Thromboinflammation Supports Complement Activation in Cancer Patients With COVID-19

Background COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients. Objective This study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation. Methods Markers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 mu g/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response. Results Increases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU. Conclusion Complement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.

Automated summary

The study found that cancer patients with COVID-19 exhibit circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation. Furthermore, complement activation in cancer patients with COVID-19 increases significantly in the presence of thromboinflammation, indicating a possible link between coagulation and complement cascades during inflammation.