New Insights into the Role of the Complement System in Human Viral Diseases

Abstract

The complement system (CS) is part of the human immune system, consisting of more than 30 proteins that play a vital role in the protection against various pathogens and diseases, including viral diseases. Activated via three pathways, the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP), the complement system leads to the formation of a membrane attack complex (MAC) that disrupts the membrane of target cells, leading to cell lysis and death. Due to the increasing number of reports on its role in viral diseases, which may have implications for research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this review aims to highlight significant progress in understanding and defining the role of the complement system in four groups of diseases of viral etiology: (1) respiratory diseases; (2) acute liver failure (ALF); (3) disseminated intravascular coagulation (DIC); and (4) vector-borne diseases (VBDs). Some of these diseases already present a serious global health problem, while others are a matter of concern and require the collaboration of relevant national services and scientists with the World Health Organization (WHO) to avoid their spread.

Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients.

“…Interleukin [IL]-6) there is growing evidence that complement activation plays a crucial role [ 6 ] as suggested by increased plasma levels of activation products (soluble C5b9 [sC5b-9], C5a) and complement deposits in the affected tissues of COVID-19 patients [ [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] ]. This finding is consistent with the complement involvement reported in several viral diseases including infections with other coronaviruses [ [27] , [28] , [29] ] and the suggested protective effects of complement blockade on COVID-19 [ 6 ].…”

Association between trauma exposure and respiratory disease-A Mendelian randomization study

“…Additionally, the accompanying pro-inflammatory environment can have a deleterious impact on cell adhesion junctions ( 25 ). Involved in this process are both the activation of the complement system pathway and the synthesis of C5a by lipopolysaccharide ( 26 ).…”

Complement C3 Facilitates Stratification of Stages of Chronic Hepatitis B and Signifies Development of Acute-on-Chronic Liver Failure in Acute Decompensated Cirrhosis

“…The complement system participates in the immune response against infection [ 6 , 7 ]. Activated complement component 3 (C3) can contribute to extensive tissue damage by increasing the production of proinflammatory cytokines from T lymphocytes [ 8 ].…”

“…Activated complement component 3 (C3) can contribute to extensive tissue damage by increasing the production of proinflammatory cytokines from T lymphocytes [ 8 ]. Deposition of C3 in infected tissue can be observed after various viral infections, including influenza, coronavirus infection and hepatitis [ 7 , 9 , 10 ]. Reduced serum C3 levels has been observed in patients with liver failure [ 11 ].…”