tetano
Editor, Senior Moderator
Front Immunol
. 2023 Mar 27;14:1162171.
doi: 10.3389/fimmu.2023.1162171. eCollection 2023.
Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups
Lisa Hurler[SUP] 1 [/SUP], Ágnes Szilágyi[SUP] 1 [/SUP], Federica Mescia[SUP] 2 3 [/SUP], Laura Bergamaschi[SUP] 2 3 [/SUP], Blanka Mező[SUP] 1 4 [/SUP], György Sinkovits[SUP] 1 [/SUP], Marienn Réti[SUP] 5 [/SUP], Veronika Müller[SUP] 6 [/SUP], Zsolt Iványi[SUP] 7 [/SUP], János Gál[SUP] 7 [/SUP], László Gopcsa[SUP] 5 [/SUP], Péter Reményi[SUP] 5 [/SUP], Beáta Szathmáry[SUP] 8 [/SUP], Botond Lakatos[SUP] 8 [/SUP], János Szlávik[SUP] 8 [/SUP], Ilona Bobek[SUP] 9 [/SUP], Zita Z Prohászka[SUP] 1 [/SUP], Zsolt Förhécz[SUP] 1 [/SUP], Dorottya Csuka[SUP] 1 [/SUP], Erika Kajdácsi[SUP] 1 [/SUP], László Cervenak[SUP] 1 [/SUP], Petra Kiszel[SUP] 4 [/SUP], Tamás Masszi[SUP] 1 [/SUP], István Vályi-Nagy[SUP] 5 [/SUP], Reinhard Würzner[SUP] 10 [/SUP]; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Paul A Lyons[SUP] 2 3 [/SUP], Erik J M Toonen[SUP] 11 [/SUP], Zoltán Prohászka[SUP] 1 4 [/SUP]
Collaborators, Affiliations
Abstract
Introduction: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.
Methods: We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.
Results: We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.
Conclusion: In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.
Keywords: COVID-19; MBL2 genotypes; lectin pathway activation; lectin pathway of complement; mannose binding lectin (MBL); severe acute respiratory coronavirus 2 (SARS-CoV-2).
. 2023 Mar 27;14:1162171.
doi: 10.3389/fimmu.2023.1162171. eCollection 2023.
Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups
Lisa Hurler[SUP] 1 [/SUP], Ágnes Szilágyi[SUP] 1 [/SUP], Federica Mescia[SUP] 2 3 [/SUP], Laura Bergamaschi[SUP] 2 3 [/SUP], Blanka Mező[SUP] 1 4 [/SUP], György Sinkovits[SUP] 1 [/SUP], Marienn Réti[SUP] 5 [/SUP], Veronika Müller[SUP] 6 [/SUP], Zsolt Iványi[SUP] 7 [/SUP], János Gál[SUP] 7 [/SUP], László Gopcsa[SUP] 5 [/SUP], Péter Reményi[SUP] 5 [/SUP], Beáta Szathmáry[SUP] 8 [/SUP], Botond Lakatos[SUP] 8 [/SUP], János Szlávik[SUP] 8 [/SUP], Ilona Bobek[SUP] 9 [/SUP], Zita Z Prohászka[SUP] 1 [/SUP], Zsolt Förhécz[SUP] 1 [/SUP], Dorottya Csuka[SUP] 1 [/SUP], Erika Kajdácsi[SUP] 1 [/SUP], László Cervenak[SUP] 1 [/SUP], Petra Kiszel[SUP] 4 [/SUP], Tamás Masszi[SUP] 1 [/SUP], István Vályi-Nagy[SUP] 5 [/SUP], Reinhard Würzner[SUP] 10 [/SUP]; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Paul A Lyons[SUP] 2 3 [/SUP], Erik J M Toonen[SUP] 11 [/SUP], Zoltán Prohászka[SUP] 1 4 [/SUP]
Collaborators, Affiliations
- PMID: 37051252
- PMCID: PMC10084477
- DOI: 10.3389/fimmu.2023.1162171
Abstract
Introduction: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.
Methods: We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.
Results: We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.
Conclusion: In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.
Keywords: COVID-19; MBL2 genotypes; lectin pathway activation; lectin pathway of complement; mannose binding lectin (MBL); severe acute respiratory coronavirus 2 (SARS-CoV-2).