Global Expansion of SARS-CoV-2 Variants of Concern: Dispersal Patterns and Influence of Air Travel

Abstract

In many regions of the world, the Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated during 2020-21 and fueled waves of infections. During 2021, these variants were almost completely displaced by the Delta variant, causing a third wave of infections worldwide. This phenomenon of global viral lineage displacement was observed again in late 2021, when the Omicron variant disseminated globally. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of SARS-CoV-2 VOCs worldwide. We find that the source-sink dynamics of SARS-CoV-2 varied substantially by VOC, and identify countries that acted as global hubs of variant dissemination, while other countries became regional contributors to the export of specific variants. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal: we estimate that India contributed <15% of all global exports of Delta to other countries and South Africa <1-2% of all global Omicron exports globally. We further estimate that >80 countries had received introductions of Omicron BA.1 100 days after its inferred date of emergence, compared to just over 25 countries for the Alpha variant. This increased speed of global dissemination was associated with a rebound in air travel volume prior to Omicron emergence in addition to the higher transmissibility of Omicron relative to Alpha. Our study highlights the importance of global and regional hubs in VOC dispersal, and the speed at which highly transmissible variants disseminate through these hubs, even before their detection and characterization through genomic surveillance.

Highlights: Global phylogenetic analysis reveals relationship between air travel and speed of dispersal of SARS-CoV-2 variants of concern (VOCs)Omicron VOC spread to 5x more countries within 100 days of its emergence compared to all other VOCsOnward transmission and dissemination of VOCs Delta and Omicron was primarily from secondary hubs rather than initial country of detection during a time of increased global air travelAnalysis highlights highly connected countries identified as major global and regional exporters of VOCs.

Figure 1:. Spatiotemporal dispersal patterns of VOCs.

A) Global dissemination and continental source-sink dynamics for each VOC, determined from ancestral state reconstruction analysis. Virus lineage exchanges are aggregated at sub-continental level and curves linking any two locations are coloured according to the mean dates of all viral movements inferred along this route. The curves denote the direction of movement in an anti-clockwise direction. Circles are drawn proportional to the number of exports per location. Source and sink continents are determined by calculating the net difference between viral exportation and importation events. The absolute numbers of exportation and importation events for each continent per VOC are shown in Figure S5. B) Largest global and regional contributors to viral exports, stratified by VOC. Countries are shown here if they contribute >0.1% of exports globally or within Europe, or >0.5% within other regions.

Figure 2:. Inferred origins of global VOC dissemination events.

A) Changes in proportions of all inferred introductions from the country of presumed origin for each VOC (bars), and the number of countries inferred to be acting as onward sources of each VOC (purple line, with scale in the second y-axis). Results shown are determined from 10 replicates of genome subsampling. B) Date of first inferred introduction per country coloured by location of origin, i.e. presumed origin (blue) or not (orange). The lines represent countries, which are ranked and labeled by the median of their dates of first introduction (from 10 replicates). The lower x-axis denotes the estimated median tMRCA and confidence interval range dates for each VOC, as reported in published studies^–,,,.

Figure 3:. Impact of global air travel on VOC dissemination.

A) Delay (number of days since TMRCA) of each VOC to be first sampled in countries around the world, and the total global monthly air passenger volumes from September 2020 to March 2022. The number of points and mean of each violin plot are indicated. The dot and error bars inside each group denote the median and interquartile range, respectively. Dates of VOC origin are taken as their published mean estimated dates of emergence (TMRCA), with crosses representing the median and high confidence range values^–,,,. The date of arrival of each VOC per country is taken to be the first sampling date of a sequenced case in GISAID (Date of access = 18 September 2022). B) Scatter plot and spearman rank correlations of either travel volumes from the first reporting country or total global travel with the delay in first sampling of VOCs in countries globally. Spearman rank correlation values are shown, with level of significance indicated.

Figure 4:. Continental epidemiology of SARS-CoV-2 cases, mortality, testing and vaccination.

A) The progression of daily reported cases per continent from February 2020 to October 2022 (log scale, first y-axis). The 7-day rolling average of daily reported case numbers is coloured by the inferred proportion of variants responsible for the infections, as calculated by genomic surveillance data (GISAID date of access: 1 October 2022) averaged over 20 days. The line shows the 7-day rolling average of the number of daily tests per thousand population per region (scale shown in the second y-axis) aggregated for countries for which this data is available for each continent. B) The 7-day rolling average of daily reported deaths coloured by the inferred proportion of variants, as calculated for case data, with an assumption of time lag of 20 days between infection and death applied (See more details in Materials and Methods). The dashed line displays the proportion of people fully vaccinated per region (scale on second y-axis) where those that received all doses prescribed by the initial vaccination protocol are considered fully vaccinated.