Immune signature of patients with cardiovascular disease – in-depth immunophenotyping predicts increased risk for a severe course of COVID-19
Authors: Günter Manina , Mueller Karin Anne Lydia , Salazar Mathew , Gekeler Sarah , Prang Carolin , Harm Tobias , Gawaz Meinrad Paul , Autenrieth Stella E. 
Published: April 2023

AbstractObjectiveSARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at hospital admission are still missing. Here, we investigated whether the severity of SARS-CoV-2 infection can be predicted by analyzing the immunophenotype in the blood of CVD patients.Approach and ResultsWe prospectively analyzed the peripheral blood of 94 participants, including CVD patients with acute SARS-CoV-2 infection, uninfected CVD patients, and healthy donors using a 36-color spectral flow cytometry panel. Clinical assessment included blood sampling, echocardiography, and electrocardiography. Patients were classified by their ISARIC WHO 4C-Mortality-Score on the day of admission into three subgroups of an expected mild, moderate, or severe course of COVID-19. Unsupervised data analysis revealed 40 clusters corresponding to major circulating immune cell populations. This revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+T cells, and plasmablasts than uninfected CVD patients. In contrast, fewer dendritic cells, CD16+monocytes, innate lymphoid cells, and CD8+T cell subsets were detected in SARS-CoV-2-infected CVD patients. We identified an immune signature characterized by low frequencies of MAIT and intermediate effector CD8+T cells in combination with a high frequency of NKT cells that is predictive for CVD patients with a severe course of SARS-CoV-2 infection on hospital admission.ConclusionAcute SARS-CoV-2 infected CVD patients revealed marked changes in abundance and phenotype of several immune cell populations associated with COVID-19 severity. Our data indicate that intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.HighlightsPatients with cardiovascular disease are at higher risk of severe courses of COVID-19 and may exhibit an altered immune responseUnsupervised data analysis revealed that patients with cardiovascular disease and SARS-CoV-2 infection showed significant changes in the abundance and the phenotype of various immune cell populationsWe identified a disease-related immune signature in patients with cardiovascular disease and SARS-CoV-2 infection associated with the severity of COVID-19Intensified immunophenotyping helps to identify cardiovascular patients at risk of a severe course of COVID-19 already at the early stages of the disease and might thereby improve clinical outcomes and specific treatment of COVID-19