SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing

ABSTRACT Co-infection with at least 2 strains of virus is the prerequisite for recombination, one of the means of genetic diversification. Little is known about the prevalence of these events in SARS-CoV-2, partly because it is difficult to detect them. We used long-read PacBio single-molecule real-...

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Main Authors: Pauline Trémeaux, Justine Latour, Noémie Ranger, Vénicia Ferrer, Agnès Harter, Romain Carcenac, Pauline Boyer, Sofia Demmou, Florence Nicot, Stéphanie Raymond, Jacques Izopet
Format: Article
Language:English
Published: American Society for Microbiology 2023-08-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.00493-23
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author Pauline Trémeaux
Justine Latour
Noémie Ranger
Vénicia Ferrer
Agnès Harter
Romain Carcenac
Pauline Boyer
Sofia Demmou
Florence Nicot
Stéphanie Raymond
Jacques Izopet
author_facet Pauline Trémeaux
Justine Latour
Noémie Ranger
Vénicia Ferrer
Agnès Harter
Romain Carcenac
Pauline Boyer
Sofia Demmou
Florence Nicot
Stéphanie Raymond
Jacques Izopet
author_sort Pauline Trémeaux
collection DOAJ
description ABSTRACT Co-infection with at least 2 strains of virus is the prerequisite for recombination, one of the means of genetic diversification. Little is known about the prevalence of these events in SARS-CoV-2, partly because it is difficult to detect them. We used long-read PacBio single-molecule real-time (SMRT) sequencing technology to sequence whole genomes and targeted regions for haplotyping. We identified 17 co-infections with SARS-CoV-2 strains belonging to different clades in 6829 samples sequenced between January and October, 2022 (prevalence 0.25%). There were 3 Delta/Omicron co-infections and 14 Omicron/Omicron co-infections (4 cases of 21K/21L, 1 case of 21L/22A, 2 cases of 21L/22B, 4 cases of 22A/22B, 2 cases of 22B/22C and 1 case of 22B/22E). Four of these patients (24%) also harbored recombinant minor haplotypes, including one with a recombinant virus that was selected in the viral quasispecies over the course of his chronic infection. While co-infections remain rare among SARS-CoV-2-infected individuals, long-read SMRT sequencing is a useful tool for detecting them as well as recombinant events, providing the basis for assessing their clinical impact, and a precise indicator of epidemic evolution. IMPORTANCE SARS-CoV-2 variants have been responsible for the successive waves of infection over the 3 years of pandemic. While co-infection followed by recombination is one driver of virus evolution, there have been few reports of co-infections, mainly between Delta and Omicron variants or between the first 2 Omicron variants 21K_BA.1 and 21L_BA.2. The 17 co-infections we detected during 2022 included cases with the recent clades of Omicron 22A, 22B, 22C, and 22E; 24% harbored recombinant variants. This study shows that long-read SMRT sequencing is well suited to SARS-CoV-2 genomic surveillance.
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spelling doaj.art-e7b903e0fb68408fa8347215bd3689d52023-08-17T13:04:15ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.00493-23SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time SequencingPauline Trémeaux0Justine Latour1Noémie Ranger2Vénicia Ferrer3Agnès Harter4Romain Carcenac5Pauline Boyer6Sofia Demmou7Florence Nicot8Stéphanie Raymond9Jacques Izopet10Virology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceVirology Laboratory, Toulouse University Hospital, Toulouse, FranceABSTRACT Co-infection with at least 2 strains of virus is the prerequisite for recombination, one of the means of genetic diversification. Little is known about the prevalence of these events in SARS-CoV-2, partly because it is difficult to detect them. We used long-read PacBio single-molecule real-time (SMRT) sequencing technology to sequence whole genomes and targeted regions for haplotyping. We identified 17 co-infections with SARS-CoV-2 strains belonging to different clades in 6829 samples sequenced between January and October, 2022 (prevalence 0.25%). There were 3 Delta/Omicron co-infections and 14 Omicron/Omicron co-infections (4 cases of 21K/21L, 1 case of 21L/22A, 2 cases of 21L/22B, 4 cases of 22A/22B, 2 cases of 22B/22C and 1 case of 22B/22E). Four of these patients (24%) also harbored recombinant minor haplotypes, including one with a recombinant virus that was selected in the viral quasispecies over the course of his chronic infection. While co-infections remain rare among SARS-CoV-2-infected individuals, long-read SMRT sequencing is a useful tool for detecting them as well as recombinant events, providing the basis for assessing their clinical impact, and a precise indicator of epidemic evolution. IMPORTANCE SARS-CoV-2 variants have been responsible for the successive waves of infection over the 3 years of pandemic. While co-infection followed by recombination is one driver of virus evolution, there have been few reports of co-infections, mainly between Delta and Omicron variants or between the first 2 Omicron variants 21K_BA.1 and 21L_BA.2. The 17 co-infections we detected during 2022 included cases with the recent clades of Omicron 22A, 22B, 22C, and 22E; 24% harbored recombinant variants. This study shows that long-read SMRT sequencing is well suited to SARS-CoV-2 genomic surveillance.https://journals.asm.org/doi/10.1128/spectrum.00493-23SARS-CoV-2co-infectiongenomic surveillancelong-read sequencingquasispeciesrecombination
spellingShingle Pauline Trémeaux
Justine Latour
Noémie Ranger
Vénicia Ferrer
Agnès Harter
Romain Carcenac
Pauline Boyer
Sofia Demmou
Florence Nicot
Stéphanie Raymond
Jacques Izopet
SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing
Microbiology Spectrum
SARS-CoV-2
co-infection
genomic surveillance
long-read sequencing
quasispecies
recombination
title SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing
title_full SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing
title_fullStr SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing
title_full_unstemmed SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing
title_short SARS-CoV-2 Co-Infections and Recombinations Identified by Long-Read Single-Molecule Real-Time Sequencing
title_sort sars cov 2 co infections and recombinations identified by long read single molecule real time sequencing
topic SARS-CoV-2
co-infection
genomic surveillance
long-read sequencing
quasispecies
recombination
url https://journals.asm.org/doi/10.1128/spectrum.00493-23
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