. However, after one dose effectiveness against hospitalisation was 94 per cent for the Pfizer vaccine compared with 71 per cent for the AstraZeneca vaccine.

Therefore, the large cohort of 60- to 69-year olds and others in Ireland who have received one dose of the AstraZeneca vaccine face the stark reality that a significant number could end up in hospital if exposed to and infected with the Delta variant.

Two doses

In spite of this reality this same group has been granted “a vaccine bonus” by being allowed to “meet indoors with other fully vaccinated people from two households” but at the same time have been advised by the HSE not to travel abroad.

The proposal to reduce the interval between vaccinations from 12 to eight weeks only serves to reduce the effectiveness of the two doses of the AstraZeneca vaccine.

One might reasonably ask: is it discriminatory to confine older and vulnerable age groups to two doses of AstraZeneca vaccine, with its higher risks of unusual blood clots and its poorer protection, especially against variants of concern?

Since one dose of this vaccine is quite effective against the Alpha (UK) variant, why not use it as the first dose in younger people where this virus is currently circulating and allow everyone to get the more effective mRNA vaccine for the second dose.

The policy on vaccination needs to be addressed with urgency by Niac, Nphet, the Department of Health and the HSE.

Kingston Mills is professor of experimental immunology and academic director of Trinity Biomedical Sciences Institute, Trinity College, Dublin,

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