A modelling study carried out by Sam Moore and colleagues from the University of Warwick, Coventry, UK showed that vaccination alone is unlikely to contain COVID-19 infections. However, gradual reopening and high vaccine uptake could minimise future waves of infection.

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The study published online on March 18, 2021, in The Lancet Infectious Diseases found that vaccinating all adults in the UK is unlikely to achieve herd immunity and fully contain the virus. The researchers used the best data available for the analysis.

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What is the way forward?

The researchers asserted that gradual release of control measures, high vaccine uptake, and a vaccine with high protection against infection is essential to minimise future waves of infection. They noted that the dynamics of vaccination against SARS-CoV-2 are complicated by age-dependent factors, changing levels of infection, and the relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines. In this context, the only way forward is to use mathematical models to analyse the factors and the final outcomes.

Researchers used epidemiological data from the UK along with estimates of vaccine efficacy to predict the possible long-term dynamics of SARS-CoV-2 under the planned vaccine rollout.

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Conclusions of the modelling study

1. COVID-19 vaccines being rolled out in the UK are effective in preventing severe disease, but the extent to which they prevent infection is still unclear.
2. The first modelling study looking at relaxing control measures (e.g. wearing masks, physical distancing, and lockdown measures), and planned vaccination rollout in the UK suggests that vaccination alone may not be enough to prevent the spread of infection – with the R* number estimated to be 1.58 even if the vaccine prevents 85% of new infections occurring after vaccine rollout is complete and all other control measures are removed.
3. Relaxing control measures is highly likely to lead to another wave of infection, but gradual reopening, high vaccine uptake, and a vaccine with high protection against infection can minimise the scale of infections, hospitalisations, and deaths.
4. As restrictions are eased and infections grow, although vaccination will reduce the total number of COVID-19 deaths significantly, there are likely to be deaths in people who have been vaccinated, as no vaccine offers 100% protection.

[* R0 pronounced as “R nought,” is a mathematical term that indicates how contagious an infectious disease is. R0 tells you the average number of people who will contract a contagious disease from one person with that disease. It specifically applies to a population of people who were previously free of infection and haven’t been vaccinated.]

The researchers did this analysis before early real-world data from vaccination rollout studies were available. Preliminary findings suggest that the vaccine does offer a level of protection against infection, but the exact level is still unclear, for this reason, the authors did what is the best possible procedure. In this study, they used a range of levels of protection against infection.

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The emergence of new variants

However, the study has limitations.

“The authors note that their model does not account for the emergence of new variants, to which the vaccine might offer less protection, nor for the effects of waning immunity, which might necessitate additional vaccination. They also note that they are unable to look at the effects of relaxing individual control measures," a press release from the journal cautioned.

“Our modelling suggests that vaccination rollout in adults alone is unlikely to completely stop COVID-19 cases spreading in the UK. We also found that early sudden release of restrictions is likely to lead to a large wave of infection, whereas gradually easing measures over a period of many months could reduce the peak of the future waves".

A press release quoted Professor Matt Keeling, from the University of Warwick, UK- "The huge success of the UK’s vaccine programme so far coupled with the government’s gradual roadmap for easing restrictions is a cause for optimism. However, some measures, such as test, trace, and isolate, good hand hygiene, mask-wearing in high-risk settings, and tracing from super-spreader events, may also be necessary for some time."

The UK hospitals identified the first COVID cases on Jan 31, 2020; cases rose, exponentially in February and March. The first lockdown which began on 23 March 2020, reversed the growth in infection, although important health metrics such as hospital occupancy and deaths continued to increase for many days. The increase was steady but spatially heterogeneous, and cases continued to decline until August 2020, when a relaxation of infection control measures and resultant increased mixing precipitated a second wave and, subsequently, the second lockdown in November 2020.

By early December 2020, 60,000 people died and 225,000 were admitted to hospitals due to COVID-19 in the UK. However, the specialists estimated that less than 20% of the population had been exposed to the virus. It suggested that the outbreak was far from over. Mass vaccination began in the UK on Dec 8, 2020, and offers a potential exit strategy while preventing excessive demands on the healthcare system.

The UK progressed remarkably in its vaccination programme. The Medicines and Healthcare products Regulatory Agency (MHRA) approved the Pfizer-BioNTech BNT162b26 vaccine for its use in the UK on Dec 2, 2020, followed by the Oxford-AstraZeneca vaccine on Dec 20, 2020, and the Moderna vaccine on Jan 8, 2021. However, Pfizer-BioNTech and Oxford-AstraZeneca vaccines were the two vaccines in widespread use in the UK as of February 2021.

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The UK and its vaccination programme

The researchers noted that as of February 2021, the UK had ordered 457 million doses of vaccines from eight different developers: 100 million doses from Oxford-AstraZeneca, 40 million doses from Pfizer-BioNTech, 17 million doses from Moderna, 60 million doses from Novavax, 100 million doses from Valneva, 60 million doses from GSK-Sanofi Pasteur, 30 million doses from Janssen, and 50 million doses from CureVac.

The researchers do not know how effective the potential vaccines are. A continuing unknown is a degree to which they are effective against transmission, rather than simply preventing symptomatic infection; this is the key uncertainty the researchers decided to investigate.

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The epidemiological model

The researchers developed an age-structured mathematical model, fitted to various UK epidemiological data, to forecast the dynamics of COVID-19 in 2021 and beyond based on multiple scenarios of Non-Pharmaceutical Intervention (NPI) relaxation and vaccine characteristics.

These model results provide possible bounds on the expected number of deaths and hospitalisations, thus providing important policy insights into the interaction between continued NPIs and the ongoing vaccination programme. Their aim was to capture the risk-structured delivery programme for the UK and focus on the consequences of relaxing NPIs and, consider the individual risks and how these are mitigated by vaccination. These insights are very useful in formulating and managing the programme.

This study modelled the combined interaction of the UK vaccination rollout with different scenarios of relaxing control measures, to predict the R number and deaths and hospital admissions due to COVID-19 from January 2021 to January 2024.

The researchers assumed that vaccine uptake would be 95% in those aged 80 years and older, 85% in those aged 50–79 years, and 75% in those aged 18–49 years, as well as looking at a more optimistic uptake scenario (95%, 90%, and 85%, respectively), and a more pessimistic scenario (90%, 80%, and 70%, respectively).

They assumed that vaccine protection against symptomatic disease to be 88% based on phase 3 trial data from the Pfizer-BioNTech and Oxford-AstraZeneca vaccines being administered in the UK (the analysis was done before early real-world data from vaccination rollout studies). Since the vaccines’ protection against infection is still uncertain, it was varied in four scenarios (0%, 35%, 60%, and 85%).

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Results

• It was found that although vaccination can substantially reduce R, it may not be enough to drive R below 1 without other control measures. Under the most optimistic scenario for protection against infection (85%), the R number is estimated to be 1.58 without other controls.
• “As vaccination alone is not expected to drive R below 1, removing all restrictions after the vaccination rollout is complete, is predicted to lead to another wave of infections with a substantial number of deaths. The scale of future waves and the number of deaths is influenced by how early and over what time-scales measures are relaxed, the vaccine’s level of protection against infection and vaccine uptake”. The researchers clarified.
• It was found that even small relaxations of measures if done abruptly could lead to large waves of infection. The authors consider abrupt releases of some measures (from current restrictions to a situation comparable to September 2020) with a vaccine that offers 85% protection against infection and calculate the number of deaths from Jan 2021 until January 2024.
• Some of the emerging numbers are instructive. Researchers estimated that a partial relaxation in February 2021 leads to 130,100 deaths by January 2024, whereas partial release in April 2021 lowers this to 61,400 deaths and partial release in June 2021 to 53,900 deaths highlighting the impact of the vaccination programme rollout. These estimates include the 49,300 deaths that have already occurred this year.
• If all control measures are removed in January 2022 (after the complete rollout of the vaccine), 21,400 COVID-19 deaths are estimated, if the vaccine prevents 85% of infections. This increases to 96,700 if the vaccine only prevents 60% of infections.
• The only scenario where case numbers remain low is if all control measures are removed in January 2022 with the optimistic vaccine uptake scenario (95%, 90%, and 85%, in those over 80, 50-79 and 18-49 respectively) and a vaccine that offers 85% protection against infection, which reduces deaths to an estimated 1,030.

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Merits of gradual relaxation

Gradual relaxation, as opposed to the immediate release of control measures, may reduce future waves of infection. For example, partial release of control measures in February 2021, was predicted to lead to a wave of infection that peaks at 1,670 deaths per day, but the gradual release of measures over the course of 5 months or 10 months leads to waves that peak at 430 and 46 deaths per day, respectively.

Although vaccination substantially decreases overall deaths, because no vaccine’s protection against symptomatic disease is 100%, the authors note that some people who have been vaccinated will still die of COVID-19. If the vaccine offers 60% protection against infection, the authors predict that 48% and 16% of deaths may be in individuals who have received one or two doses of the vaccine, respectively.

Dr Sam Moore, from the University of Warwick, UK, says “We’re rapidly learning more about vaccine efficacy as vaccination programmes are rolled out across the world. Since we conducted this study, new evidence suggests there may be a higher level of protection against severe disease offered by both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines than the level we assumed. This may reduce the size of future hospital admissions and deaths we estimated, making future waves more manageable for the health service. As for protection against infection, some preliminary findings have suggested that the vaccine does offer a level of protection against infection, but the exact level of protection offered by vaccines is still unclear. We will continue to update our predictions as new data on vaccine efficacy becomes available."

“The authors caution that vaccine uptake is likely to be uneven (clustering among certain households and socioeconomic groups), potentially giving rise to pockets of infection, as control measures are relaxed. They stress the importance of intensive test, trace, and isolate capabilities to target these pockets of infection," the press release added.

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Comments

Writing in a linked Comment, Dr Viola Priesemann (who was not involved in the study), from Max Planck Institute for Dynamics and Self-Organization, Germany, noted that the policymakers started to work side-by-side with theoreticians, as there were and still are many unknowns, especially regarding properties of virus variants and the subsequent future development of the pandemic. In times of uncertainty, mathematical models have shed light on the evolution of the pandemic to the best of current scientific knowledge.

She commented on the importance of using the protection from vaccines wisely to prevent further waves of infection, “The advantage of avoiding another pandemic wave is clear: less so-called long COVID-19, less quarantine, fewer deaths, and reducing the impact of the pandemic on societies and economies. Finally, more infections mean more scope for the spread and evolution of escape variants, which risk a major setback for any vaccination strategy, so avoiding this eventuality will be crucial”. She cautioned.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board and a former Raja Ramanna Fellow, Department of Atomic Energy. A PhD from the University of Leeds, UK, he is a medical physicist with a specialisation in radiation safety and regulatory matters. He was a Research Associate in the University of Virginia Medical Centre, Charlottesville, USA. He served the International Atomic Energy Agency as an expert and member in its Technical and Advisory Committees