A persistent neutrophil-associated immune signature characterizes post–COVID-19 pulmonary sequelae-Reference-Cited by-同舟云学术

A persistent neutrophil-associated immune signature characterizes post–COVID-19 pulmonary sequelae

Published:2022-11-16 Issue:671 Volume:14 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

George Peter M.¹²^ORCID,Reed Anna¹²^ORCID,Desai Sujal R.¹²,Devaraj Anand¹²,Faiez Tasnim Shahridan³,Laverty Sarah⁴,Kanwal Amama⁵^ORCID,Esneau Camille⁵^ORCID,Liu Michael K.C.⁴^ORCID,Kamal Faisal⁶,Man William D.-C.¹²⁷,Kaul Sundeep¹^ORCID,Singh Suveer¹^ORCID,Lamb Georgia¹^ORCID,Faizi Fatima K.³^ORCID,Schuliga Michael⁵^ORCID,Read Jane⁵^ORCID,Burgoyne Thomas¹⁸^ORCID,Pinto Andreia L.¹^ORCID,Micallef Jake⁹,Bauwens Emilie⁹,Candiracci Julie⁹,Bougoussa Mhammed⁹^ORCID,Herzog Marielle⁹^ORCID,Raman Lavanya²,Ahmetaj-Shala Blerina²,Turville Stuart¹⁰^ORCID,Aggarwal Anupriya¹⁰,Farne Hugo A.²¹⁰¹¹^ORCID,Dalla Pria Alessia⁴¹²,Aswani Andrew D.¹³¹⁴,Patella Francesca¹⁵,Borek Weronika E.¹⁵^ORCID,Mitchell Jane A.²^ORCID,Bartlett Nathan W.⁵^ORCID,Dokal Arran¹⁵^ORCID,Xu Xiao-Ning⁴,Kelleher Peter¹¹²¹⁶¹⁷^ORCID,Shah Anand¹¹⁸^ORCID,Singanayagam Aran³^ORCID

Affiliation:

1. Royal Brompton and Harefield Clinical Group, Guy’s and St. Thomas’ NHS Foundation Trust, London SW3 6NR, UK.

2. National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.

3. Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Imperial College London, London SW7 2DD, UK.

4. Section of Virology, Department of Infectious Disease, Imperial College London, London W2 1PG, UK.

5. Faculty of Health, Medicine and Wellbeing, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.

6. Royal Berkshire Hospital, Reading RG1 5AN, UK.

7. Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK.

8. UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK.

9. Belgian Volition SRL, 22 rue Phocas Lejeune, Parc Scientifique Créalys, Isnes 5032, Belgium.

10. The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.

11. Chest and Allergy Department, St Mary’s Hospital, Imperial College NHS Trust, London W2 1NY, UK.

12. Department of HIV and Genitourinary Medicine, Chelsea and Westminster NHS Foundation Trust, London SW10 9NH, UK.

13. Department of Intensive Care Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH, UK.

14. Santersus AG, Buckhauserstrasse 34, Zurich 8048, Switzerland.

15. Kinomica Ltd, Biohub, Alderley Park, Alderley Edge, Macclesfield, Cheshire SK10 4TG, UK.

16. Immunology of Infection Section, Department of Infectious Disease, Imperial College London, London W2 1PG, UK.

17. Department of Infection and Immunity Sciences, North West London Pathology NHS Trust, London W2 1NY, UK.

18. MRC Centre of Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.

Abstract

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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