The accelerated rate of vaccine development against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in an attempt to bring an end to the coronavirus disease 2019 (COVID-19) pandemic, culminated in the approval of the Pfizer/BioNTech and Moderna vaccines under Emergency Use Authorization by the US Food and Drug Administration, as well as its European counterparts.
Both vaccines claim 95% efficacy after two doses, given three and four weeks apart for the Pfizer and Moderna vaccines, respectively.
A thought-provoking new preprint on the medRxiv* server discusses the factors that determine the successful use of available vaccines to mitigate incidence and mortality rates for COVID-19. These include non-pharmaceutical interventions (NPIs) and enhanced rates of vaccine administration.
NPIs include social distancing, sheltering in place, face mask use in public, and hand hygiene. These have been in place since the beginning of the pandemic.
In the USA, the vaccine rollout followed prioritization protocols at first, targeting first the healthcare workers and residents in care homes, secondly frontline essential workers, and thirdly other essential workers, people aged 65-75 years, and those with chronic medical conditions.
The Pfizer/BioNTech (BNT162b2) vaccine began to be administered on December 14, 2020, and the Moderna (mRNA-1273) a week later. While current USA stocks and commitments are adequate to cover the whole population by July 2021, bottlenecks and unexpected natural events, as well as large-scale vaccine hesitancy or frank unwillingness, have made it difficult to move forward with vaccination as rapidly as envisaged.
By December end, less than 3 million doses had been distributed, meeting less than 15% of the target.
The researchers first implemented several different scenarios, from N0, in which no vaccination or NPIs, to N5, in which all NPIs are maintained until 140 million people have received one or more doses of vaccine. At 10 days from this point, NPIs are relaxed in three steps a month apart.
The simulated scenario envisages the completion of the three phases of vaccination at 23, 66 and 154 days from January 11, on average. The 140 million mark was achieved 193 days from this point.
A vaccine coverage of 80% for healthcare workers, 70% for high-risk groups, 60% for other adults and children as long as stocks were available was implemented.
The scenarios in which the NPIs were either maintained or strengthened initially resulted in the lowest attack rates in all the states, at about 15%, vs 45% for N0. The reduced efficacy of vaccination in the scenario when NPIs are relaxed by the time the first two phases are completed is due to the increased transmission rate of the virus at this time point.
The researchers estimated that almost half and three-quarters of the population would be immunized or will have passed away, following natural infection, by the end of the first and second phases, respectively.
A decrease in both figures, to 40% and 50%, approximately, is evident if NPIs are first strictly enforced and relaxed in three steps, at the end of each of the three phases.
The reasons include reducing the susceptible population, which impacts the rate of effective vaccination (vaccination of those not already infected or immune).
Assuming the same coverage targets as in the first analysis, the researchers implemented very different vaccination rates, from 3 to 13 million entries into the vaccination program each week over the whole country. Four NPI policies were also combined with these different schedules, from low to high intensity of distancing, leading to relaxation of NPIs over one to six months.
The time-dependent relaxation of NPIs was intentionally implemented since the different deployment rates lead to vastly different rates of completion of the three phases of prioritized vaccination.
This showed that with 7 million new people being vaccinated each week, rather than 5 million, the number of infections avoided could be increased by 3-6%, and deaths averted could be increased by 4-8%.
The corresponding figures if 11 million new people were vaccinated each week rather than 5 million were 9-16% and 7-18%, for the increase in the averted infections and deaths.
The more relaxed the NPIs, the greater is the need for rapid vaccination coverage since infections increase fastest during the initial period of relaxation when immunity is at its lowest.
Given that vaccine acceptance and access are not alike in all subgroups of the population, the researchers found that with 400 million doses, that is, the number of doses committed to or available with the USA government at the time of the study, 62% of the population could be covered overall.
Given this fact, the effect of non-uniform vaccine uptake was greatest if the uptake was highest in the high-risk groups, with the result being the greatest number of deaths averted.
Compared to the scenario of No-intervention (neither vaccination nor NPIs), a uniform doubling of vaccine uptake from 32% to 64% was necessary to reduce infections by an additional 2-4%, and deaths by an additional 3-5%, and only if some NPIs were put in place. Conversely, if the coverage was increased to 99% for only the high-risk groups, the number of deaths averted was 4% more.
The reasons could be the higher impact of vaccination in the initial phase as natural infections are fewer, and the fact that vaccine deployment in groups at lower risk delays its reach to high-risk groups since they are in a lower priority group. To overcome this, the weekly vaccination rate must be increased so that these high-risk lower-priority groups are covered as fast as possible, even if only partially.
What are the implications?
The strongest modulator of the impact of vaccination, measured by averted infections and deaths for a broad range of realistic scenarios was the enforcement of NPIs throughout the vaccination campaign.”
With strict NPIs for the initial phase of vaccination, the transmission drops, allowing more susceptible people to be reached by the campaign before the virus reaches them. With premature relaxation, say, at one month following the beginning of the campaign, the reduction in infections may be only about a quarter of that achievable by strong NPIs.
Despite pandemic fatigue and economic hardship, these vaccines offer the best chance of reducing the toll of this virus. However, the administration rate is also a key factor, and could partly mitigate the low NPI implementation, indicating that “it is therefore essential to increase efforts to produce, distribute, and administer the vaccine.”
Vaccine acceptance may not be as important as the other two factors because it does not prevent high-risk groups from being vaccinated earlier.
The findings may not be realistic if the reduction in infections is not as impressive as the fall in symptomatic disease incidence following vaccination. More data is required to understand vaccine impact on transmission.
Other sources of error include vaccine-resistant variants, waning of immunity, and the occurrence of re-infections. Overall, “the public health objective is to vaccinate as many people as possible prior to infection. To do so, production, distribution and administration of vaccine must be accelerated and NPIs kept in place until enough doses are delivered to prevent sustained community transmission.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.