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

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.