Genomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity

Butera, Yvan; Mukantwari, Enatha; Artesi, Maria; Umuringa, Jeanne d’Arc; O’Toole, Áine; Hill, Verity; Rooke, Stefan; Hong, Samuel L.; Dellicour, Simon; Majyambere, Onesphore; Bontems, Sébastien; Boujemla, Bouchra; Quick, Joshua; Resende, Paola Cristina; Loman, Nicholas J.; Umumararungu, Esperance; Kabanda, Alice; Murindahabi, Marylin Milumbu; Tuyisenge, Patrick; Gashegu, Misbah; Rwabihama, Jean-Paul; Sindayiheba, Reuben; Gikic, Djordje; Souopgui, Jacob; Ndifon, Wilfred; Rutayisire, Robert; Gatare, Swaibu; Mpunga, Tharcisse; Ngamije, Daniel; Bours, Vincent; Rambaut, Andrew; Nsanzimana, Sabin; Baele, Guy; Durkin, Keith; Mutesa, Léon; Rujeni, Nadine

doi:10.1038/s41467-021-25985-7

Cited by 32 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our global discrete phylogeographic analysis, based on a fixed phylogeny and including 315 Delta genomes collected in Rwanda (Figure 8), identified a minimum number of 66 distinct introduction events of the Delta variant (95% HPD interval = [64-68]) into Rwanda (Supplementary Figure S2). This further confirms our earlier findings regarding the relative importance of incoming travelers on establishing the waves of A.23.1 and B.1.380 infections in Rwanda earlier in the pandemic (Butera et al, 2021). Note that the size of the data set, owing to the magnitude of the Delta wave of infections, did not permit performing a full Bayesian discrete phylogeographic analysis between all locations while accommodating phylogenetic uncertainty.…”

Section: Resultssupporting

confidence: 91%

SARS-CoV-2 genomic surveillance in Rwanda: Introductions and local transmission of the B.1.617.2 (Delta) variant of concern

Butera

Hong

Semakula

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

The emergence of the SARS-CoV-2 Delta variant of concern (lineage B.1.617.2) in late 2020 resulted in a new wave of infections in many countries across the world, where it often became the dominant lineage in a relatively short amount of time. We here report on a novel genomic surveillance effort in Rwanda in the time period from June to September 2021, leading to 201 SARS-CoV-2 genomes being generated, the majority of which were identified as the Delta variant of concern. We show that in Rwanda, the Delta variant almost completely replaced the previously dominant A.23.1 and B.1.351 (Beta) lineages in a matter of weeks, and led to a tripling of the total number of COVID-19 infections and COVID-19-related fatalities over the course of only three months. We estimate that Delta in Rwanda had an average growth rate advantage of 0.034 (95% CI 0.025-0.045) per day over A.23.1, and of 0.022 (95% CI 0.012-0.032) over B.1.351. Phylogenetic analysis reveals the presence of at least seven local Delta transmission clusters, with two of these clusters occurring close to the border with the Democratic Republic of the Congo, and another cluster close to the border with Tanzania. A smaller Delta cluster of infections also appeared close to the border with Uganda, illustrating the importance of monitoring cross-border traffic to limit the spread between Rwanda and its neighboring countries. We discuss our findings against a background of increased vaccination efforts in Rwanda, and also discuss a number of breakthrough infections identified during our study. Concluding, our study has added an important collection of data to the available genomes for the Eastern Africa region, with the number of Delta infections close to the border with neighboring countries highlighting the need to further strengthen genomic surveillance in the region to obtain a better understanding of the impact of border crossings on lowering the epidemic curve in Rwanda.

show abstract

Section: Resultssupporting

confidence: 91%

SARS-CoV-2 genomic surveillance in Rwanda: Introductions and local transmission of the B.1.617.2 (Delta) variant of concern

Butera

Hong

Semakula

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 72%

“…This makes the mutational pattern of lineage A.27 of particular interest as it shows the independent acquisition of the same mutations found in B.1-derived VOCs and VOIs in a different genomic background. A similar pattern of concerning mutations in an emerging A-derived lineage has so far only been described for the A.23/A.23.1 lineage first discovered in Uganda and Rwanda 39 , 40 . The early detection in multiple countries in Western Africa in late December 2020, an outbreak in January 2021 in Mayotte and A.27 infections of Belgian military personnel returning from Mali pointed to a suspected origin in the African continent 41 , 42 .…”

Section: Discussionsupporting

confidence: 71%

Antibody escape and global spread of SARS-CoV-2 lineage A.27

et al. 2022

Self Cite

View full text Add to dashboard Cite

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

show abstract

“…However, the A. 23.1 viral lineage is one of a few lineage A viruses that, due to local circumstances, became abundant in Uganda (5), Rwanda (6) and South Sudan (7). A.23.1 evolved from the A.23 virus variant first identified in Uganda in July 2020 and is characterized by three spike mutations F157L, V367F and Q613H (5).…”

Section: Introductionmentioning

confidence: 99%

“…Compared with the lineage B.1 viruses that have successfully evolved into multiple variants of concern (VOC), including B.1.1.7 (Alpha) B.1.351 (Beta), B.1.1.28.1/P.1 (Gamma), B.1.617.2 (Delta), most of lineage A viruses remained at fairly lower frequency and were more prevalent at the beginning of the pandemic in Asia. However, the A.23.1 viral lineage is one of a few lineage A viruses that, due to local circumstances, became abundant in Uganda (5), Rwanda (6) and South Sudan (7). A.23.1 evolved from the A.23 virus variant first identified in Uganda in July 2020 and is characterized by three spike mutations F157L, V367F and Q613H (5).…”

Section: Introductionmentioning

confidence: 99%

Spike protein cleavage-activation mediated by the SARS-CoV-2 P681R mutation: a case-study from its first appearance in variant of interest (VOI) A.23.1 identified in Uganda

Lubinski

Frazier

Phan

et al. 2021

Preprint

View full text Add to dashboard Cite

The African continent is currently notable as a source of novel SARS-CoV-2 variants. The A.23 viral lineage, characterized by three spike mutations F157L, V367F and Q613H, was first identified in a Ugandan prison in July 2020, and then spilled into the general population adding additional spike mutations (R102I, L141F, E484K and P681R) to comprise lineage A.23.1 by September 2020—with this virus being designated a variant of interest (VOI) in Africa and with subsequent spread to 26 other countries. The P681R spike mutation of the A.23.1 VOI is of note as it increases the number of basic residues in the sub-optimal SARS-CoV-2 spike protein furin cleavage site; as such, this mutation may affect viral replication, transmissibility or pathogenic properties. Here, we performed assays using fluorogenic peptides mimicking the S1/S2 sequence from A.23.1 and observed significantly increased cleavability with furin, compared to sequences matching Wuhan-Hu1 S1/S2. We performed functional infectivity assays using pseudotyped MLV particles harboring SARS-CoV-2 spike proteins and observed an increase in transduction for A.23.1-pseudotyped particles in Vero-TMPRSS2 and Calu-3 cells, compared to Wuhan-Hu1, and a lowered infection in Vero E6 cells. However, these changes in infectivity were not reproduced in a P681R point mutant of Wuhan-Hu1 spike. Our findings suggest that while A.23.1 has increased furin-mediated cleavage linked to the P681R mutation—which may affect viral infection and transmissibility—this mutation needs to occur on the background of other spike protein changes to enable its functional consequences.

show abstract

Genomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity

Cited by 32 publications

References 35 publications

SARS-CoV-2 genomic surveillance in Rwanda: Introductions and local transmission of the B.1.617.2 (Delta) variant of concern

SARS-CoV-2 genomic surveillance in Rwanda: Introductions and local transmission of the B.1.617.2 (Delta) variant of concern

Antibody escape and global spread of SARS-CoV-2 lineage A.27

Spike protein cleavage-activation mediated by the SARS-CoV-2 P681R mutation: a case-study from its first appearance in variant of interest (VOI) A.23.1 identified in Uganda

Contact Info

Product

Resources

About