Front Immunol: In SARS-CoV-2 infection, excessive activation and consumption of complement can increase hospital mortality!

Infection-mediated endothelial injury and inflammation have been observed in the blood vessels of various organs of COVID-19 , which may lead to excessive thrombin, trigger thrombus inflammation and ultimately lead to microthrombus deposition and microvascular dysfunction
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In the case of rapid virus replication, T cell lymphatic failure, interferon signaling is suppressed, innate immunity is over-activated , and pro-inflammatory cytokines such as IL-6 and TNFα are produced in large quantities, resulting in immune response disorders and cytokine release syndrome .

Endothelial injury and inflammation micro thrombus deposition and microvascular dysfunction overactivation of the immune response and cytokine release syndrome disorders Severe

Purpose: Out -of- control thrombotic inflammation plays an important role in the pathogenesis of coronavirus (COVID-19) caused by SARS-CoV-2 virus
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Complement is considered to be a key factor in this process, so we speculate that the markers of complement system activation may be related to the severity and mortality of COVID-19

Thrombotic inflammation out of control

Methods: In this prospective cohort study, samples of 102 hospitalized patients and 26 patients with COVID-19 confirmed by PCR were analyzed
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The main result is COVID-19-related mortality during hospitalization, and the secondary result is the severity of COVID-19 as assessed by the WHO sequential score

Results: Hospitalized COVID-19 patients have the characteristics of enhanced complement activation
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Complement activation is significantly associated with inflammatory markers such as interleukin-6, C-reactive protein, and ferritin

Uncontrolled complement activation leads to a higher mortality rate in patients with complement C3 depletion and decreased complement activity than patients with complement activation but not depletion

Table 1 Correlation between complement parameters and inflammation and fibrinolysis indicators
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Table 1 Correlation between complement parameters and inflammation and fibrinolysis indicators
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Table 2 Univariate and multivariate Cox proportional hazards regression model results analysis of the effect of complement overactivation on hospital mortality; C3a level and C3a/C3 ratio are used as categorical variables,

Table 2 Univariate and multivariate Cox proportional hazards regression model results analysis of the effect of complement overactivation on hospital mortality; C3a level and C3a/C3 ratio are used as categorical variables,

Distinguish patients with high or low levels of complement activation (C3a cut-off point is 324 ng/mL, C3a/C3 cut-off point is 200); HR, hazard ratio; CI, confidence interval
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Distinguish patients with high or low levels of complement activation (C3a cut-off point is 324 ng/mL, C3a/C3 cut-off point is 200); HR, hazard ratio; CI, confidence interval
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Conclusion: complement activation and COVID-19 to enhance the progress of the disease related
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When COVID-19 is accompanied by excessive activation and consumption of C3, patients infected with SARS-CoV-2 are more likely to die

Complement activation and COVID-19 to enhance the progress of the disease related

 Sinkovits G, Mező B, Réti M, et al, Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection.

Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection.
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