Analysis of SARS-CoV-2 Recombinant Lineages XBC and XBC.1 in the Philippines and Evidence for Delta-Omicron Co-infection as a Potential Origin

Pangilinan, Elcid Aaron R; Egana, John Michael C.; Mantaring, Renato Jacinto Q.; Telles, Alyssa Joyce E; Tablizo, Francis A.; Lapid, Carlo M.; Yangzon, Maria Sofia L.; Endozo, Joshua Jose S; Padilla, Karol Sophia Agape R.; Nipales, Jarvin E.; Carandang, Lindsay Clare D.L.; Enriquez, Zipporah Mariebelle R.; Barot, Tricia Anne U.; Manlimos, Romano A.; Mangonon, Kelly Nicole P.; Plantig, Ma. Exanil L.; Araiza, Shiela Mae M.; Llames, Jo-Hannah S.; Punayan, Kris P.; Serrano, Rachelle P.; Drueco, Anne M.; Lagnas, Honeylett T.; Bistayan, Philip A.; Aguilar, Aristio C.; Apo, Joie G. Charisse; Austria, Yvonne Valerie D.; Bustamante, Niña Francesca M.; Caelian, Alyssa Jamila R.; Fernandez, Rudy E.; Galilea, Xerxanne A.; Gamboa, Marielle M.; Gervacio, Clarence Jane A.; Mollejon, Zyrel V.; Pineda, Joshua Paul N.; Rico, Kristel B.; Yap, Jan Michael C.; Abad, Ma. Celeste S.; Maralit, Benedict A.; Ayes, Marc Edsel C.; Paz, Eva Maria Cutiongco‐de la; Saloma, Cynthia P.

doi:10.1101/2023.04.12.534029

“…A study by Jackson et al (2021) described multiple independent recombination events involving UK lineages, highlighting the significance of co-infections during periods of high viral prevalence in driving the emergence of new recombinant lineages. In the Philippines, a recent study investigating the emergence of a recombinant lineage XBC described one sample with an allele fraction pattern and an abundance of within-host mutations consistent with an active co-infection case (Pangilinan et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

“…To date, there have been no officially documented cases of co-infection in the Philippines. However, there is speculation that cases of co-infection in the Philippines have been occurring as early as March 2022 (Pangilinan et al, 2023). Here, we investigate two samples flagged as possible Delta and Omicron co-infections, due to the inconsistencies in lineage assignment and the presence of unusual private mutations, by routine genomic surveillance efforts at the Research Institute for Tropical Medicine (RITM).…”

Section: Introductionmentioning

confidence: 99%

Detecting Delta and Omicron co-infection cases in the Philippines from SARS-CoV-2 genomic surveillance

Realingo,

Polotan,

Abulencia

et al. 2024

Preprint

0

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Co-infection with two SARS-CoV-2 variants is rarely detected, but may have clinical implications and is hypothesized to be a precursor to SARS-CoV-2 variant recombination. It is therefore important to rapidly identify co-infection cases. Here, we report two cases of co-infection detected during routine genomic surveillance. Both samples were initially suspected to have been cross-contaminated due to the unusual number of private mutations identified by Nextclade and positions flagged for nucleotide mixtures by Bammix. To rule out cross-contamination, we decontaminated the workspaces and resequenced the samples. However, the anomalies remained and the samples were therefore investigated for co-infection. To validate this hypothesis, we created a bioinformatics pipeline to determine the lineages present in the samples, performedde novoassembly, and investigated the alternative allele fraction of mutations mapping to both variants. Freyja was used and showed an estimated lineage abundance of 49.81% and 48.09% for Delta and Omicron, respectively, in the first sample. For the second sample, Delta had 82.76% abundance and Omicron had 4.99% abundance, with the presence of 12.24% abundance for other variants. Our findings support that the first sample is a case of co-infection of Delta and Omicron variants while the second sample is a cryptic co-infection of both variants, potentially undergoing recombination events. This study highlights the importance of developing a more stringent bioinformatics workflow to identify co-infection cases in genomic surveillance.

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“…Recently, mainly recombinant lineages are circulating around the globe (Omicron XBB-variants) and also several recombinant lineages have been classi ed by pangolin [12][13][14] . For recombination to occur, an individual has to be infected with two different lineages 14,15 which leads to the hypothesis that co-infection should take place frequently. This can happen in immunocompromised individuals, who have been described to be prolongedly infected with SARS-CoV-2 16 , but also in the general population [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples

Medgyes-Horváth

¹

,

Pipek

²

,

Stéger

³

et al. 2023

Preprint

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Systematic monitoring of SARS-CoV-2 co-infections between different lineages and assessing the risk of intra-host recombinant emergence are crucial for forecasting viral evolution. Here we present a comprehensive analysis of more than 2 million SARS-CoV-2 raw read datasets submitted to the European COVID-19 Data Portal to identify co-infections and intra-host recombination. Co-infection was observed in 0.35% of the investigated cases. Two independent procedures were implemented to detect intra-host recombination. We show that sensitivity is predominantly determined by the density of lineage-defining mutations along the genome, thus we used an expanded list of mutually exclusive defining mutations of specific variant combinations to increase statistical power. We call attention to multiple challenges rendering recombinant detection difficult and provide guidelines for the reduction of false positives arising from chimeric sequences produced during PCR amplification. Additionally, we identify three recombination hotspots of Delta – Omicron BA.1 intra-host recombinants.

show abstract

Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples

Pipek,

Medgyes-Horváth,

Stéger

et al. 2024

View full text Add to dashboard Cite

Systematic monitoring of SARS-CoV-2 co-infections between different lineages and assessing the risk of intra-host recombinant emergence are crucial for forecasting viral evolution. Here we present a comprehensive analysis of more than 2 million SARS-CoV-2 raw read datasets submitted to the European COVID-19 Data Portal to identify co-infections and intra-host recombination. Co-infection was observed in 0.35% of the investigated cases. Two independent procedures were implemented to detect intra-host recombination. We show that sensitivity is predominantly determined by the density of lineage-defining mutations along the genome, thus we used an expanded list of mutually exclusive defining mutations of specific variant combinations to increase statistical power. We call attention to multiple challenges rendering recombinant detection difficult and provide guidelines for the reduction of false positives arising from chimeric sequences produced during PCR amplification. Additionally, we identify three recombination hotspots of Delta – Omicron BA.1 intra-host recombinants.

show abstract

Analysis of SARS-CoV-2 Recombinant Lineages XBC and XBC.1 in the Philippines and Evidence for Delta-Omicron Co-infection as a Potential Origin

Cited by 5 publications

References 21 publications

Detecting Delta and Omicron co-infection cases in the Philippines from SARS-CoV-2 genomic surveillance

Detecting Delta and Omicron co-infection cases in the Philippines from SARS-CoV-2 genomic surveillance

Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples

Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples

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