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 I. Labzin, Laura Ziser, Katharina Ronacher, Leanne Wallace, Yiwen Zhang, Kyle L. Macauslane, Daniel Ellis, Sudha Rao, Lucy Burr, Amanda L. Bain, Anjana C. Karawita, Benjamin L. Schulz, Junrong Li, David J. Lynn, Nathan J. Palpant, Alain Wuethrich, Matt Trau, Kirsty R. Short
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. Sinclair et al. explore the contribution of chronic inflammation to cardiovascular symptoms associated with post-acute sequelae of SARS-CoV-2 infection (PASC-CVS). The authors identify trace levels of inflammatory cytokines in individuals with PASC-CVS that impair the function of cardiomyocytes derived from induced pluripotent stem cells.