Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

Immunophenotypes of monocyte subsets and platelets during acute SARS-CoV-2 infection and three months after COVID-19 in patients with cardiovascular disease
C. Langnau1, K.-P. Kreißelmeier1, M. Günter2, S. Pöschel3, S. Gekeler1, Á. Petersen Uribe1, P. Jaeger1, I. I. Müller1, B. Koch1, H. Janning1, T. Castor1, D. Rath1, M. Gawaz1, S. Autenrieth2, K. A. L. Müller1
1Innere Medizin III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Tübingen; 2Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; 3Innere Medizin 2, Universitätsklinikum Tübingen, Tübingen;

Background:
COVID-19 is caused by SARS-CoV-2 and can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. Therefore, we aimed to describe and compare the immunological features of CVD patients during acute SARS-CoV-2 infection and after a three month recovery period. We hypothesized to identify disease-related immunophenotypes of monocytes in the immune response of patients with CVD and specific patterns of platelet activation.

Methods:
We prospectively studied a cohort of 23 patients with CVD and acute SARS-CoV-2 infection. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 hours of admission. Clinical follow up (FU) was performed after 3 months of recovery to evaluate changes in platelet activation and monocyte immunophenotypes. The three subsets of monocytes were defined as classical (CD14++CD16-), intermediate (CD14+CD16+), and non-classical (CD14dimCD16++) monocytes.

Results:
The numbers of white blood cells (WBC) were significantly decreased during acute SARS-CoV-2 infection compared to the recovery phase at 3 months FU. Numbers of classical and non-classical monocytes were also significantly decreased during acute SARS-CoV-2 infection. While classical monocytes reached their expected amounts in peripheral blood (pre-defined by analyses of a healthy control group) after 3 months recovery, numbers of non-classical monocyte increased, however were still significantly reduced compared to levels in peripheral blood of healthy controls during FU. Numbers of platelets did not show any differences in the acute and recovery phase, but platelet-leucocyte aggregates showed a significant reactive increase during the recovery phase. Moreover, all three monocyte subsets showed changes in the expression of established markers of adhesion, migration, and T cell activation (CD62L, CX3CR1, CCR2, CCR7, CD 11b, HLA-DR) and most interestingly also expressed higher amounts of pro-inflammatory chemokines like macrophage migration inhibitory factor (MIF) at the time of recovery. MIF was only mildly increased during the acute phase. In contrast, CXCL12 expression was already significantly enhanced during the acute phase and went down to normal levels during the recovery phase. Our findings in monocyte subsets might indicate prolonged pro-inflammatory regulations of monocyte function mediated by MIF after acute SARS-CoV-2 infection in CVD patients. However, altered MIF expression was not associated with the occurrence of cardiovascular events during three months FU. Finally, platelet activation defined by high expression of CD62P was significantly enhanced during acute SARS-CoV-2 infection and reached normal levels at the time of 3 months recovery.

Conclusion:
Patients with CVD and acute SARS-CoV-2 infection showed changes regarding their phenotype of monocytes and platelet activation after three months recovery. Altered monocyte function and chemokine expression, in particular MIF, was characteristic for the recovery phase at 3 months after acute SARS-CoV-2 infection. MIF might play a key role in prolonged enhancement of pro-inflammatory response mediated by monocytes even three months after acute SARS-Cov-2 infection. Therefore, MIF expression in monocytes may serve as additional biomarker to identify patients at risk for an altered, possibly prolonged immune response after acute SARS-CoV-2 infection.


https://dgk.org/kongress_programme/jt2022/aV27.html