Abstract
BackgroundCOVID-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.ObjectiveThis study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation.MethodsMarkers 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 μg/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.ResultsIncreases 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.ConclusionComplement 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.
Highlights
The global pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with significant morbidity and mortality [1]
Since complement activation culminates in the production of anaphylatoxins C3a and C5a, as well as the C5b-9 membrane attack complex, which fuel inflammation and tissue damage [15], the current study was designed to investigate the effect of COVID-19 on circulating markers of complement activation (C3a, C5a, sC5b-9), in cancer patients with and without thromboinflammation as evidenced by plasma D-dimer levels
Complement activation was similar in COVID-19 positive and negative cohorts with low D-dimers
Summary
The global pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with significant morbidity and mortality [1]. The D-dimer, which represents a fibrin degradation product, is indicative of activation of coagulation and fibrinolysis, and elevated levels are associated with poor prognosis in patients with COVID-19 [12]. Since complement activation culminates in the production of anaphylatoxins C3a and C5a, as well as the C5b-9 membrane attack complex, which fuel inflammation and tissue damage [15], the current study was designed to investigate the effect of COVID-19 on circulating markers of complement activation (C3a, C5a, sC5b-9), in cancer patients with and without thromboinflammation as evidenced by plasma D-dimer levels. COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation.
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