Rapid dynamic changes of FL.2 variant: A case report of COVID-19 breakthrough infection.

Wonderful T Choga, Gobuiwang Khilly Kurusa Gasenna, James Emmanuel San, Tidimalo Ookame, Irene Gobe, Mohammed Chand, Badisa Phafane, Kedumetse Seru, Patience Matshosi, Boitumelo Zuze, Nokuthula Ndlovu, Teko Matsuru, Dorcas Maruapula, Ontlametse T Bareng, Kutlo Macheke, Lesego Kuate-Lere, Labapotswe Tlale, Onalethata Lesetedi, Modiri Tau, Mpaphi B Mbulawa, Pamela Smith-Lawrence, Mogomotsi Matshaba, Roger Shapiro, Joseph Makhema, Darren P Martin, Tulio de Oliveira, Richard J Lessells, Shahin Lockman, Simani Gaseitsiwe, Sikhulile Moyo
Author Information
  1. Wonderful T Choga: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; School of Allied Health Sciences, Faculty of Health Sciences, Gaborone, Botswana; Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.
  2. Gobuiwang Khilly Kurusa Gasenna: Lenmed-Bokamoso Private Hospital, Gaborone, Botswana.
  3. James Emmanuel San: Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory. Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
  4. Tidimalo Ookame: Ministry of Health and Wellness, Gaborone, Botswana.
  5. Irene Gobe: School of Allied Health Sciences, Faculty of Health Sciences, Gaborone, Botswana.
  6. Mohammed Chand: Diagnofirm Medical Laboratories, Plot 12583, Nyerere Drive MiddleStar, Gaborone, Botswana.
  7. Badisa Phafane: Diagnofirm Medical Laboratories, Plot 12583, Nyerere Drive MiddleStar, Gaborone, Botswana.
  8. Kedumetse Seru: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  9. Patience Matshosi: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  10. Boitumelo Zuze: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  11. Nokuthula Ndlovu: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  12. Teko Matsuru: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  13. Dorcas Maruapula: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  14. Ontlametse T Bareng: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; School of Allied Health Sciences, Faculty of Health Sciences, Gaborone, Botswana.
  15. Kutlo Macheke: National Health laboratory, Gaborone, Botswana.
  16. Lesego Kuate-Lere: National Health laboratory, Gaborone, Botswana.
  17. Labapotswe Tlale: National Health laboratory, Gaborone, Botswana.
  18. Onalethata Lesetedi: National Health laboratory, Gaborone, Botswana.
  19. Modiri Tau: National Health laboratory, Gaborone, Botswana.
  20. Mpaphi B Mbulawa: National Health laboratory, Gaborone, Botswana.
  21. Pamela Smith-Lawrence: National Health laboratory, Gaborone, Botswana.
  22. Mogomotsi Matshaba: Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone, Botswana; Department of Pediatrics, Baylor College of Medicine, Houston, USA.
  23. Roger Shapiro: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, USA.
  24. Joseph Makhema: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
  25. Darren P Martin: Institute of Infectious Diseases and Molecular Medicine, Division of Computational Biology, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa.
  26. Tulio de Oliveira: Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory. Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Department of Global Health, University of Washington, Seattle, USA.
  27. Richard J Lessells: Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory. Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
  28. Shahin Lockman: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, USA.
  29. Simani Gaseitsiwe: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, USA.
  30. Sikhulile Moyo: Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, USA; School of Health Systems and Public Health, University of Pretoria, South Africa; Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: smoyo@bhp.org.bw.

Abstract

We investigated intra-host genetic evolution using two SARS-CoV-2 isolates from a fully vaccinated (primary schedule x2 doses of AstraZeneca plus a booster of Pfizer), >70-year-old woman with a history of lymphoma and hypertension who presented a SARS-CoV-2 infection for 3 weeks prior to death due to COVID-19. Two full genome sequences were determined from samples taken 13 days apart with both belonging to Pango lineage FL.2: the first detection of this Omicron sub-variant in Botswana. FL.2 is a sub-lineage of XBB.1.9.1. The repertoire of mutations and minority variants in the Spike protein differed between the two time points. Notably, we also observed deletions within the ORF1a and Membrane proteins; both regions are associated with high T-cell epitope density. The internal milieu of immune-suppressed individuals may accelerate SARS-CoV-2 evolution; hence, close monitoring is warranted.

Keywords

References

  1. Genomics Proteomics Bioinformatics. 2022 Feb;20(1):60-69 [PMID: 35033679]
  2. Signal Transduct Target Ther. 2022 Apr 26;7(1):138 [PMID: 35474215]
  3. Biol Methods Protoc. 2020 Jul 18;5(1):bpaa014 [PMID: 33029559]
  4. Nat Methods. 2023 Apr;20(4):512-522 [PMID: 36823332]
  5. Virus Evol. 2022 Aug 26;8(2):veac080 [PMID: 36533153]
  6. Microbiol Spectr. 2022 Apr 27;10(2):e0273221 [PMID: 35352942]
  7. Bioinformatics. 2019 Mar 1;35(5):871-873 [PMID: 30124794]
  8. PLoS One. 2023 Jan 26;18(1):e0278898 [PMID: 36701309]
  9. JCO Glob Oncol. 2021 Aug;7:1286-1305 [PMID: 34406802]
  10. Clin Infect Pract. 2022 Nov;16:100210 [PMID: 36405361]
  11. Int J Infect Dis. 2022 Jan;114:178-182 [PMID: 34757008]
  12. N Engl J Med. 2020 Dec 3;383(23):2291-2293 [PMID: 33176080]
  13. Clin Infect Dis. 2023 Feb 8;76(3):e522-e525 [PMID: 35793242]
  14. Nat Rev Microbiol. 2023 Mar;21(3):147-161 [PMID: 36460930]

Grants

  1. K43 TW012350/FIC NIH HHS
  2. K24 AI131928/NIAID NIH HHS
  3. D43 TW009610/FIC NIH HHS
  4. K24 AI131924/NIAID NIH HHS
  5. /Wellcome Trust

MeSH Term

Female
Humans
Aged
COVID-19
SARS-CoV-2
Botswana
Breakthrough Infections

Word Cloud

Created with Highcharts 10.0.0SARS-CoV-2FL2evolutiontwoinfectionCOVID-19Botswana1investigatedintra-hostgeneticusingisolatesfullyvaccinatedprimaryschedulex2dosesAstraZenecaplusboosterPfizer>70-year-oldwomanhistorylymphomahypertensionpresented3weekspriordeathdueTwofullgenomesequencesdeterminedsamplestaken13daysapartbelongingPangolineage2:firstdetectionOmicronsub-variantsub-lineageXBB9repertoiremutationsminorityvariantsSpikeproteindifferedtimepointsNotablyalsoobserveddeletionswithinORF1aMembraneproteinsregionsassociatedhighT-cellepitopedensityinternalmilieuimmune-suppressedindividualsmayacceleratehenceclosemonitoringwarrantedRapiddynamicchangesvariant:casereportbreakthroughEvolutionImmunocompromised

Similar Articles

Cited By