The beneficial and pathogenic roles of complement in COVID-19

Kim, Alfred H.J.; Wu, Xiaobo; Atkinson, John P.

doi:10.3949/ccjm.87a.ccc065

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Given that C2 is expressed at higher levels in the liver and lungs, and C9 expression is restricted to the liver 85 , our finding of elevated levels of C2 and C9 proteins in the COVID-19 groups could be indicative of the unregulated activation of the complement system in these organs. Currently, it is believed that the complement system has a contradictory role in COVID-19 infection where it is beneficial in mild or asymptomatic cases and harmful in severe cases 78,86 .…”

Section: Complement Activationmentioning

confidence: 99%

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Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Rahnavard

Mann

Giri

et al. 2021

Preprint

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Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.

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Section: Complement Activationmentioning

confidence: 99%

“…The complement system involves a protein cascade that is typically classified as either the classical lectin or alternative pathways [76][77][78] . This system plays a major role in B lymphocyte regulation, inflammation, and host protection 79 , and consequently has been associated with proinflammatory actions and diseases 80 .…”

Section: Complement Activationmentioning

confidence: 99%

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Rahnavard

Mann

Giri

et al. 2021

Preprint

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“…SARS-CoV-2 infection triggers an innate immune response including CS activation which is a key weapon both implicated in disease resolution and organ damage depending on the time of infection (15).…”

Section: Discussionmentioning

confidence: 99%

Complement Alternative and Mannose-Binding Lectin Pathway Activation Is Associated With COVID-19 Mortality

et al. 2021

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BackgroundThe SARS-CoV-2 infection triggers excessive immune response resulting in increased levels of pro-inflammatory cytokines, endothelial injury, and intravascular coagulopathy. The complement system (CS) activation participates to this hyperinflammatory response. However, it is still unclear which activation pathways (classical, alternative, or lectin pathway) pilots the effector mechanisms that contribute to critical illness. To better understand the immune correlates of disease severity, we performed an analysis of CS activation pathways and components in samples collected from COVID-19 patients hospitalized in Grenoble Alpes University Hospital between 1 and 30 April 2020 and of their relationship with the clinical outcomes.MethodsWe conducted a retrospective, single-center study cohort in 74 hospitalized patients with RT-PCR-proven COVID-19. The functional activities of classical, alternative, and mannose-binding lectin (MBL) pathways and the antigenic levels of the individual components C1q, C4, C3, C5, Factor B, and MBL were measured in patients’ samples during hospital admission. Hierarchical clustering with the Ward method was performed in order to identify clusters of patients with similar characteristics of complement markers. Age was included in the model. Then, the clusters were compared with the patient clinical features: rate of intensive care unit (ICU) admission, corticoid treatment, oxygen requirement, and mortality.ResultsFour clusters were identified according to complement parameters. Among them, two clusters revealed remarkable profiles: in one cluster (n = 15), patients exhibited activation of alternative and lectin pathways and low antigenic levels of MBL, C4, C3, Factor B, and C5 compared to all the other clusters; this cluster had the higher proportion of patients who died (27%) and required oxygen support (80%) or ICU care (53%). In contrast, the second cluster (n = 19) presented inflammatory profile with high classical pathway activity and antigenic levels of complement components; a low proportion of patients required ICU care (26%) and no patient died in this group.ConclusionThese findings argue in favor of prominent activation of the alternative and MBL complement pathways in severe COVID-19, but the spectrum of complement involvement seems to be heterogeneous requiring larger studies.

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“…[ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] ].…”

Section: Uncited Referencesunclassified

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade

Vitiello¹,

Porta²,

D’Aiuto³

et al. 2021

Human Immunology

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The beneficial and pathogenic roles of complement in COVID-19

Cited by 7 publications

References 14 publications

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

Complement Alternative and Mannose-Binding Lectin Pathway Activation Is Associated With COVID-19 Mortality

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade

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