Delayed viral clearance and exacerbated airway hyperinflammation in hypertensive COVID-19 patients
Abstract In COVID-19, hypertension and cardiovascular diseases have emerged as major risk factors for critical disease progression. Concurrently, the impact of the main anti-hypertensive therapies, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), on COVID-19 severity is controversially discussed. By combining clinical data, single-cell sequencing data of airway samples andin vitroexperiments, we assessed the cellular and pathophysiological changes in COVID-19 driven by cardiovascular disease and its treatment options. Anti-hypertensive ACEi or ARB therapy, was not associated with an altered expression of SARS-CoV-2 entry receptorACE2in nasopharyngeal epithelial cells and thus presumably does not change susceptibility for SARS-CoV-2 infection. However, we observed a more critical progress in COVID-19 patients with hypertension associated with a distinct inflammatory predisposition of immune cells. While ACEi treatment was associated with dampened COVID-19-related hyperinflammation and intrinsic anti-viral responses, under ARB treatment enhanced epithelial-immune cell interactions were observed. Macrophages and neutrophils of COVID-19 patients with hypertension and cardiovascular comorbidities, in particular under ARB treatment, exhibited higher expression ofCCL3, CCL4, and its receptorCCR1, which associated with critical COVID-19 progression. Overall, these results provide a potential explanation for the adverse COVID-19 course in patients with cardiovascular disease, i.e. an augmented immune response in critical cells for the disease course, and might suggest a beneficial effect of clinical ACEi treatment in hypertensive COVID-19 patients..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 08. Okt. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2020.09.22.20199471 |
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| PPN (Katalog-ID): |
XBI018806686 |
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| 520 | |a Abstract In COVID-19, hypertension and cardiovascular diseases have emerged as major risk factors for critical disease progression. Concurrently, the impact of the main anti-hypertensive therapies, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), on COVID-19 severity is controversially discussed. By combining clinical data, single-cell sequencing data of airway samples andin vitroexperiments, we assessed the cellular and pathophysiological changes in COVID-19 driven by cardiovascular disease and its treatment options. Anti-hypertensive ACEi or ARB therapy, was not associated with an altered expression of SARS-CoV-2 entry receptorACE2in nasopharyngeal epithelial cells and thus presumably does not change susceptibility for SARS-CoV-2 infection. However, we observed a more critical progress in COVID-19 patients with hypertension associated with a distinct inflammatory predisposition of immune cells. While ACEi treatment was associated with dampened COVID-19-related hyperinflammation and intrinsic anti-viral responses, under ARB treatment enhanced epithelial-immune cell interactions were observed. Macrophages and neutrophils of COVID-19 patients with hypertension and cardiovascular comorbidities, in particular under ARB treatment, exhibited higher expression ofCCL3, CCL4, and its receptorCCR1, which associated with critical COVID-19 progression. Overall, these results provide a potential explanation for the adverse COVID-19 course in patients with cardiovascular disease, i.e. an augmented immune response in critical cells for the disease course, and might suggest a beneficial effect of clinical ACEi treatment in hypertensive COVID-19 patients. | ||
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