Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2

Jaclyn M L Walsh; Vincent N Miao; Anna H Owings; Ying Tang; Joshua D Bromley; Samuel W Kazer; Kyle Kimler; Chelsea Asare; Carly G K Ziegler; Samira Ibrahim; Tasneem Jivanjee; Micayla George; Andrew W Navia; Riley S Drake; Adam Parker; Benjamin C Billingsley; Paul Dotherow; Spurthi Tarugu; Sai K Kota; Hannah Laird; T Grant Wichman; Yesenia T Davis; Neha S Dhaliwal; Yilianys Pride; Yanglin Guo; Michal Senitko; Jessie Harvey; John T Bates; Gill Diamond; Michael R Garrett; D Ashley Robinson; I J Frame; Jonathan J Lyons; Tanya O Robinson; Alex K Shalek; Bruce H Horwitz; Sarah C Glover; Jose Ordovas-Montanes

doi:10.1038/s41590-024-02052-z

Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2

Nat Immunol. 2025 Jan 20. doi: 10.1038/s41590-024-02052-z. Online ahead of print.

Authors

Jaclyn M L Walsh^#^{1

2

3

4}, Vincent N Miao^#^{4

5

6

7}, Anna H Owings^#^{8

9}, Ying Tang^#¹, Joshua D Bromley^#^{4

5

6

10}, Samuel W Kazer^{1

2

4

5}, Kyle Kimler^{1

4

5

6

11

12}, Chelsea Asare^{1

4}, Carly G K Ziegler^{4

5

6

7

13}, Samira Ibrahim^{4

5

6}, Tasneem Jivanjee^{4

5

6}, Micayla George^{4

5

6}, Andrew W Navia^{4

5

6

11}, Riley S Drake^{4

5

6}, Adam Parker⁹, Benjamin C Billingsley⁸, Paul Dotherow⁹, Spurthi Tarugu⁸, Sai K Kota⁹, Hannah Laird^{8

9}, T Grant Wichman⁸, Yesenia T Davis⁹, Neha S Dhaliwal^{8

9}, Yilianys Pride⁹, Yanglin Guo¹⁴, Michal Senitko¹⁴, Jessie Harvey⁸, John T Bates¹⁵, Gill Diamond¹⁶, Michael R Garrett^{8

15}, D Ashley Robinson¹⁵, I J Frame¹⁷, Jonathan J Lyons^{18

19}, Tanya O Robinson⁹, Alex K Shalek^{3

4

5

6

7

11

13

20}, Bruce H Horwitz^{1

3

21}, Sarah C Glover^{9

15

22}, Jose Ordovas-Montanes^{23

24

25

26

27}

Affiliations

¹ Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
² Department of Immunology, Harvard Medical School, Boston, MA, USA.
³ Program in Immunology, Harvard Medical School, Boston, MA, USA.
⁴ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Program in Health Sciences and Technology, Harvard Medical School and MIT, Boston, MA, USA.
⁸ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁹ Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁰ Graduate Program in Microbiology, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹¹ Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹² Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
¹³ Harvard Graduate Program in Biophysics, Cambridge, MA, USA.
¹⁴ Division of Pulmonary, Critical Care and Sleep Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁵ Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁶ Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, USA.
¹⁷ Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁸ Division of Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
¹⁹ Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.
²⁰ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
²¹ Division of Emergency Medicine, Boston Children's Hospital, Boston, MA, USA.
²² Department of Medicine, Section of Gastroenterology and Hepatology, Tulane University, New Orleans, LA, USA.
²³ Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. [email protected].
²⁴ Program in Immunology, Harvard Medical School, Boston, MA, USA. [email protected].
²⁵ Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
²⁶ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. [email protected].
²⁷ Harvard Stem Cell Institute, Cambridge, MA, USA. [email protected].

^# Contributed equally.

PMID: 39833605
DOI: 10.1038/s41590-024-02052-z

Abstract

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2^hi cell subsets, which was distinct from that of ancestral cases. Delta-infected samples had a marked increase in viral RNA, and a subset of PER2⁺EGR1⁺GDF15⁺ epithelial cells was enriched in SARS-CoV-2 RNA⁺ cells in all variants. Prior vaccination was associated with increased frequency and activation of nasal macrophages. Expression of interferon-stimulated genes negatively correlated with coronavirus disease 2019 (COVID-19) severity in patients with ancestral and Delta but not Omicron variants. Our study defines nasal cell responses and signatures of disease severity across SARS-CoV-2 variants and vaccination.

Abstract

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