Unique immune signatures predict potential cardiometabolic risk in severe COVID-19 patients and COVID-19 recovered individuals

Abstract Covid-19, the disease caused by SARS-CoV-2 infection, has resulted in millions of deaths and led to a global public health emergency. SARS-CoV-2 infected patients exhibit a wide variety of phasic clinical manifestations ranging from asymptomatic to severe complications and death. SARS-CoV-2 infection can lead to excessive immune activation, inflammation and multi-organ damage. Clinical data showed that COVID-19 may promote the development of cardiovascular disorders (CVDs). Immune activation, thrombosis, cytokine storm, and altered adhesion molecule expression on leukocyte populations have been proposed as possible mechanisms that trigger COVID-19 associated CVDs. A lack of systematic studies on how SARS-CoV-2 infection triggered immune responses that may lead to CVDs, hinder early risk identification and therapeutic interventions. In this study, by using deep immune profiling and extensive cytokine and chemokine profiling, we explore potential mechanisms of developing CVDs in severe COVID-19 patients (ICU) (n=20) as well as patients recovered from COVID-19 (RD) (n=30). We identify core immune signatures in ICU patients and RD compared to healthy controls (n=17) that may predict potential cardiovascular risk. We found that significantly elevated eosinophils and neutrophils and increased circulating levels of tissue factor, fatty acid binding protein 4 and, LPS binding protein in ICU patients suggested increased immune activation and thrombotic risk. Interestingly, we found significant elevation of several immune parameters (TIMP-1, TIMP-2, Monocytes) that were associated with cardiometabolic risk, in RD group. Thus, our data suggest a possible mechanistic link between severe COVID-19 and cardiometabolic risk.