With second waves of COVID-19 emerging around the world, the need for effective vaccines is even more important. With the large pool of vulnerable individuals still around, a complete relaxation of virus control measures is likely to generate more significant waves. As several vaccines are already in stage 3 clinical trials, a study by researchers at the University of Warwick, published in September 2020 on the preprint server medRxiv *, discusses the use of computer modeling techniques to achieve optimal vaccine coverage.
COVID-19 mortality was high in the elderly due to the development of severe pneumonia, sepsis, and kidney failure in this cohort. It is therefore important to model optimal strategies for planning and allocating resources in order to implement public health strategies aimed at containing the virus.
Representation of model states and transitions
The need to prioritize vaccine administration
However, it is uncertain how any given vaccine will actually perform in the human population, although promising results have been obtained from preclinical experiments on non-human primates and a relatively small number of humans. Because of this, the current study focuses on adapting an earlier model of virus transmission to reflect the changes that can occur when a vaccine is used.
Along with the effectiveness of the vaccine, the way the vaccine should be used is of equal value but has been less discussed. One question in this context is whether those factors that drive transmission should be vaccinated first, or those at greatest risk for severe morbidity and death.
Three types of vaccines
The researchers chose three types of vaccines to get a fuller picture of the outcome that is likely with the use of a particular vaccine. Type I vaccines reduce an individual’s susceptibility to infection; Type 2 and 3 vaccines reduce the incidence and severity of symptoms.
The first protects the individual vaccine and also limits transmission. The second reduces the spread somewhat by reducing the incidence of symptoms, since asymptomatic individuals may have a lower risk of transmission. The third only protects the vaccinated person from undesirable results.
The current model examines the possible effects in each scenario, adjusted for age-dependent differences in effectiveness and the extent of coverage. They also examine the criteria for prioritizing vaccine administration.
In addition, the researchers assessed the vaccination protocol for the minimal loss of quality-adjusted life year saved (QALY) as well as for deaths averted per vaccine dose. This approach enables a cost-benefit assessment of vaccine policy.
In the current study, they plotted vaccinated people (up to 70% in each considered group) against the number of deaths or QALY losses. The group associated with the highest reduction in any of these episodes per dose was identified. The results were then optimized for one of these episodes as the two are closely related.
Consistent priority ordering favors older ones first
When classified by various parameters, including age, the most significant effect on future mortality was found when the oldest were vaccinated first. Although they are not the group most closely linked to virus spread or mobility, they are the ones most affected by the infection in terms of serious and deadly diseases.
Second, regardless of the criteria, a targeted vaccination approach was found to be superior to indiscriminate vaccination. On the other hand, the comorbidities to be prioritized are age-dependent. Therefore, the type of chronic disease that requires priority vaccination varied between those under 60 years of age beyond young adulthood and those over 80 years of age.
They found that the success of a vaccination program depends on five criteria:
- the type of vaccine, with Type 1 being by far the most desirable;
- Effectiveness of the vaccine;
- the reproduction number;
- the proportion vaccinated in relation to the effectiveness of the vaccine;
- the vaccination priority.
The authors say, “We have consistently shown that prioritizing vaccination of the elderly is by far the most effective strategy for reducing the number of deaths in a second wave.” This may come as a surprise given that QALYs are more relevant at a younger age, but it is explained by the much greater severity of the disease in older people.
Vaccination for health workers
The researchers also looked at the priority position of health care workers (HCW) in a vaccination schedule. Not only are they vulnerable to increased exposure, but they can also drive transmission. In addition, they only make up 2% of the population.
For type I vaccines, HCWs are only relevant for the oldest age group (80 years or older) or even higher, depending on the number of transmission.
Compare vaccine types for optimal priority
The researchers then examined the three vaccination actions and their levels of effectiveness against the theoretical background of an age- and disease-oriented vaccination approach with a low NPI value. They also modeled what could happen if the most effective type of vaccine, namely the Type 1 vaccine, were given without an NPI.
Type 1 vaccine
The researchers found that even sub-optimal Type I vaccines (50% effectiveness) can prevent further deaths if there is limited social distancing (reduction in transmission number R to around 1.8) and 70% of the population over 20 years of age vaccinated . The 80-year-olds should be vaccinated first, then those with comorbidities, the rest in order of age from oldest down. With higher effectiveness, only those over 40 years of age need to be vaccinated.
Type 2 vaccine
If social distancing measures keep R at ~ 1.8, an effective type 2 vaccine for high-risk groups could prevent a significant number of deaths, even if a second wave occurs. Vaccinating low risk cases brings little additional benefit. The same order of priority applies here. If the effectiveness is lower (50% or less), the extent and mortality of the second wave mimick the first, the researchers say.
Vaccine type 3
Type 3 vaccines do not limit transmission, and therefore both vaccinations and rigorous containment measures are required to prevent sizeable future waves. The benefits of this vaccine are likely to remain important for those at high risk, especially those over the age of 60, including those with chronic illnesses.
Type 1 vaccine, no NPIs
The researchers conclude that the best vaccine would be able to stop the pandemic on its own, which could ease any NPIs with a transmission number of around 2.3. This description would fit a type 1 vaccine with an effectiveness greater than 80% and covering 70% or more of the total population. At other levels of effectiveness, of course, the percentage of vaccine coverage required increases. When older people at higher risk are vaccinated, fewer young people need to be vaccinated.
A type 1 vaccine can be administered in an age-appropriate manner without additional NPIs, without considering the presence of comorbidities, as this makes little difference to the outcome measures.
Slow or fast delivery
The above results assume rapid vaccination coverage so that almost all eligible groups will be vaccinated at the same time. The slower deployment will have fewer post-relaxation cases if the transmission number is consistently kept less than 1 through NPIs.
However, the researchers suggest, “More realistic delivery scenarios can be simulated if the vaccination schedules are better understood.”
As the pandemic escalates, the competition between the pace of vaccination and virus transmission suggests rapid indiscriminate vaccination rather than slower targeted campaigns. Therefore, an order is not strictly necessary if vaccine delivery is either very fast or very slow, as in these situations the number of new infections is negligible or the epidemic will be over before vaccine delivery is complete.
The effectiveness of the vaccination varies from a peak under 45 years of age, through a steady decline, to a low after 85 years. This confirms the robustness of the early priority order, even with a low vaccine effectiveness of only 20%.
At even lower levels of effectiveness, however, people with underlying chronic diseases or in the 40 to 60 age group come first. The researchers say, “The estimated number of deaths [is] relatively constant across a range of efficacy values for older and younger age groups. “
In fact, with the type 3 vaccine, up to only 10% effectiveness, the elderly remain the highest vaccine priority group.
Cost per vaccine dose
The researchers estimate that if the transmission count was 1.8, the loss of QALYs would be ~ 1.6 million when a second wave occurs. To prevent this from happening, ~ 21 million targets must be vaccinated with ~ 41 million doses of vaccine, which is 90% effective. This suggests a cost per dose of £ 767 as opposed to the low cost threshold of £ 20,000 per QALY which is a huge benefit by any measure.
Implications and Future Directions
The conclusion is likely to be true in all countries and reflect what is currently known about the virus: “It is important that the vaccine is used as efficiently as possible so that early limited supplies are used to the greatest effect.”
Future research will consider other observed parameters as they become known, including the percentage of the population accepting a vaccination and the effectiveness of the vaccine across age groups. The actual expected delay in vaccine use must also be included in the model parameters.
* Important NOTE
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.