SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing
Abstract Background Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-10-01
|
| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-022-01896-x |
| _version_ | 1811249931964383232 |
|---|---|
| author | Steinar Mannsverk Julia Bergholm Navaneethan Palanisamy Patrik Ellström René Kaden Johan Lindh Johan Lennerstrand |
| author_facet | Steinar Mannsverk Julia Bergholm Navaneethan Palanisamy Patrik Ellström René Kaden Johan Lindh Johan Lennerstrand |
| author_sort | Steinar Mannsverk |
| collection | DOAJ |
| description | Abstract Background Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health measures. Methods We utilized the ARTIC Network SARS-CoV-2 tiled amplicon approach and Nanopore sequencing to sequence 4,674 COVID-19 positive patient samples from Uppsala County, Sweden, between week 15 and 52 in 2021. Using this data, we mapped the circulating variants of concern (VOC) in the county over time and analysed the Spike (S) protein mutational dynamics in the Delta variant throughout 2021. Results The distribution of the SARS-CoV-2 VOC matched the national VOC distribution in Sweden, in 2021. In the S protein of the Delta variant, we detected mutations attributable to variants under monitoring and variants of interest (e.g., E484Q, Q613H, Q677H, A222V and Y145H) and future VOC (e.g., T95I and Y144 deletion, which are signature mutations in the Omicron variant). We also frequently detected some less well-described S protein mutations in our Delta sequences, that might play a role in shaping future emerging variants. These include A262S, Q675K, I850L, Q1201H, V1228L and M1237I. Lastly, we observed that some of the Delta variant’s signature mutations were underrepresented in our study due to artifacts of the used bioinformatics tools, approach and sequencing method. We therefore discuss some pitfalls and considerations when sequencing SARS-CoV-2 genomes. Conclusion Our results suggest that genomic surveillance in a small, representative cohort can be used to make predictions about the circulating variants nationally. Moreover, we show that detection of transient mutations in currently circulating variants can give valuable clues to signature mutations of future VOC. Here we suggest six such mutations, that we detected frequently in the Delta variant during 2021. Lastly, we report multiple systematic errors that occurred when following the ARTIC Network SARS-CoV-2 tiled amplicon approach using the V3 primers and Nanopore sequencing, which led to the masking of some of the important signature mutations in the Delta sequences. |
| first_indexed | 2024-04-12T15:56:07Z |
| format | Article |
| id | doaj.art-77df97fe367543a98c38a76ebd433877 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-04-12T15:56:07Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-77df97fe367543a98c38a76ebd4338772022-12-22T03:26:22ZengBMCVirology Journal1743-422X2022-10-0119111210.1186/s12985-022-01896-xSARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencingSteinar Mannsverk0Julia Bergholm1Navaneethan Palanisamy2Patrik Ellström3René Kaden4Johan Lindh5Johan Lennerstrand6Department of Medical Sciences, Section for Clinical Microbiology and Hospital Hygiene, Uppsala UniversityDepartment of Medical Sciences, Section for Clinical Microbiology and Hospital Hygiene, Uppsala UniversityChester Medical School, University of ChesterDepartment of Medical Sciences, Section for Clinical Microbiology and Hospital Hygiene, Uppsala UniversityDepartment of Medical Sciences, Section for Clinical Microbiology and Hospital Hygiene, Uppsala UniversityDepartment of Medical Sciences, Section for Clinical Microbiology and Hospital Hygiene, Uppsala UniversityDepartment of Medical Sciences, Section for Clinical Microbiology and Hospital Hygiene, Uppsala UniversityAbstract Background Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health measures. Methods We utilized the ARTIC Network SARS-CoV-2 tiled amplicon approach and Nanopore sequencing to sequence 4,674 COVID-19 positive patient samples from Uppsala County, Sweden, between week 15 and 52 in 2021. Using this data, we mapped the circulating variants of concern (VOC) in the county over time and analysed the Spike (S) protein mutational dynamics in the Delta variant throughout 2021. Results The distribution of the SARS-CoV-2 VOC matched the national VOC distribution in Sweden, in 2021. In the S protein of the Delta variant, we detected mutations attributable to variants under monitoring and variants of interest (e.g., E484Q, Q613H, Q677H, A222V and Y145H) and future VOC (e.g., T95I and Y144 deletion, which are signature mutations in the Omicron variant). We also frequently detected some less well-described S protein mutations in our Delta sequences, that might play a role in shaping future emerging variants. These include A262S, Q675K, I850L, Q1201H, V1228L and M1237I. Lastly, we observed that some of the Delta variant’s signature mutations were underrepresented in our study due to artifacts of the used bioinformatics tools, approach and sequencing method. We therefore discuss some pitfalls and considerations when sequencing SARS-CoV-2 genomes. Conclusion Our results suggest that genomic surveillance in a small, representative cohort can be used to make predictions about the circulating variants nationally. Moreover, we show that detection of transient mutations in currently circulating variants can give valuable clues to signature mutations of future VOC. Here we suggest six such mutations, that we detected frequently in the Delta variant during 2021. Lastly, we report multiple systematic errors that occurred when following the ARTIC Network SARS-CoV-2 tiled amplicon approach using the V3 primers and Nanopore sequencing, which led to the masking of some of the important signature mutations in the Delta sequences.https://doi.org/10.1186/s12985-022-01896-xSARS-CoV-2SpikeMutationsVariants of concernDelta variantARTIC network |
| spellingShingle | Steinar Mannsverk Julia Bergholm Navaneethan Palanisamy Patrik Ellström René Kaden Johan Lindh Johan Lennerstrand SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing Virology Journal SARS-CoV-2 Spike Mutations Variants of concern Delta variant ARTIC network |
| title | SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing |
| title_full | SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing |
| title_fullStr | SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing |
| title_full_unstemmed | SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing |
| title_short | SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing |
| title_sort | sars cov 2 variants of concern and spike protein mutational dynamics in a swedish cohort during 2021 studied by nanopore sequencing |
| topic | SARS-CoV-2 Spike Mutations Variants of concern Delta variant ARTIC network |
| url | https://doi.org/10.1186/s12985-022-01896-x |
| work_keys_str_mv | AT steinarmannsverk sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing AT juliabergholm sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing AT navaneethanpalanisamy sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing AT patrikellstrom sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing AT renekaden sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing AT johanlindh sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing AT johanlennerstrand sarscov2variantsofconcernandspikeproteinmutationaldynamicsinaswedishcohortduring2021studiedbynanoporesequencing |