Publication date: Dec 13, 2025
Patients with cardiovascular disease (CVD) have an increased risk of developing severe respiratory infections, including COVID-19. However, the underlying molecular mechanisms are not completely understood. It has been previously shown that cardiovascular disease predisposes to an altered responsiveness to subsequent inflammatory triggers by an imprinted epigenetic memory in innate immune cells. Therefore, we hypothesized that patients with preexisting atherosclerotic cardiovascular disease (ASCVD) and COVID-19 display a dysregulated inflammatory response compared to patients without ASCVD due to epigenetically altered immune cells leading to increased disease severity. Single-cell RNA sequencing revealed a dysregulated myeloid immune response with hyperinflammatory and immunosuppressive features in patients with ASCVD and moderate COVID-19. Assay for Transposase-Accessible Chromatin sequencing and in-vitro experiments with isolated monocytes infected with SARS-CoV-2 showed epigenetic priming of monocytes from patients with ASCVD towards increased expression of inflammatory mediators and type I interferon signalling. In a German nationwide cohort (NAPKON), using multiplex cytokine assays, enzyme-linked immunosorbent assays, and bulk-RNA-sequencing, we confirmed that patients with ASCVD display an exaggerated inflammatory response during moderate COVID-19. This study demonstrates that patients with ASCVD show a dysregulated myeloid immune response in moderate COVID-19 disease. Mechanistically, epigenetic imprinting sensitizes myeloid cells of patients with ASCVD to an exaggerated type I interferon-associated immune response. This study evaluates the underlying molecular mechanisms of worse outcomes of patients with atherosclerotic cardiovascular disease during respiratory infections, specifically COVID-19. Patients with atherosclerotic cardiovascular disease present with a dysregulated hyperinflammatory, type I interferon-driven immune response already during moderate COVID-19. This not only explains a major risk factor for severe COVID-19 but might also enable targeted therapies for this specific risk group.
| Concepts | Keywords |
|---|---|
| Atherosclerosis | Cardiovascular inflammation |
| Cardiovascular | COVID-19 |
| German | NAPKON |
| Molecular | SARS-CoV-2 |
| Nationwide | Single-cell-RNA-sequencing |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Atherosclerosis |
| disease | MESH | COVID-19 |
| disease | MESH | cardiovascular disease |
| disease | MESH | respiratory infections |
| disease | MESH | inflammation |