Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics

Abstract

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.

Fig. 1. Infection burden for illustrative variant of concern (VOC) scenarios, produced using the parsimonious SARS-CoV-2 transmission model.

We considered three putative VOCs with differing transmissibility and immune-escape characteristics: more transmissible (VOC MT, blue line with square markers), equal transmissibility with immune escape (VOC E, orange line with plus sign markers), less transmissible with immune escape (VOC LT+E, yellow line with circle markers). We also present temporal dynamics for resident variants in the absence of any VOC being introduced (black line with no markers). Additionally, in panels a and c, we represent the vaccine uptake in the population through time via background shading, the transition time into Step 4 of the relaxation roadmap by the vertical solid line, and we state the assumed R excluding immunity values for resident variants (R_excl) throughout Steps 3 and 4, respectively. a VOC infectious prevalence over time. In each scenario, alongside resident variants, we introduced one of the VOCs on 17th May 2021 with 2000 initial infecteds. c Instantaneous R of a VOC accounting for population-level immunity (y axis) calculated at the time of its introduction (x axis). For the “Resident variants with no VOCs” scenario, the displayed profile corresponds to the instantaneous R with immunity of resident variants. In panels b and d, we explore the sensitivity of two epidemiological outcomes to the relative transmissibility of the VOC compared with resident variants and the proportional efficacy (vaccine and natural immunity) against the VOC: b outbreak final size; d peak in VOC-infection cases.

Fig. 2. Estimated COVID-19 hospitalisations, using the age-structured SARS-CoV-2 transmission model, across the illustrative variant-of-concern (VOC) scenarios.

We considered four putative VOCs with differing transmissibility, severity, and immune-escape characteristics: more transmissible (VOC MT, blue, square markers), equal transmissibility with immune escape (VOC E, orange, plus-sign markers), less transmissible with immune escape (VOC LT + E, yellow, circle markers), and equal transmissibility with the same immune-escape properties of VOC E with the exception of a lesser reduction in vaccine-derived efficacy against hospitalisation (VOC E + LH, purple, inverted triangle markers). a Time series of daily hospital admissions (thousands). Solid lines show the mean at each timepoint and the shaded ribbons the 95% prediction intervals. The dashed horizontal line denotes the peak in daily hospital admissions in England during the January 2021 wave. Vertical grey lines give the timing of each Step of the relaxation roadmap (RM), with Step 4 being placed at the earliest stipulated date that it may begin (21st June 2021). The vertical light-red line corresponds to the projected date under our vaccine roll-out speed assumption where all those in the adult population (18+ years of age) in England who accept the vaccine would have received two doses. b Relationship between mean peak hospital occupancy with VOC (thousands) and the level of NPIs toward the population following Step 4 of the relaxation roadmap. c Age distribution of infections from the historical data up to May 2021 (black bars) alongside the projected distributions for the resident variant in the absence of any VOCs (grey bars) and each VOC scenario (VOC MT: blue bars; VOC E: red bars; VOC LT + E: orange bars).

Fig. 3. Outbreak potential and sensitivity of epidemic trajectories to the introduction time of a variant of concern (VOC) targeted vaccine for VOC E.

a The probability of an epidemic for varying relative transmissibilities (compared with resident variants) versus a given count of VOC-effective imports per day (corresponding to the second generation cases that result from a single-index case). In panels b–d, we performed simulations using the parsimonious SARS-CoV-2 transmission model for differing effective VOC importation counts and introduction date of a VOC-targeted vaccine and evaluated the following epidemiological summary statistics for the resultant VOC outbreak; b final size; c peak in infectious prevalence; d time of peak in infectious prevalence.