ABSTRACT
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic corona virus which causes COVID-19 and resulted in millions of deaths and led to a global public health emergency. SARS-CoV-2 infected patients exhibit a wide variety of 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. Methods: In this study, by using deep immune cell profiling (high dimensional flowcytometry) in fresh whole blood and extensive plasma cytokine and chemokine profiling, we explore potential mechanisms that could lead to CVDs in severe COVID-19 patients that did not have previous known CVDs (ICU) (n=20) as well as patients recovered from COVID-19 (RD) (n=30) compared to healthy donors (n=17). To identify the major statistically significant immune signatures that predict CVD risk in ICU patients and RD, we performed parametric (ANOVA) and non-parametric (Kruskal-Wallis) statistical tests with Dunn's and Tukey's post hoc tests. Integrative correlation and network analysis were performed by computing Spearman's coefficients. Correlations with r > 0.3 , r <-0.3 and P < 0.01 were considered significant. Results: We found that significantly elevated eosinophils, 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, M-CSF, Monocytes) that were associated with cardiometabolic risk, even 3-4 months after the recovery of initial COVID-19 infection in RD. Furthermore, we found unique relationship with cytokine and cellular responses in ICU and RD groups compare with HD. Conclusion: Our data strongly suggest a possible mechanistic link between SARS-CoV-2 induced dysregulated immune responses and increased cardiometabolic risk in severe COVID-19 patients.