Oral Presentation 12th Australasian Virology Society Meeting 2024

Cardiovascular symptoms of PASC are associated with trace-level circulatory cytokines that affect the function of primary human cardiomyocytes (#40)

Jane E Sinclair 1 , Courtney Vedelago 2 , Feargal J Ryan 3 , Meagan Carney 4 , Meredith Redd 5 , Miriam A Lynn 3 , Branka Grubor-Bauk 6 , Yuanzhao Cao 5 , Anjali K Henders 5 , Keng Yih Chew 1 , Deborah Gilroy 5 , Kim Greaves 7 8 , Larisa Labzin 5 , Laura Ziser 5 , Katharina Ronacher 9 10 , Leanne M Wallace 5 , Yiwen Zhang 2 , Kyle Macauslane 1 9 , Daniel J Ellis 1 9 , Sudha Rao 11 , Lucy Burr 10 12 13 , Amanda Bain 11 , Anjana Karawita 14 , Benjamin L Schulz 15 , Junrong Li 2 , David J Lynn 3 , Nathan Palpant 5 , Alain Wuethrich 2 , Matt Trau 2 , Kirsty R Short 1 9 14
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  2. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, Australia
  3. Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
  4. School of Mathematics and Physic, The University of Queensland, St Lucia, QLD, Australia
  5. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
  6. Viral Immunology Group,, Adelaide Medical School, Adelaide, SA, Australia
  7. Sunshine Coast University Hospital, Queensland Health, Birtinya, QLD, Australia
  8. National Centre for Epidemiology and Population Health, ANU College of Health and Medicine, Australian National University, Canberra, ACT, Australia
  9. Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia
  10. Mater Research Institute, The University of Queensland, St Lucia, QLD, Australia
  11. Gene Regulation and Translational Medicine Laboratory, Department of Infection and Inflammation, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  12. Department of Respiratory Medicine, Mater Adult Hospital, South Brisbane, QLD, Australia
  13. Faculty of Medicine, The University of Queensland, St Lucia, QLD, Australia
  14. Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, QLD, Australia
  15. The University of Queensland, St Lucia, QLD, Australia

Introduction: Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC)1. Many individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS)2. The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be determined.

Methods: Plasma samples were donated from healthy and fully recovered patients, and individuals with long-term PASC-CVS (defined by self-reported symptoms of chest pain and/or heart palpitations persisting for >1 year after SARS-CoV-2 infection). Samples were investigated for differences in transcriptome and proteome, and inflammatory cytokine and cardiac damage biomarker levels. Both samples and recombinant human cytokines were used to treat human cardiomyocytes to assess direct effects on cardiac physiology.

Results: Here, we show that compared to individuals with a resolved SARS-CoV-2 infection (and no persistent symptoms), individuals with prolonged PASC-CVS had elevated levels of pro-inflammatory cytokines. However, these cytokines were found to be present in trace amounts, such that they could only be detected with the use of novel nanotechnology3. Importantly, these trace-level cytokines had a direct effect on the functionality of primary human cardiomyocytes in vitro. Proteomics analyses demonstrated further differences in PASC-CVS and recovered plasma including increased abundance of complement and coagulation associated proteins.

Conclusion: Together, these data provide important new insights into the cardiovascular complications of the complex disease that is PASC and offers opportunities to improve the diagnosis, treatment and understanding of the ever-growing number of individuals living with PASC-CVS.

  1. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology 2023; 21(3): 133-46.
  2. Sato K, Sinclair JE, Sadeghirad H, Fraser JF, Short KR, Kulasinghe A. Cardiovascular disease in SARS‐CoV‐2 infection. Clinical & Translational Immunology 2021; 10(9): e1343.
  3. Li J, Wuethrich A, Sina AA, et al. A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy. Nature communications 2021; 12(1): 1-12.