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[Preprint]. 2023 Jan 5:2023.01.04.23284195.

doi: 10.1101/2023.01.04.23284195.

The 2022 RSV surge was driven by multiple viral lineages

Gordon Adams^{1

2}, Gage K Moreno², Brittany A Petros^{2

3

4

5}, Rockib Uddin^{1

2}, Zoe Levine^{2

4

6}, Ben Kotzen^{1

2}, Katelyn Messer², Sabrina T Dobbins², Katherine C DeRuff², Christine Loreth², Taylor Brock-Fisher², Stephen F Schaffner^{2

7

8}, Sushma Chaluvadi², Sanjat Kanjilal⁸, Jeremy Luban^{2

9

10}, Al Ozonoff^{2

11}, Daniel Park², Sarah Turbett^{1

2}, Katherine J Siddle², Bronwyn L MacInnis², Pardis Sabeti^{2

7

8

12}, Jacob Lemieux^{1

2}

Affiliations

¹ Massachusetts General Hospital, Boston, MA, 02142.
² Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
³ Division of Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Harvard/Massachusetts Institute of Technology, MD-PhD Program, Boston, MA, USA.
⁵ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁶ Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
⁷ Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
⁸ Brigham and Women's Hospital, Boston, MA, 02115.
⁹ Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
¹⁰ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
¹¹ Harvard Medical School, Boston, MA, 02115, USA.
¹² Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.

PMID: 36656774
PMCID: PMC9844019
DOI: 10.1101/2023.01.04.23284195

The 2022 RSV surge was driven by multiple viral lineages

Gordon Adams et al. medRxiv. 2023.

[Preprint]. 2023 Jan 5:2023.01.04.23284195.

doi: 10.1101/2023.01.04.23284195.

Authors

Affiliations

¹ Massachusetts General Hospital, Boston, MA, 02142.
² Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
³ Division of Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Harvard/Massachusetts Institute of Technology, MD-PhD Program, Boston, MA, USA.
⁵ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁶ Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
⁷ Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
⁸ Brigham and Women's Hospital, Boston, MA, 02115.
⁹ Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
¹⁰ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
¹¹ Harvard Medical School, Boston, MA, 02115, USA.
¹² Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.

PMID: 36656774
PMCID: PMC9844019
DOI: 10.1101/2023.01.04.23284195

Update in

Viral Lineages in the 2022 RSV Surge in the United States.
Adams G, Moreno GK, Petros BA, Uddin R, Levine Z, Kotzen B, Messer KS, Dobbins ST, DeRuff KC, Loreth CM, Brock-Fisher T, Schaffner SF, Chaluvadi S, Kanjilal S, Luban J, Ozonoff A, Park DJ, Turbett SE, Siddle KJ, MacInnis BL, Sabeti PC, Lemieux JE. Adams G, et al. N Engl J Med. 2023 Apr 6;388(14):1335-1337. doi: 10.1056/NEJMc2216153. Epub 2023 Feb 22. N Engl J Med. 2023. PMID: 36812457 Free PMC article. No abstract available.

Abstract

The US experienced an early and severe respiratory syncytial virus (RSV) surge in autumn 2022. Despite the pressure this has put on hospitals and care centers, the factors promoting the surge in cases are unknown. To investigate whether viral characteristics contributed to the extent or severity of the surge, we sequenced 105 RSV-positive specimens from symptomatic patients diagnosed with RSV who presented to the Massachusetts General Hospital (MGH) and its outpatient practices in the Greater Boston Area. Genomic analysis of the resulting 77 genomes (54 with >80% coverage, and 23 with >5% coverage) demonstrated that the surge was driven by multiple lineages of RSV-A (91%; 70/77) and RSV-B (9%; 7/77). Phylogenetic analysis of all US RSV-A revealed 12 clades, 4 of which contained Massachusetts and Washington genomes. These clades individually had times to most recent common ancestor (tMRCA) between 2014 and 2017, and together had a tMRCA of 2009, suggesting that they emerged well before the COVID-19 pandemic. Similarly, the RSV-B genomes had a tMRCA between 2016 and 2019. We found that the RSV-A and RSV-B genomes in our sample did not differ statistically from the estimated clock rate of the larger phylogenetic tree (10.6 and 12.4 substitutions per year, respectively). In summary, the polyphyletic nature of viral genomes sequenced in the US during the autumn 2022 surge is inconsistent with the emergence of a single, highly transmissible causal RSV lineage.

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Conflict of interest statement

Conflicts of interest

Dr. Sabeti is a co-founder and consultant at Sherlock Biosciences Inc. and Delve Bio, and is a Board Member of Danaher Corporation; she holds equity in all three companies. She has several patents related to diagnostics, genome sequencing, and informatics, including two patents licensed to Sherlock Biosciences.

Figures

**Figure 1:. Epidemiological and genomic trends of the 2022 RSV surge.**
A) The number of PCR positive tests for RSV reported by the CDC in MA (blue, left axis) and the US (slate gray, right axis), along with the number of RSV positive tests conducted at MGH (red, left axis). The 105 sequenced samples were drawn from the gray Nov 2 - Nov 15 window. B) RSV hospitalization rates for CDC’s RSV-NET (shaded gray) and MGH RSV cases (red) for 2017 – 2022. (Pearson r = 0.82; p < 0.0001 via permutation).C) Maximum likelihood tree of all RSV-A genomes (N=1,267) (MA tips in blue, WA tips in green, others in gray). The tMRCA for 2022 RSV-A genomes was no later than 2008 (ML CI: 2008–04, 2008–09). In the box are zoomed in plots of the clades containing MA and WA with lines corresponding to clades on the tree. D) Maximum likelihood tree of all RSV-B genomes (N=944) (MA tips in orange, WA tips in yellow, others in gray). The tMCRCA for 2022 RSV-B genomes was approximately 2016 (ML CI: 2015–08, 2016–08). In the box are zoomed in plots of the clades containing MA and WA with lines corresponding to clades on the tree. Explosion plot of E) RSV-A and F) RSV-B lineages circulating in autumn 2022 with the inferred tMRCA (gray dots) and associated confidence intervals (shaded regions) for each lineage.

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References

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1. Goya S, Sereewit J, Pfalmer D, et al. Genomic characterization of respiratory syncytial virus 2022–2023 outbreak in Washington State, USA [Internet]. medRxiv. 2022;Available from: https://www.medrxiv.org/content/10.1101/2022.12.12.22283375v1 - DOI - PMC - PubMed
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This is a preprint.

The 2022 RSV surge was driven by multiple viral lineages

Affiliations

The 2022 RSV surge was driven by multiple viral lineages

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

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References

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