Variant-specific interventions to slow down replacement and prevent outbreaks

Highlights

• A novel mathematical model incorporating emergence of variants of concern VOC.

• Limited testing and whole genome sequencing (WGS) capacity is considered.

• Variant-specific interventions is shown to be effective in preventing outbreak of VOC.

• A large COVID-19 test capacity is required in controlling VOC epidemic waves.

• Short delay in COVID and WGS test is essential to prevent or mitigate an outbreak.

• Intensive contact-tracing and quarantine is key to avoiding VOC-driven outbreaks.

Abstract

Emergency and establishment of variants of concern (VOC) impose significant challenges for the COVID-19 pandemic control specially when a large portion of the population has not been fully vaccinated. Here we develop a mathematical model and utilize this model to examine the impact of non pharmaceutical interventions, including the COVID-test (PCR, antigen and antibody test) and whole genome sequencing (WGS) test capacity and contact tracing and quarantine strength, on the VOC-induced epidemic wave. We point out the undesirable and unexpected effect of lukewarm tracing and quarantine that can potentially increase the VOC-cases at the outbreak peak time, and we demonstrate the significance of strain-specific interventions to either prevent a VOC-induced outbreak, or to mitigate the epidemic wave when this outbreak is unavoidable.

Introduction

Genetic mutations play an important role in the evolution of virus in general, and in the ongoing evolution and emergence of novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants in particular [1]. These genetic variations can lead to emergence of new variants with selection of phenotypes increasing viral fitness (replication, transmissibility, immune escape).

Characterizations of these variants depend on the type and number of mutations [2], [3]. For SARS-CoV-2, a “variant of interest” (VOI) can elevate to “variant of concern” (VOC), under the definition of the World Health Organization (WHO), when it transmits more quickly in a population than its ancestral lineage, and/or when it has the ability to evade natural or vaccine-induced immunity making available vaccines ineffective. Several variants of concern have indeed led to a large increase of incidence, hospitalization and mortality in many countries after more than a year of initial report of the COVID-19 outbreak. As of May 16, 2021, most common VOC internationally identified include: B.1.1.7 (identified in September, 2020) [4], B.1.351 (identified in October, 2020), P1 (identified in December, 2020) and B.1.617 (identified in December, 2020) [5], [6], [7], [8]. Strain-specific interventions are needed in an already strained public health system where there is little additional resource available for mitigating VOC emergency and establishment.

Genome sequencing methods are used to decode the genes to better understand the virus mutations. Genomic sequencing permits recognition of pathogen, monitoring its evolution over time, and detecting appearance of a new variant [9]. Any VOC-specific intervention relies on the use of whole genome sequencing test to specify the strain. Here, we develop a modeling framework and analysis, in order to quantify the role of variant-specific interventions in preventing replacement and outbreak of the VOC under consideration. Obviously, this design and implementation of variant-specific interventions needs rapid whole genome sequencing (WGS) of confirmed cases, this in turn requires that (1) the total confirmed cases (for both the original or resident lineage and its variant) to be sufficiently small such that the time delay from contact tracing to testing and to case and strain confirmation can be minimized, and (2) the WGS can be performed on majority, if not all, COVID-19 test positive cases.

Some countries, such as South Korea, Australia and New Zealand have indeed used rapid testing, contact tracing, isolation and mandatory quarantining of international travelers as effective tools to keep case counts significantly low. The role of rapid tests to enhance contact tracing and quarantine/isolation for controlling past outbreaks has been modeled and analyzed [10], [11], [12], [13], [14], [15], and other modeling studies have addressed VOC-relevant issues including evaluating the impact of increasing transmissibility and estimating the replacement time [5], [6], [7], [8], [16], [17], [18], [19]. In contrast, we seek to evaluate, under different scenarios of clinical COVID-19 and WGS testing capacity, the impact of the co-circulation of old-lineage and VOC on testing delays, the impact of these delays on contact tracing and quarantine/isolation, and the impact of strain-specific contact tracing and quarantine/isolation measures on the disease spread potential and disease burden. In particular, we seek to answer the question of whether VOC-specific public health investments and interventions can optimize the resources to avoid a new VOC-induced outbreak or, if this outbreak is unavoidable, to mitigate the outbreak.