An update: the emerging evidence of complement involvement in COVID-19

Abstract

The current outbreak of coronavirus disease 2019 (COVID-19) has affected people around the world. Typically, COVID-19 originates in the lung, but lately it can extend to other organs and lead to tissue injury and multiorgan failure in severe patients, such as acute respiratory distress syndrome (ARDS), kidney failure and sepsis or systemic inflammation. Given that COVID-19 has been detected in a range of other organs, the COVID-19-associated disease is an alert of aberrant activation of host immune response which drives un-controlled inflammation that affects multiple organs. Complement is a vital component of innate immunity where it forms the first line of defense against potentially harmful microbes, but its role in COVID-19 is still not clear. Notably, the abnormal activation and continuous deposits of complement components were identified in the pre-clinical samples from COVID-19 patients, which have been confirmed in animal models. Recent evidence has revealed that the administration of complement inhibitors leads to relieve inflammatory response in ARDS. Hence, we speculate that the targeting complement system could be a potential treatment option for organ damage in COVID-19 patients.

Distinct Immune Response at 1 Year Post-COVID-19 According to Disease Severity

“…In fact, complement hyperactivation by NC is a key feature of severe COVID-19 ( 42 ). It is implicated in its pathogenesis ( 43 , 44 ), but a correlation between anti-SARS-CoV-2 Abs and complement hyperactivation has not been clearly identified ( 45 , 46 ). A recent report suggested that anti-NC Abs are capable of suppressing NC-mediated complement hyperactivation ( 46 ).…”

Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes

“…Hyperactivation of the complement system and neutrophilic immune responses have been associated with worse outcomes in COVID-19 patients [ [10] , [11] , [12] , 16 , 23 , 28 , 35 , 42 ]. It remains unclear, however, whether these are two independent events or are interrelated components of a broader immune cascade.…”

“…Complement is an integral component of the innate immune system that eliminates viral pathogens directly and indirectly through opsonization, formation of the membrane attack complex (MAC) C5b-9 and recruitment of other leukocytes to promote an anti-viral inflammatory response [ 8 , 9 ]. However, clinical data have revealed that increased activation of the complement system is a distinct immunologic feature correlating with worse COVID-19 outcomes [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] . Elevated levels of circulating complement markers were present in patients with COVID-19 compared with other etiologies of acute respiratory failure, and these markers can distinguish those with worse outcomes in the setting of SARS-CoV-2 infection [10] .…”

Atypical Hemolytic Uremic Syndrome after SARS-CoV-2 Infection: Report of Two Cases

“…Although the pathogenesis of multiorgan damage in SARS-CoV-2 differs from aHUS, uncontrolled activation of the complement pathway plays a key role in both diseases. It is associated with the formation of the final products of the complement cascade, responsible for the pro-inflammatory, prothrombotic effects, and cell apoptosis [ 10 , 11 ]. In the past, the standard of care for aHUS patients included plasma infusion (PI) or plasma exchange (PE).…”