Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology
Abstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55938-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544439873404928 |
|---|---|
| author | Arthur Wickenhagen Meaghan Flagg Julia R. Port Claude Kwe Yinda Kerry Goldin Shane Gallogly Jonathan E. Schulz Tessa Lutterman Brandi N. Williamson Franziska Kaiser Reshma K. Mukesh Sarah van Tol Brian Smith Neeltje van Doremalen Colin A. Russell Emmie de Wit Vincent J. Munster |
| author_facet | Arthur Wickenhagen Meaghan Flagg Julia R. Port Claude Kwe Yinda Kerry Goldin Shane Gallogly Jonathan E. Schulz Tessa Lutterman Brandi N. Williamson Franziska Kaiser Reshma K. Mukesh Sarah van Tol Brian Smith Neeltje van Doremalen Colin A. Russell Emmie de Wit Vincent J. Munster |
| author_sort | Arthur Wickenhagen |
| collection | DOAJ |
| description | Abstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT. |
| format | Article |
| id | doaj-art-729671bfdc7d4bed866ee588a980cad8 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-729671bfdc7d4bed866ee588a980cad82025-01-12T12:31:44ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-55938-3Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathologyArthur Wickenhagen0Meaghan Flagg1Julia R. Port2Claude Kwe Yinda3Kerry Goldin4Shane Gallogly5Jonathan E. Schulz6Tessa Lutterman7Brandi N. Williamson8Franziska Kaiser9Reshma K. Mukesh10Sarah van Tol11Brian Smith12Neeltje van Doremalen13Colin A. Russell14Emmie de Wit15Vincent J. Munster16Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthRocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Center, University of AmsterdamLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.https://doi.org/10.1038/s41467-025-55938-3 |
| spellingShingle | Arthur Wickenhagen Meaghan Flagg Julia R. Port Claude Kwe Yinda Kerry Goldin Shane Gallogly Jonathan E. Schulz Tessa Lutterman Brandi N. Williamson Franziska Kaiser Reshma K. Mukesh Sarah van Tol Brian Smith Neeltje van Doremalen Colin A. Russell Emmie de Wit Vincent J. Munster Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology Nature Communications |
| title | Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology |
| title_full | Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology |
| title_fullStr | Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology |
| title_full_unstemmed | Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology |
| title_short | Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology |
| title_sort | evolution of omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology |
| url | https://doi.org/10.1038/s41467-025-55938-3 |
| work_keys_str_mv | AT arthurwickenhagen evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT meaghanflagg evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT juliarport evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT claudekweyinda evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT kerrygoldin evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT shanegallogly evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT jonathaneschulz evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT tessalutterman evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT brandinwilliamson evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT franziskakaiser evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT reshmakmukesh evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT sarahvantol evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT briansmith evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT neeltjevandoremalen evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT colinarussell evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT emmiedewit evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology AT vincentjmunster evolutionofomicronlineagetowardsincreasedfitnessintheupperrespiratorytractintheabsenceofseverelungpathology |