Delayed viral clearance and exacerbated airway hyperinflammation in hypertensive COVID-19 patients

Trump, S.; Lukassen, S.; Anker, M. S.; Chua, R. L.; Liebig, J.; Thürmann, L.; Corman, V. M.; Binder, M.; Loske, J.; Klasa, C.; Krieger, T. G.; Hennig, B. P.; Messingschlager, M.; Pott, F.; Kazmierski, J.; Twardziok, S.; Albrecht, J. P.; Eils, J.; Hadzibegovic, S.; Lena, A.; Heidecker, B.; Goffinet, C.; Kurth, F.; Witzenrath, M.; Völker, M. T.; Müller, S. D.; Liebert, U. G.; Ishaque, N.; Kaderali, L.; Sander, L. E.; Laudi, S.; Drosten, C.; Eils, R.; Conrad, C.; Landmesser, U.; Lehmann, I.

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 and in vitro experiments, 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 receptor ACE2 in 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 of CCL3, CCL4, and its receptor CCR1, 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-patients.