Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa
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Abstract
Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69–70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69–70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08–0.09) and 0.10 (95% CI: 0.09–0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.
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SciScore for 10.1101/2022.05.01.22274406: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources A GridION X5 or MinION sequencing run was initiated using MinKNOW software with the base-call setting switched off. MinIONsuggested: (MinION, RRID:SCR_017985)MinKNOWsuggested: NoneTRINITY was used for de novo assembly and the Iterative Refinement Meta-Assembler (IRMA) was used for genome assisted assembly as well as FastQC for quality checks. FastQCsuggested: (FastQC, RRID:SCR_014583)For Illumina assembly, the GATK HaploTypeCaller --min-pruning 0 argument was added to increase mutation calling sensitivity near sequencing gaps. GATKsuggested: (GATK, RRID:SCR_001876)bam files using Geneious … SciScore for 10.1101/2022.05.01.22274406: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources A GridION X5 or MinION sequencing run was initiated using MinKNOW software with the base-call setting switched off. MinIONsuggested: (MinION, RRID:SCR_017985)MinKNOWsuggested: NoneTRINITY was used for de novo assembly and the Iterative Refinement Meta-Assembler (IRMA) was used for genome assisted assembly as well as FastQC for quality checks. FastQCsuggested: (FastQC, RRID:SCR_014583)For Illumina assembly, the GATK HaploTypeCaller --min-pruning 0 argument was added to increase mutation calling sensitivity near sequencing gaps. GATKsuggested: (GATK, RRID:SCR_001876)bam files using Geneious v. Geneioussuggested: (Geneious, RRID:SCR_010519)Raw reads from the Illumina COVIDSeq protocol were assembled using the Exatype NGS SARS-CoV-2 pipeline v. SARS-CoV-2suggested: (Active Motif Cat# 91351, RRID:AB_2847848)To resolve this, the raw reads from the IonTorrent platform were assembled using the SARSCoV2 RECoVERY (Reconstruction of Coronavirus Genomes & Rapid Analysis) pipeline implemented in the Galaxy instance ARIES (https://aries.iss.it). Galaxysuggested: (Galaxy, RRID:SCR_006281)These consensus sequences were manually inspected and polished using Aliview v. Aliviewsuggested: (AliView, RRID:SCR_002780)The pipeline contains several Python scripts that manage the analysis workflow. Pythonsuggested: (IPython, RRID:SCR_001658)We extracted these clusters and constructed a preliminary maximum-likelihood tree with a subset of BA.2 sequences (n=52) in IQ-tree. IQ-treesuggested: (IQ-TREE, RRID:SCR_017254)We inspected this maximum-likelihood tree in TempEst v. TempEstsuggested: (TempEst, RRID:SCR_017304)We then estimated time-calibrated phylogenies using the Bayesian software package BEAST v.1.10.432. BEASTsuggested: (BEAST, RRID:SCR_010228)As described in ‘Phylogenetic analysis’, MCMC chains were run in duplicate for 10 million generations and sampled every 1,000 steps, with convergence assessed using Tracer v.1.7.1. Tracersuggested: (Tracer, RRID:SCR_019121)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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