Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups
Copyright © 2023 Hurler, Szilágyi, Mescia, Bergamaschi, Mező, Sinkovits, Réti, Müller, Iványi, Gál, Gopcsa, Reményi, Szathmáry, Lakatos, Szlávik, Bobek, Prohászka, Förhécz, Csuka, Kajdácsi, Cervenak, Kiszel, Masszi, Vályi-Nagy, Würzner, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Lyons, Toonen and Prohászka..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 10., Seite 1162171 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hurler, Lisa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.04.2023 Date Revised 24.04.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1162171 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups |
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| 500 | |a Date Revised 24.04.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Hurler, Szilágyi, Mescia, Bergamaschi, Mező, Sinkovits, Réti, Müller, Iványi, Gál, Gopcsa, Reményi, Szathmáry, Lakatos, Szlávik, Bobek, Prohászka, Förhécz, Csuka, Kajdácsi, Cervenak, Kiszel, Masszi, Vályi-Nagy, Würzner, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Lyons, Toonen and Prohászka. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a MBL2 genotypes | |
| 650 | 4 | |a lectin pathway activation | |
| 650 | 4 | |a lectin pathway of complement | |
| 650 | 4 | |a mannose binding lectin (MBL) | |
| 650 | 4 | |a severe acute respiratory coronavirus 2 (SARS-CoV-2) | |
| 650 | 7 | |a Lectins |2 NLM | |
| 650 | 7 | |a MBL2 protein, human |2 NLM | |
| 650 | 7 | |a Mannose-Binding Lectin |2 NLM | |
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| 700 | 1 | |a Toonen, Erik J M |e verfasserin |4 aut | |
| 700 | 1 | |a Prohászka, Zoltán |e verfasserin |4 aut | |
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