Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function

Jane E Sinclair; Courtney Vedelago; Feargal J Ryan; Meagan Carney; Meredith A Redd; Miriam A Lynn; Branka Grubor-Bauk; Yuanzhao Cao; Anjali K Henders; Keng Yih Chew; Deborah Gilroy; Kim Greaves; Larisa Labzin; Laura Ziser; Katharina Ronacher; Leanne M Wallace; Yiwen Zhang; Kyle Macauslane; Daniel J Ellis; Sudha Rao; Lucy Burr; Amanda Bain; Anjana Karawita; Benjamin L Schulz; Junrong Li; David J Lynn; Nathan Palpant; Alain Wuethrich; Matt Trau; Kirsty R Short

doi:10.1038/s41564-024-01838-z

Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function

Nat Microbiol. 2024 Dec;9(12):3135-3147. doi: 10.1038/s41564-024-01838-z. Epub 2024 Oct 30.

Authors

Jane E Sinclair^#¹, Courtney Vedelago^#², Feargal J Ryan^#^{3

4}, Meagan Carney⁵, Meredith A Redd⁶, Miriam A Lynn^{3

4}, Branka Grubor-Bauk⁷, Yuanzhao Cao⁶, Anjali K Henders⁶, Keng Yih Chew¹, Deborah Gilroy⁶, Kim Greaves^{8

9}, Larisa Labzin⁶, Laura Ziser⁶, Katharina Ronacher^{10

11}, Leanne M Wallace⁶, Yiwen Zhang², Kyle Macauslane^{1

10}, Daniel J Ellis^{1

10}, Sudha Rao¹², Lucy Burr^{13

14

15}, Amanda Bain¹², Anjana Karawita¹⁶, Benjamin L Schulz^{1

10}, Junrong Li^#², David J Lynn^#^{3

4}, Nathan Palpant^#⁶, Alain Wuethrich^#², Matt Trau^#^{1

2}, Kirsty R Short^#^{17

18

19}

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia.
² Centre for Personalised Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
³ Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁴ College of Medicine and Public Health and Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia.
⁵ School of Mathematics and Physics, University of Queensland, Brisbane, Queensland, Australia.
⁶ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
⁷ Viral Immunology Group, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
⁸ Sunshine Coast University Hospital, Queensland Health, Birtinya, Queensland, Australia.
⁹ National Centre for Epidemiology and Population Health, ANU College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Australia.
¹⁰ Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia.
¹¹ Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
¹² Gene Regulation and Translational Medicine Laboratory, Department of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹³ Mater Research Institute, The University of Queensland, South Brisbane, Queensland, Australia.
¹⁴ Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, Queensland, Australia.
¹⁵ Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
¹⁶ Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, Victoria, Australia.
¹⁷ School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia. [email protected].
¹⁸ Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland, Australia. [email protected].
¹⁹ Queensland Immunology Research Centre, The University of Queensland, St Lucia, Queensland, Australia. [email protected].

^# Contributed equally.

Abstract

An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups-recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals-revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation's role in the symptoms of PASC-CVS.

MeSH terms

Adult
Aged
COVID-19* / blood
COVID-19* / complications
COVID-19* / immunology
Cardiovascular Diseases / etiology
Cytokines* / blood
Female
Humans
Inflammation / blood
Male
Middle Aged
Myocytes, Cardiac* / metabolism
Myocytes, Cardiac* / virology
Post-Acute COVID-19 Syndrome
Proteomics / methods
SARS-CoV-2* / immunology

Substances

Cytokines

Grants and funding

2007919/Department of Health | National Health and Medical Research Council (NHMRC)