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COVID-19 Vaccine Prioritization and the Impact of Non-Pharmaceutical Interventions

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To effectively reduce SARS-CoV-2 transmission and improve long-term health, tactical delivery of COVID-19 vaccines is essential. This was the conclusion of a recent study published in PLOS Computational Biology. A team of UK-based researchers found that prioritizing the distribution of the vaccine to at-risk groups, including the elderly and those with underlying health conditions, had the greatest impact in terms of minimizing the number of lives lost to the disease. They also noted that vaccinating older individuals could help to curb the pandemic if the vaccine prevents transmission as well as disease.

The UK, along with many countries worldwide, has relied on non-pharmaceutical interventions (NPIs) (e.g., social distancing) to combat the spread of SARS-CoV-2. However, with
several COVID-19 vaccines now being produced at scale and administered globally, focus is shifting towards re-establishing a “new normal”. The paper’s first author, Dr Sam Moore from The Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, University of Warwick, elaborates: “While non-pharmaceutical social measures have proved effective in reducing the healthcare burden compared to an uncontrolled outbreak, this is achieved to the detriment of the economy, education and many other societal factors. The development of vaccines gives us a second option which may to a large extent be effective in replacing social measures.”

“It is essential that we do not relax NPI measures too quickly so as to risk another major wave of infection before the vaccination program has progressed sufficiently to mitigate disease effects," – Sam Moore, University of Warwick

Moore cautions that it is important to consider who should be prioritized to receive the vaccine first, due to supply and demand issues worldwide. He says that modeling is a useful tool here:
“To enable the transition back to pre-COVID-19 normality as soon as possible it is important to target the correct members of society first so that each new dose has the maximum impact on reducing future illness. The balance of whether it is optimal to target those first that are most responsible for spreading the disease, or those who are most vulnerable to its impacts is not an obvious one however, and this is where modeling is essential,” explains Moore.

In the study, the team's analysis was based on a compartmental epidemic model where the population is assigned to one of several compartments dependent upon infection and vaccine status. “People progress between the different compartments at rates dependent on relative compartment sizes as well as age and presence of comorbidities. Simulations involve solving a set of differential equations that describe these dynamics. Parameters for the model are estimated from COVID-19 infection data using Markov Chain Monte Carlo algorithms,” says Moore.

The researchers simulated the spread of SARS-CoV-2 within different regions of the UK and assessed three different vaccine types based on mechanism, rather than modality (Table 1).

Table 1: Overview of the different vaccine types studied. 
Type oneA vaccine that reduces susceptibility (inhibits viral transmission and protects the vaccinated individual)
Type twoA vaccine that reduces the probability of becoming symptomatic (some benefit in reducing transmission)
Type threeA vaccine that prevents severe symptoms (direct protection to the vaccinated individual only)

They then explored various scenarios, taking into consideration NPIs as well as vaccine effectiveness and scale and targeting of vaccine deployment. They then added another “layer” of analysis, by “considering different orders of prioritization in terms of age group and health conditions”. The team set out to identify a vaccine strategy that achieves the greatest reduction in impact of COVID-19 considering the number of vaccine doses delivered.

Moore discusses what impact previous SARS-CoV-2 infection provides in terms of protection against the disease and whether this should be considered when rolling out vaccines: “Concentrating initial vaccination on just those that have not been previously infected would likely be an effective strategy. However, this is impractical in reality as establishing infection status is not always obvious.”

Due to many cases being asymptomatic and difficult to detect, according to Moore, there would likely be “many cases of misjudgment”. He continues, “Symptoms of flu or other illness are frequently mistaken for COVID-19. Vaccinating someone who has been previously infected is also not a wasted dose since there is strong evidence that vaccination provides longer-lasting and stronger protection than natural immunity alone. For these reasons, this strategy is not considered.”

Assessing vaccine types and prioritization

The team found that prioritizing vaccine administration to older age groups was most effective at reducing the number of deaths and
quality-adjusted life year losses. This finding was observed despite the role younger age groups (who are not advised to shield) play in the spread of the disease.

 Studying the effects of three different vaccination mechanisms.

Type one

  • The authors found that type one vaccines, even with reasonably low efficacy, could be highly effective in preventing further COVID-19 mortality if used in combination with limited social distancing (when R ≈ 1.8).

  • The best performing prioritization order begins with those aged ≥ 80 years, followed by individuals with health conditions, before the rest of the population in order of age (oldest to youngest). 

  • The team proposes that a type one vaccine with 50% efficacy administered to 70% of the population above 20 years of age is sufficient to prevent a SARS-CoV-2 resurgence. 

  • A vaccine with higher efficacy could achieve the same results by only vaccinating those above 40 years.

Type two

  • When combined with limited social-distancing measures (R = 1.8), type two vaccines with a reasonable efficacy may still be sufficient at preventing significant further mortality.

  • However, the authors note that there is very little additional benefit from vaccinating lower-risk individuals (e.g., lower age groups) due to type two vaccines having a limited ability to reduce transmission.

  • Similar to type one, the best performing prioritization order begins with those aged ≥ 80 years, followed by individuals with health conditions, before the rest of the population in order of age (oldest to youngest).

  • The authors predict that for type two vaccines with an efficacy of ≤ 50% or below, a large-scale subsequent wave of infection would occur upon relaxation of control measures, resulting in a similar number of deaths experienced during the “first wave” of infection.

Type three

  • Type three vaccines can only reduce the likelihood of a recipient experiencing severe disease and do not reduce the risk of transmission; therefore, the authors predict that the use of a type three vaccine would result in a large-scale second outbreak upon the lifting of containment measures.

  • However, type three vaccines can still be of considerable benefit when administered to high-risk patients (particularly in those > 60 years).

  • For the most efficacious type three vaccines, immunizing 70% of individuals > 60 years could halve the number of deaths.

  • The best performing prioritization order begins with those aged 60–80 years, above all those with health conditions. 

The “best” vaccine scenario would involve the rollout of a vaccine candidate that sufficiently contains the pandemic without the requirement for additional interventions (e.g., social distancing)
(R 2.3). The team found that from the above vaccines (Table 1) modeled in the study, the only one that could potentially prevent SARS-CoV-2 resurgence was a type one vaccine, with an efficacy > 80% and it would require 70% of the entire population to have been administered the vaccine.

In addition, the authors we able to identify from the simulations five key factors that can affect the success of a vaccination program:

1.       Characteristics of the vaccine.

2.       Vaccine efficacy.

3.       Reproduction number once the vaccine program is completed.

4.       Proportion vaccinated.

5.       Who is vaccinated.

Moore and colleagues have
previously explored the balance between NPIs and vaccination. In the study, published in The Lancet Infectious Disease, they found that “vaccination alone is insufficient to contain the outbreak.

It is essential that we do not relax NPI measures too quickly so as to risk another major wave of infection before the vaccination program has progressed sufficiently to mitigate disease effects. We have been successful up to now in protecting many of the most vulnerable members of society by the use of NPIs and it would be a tragedy if these efforts were thrown away now that we’re so close to having an effective exit strategy,” concludes Moore.

Moore S, Hill EM, Dyson L, Tildesley MJ, Keeling MJ. Modelling optimal vaccination strategy for SARS-CoV-2 in the UK. PLoS Comput. Biol. 2021;17(5):e1008849. doi:10.1371/journal.pcbi.1008849

Sam Moore was speaking with Laura Elizabeth Lansdowne, Managing Editor for Technology Networks.