Model shows booster doses and antiviral pills may enable relaxation of SARS-CoV-2 social distancing

By Dr. Liji Thomas, MDFeb 11 2022Reviewed by Aimee Molineux

A new mathematical model from the Republic of Korea suggests that social distancing could be relaxed in order to reduce the number of severe cases of coronavirus disease 2019 (COVID-19), rather than stop the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The measures that could be adopted to achieve this include effective antiviral pills and booster shots of COVID-19 vaccines.

Introduction

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

At present, the Omicron variant of SARS-CoV-2 dominates the pandemic worldwide. It has been found to spread faster and be more transmissible than the Delta variant, and evades antibodies elicited by the spike protein of earlier variants. However, it appears to be less severe in its clinical phenotype, and is more likely to cause reinfection, than earlier variants.

Vaccination programs are an important measure in protecting people against severe or fatal disease with the novel coronavirus, even though vaccine effectiveness and antibody titers wane over time. Booster shots have been mandated in many countries to prevent breakthrough infections. However, non-pharmaceutical interventions such as social distancing and mask use remain key to bringing down Omicron transmission rates.

South Korean responses to the pandemic comprised of a highly efficient testing-tracing-treatment plan and social distancing guidelines. Vaccination was rolled out, first to the elderly and healthcare workers, in February 2021. In July 2021, a tiered social distancing (SD) scheme was put in place. Level 2 SD at this time gave way to level 4, at which time the fourth wave of COVID-19 began.

Cases began to decline in October 2021, with 75% vaccination coverage. The government then implemented a slow relaxation in SD, calling it part of its “gradual recovery (GR) to a new normal”.

This was associated with a steep rise in daily cases, occurring towards the end of the same month, caused in almost all cases by Delta, with almost 60% being breakthrough infections. Since then, over 100,000 booster shots have been given, at three months from the second vaccine dose.

The Omicron variant began to spread in December 2021, and made up over a quarter of cases by mid-January 2022, by which time daily cases and deaths were approximately 5,000 and 500, respectively. This led to suspension of GR (SGR), from December 18, 2021. Around mid-January, however, the Pfizer antiviral pill Paxlovid was made available, with 89% protection against severe infection.

The current study, which appears as a preprint on the Research Square* server, whilst under consideration at Scientific Reports, models the effects of various NPIs implemented in the period from the end of February 2021 to January 16, 2022, in terms of the number of cases and the number of severe cases. The researchers also examined the effects, if various parameters were tweaked, such as Omicron transmissibility, severity, and response to vaccine-induced antibodies. The aim was to predict possible outcomes pending the relaxation of SD, but this time with a large population of booster dose recipients and with the antiviral pill.

Findings

The researchers assessed viral transmission over four SD policies, namely, SD2, SD4, GR, and SGR. They adopted the parameter μ(t), a quantified estimate of NPIs per SD policy in place. They found that a slow steady rise in cases gave way to a steep rise in daily cases during GR, peaking on December 19, 2021, one day after SGR came into effect. Subsequently, there was a sharp drop in cases, and then a slower fall.

The reproductive number Rt hovered near 1 during SD2, except when it jumped to 1.54 during the two weeks before SD4 came into force. This phase saw the lowest NPIs, and the beginning of the steep rise in cases. The μ(t) remained between 0.6 and 0.7 until July 2021.

It was lowest in the last two weeks of SD2, and associated with an Rt of 1.41. The SD4 phase from July to October 31, 2021, saw the μ(t) go up to 0.76. In November and December 2021, GR was in force, and the μ(t) averaged 0.65. With the later spread of Omicron, SGR came into force from December 19, 2021 onwads, and μ(t) went up to 0.73, with a low Rt of 0.7.

Vaccination coverage reached 70% in the SD4 phase, from July to October 2021, followed by booster shot administration. Breakthrough infections comprised a larger proportion of infections, first with Delta, and then, once GR ended, Omicron. At present, over 90% of all infections are due to Omicron, overall, with a quarter of Omicron infections being in unvaccinated individuals.

With 450,000 daily booster shots, they predict more than 7,800 daily cases by the end of February 2022, under GR or SGR conditions. Severe infections will reach the available hospital bed limit at GR level, with daily cases and severe infections going up to 50,000 and 3,000, respectively.

SGR levels must be exceeded, with μ(t) > 0.79 or 0.77, for daily and severe cases, respectively, to go down. At SGR levels, the rise cannot be curtailed even by doubling the number of booster shots. However, at higher μ(t) levels, increasing booster shots reduces the number of infections.

Case numbers will double at all μ(t) values among unvaccinated individuals, at 450,000 booster shots per day. Severe cases will be eight-fold greater in this population. Under SGR conditions, they predict 18 breakthrough infections per 100,000 vaccinated, but 40 among the unvaccinated. Similarly, severe cases amount to 0.8 and 6.5 per 100,000, respectively.

Without Omicron-specific booster shots, SGR levels must be maintained to ensure that severe cases do not overwhelm the hospitals. However, with 90% effective boosters, a lower level of NPIs can be implemented, provided Omicron severe cases are less than 20% of the proportion seen with Delta.

Antiviral therapy reduces the number of severe cases, and keeps them below the threshold of available beds if given to all infected patients. This will allow more relaxed SD levels provided the pill is effective against Omicron hospitalization.

Implications

The study shows the interacting and dynamic effects of NPI stringency coupled with varying proportions of infections due to Delta and Omicron, which lead to differences in the Rt over time. With similar μ(t) values, different phases show different Rt values due to dominance by these variants compared to the earlier ones, with higher transmissibility.

For instance, “daily confirmed cases increased from about 2,000 to 7,000 within 40 days during GR compared to about 400 to 1000 cases within 130 days during SD2,” because of the dominance of Delta during GR. The decrease in SD4, despite similar μ(t) values to SGR, could be due to an early proactive increase in stringency of restrictions, before Omicron cases reached 1% of the total, 95% adult vaccination coverage, and over 400,000 daily booster shots. This held down Omicron spread even with its higher transmissibility and >30% waning of vaccine effectiveness.

Less than 40% of the population is expected to be fully protected with a booster shot by the end of February 2022. Most unvaccinated individuals are now underage, and safe effective vaccines need to be designed, keeping them in mind.

With μ(t) values of 0.73 and 0.81, severe cases can be kept at subthreshold values, but in the former case, they are still increasing.

This suggests while keeping a high level of population immunity is important, maintaining enhanced NPIs is also necessary to suppress the number of Delta and Omicron infections.”, the scientists explained.

The relaxation of restrictions can be made possible by highly effective Omicron-specific booster shots and reducing Omicron severity by antiviral pill use – though the availability of these pills will be a constraint.

Further research is necessary to decode the age-related differences in disease severity and vaccination priorities, as well as the prioritization of Paxlovid pills.  However, this model offers five lessons:

• Waning of vaccine-induced immunity is correlated with rising breakthrough infections.
• Booster shots protect against infection and reinfection, and very effective boosters protect against severe cases.
• Unvaccinated people are more susceptible to infection and severe illness.
• Vaccination and booster shots are key, along with NPIs, to limiting the impact of the outbreak.
• Relaxation is possible if, in addition, antiviral therapies are available.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources