15/09/2021
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Keep calm, get vaccinated!

By Dr Rais Hussin / Dr Margarita Peredaryenko

Recently there has been somewhat exacerbated focus by the public on the vaccination status of daily Covid-19 cases according to the categories of severity.

However, it must be made clear to the public that although daily Covid-19 cases data provide some important pandemic insights, it nevertheless cannot and should not be used to make any inferences to population country-wide due to its biasness.

In the article titled “Malaysia needs to accelerate Covid-19 testing”, EMIR Research has discussed the problem of inadequate testing in terms of randomness and reach and how it hampers and blinds pandemic decision-making in general.

Apart from that, when it comes to vaccination, the datasets gathered through routine symptomatic testing programs can be further biased due to differential “healthcare-seeking behavior”. For example, if vaccinated are less likely to exhibit test-seeking behavior or more likely to be even unaware of their infection status due to its asymptomatic nature, national Covid-19 daily test samples are more likely to under-represent the vaccinated population in asymptomatic or mild-symptomatic categories.

However, the public overreaction or apprehension to the reported data on vaccination status of daily Covid-19 cases is understood as even scientists are still trying to ascertain the Delta-variant effect on national Covid-19 immunization programs. For this properly designed studies through following randomly selected individuals nationwide with fixed-schedule data collection (independent of symptoms and vaccination status) over a long time (alongside long-term Covid-19 post-vaccination surveillance studies) are crucial.

In this regard, the “Covid-19 Infection Survey” by the United Kingdom (UK) Office for National Statistics is one of the best examples of such a methodological approach to inform decision-makers and the general public that other nations should emulate. This kind of effort is critical for answering questions with regards to real-world vaccine effectiveness (VE), duration of protection in the presence of emerging variants or within various population cohorts, etc.

The very recent study coming from the University of Oxford, which used the “Covid-19 Infection Survey” data to ascertain the impact of Delta on VE, certainly deserves the attention of policy-makers worldwide. This well representative and much needed scientific data comprised an extensive community-based survey of over 350,000 individuals living in randomly selected private households across the UK.

The survey participants have been followed since December 1, 2020. Therefore, the researchers evaluated VE over time and, importantly, compared it in two periods: December 1, 2020 – May 16, 2021 (Alpha-dominant) and May 17, 2021 – August 1, 2021 (Delta-dominant) as identified through genomic sequencing in the same survey. Keep in mind that UK has been gradually lifting up the restrictions measures as reflected in their Stringency Index over the same period of time.

Over this period, the researchers evaluated VE for Pfizer and AstraZeneca but they had limited data for Moderna. Also, they could not compare VE in individuals above 65 years old as very few individuals of this age group remained unvaccinated during the Delta-dominant period.

In summary, the findings showed that in the Delta-dominant period, as compared to the Alpha-dominant period, the protection from the severity of the disease was strongly maintained. For both Pfizer and AstraZeneca, there was no evidence of reduced VE against all new PCR-positives 14 days after the second dose. However, the researchers have found evidence of reduced VE for both vaccines against the self-reported symptoms and high viral load (measured by the cycle threshold in RT-PCR).

Interestingly, even in the Delta-dominant period for unvaccinated but previously PCR-positive individuals, there was no evidence of reduced protection against all new PCR-positives, and it was found to be at least as good as 14 days past two doses of Pfizer or AstraZeneca.

On top of that, protection against new PCR-positives was significantly higher for fully vaccinated individuals with prior infection than fully vaccinated individuals without prior infection (kind of “booster” dose effect).

What can we learn about Delta-variant while contrasting the above findings with the recent increased Covid-19 hospitalizations, including in vaccinated individuals and even among children whom we considered to be nearly immune to the severity of Covid-19?

The logical answer is that what we observe is not due to Delta’s higher virulence, but its higher transmissibility and community reach. It reaches further and faster to the remaining vulnerable pockets of the community, for example, unvaccinated individuals, vulnerable children (even though such cases might be rare in the entire population), people who even despite being fully-vaccinated, probably did not form a strong systemic immune response due to seriously dysregulated immune system (again, such cases might be rare in the population as a whole).

Delta’s higher transmissibility is explained by its mutations on S-protein that created a greater affinity between S-protein and ACE2 receptor used by the virus to infect a cell. Therefore Delta-variant or its newly formed viral copies can enter the next cell faster, and a higher viral load can be created within the same period compared to the wild type (original Wuhan virus).

Based on the above, Delta probably kills the same number of people who might be otherwise killed by the wild type but faster.

The aforementioned VE study from the UK provides many more insights and data visualizations and should be of great interest to the policy-makers.

For example, researchers also found a similar peak viral burden in PCR-positive individuals regardless of their vaccination status, pointing to the fact that viral transmission in the population may continue even despite a high vaccination rate.

Given the vaccine protection against the severity of the disease maintained even in the presence of Delta-variant, Covid-19 ongoing transmission may have limited consequences to the vaccinated population and therefore “booster vaccinations may not be needed, particularly since infection post-vaccination may provide a natural antibody boost”.

However, the same cannot be said about those who are not vaccinated. The Covid-19 infection without vaccination possess serious risks, and it is still largely unknown who is more likely to die or become a long-hauler with drastic long-term health consequences.

Furthermore, more extensive scale and real-world data are needed to understand better who among the vaccinated is still vulnerable to the severity of Covid-19. Nevertheless, because this vulnerability might be due to severe dysregulation of the immune system, this category should be considered for passive immunization instead, for example, in the form of monoclonal antibodies, which could be the feasible strategy as has been argued in the article titled “Get high-end drugs for high-risk Covid-19 patients” by EMIR Research earlier.

Finally, with the constantly emerging new variants, the national health and statistics authorities should continuously monitor the situation around the VE through methodologically robust population-wide studies and present it in full transparency to the public.

(Dr. Rais Hussin and Dr. Margarita Peredaryenko are part of the research team at EMIR Research, an independent think tank focused on strategic policy recommendations based on rigorous research.)

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Dr Rais Hussin
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