SARS-CoV-2 Upregulates CD55 Complement Regulator And Prolongs Its Activation Causing An Immune Dysfunction 


A new study by Greek researchers from Kapodistrian University of Athens, Evangelismos General Hospital-Greece and the Institute for Bioinnovation-Greece has found that the upregulation of CD55 complement regulator in distinct PBMC subpopulations of COVID-19 patients is associated with suppression of interferon responses.

The study findings were published on a preprint server and are currently being peer reviewed.

The complement system acts as an immune surveillance mechanism constantly in search of pathogens 1. Upon recognition of pathogens such as bacteria or viruses its activation results in a cascade of reactions ultimately leading to the lysis and killing of the identified pathogen 2.

Activation of the complement cascade may be regarded as a protective mechanism ultimately leading to the elimination of virus particles and disease progression. However, uncontrolled or prolonged complement activation may have a negative effect contributing to disease pathogenesis.

We have previously reported overactivation of complement in patients with severe and critical COVID-19 in line with similar studies which also showed elevated levels of anaphylatoxins C3a and C5a and increased circulating C5b-9 levels in serum and plasma patient samples 3, 4, 5.

Furthermore, C3a and C5b-9 have been reported as independent predictors of COVID-19 severity and mortality3,6. Significant deposition of C4d, C5b–9 as well as mannan- binding lectin serine protease 2 (MASP2) has been detected in skin and lung samples of COVID-19 patients with a co-localisation of C4d and C5b-9 with SARS-COV-2 spike protein 7.

Complement regulatory proteins (CRPs) CD55, CD59, CD46, and CR1 are all cell surface proteins which act to control complement cascade activation by cleaving complement factors and halting pathway activation (8). Specifically, CR1, CD55 and CD46 act at both the C3 and C5 steps promoting decay of C3 and C5 convertases whereas CD59 acts exclusively at the final step preventing formation of the membrane attack complex (MAC) complex and therefore cell lysis 9.

Taken together the above observations raise the question of whether a dysregulated expression pattern of CRPs may be present in COVID-19 contributing to complement overactivation.

Using single-cell RNA sequencing (scRNA-seq) on PBMC isolated from COVID-19 patients of different disease states we characterised the immune response, assessed the expression signatures of CRPs in the various cellular populations and investigated the probable involvement of CRPs in COVID-19 pathogenesis.


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