Genomic Sequencing of SARS-CoV-2 in Rwanda: evolution and regional dynamics

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 19 (COVID-19), is a single-stranded positive-sense ribonucleic acid (RNA) virus that typically undergoes one to two single nucleotide mutations per month. COVID-19 continues to spread globally, with case fatality and test positivity rates often linked to locally circulating strains of SARS-CoV-2. Furthermore, mutations in this virus, in particular those occurring in the spike protein (involved in the virus binding to the host epithelial cells) have potential implications in current vaccination efforts. In Rwanda, more than twenty thousand cases have been confirmed as of March 14th 2021, with a case fatality rate of 1.4% and test positivity rate of 2.3% while the recovery rate is at 91.9%. Rwanda started its genomic surveillance efforts, taking advantage of pre-existing research projects and partnerships, to ensure early detection of SARS-CoV-2 variants and to potentially contain the spread of variants of concern (VOC). As a result of this initiative, we here present 203 SARS-CoV-2 whole genome sequences analyzed from strains circulating in the country from May 2020 to February 2021. In particular, we report a shift in variant distribution towards the newly emerging sub-lineage A.23.1 that is currently dominating. Furthermore, we report the detection of the first Rwandan cases of the VOCs, B.1.1.7 and B.1.351, among incoming travelers tested at Kigali International Airport. We also discuss the potential impact of COVID-19 control measures established in the country to control the spread of the virus. To assess the importance of viral introductions from neighboring countries and local transmission, we exploit available individual travel history metadata to inform spatio-temporal phylogeographic inference, enabling us to take into account infections from unsampled locations during the time frame of interest. We uncover an important role of neighboring countries in seeding introductions into Rwanda, including those from which no genomic sequences are currently available or that no longer report positive cases. Our results point to the importance of systematically screening all incoming travelers, regardless of the origin of their travels as well as regional considerations for durable response to COVID-19.

Emergence and spread of a SARS-CoV-2 lineage A variant (A.23.1) with altered spike protein in Uganda

“…We report the emergence and spread of a SARS-CoV-2 variant of the A lineage (A.23.1) with multiple protein changes throughout the viral genome. The pattern of A.23.1 emergence and dominance has also been observed in the neighbouring country of Rwanda 25 . A similar phenomenon recently occurred with the B.1.1.7 lineage, detected first in the southeast of England 5 and now globally, and with the B.1.351 lineage in South Africa 6 and the P.1 lineage in Brazil 26 suggesting that local evolution (perhaps to avoid the initial population immune responses) and spread may be a common feature of SARS-CoV-2.…”

Travel-driven emergence and spread of SARS-CoV-2 lineage B.1.620 with multiple VOC-like mutations and deletions in Europe

“…As more countries launch their own SARS-CoV-2 sequencing programmes, introduced strains are easier to detect since they tend to be atypical of a host country’s endemic SARS-CoV-2 diversity, particularly so when introduced lineages have accumulated genetic diversity not observed previously, a phenomenon that is characterised by long branches in phylogenetic trees. In Rwanda, this was exemplified by detection of lineage B.1.380 (Butera et al, 2021) which was characteristic of Rwandan and Ugandan epidemics at the time. The same sequencing programme was then perfectly positioned to observe a sweep where B.1.380 was replaced by lineage A.23.1 (Butera et al, 2021), which was first detected in Uganda (Bugembe et al, 2021), and to detect the country’s first cases of B.1.1.7 and B.1.351.…”

“…In some cases a lineage may rise to high frequency in one location and seed others in its vicinity, such as lineage B.1.177 that became prevalent in Spain and was later spread across the rest of Europe (Hodcroft et al, 2021). In others, reductions in human mobility, insufficient surveillance and passage of time allowed lineages to emerge and rise to high frequency in certain areas, as has happened with lineage A.23.1 in Uganda (Butera et al, 2021), a pattern reminiscent of holdover H1N1 lineages discovered in West Africa years after the 2009 pandemic (Nelson et al, 2014). In the absence of routine genomic surveillance at their origin location, diverged lineages may still be observed as travel cases or transmission chains sparked by such in countries that do have sequencing programmes in place.…”

Variant Analysis of SARS-CoV-2 Genomes from Belgian Military Personnel Engaged in Overseas Missions and Operations

“…Associated metadata can hence contribute to the accuracy of phylogeographic inference in the absence of genomic data, as these data can be used to mitigate sampling bias (to a certain extent). Such methods are seeing increased application for various lineages, such as A.23.1 [ 61 ] and B.1.380 [ 61 ], B.1.620 [ 62 ] and A [ 63 ].…”