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  • Complement lectin pathway a...
    Hurler, Lisa; Szilágyi, Ágnes; Mescia, Federica; Bergamaschi, Laura; Mező, Blanka; Sinkovits, György; Réti, Marienn; Müller, Veronika; Iványi, Zsolt; Gál, János; Gopcsa, László; Reményi, Péter; Szathmáry, Beáta; Lakatos, Botond; Szlávik, János; Bobek, Ilona; Prohászka, Zita Z; Förhécz, Zsolt; Csuka, Dorottya; Kajdácsi, Erika; Cervenak, László; Kiszel, Petra; Masszi, Tamás; Vályi-Nagy, István; Würzner, Reinhard; Lyons, Paul A; Toonen, Erik J M; Prohászka, Zoltán

    Frontiers in immunology, 03/2023, Letnik: 14
    Journal Article

    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. 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. 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. 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.