AUTHOR=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 , Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration , Lyons Paul A. , Toonen Erik J. M. , Prohászka Zoltán , Baker Stephen , Bradley John R. , Chinnery Patrick F. , Cooper Daniel J. , Dougan Gordon , Goodfellow Ian G. , Gupta Ravindra K. , Kingston Nathalie , Lehner Paul J. , Lyons Paul A. , Matheson Nicholas J. , Saunders Caroline , Smith Kenneth G. C. , Summers Charlotte , Thaventhiran James , Torok M. Estee , Toshner Mark R. , Weekes Michael P. , Alvio Gisele , Baker Sharon , Bermperi Areti , Brookes Karen , Bucke Ashlea , Calder Jo , Canna Laura , Crucusio Cherry , Cruz Isabel , de Jesus Rnalie , Dempsey Katie , Di Stephano Giovanni , Domingo Jason , Elmer Anne , Harris Julie , Hewitt Sarah , Jones Heather , Jose Sherly , Kennet Jane , King Yvonne , Kourampa Jenny , Li Emily , McMahon Caroline , Meadows Anne , Mendoza Vivien , O’Brien Criona , Ocaya Charmain , Pascuale Ciro , Perales Marlyn , Price Jane , Rastall Rebecca , Ribeiro Carla , Rowlands Jane , Ruffolo Valentina , Tordesillas Hugo , Vargas Phoebe , Vergese Bensi , Watson Laura , Worsley Jieniean , Zerrudo Julie-Ann , Bergamaschi Laura , Betancourt Ariana , Bower Georgie , Bullman Ben , Cossetti Chiara , De Sa Aloka , Dunore Benjamin J. , Epping Maddie , Fawke Stuart , Gräf Stefan , Grenfell Richard , Hinch Andrew , Hodgson Josh , Huang Christopher , Huhn Oisin , Hunter Kelvin , Jarvis Isobel , Jones Emma , Josipović Maša , Legchenko Ekaterina , Lewis Daniel , Marsden Joe , Martin Jennifer , Mescia Federica , Nice Francesca , O’Donnell Ciara , Omarjee Ommar , Perera Marianne , Pointon Linda , Pond Nicole , Richoz Nathan , Romashova Nika , Savoinykh Natalia , Sharma Rahul , Shih Joy , Strezlecki Mateusz , Sutcliffe Rachel , Tilly Tobias , Tong Zhen , Treacy Carmen , Turner Lori , Wood Jennifer , Wylot Marta , Allison John , Biggs Heather , Butcher Helen , Caputo Daniela , Clapham-Riley Debbie , Dewhurst Eleanor , Fernandez Christian , Furlong Anita , Graves Barbara , Gray Jennifer , Ivers Tasmin , Le Gresley Emma , Linger Rachel , Kasanicki Mary , Meloy Sarah , Muldoon Francesca , Ovington Nigel , Papadia Sofia , Penkett Christopher J. , Phelan Isabel , Ranganath Venkatesh , Sambrook Jennifer , Schon Katherine , Stark Hannah , Stirrups Kathleen E. , Townsend Paul , von Ziegenweidt Julie , Webster Jennifer , Asaripour Ali , Mwaura Lucy , Patterson Caroline , Polwarth Gary , Bunclark Katherine , Mackay Michael , Michael Alice , Rossi Sabrina , Selvan Mayurun , Spencer Sarah , Yong Cissy , Polgarova Petra TITLE=Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1162171 DOI=10.3389/fimmu.2023.1162171 ISSN=1664-3224 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.